Composition of cannabinoid extract of cw1as1 for the treatment of autism and associated symptoms

Abstract

The present disclosure provides botanical drug compositions and methods of their use for treating nervous system and / or mental diseases, conditions, disorders, and / or symptoms.

Description

Attorney Docket No.38383.0001P1 COMPOSITION OF CANNABINOID EXTRACT OF CW1AS1 FOR THE TREATMENT OF AUTISM AND ASSOCIATED SYMPTOMS INCORPORATION BY REFERENCE This application claims priority to U.S. Provisional Application No.63 / 519,006 which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION

[0001] The present disclosure relates to a Cannabis sativa L.-derived compositions and methods of their use for treating autism, epilepsy, and / or symptoms. BACKGROUND OF THE DISCLOSURE

[0002] Botanical cannabinoid extracts with cannabidiol (CBD) as the dominant cannabinoid have the potential to be effective in the treatment of nervous system, including central nervous system (CNS), and mental diseases, conditions, disorders, and / or symptoms.

[0003] One example of a CNS-associated disease includes but is not limited to autism spectrum disorder (ASD). It is estimated that 1 in 68 children may have ASD (CDC 2014). ASD is characterized by deficits in social communication, irritability, repetitive behaviors, impulsivity, temper tantrums, and high caregiver burden (Lecavalier et al 2006).

[0004] There is a long felt need for effective CBD-based botanical pharmaceuticals to use for treating one or more symptoms of autism and epilepsy. SUMMARY OF THE DISCLOSURE

[0005] The present disclosure provides pharmaceutical compositions comprising a cannabinoid extract of Cannabis sativa L. and having a concentration of from beta-caryophyllene at an amount that is 3% to 25% percent of the amount of beta caryophyllene in the air dried plant material from which the extract is obtained, and / or α-bisabolol at an amount that is 3% to 20% percent of the amount of α-bisabolol in the air dried plant material from which the extract is obtained and / or α- humulene at an amount that is 3% to 30% percent of the amount of α-humulene in the air dried plant material from which the extract is obtained.Attorney Docket No.38383.0001P1

[0006] Another aspect of the present disclosure is a pharmaceutical compositions comprising a cannabinoid extract of hemp variety ‘CW1AS1’, wherein representative seeds of the variety have been deposited under NCIMB No.43291. In some embodiments, the extract is a cannabinoid and terpenoid extract of hemp variety ‘CW1AS1’.

[0007] In some embodiments, the pharmaceutical compositions of the present disclosure comprise, consists of, or consists essentially of a cannabinoid extract and glyceryl monolinoleate, such as unsaturated glycerol monolinoleate, and optionally a flavoring agent. In some embodiments, the composition is not an emulsion.

[0008] Another aspect of the present disclosure is methods of treating autism, epilepsy, or one or more symptoms thereof by administering an effective amount of the pharmaceutical compositions of the present disclosure.

[0009] In some embodiments, the methods of treating as disclosed herein are for treating a primary indication of a disease, disorder, condition, or symptom.

[0010] In some embodiments, the methods of treating as disclosed herein are for treating a secondary indication of a disease, disorder, condition, or symptom. In some embodiments, the methods of treating as disclosed herein are for treating anxiety and / or irritability associated with autism.

[0011] The present disclosure provides methods of treating a disease, disorder, condition, and / or symptom, including symptoms associated with autism spectrum disorder, by administering the pharmaceutical composition with the cannabinoid extract of CW1AS1 being about 25 mg to about 650 mg for a <14 year old patient daily dose and about 50 mg to about 650 mg for an adult daily dose.

[0012] Current autism spectrum disorder (ASD) treatments are limited in efficacy and are associated with debilitating side effects. The botanical drug product of the present disclosure has the potential to have therapeutic effects in the treatment of irritability, repetitive behaviors, improved cognition, sociability, and quality of life for ASD patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG.1 provides an example study design for the clinical protocol of the present disclosure.Attorney Docket No.38383.0001P1 DETAILED DESCRIPTION OF THE DISCLOSURE I. Definitions

[0014] Unless stated otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the disclosure belongs. While the following terms are believed to be well understood by one of ordinary skills in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, preferred methods and materials are described. The following terms are defined below. These definitions are for illustrative purposes and are not intended to limit the common meaning in the art of the defined terms.

[0015] The term “a” or “an” refers to one or more of that entity, i.e., can refer to a plural referent. As such, the terms “a” or “an”, “one or more” and “at least one” are used interchangeably herein. In addition, reference to “an element” by the indefinite article “a” or “an” does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements.

[0016] As used in this specification, the term “and / or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise.

[0017] Throughout this specification, unless the context requires otherwise, the words “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.

[0018] As used in this application, the terms “about” and “approximately” are used as equivalents. Any numerals used in this application with or without about / approximately are meant to cover any normal fluctuations appreciated by one of ordinary skill in the relevant art. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 10% in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0019] As used herein, “λz” refers to a terminal rate constant.Attorney Docket No.38383.0001P1

[0020] As used herein, “AE” refers to an adverse event.

[0021] As used herein, “Aer” refers to a cumulative amount excreted renally.

[0022] As used herein, “AESI” refers to an adverse event of special interest.

[0023] As used herein, “ALP” refers to alkaline phosphatase.

[0024] As used herein, “ALT” refers to alanine aminotransferase.

[0025] As used herein, “ANOVA” refers to analysis of variance.

[0026] As used herein, “ALT” refers to alanine aminotransferase.

[0027] As used herein, “API” refers to an active pharmaceutical ingredient.

[0028] As used herein, “ASM” refers to anti-seizure medication.

[0029] As used herein, “ASD” refers to autism spectrum disorder.

[0030] As used herein, “AST” refers to aspartate aminotransferase.

[0031] As used herein, “AUC0-inf”refers to the area under the concentration-time curve from time zero to infinity (extrapolated).

[0032] As used herein, “AUC0-last” refers to the area under the concentration-time curve from time zero until the last observed concentration.

[0033] As used herein, “AUC0-tau” refers to the area under the concentration-time curve from time zero to the end of dosing interval (tau) at steady state.

[0034] As used herein, “BDP” refers to a botanical drug product.

[0035] As used herein, “BDS” refers to a botanical drug substance.

[0036] As used herein, “BID” refers to twice a day.

[0037] As used herein, “BMI” refers to body mass index.

[0038] As used herein, “BP” refers to blood pressure.

[0039] As used herein, “BT” refers to body temperature.

[0040] As used herein, “CB” refers to G protein-coupled cannabinoid receptors.

[0041] As used herein, “CB1” refers to cannabinoid Type 1.

[0042] As used herein, “CB2” refers to cannabinoid Type 2.Attorney Docket No.38383.0001P1

[0043] As used herein, “CBC” refers to cannabichromene.

[0044] As used herein, “CBD” refers to cannabidiol.

[0045] As used herein, “CBDA” refers to cannabidiolic acid.

[0046] As used herein, “CBG” refers to cannabigerol.

[0047] As used herein, “CBN” refers to cannabinol.

[0048] As used herein, “CI” refers to the confidence interval.

[0049] As used herein, “CK” refers to creatine kinase.

[0050] As used herein, “Cl / F” refers to apparent clearance.

[0051] As used herein, “Cl / F,ss” refers to an apparent clearance at steady state.

[0052] As used herein, “ClR” refers to renal clearance.

[0053] As used herein, “Cmax” refers to maximal observed concentration.

[0054] As used herein, “Cmin” refers to minimal observed concentration.

[0055] As used herein, “CNS” refers to the central nervous system.

[0056] As used herein, “CRO” refers to a contract research organization.

[0057] As used herein, “CS” refers to clinically significant.

[0058] As used herein, “C-SSRS” refers to Columbia suicidality severity rating scale.

[0059] As used herein, “CSR” refers to clinical study report.

[0060] As used herein, “CTCAE” refers to Common Terminology Criteria for Adverse Events.

[0061] As used herein, “CTlast” refers to concentration at last time point.

[0062] As used herein, “CTU” refers to a Clinical Trial Unit.

[0063] As used herein, “CV” refers to the coefficient of variation.

[0064] As used herein, “CYP” refers to cytochrome P450.

[0065] As used herein, “DRF” refers to dose range finding.

[0066] As used herein, “DS” refers to Dravet Syndrome.

[0067] As used herein, “DSST” refers to Digit Symbol Substitution Test.

[0068] As used herein, “DEQ” refers to Drug Effects Questionnaire.

[0069] As used herein, “ECG” refers to electrocardiogram.Attorney Docket No.38383.0001P1

[0070] As used herein, “EC” refers to an ethics committee.

[0071] As used herein, “ECS” refers to the endogenous cannabinoid system.

[0072] As used herein, “eCRF” refers to an electronic case report form.

[0073] As used herein, “eGFR” refers to an estimated glomerular filtration rate.

[0074] As used herein, “EIU” refers to exposure in utero.

[0075] As used herein, “EMA” refers to the European Medicines Agency.

[0076] As used herein, “ENT” refers to an equilibrative nucleoside transporter.

[0077] As used herein, “EOS” refers to the end of study.

[0078] As used herein, “ET” refers to early termination.

[0079] As used herein, “FAAH” refers to fatty acid amide hydrolase.

[0080] As used herein, “fe%” refers to the fraction of unchanged drug excreted.

[0081] As used herein, “FE” refers to food-effect.

[0082] As used herein, “FIH” refers to First-in-Human.

[0083] As used herein, “FDA” refers to the Food and Drug Administration.

[0084] As used herein, “FSHE” refers to a full spectrum hemp extract.

[0085] As used herein, a “full-spectrum extract” refers to a CBD product that contains multiple cannabis plant extracts, including essential oils, terpenes, and other cannabinoids.

[0086] As used herein, “GACPs” refers to good agriculture and collection practices.

[0087] As used herein, “GCP” refers to Good Clinical Practice.

[0088] As used herein, “GGT” refers to gamma-glutamyl transferase.

[0089] As used herein, “GI” refers to gastrointestinal.

[0090] As used herein, “GLM” refers to a general linear model.

[0091] As used herein, “GLP” refers to Good Laboratory Practice.

[0092] As used herein, “GMP” refers to Good Manufacturing Practice.

[0093] As used herein, “GPR55” refers to G protein-coupled receptor 55.

[0094] As used herein, “5-HT1A” refers to a 5-hydroxytryptamine 1A receptor.

[0095] As used herein, “HBsAg” refers to a hepatitis B surface antigen.

[0096] As used herein, “HCV” refers to hepatitis C virus.Attorney Docket No.38383.0001P1

[0097] As used herein, “HED” refers to human equivalent doses.

[0098] As used herein, “HEENT” refers to the head, eyes, ears, nose, and throat.

[0099] As used herein, “hERG” refers to human Ether-à-go-go-Related Gene.

[0100] As used herein, “HIV” refers to the human immunodeficiency virus.

[0101] As used herein, “HR” refers to the heart rate.

[0102] As used herein, “HREC” refers to the Human Research Ethics Committee.

[0103] As used herein, “IB” refers to an Investigator’s Brochure.

[0104] As used herein, “ICF” refers to an informed consent form.

[0105] As used herein, “ICH” refers to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.

[0106] As used herein, “ICR” refers to the Institute of Cancer Research.

[0107] As used herein, “IP” refers to an investigational product.

[0108] As used herein, “IUD” refers to an intrauterine device.

[0109] As used herein, “IUS” refers to an intrauterine system.

[0110] As used herein, “Kel” refers to a terminal elimination rate constant.

[0111] As used herein, “LGS” refers to Lennox-Gastaut Syndrome.

[0112] As used herein, “LLN” refers to a lower limit of normal.

[0113] As used herein, “MAD” refers to a multiple ascending dose.

[0114] As used herein, “MCH” refers to mean cell hemoglobin.

[0115] As used herein, “MCHC” refers to mean cell hemoglobin concentration.

[0116] As used herein, “MCV” refers to mean cell volume.

[0117] As used herein, “MDMA” refers to 3,4-methylenedioxymethamphetamine.

[0118] As used herein, “MedDRA” refers to Medical Dictionary for Regulatory Activities.

[0119] As used herein, “MTD” refers to maximal tolerated dose.

[0120] As used herein, “NF” or “(NF)” refers to National Formulary-compliant excipients. NFs are standard for the pharmaceutical industry. Traditionally, a formulary contains a collection of formulas for the compounding and testing of medication.

[0121] As used herein, “NCS” refers to not clinically significant.Attorney Docket No.38383.0001P1

[0122] As used herein, “NOAEL” refers to no observed adverse effect level.

[0123] As used herein, “Orphan Drug” refers to the orphan status given to drugs and biologics for rare diseases that meet certain criteria as set by FDA’s Orphan Drug Designation program.

[0124] As used herein, “OTC” refers to over-the-counter.

[0125] As used herein, “PASAT” refers to Paced Auditory Serial Addition Test.

[0126] As used herein, “PCP” refers to phencyclidine.

[0127] As used herein, “PICF” refers to a participant information and informed consent form.

[0128] As used herein, “PK” refers to pharmacokinetic(s).

[0129] As used herein, “PD” refers to pharmacodynamics.

[0130] As used herein, “PPND” refers to pre- and postnatal development.

[0131] As used herein, “PPARγ” refers to nuclear peroxisome proliferator-activated receptor-γ. As used herein, “po” refers to oral.

[0132] As used herein, “PR” refers to the PR interval.

[0133] As used herein, “QA” refers to quality assurance.

[0134] As used herein, “QC” refers to quality control.

[0135] As used herein, “QD” refers to quaque die (once a day).

[0136] As used herein, “QT” refers to the QT interval.

[0137] As used herein, “QTcF” refers to Fridericia’s corrected QT interval.

[0138] As used herein, “RBC” refers to a red blood cell.

[0139] As used herein, “RP2D” refers to Recommended Phase 2 Dose.

[0140] As used herein, “RR” refers to the respiratory rate.

[0141] As used herein, “SAE” refers to a serious adverse event.

[0142] As used herein, “SAD” refers to a single ascending dose.

[0143] As used herein, “SAP” refers to a statistical analysis plan.

[0144] As used herein, “SAS” refers to statistical analysis system.

[0145] As used herein, “SBA” refers to a Summary Basis of Approval (SBA) prepared by the FDA Center for Drugs and Biologics for many newly approved drugs. The SBA is used to evaluateAttorney Docket No.38383.0001P1 and approve new drugs for marketing based on safety and effectiveness (efficacy), to assure that these drugs are properly labeled, and to share with the public the key facts on which approval is based.

[0146] As used herein, “SD” refers to the standard deviation.

[0147] As used herein, “SOC” refers to a system organ class.

[0148] As used herein, “SOP” refers to a standard operation procedure.

[0149] As used herein, “SPT” refers to a serum pregnancy test.

[0150] As used herein, “SRC” refers to a safety review committee.

[0151] As used herein, “SUSAR” refers to a suspected, unexpected, serious adverse reaction.

[0152] As used herein, “T½ el” refers to terminal elimination half-life.

[0153] As used herein, “TEAE” refers to a treatment-emergent adverse event.

[0154] As used herein, “TGA” refers to Therapeutic Goods Administration.

[0155] As used herein, “THC” refers to tetrahydrocannabinol.

[0156] As used herein, “THCA” refers to tetrahydrocannabinolic acid.

[0157] As used herein, “Tmax” refers to a time when the maximal concentration is observed.

[0158] As used herein, “TRPV1” refers to a transient receptor potential cation channel subfamily V member 1.

[0159] As used herein, “TRPV2” refers to a transient receptor potential cation channel subfamily V member 2.

[0160] As used herein, “UGT” refers to glucuronosyltransferase.

[0161] As used herein, “ULN” refers to the upper limit of normal.

[0162] As used herein, “UPT” refers to a urinary pregnancy test.

[0163] As used herein, “USP-NF” refers to a combination of two compendia, the United States Pharmacopeia (USP) and the NF.

[0164] As used herein, “Vd / F,ss” refers to an apparent volume of distribution at steady state.

[0165] As used herein, “VPA” refers to divalproex sodium.Attorney Docket No.38383.0001P1

[0166] As used herein, “Vz / F” refers to apparent volume of distribution.

[0167] As used herein, “V / F,ss” refers to volume of distribution at steady state.

[0168] As used herein, “WBC” refers to a white blood cell.

[0169] As used herein, “WOCBP” refers to women of childbearing potential.

[0170] As used herein, “treatment” “treat” or “treating” refers to a method for obtaining beneficial or desired results for a patient, including clinical results. For purposes of the present disclosure, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, condition, disorder, and / or symptom; reducing the severity of the disease, condition, disorder, and / or symptom; stabilizing the disease, condition, disorder, and / or symptom (e.g., preventing or delaying its worsening); preventing or delaying the spread of the disease (e.g., metastasis), condition, disorder, and / or symptom; preventing or delaying the recurrence of the disease, condition, disorder, and / or symptom; delaying or slowing the progression of the disease, condition, disorder, and / or symptom; ameliorating the state of the disease, condition, disorder, and / or symptom; providing response (partial or total) to the disease, condition, disorder, and / or symptom; reducing the dose of one or more other drugs required to treat the disease, condition, disorder, and / or symptom; delaying the progression of the disease, condition, disorder, and / or symptom; improving the quality of life, and / or prolonging survival time. The compositions and methods of the present disclosure contemplate any one or more of these treatment aspects.

[0171] As used herein, a “pharmaceutically effective amount” refers to an amount sufficient to treat the disease, condition, disorder, and / or symptom, such as ameliorate, reduce the rate of occurrence of, or prevent a symptom of a sign of a medical disorder. Pharmaceutically effective amount also refers to an amount sufficient to allow or facilitate diagnosis. The effective amount for a particular patient may vary depending on factors such as the disease to be treated, the general health of the patient, the route of method, the dose of administration, and the severity of side effects. The pharmaceutically effective amount may be the maximum dose or administration regimen that avoids significant side effects or toxic effects. The effect will result in an improvement of the diagnostic measure or parameter by at least 5%, such as at least 10%, further such as at least 20%, further such as at least 30%, further such as at least 40%, further such as atAttorney Docket No.38383.0001P1 least 50%, further such as at least 60%, further such as at least 70%, further such as at least 80%, and even further such as at least 90%, wherein 100% is defined as the diagnostic parameter displayed by a normal subject.

[0172] As used herein, “active ingredient” refers to any component that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals. Active ingredients can include CBD, THC, and / or terpenoids.

[0175] As used herein, “disease” refers to a pathological process having a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.

[0176] As used herein, “symptom” refers to any morbid phenomenon or departure from the normal in structure, function, or sensation experienced by a patient and indicative of disease or mental disorder. With respect to mental disorders,

[0177] As used herein, “disorder” refers to an abnormality, alteration, or derangement of function leading to a morbid or abnormal physical or mental state.

[0178] As used herein, a “medical condition” refers to its use as a broad term that includes all diseases, lesions, and disorders. The Diagnostic and Statistical Manual of Mental Disorders (DSM) uses the term "general medical condition" to refer to all diseases, illnesses, and injuries except for mental disorder. In some contexts, the term medical condition is also a synonym for medical state, which describes an individual patient's current state from a medical standpoint.

[0179] As used herein, the term “appropriate period of time” or “suitable period of time” refers to the period necessary to achieve a desired effect or result. For example, a mixture may be blended until a potency distribution is reached that is within an acceptable qualitative range for a given application or use of the blended mixture.

[0180] As used herein, the term “dose” or “unit dose” or “unit dosage” refers to a physically discrete unit that contains a predetermined quantity of active ingredient calculated to produce a desired therapeutic effect. The unit dose or unit dosage may be in the form of a tablet, capsule, sachet, liquid dispensing device, etc. referred to herein as a “unit dosage form.”Attorney Docket No.38383.0001P1 II. Chemical Constituents of Cannabis

[0173] Cannabis sativa L. is a complex plant with over 400 chemical entities of which more than 60 of them are cannabinoid compounds. Atakan Z., Cannabis, a complex plant: different compounds and different effects on individuals, (Dec.2012) Ther Adv Psychopharmacol 2(6):241- 54.

[0174] Dried cannabis was found to contain a wide variety of compounds, including cannabinoids, terpenoids, flavonoids, hydrocarbons, fatty acids, phenols, and other miscellaneous classes of compounds and their metabolites. A comprehensive literature analyses and the chemical analyses of mass spectral signals identified up to 62 unique compounds in the cannabis extract attributable to 22 unique signals based on the corresponding molecular weights of the compounds or the corresponding fragments. Lewis et al., (2017) ACS Omega 2, 9, 6091–6103.

[0175] Cannabinoids in cannabis that have been confirmed include the following: Cannabicyclols (Cannabicyclolic acid (CBLA), Cannabicyclol (CBL), Cannabicyclovarin (CBLV)); Cannabichromenes (Cannabichromene (CBC), Cannabichromevarinic acid (CBCVA), Cannabichromenic acid (CBCA), Cannabichromevarin (CBCV)); Cannabielsoins (Cannabielsoin (CBE), Cannabielsoin acid A (CBEA-A), Cannabielsoic acid B (CBEA-B)); Cannabitriols (10- Ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-Dihydroxy-delta-6a-tetrahydrocannabinol, Cannabitriol (CBT), Cannabitriolvarin (CBTV)); Cannabidiols (Cannabidiol (CBD), Cannabidiol monomethylether (CBDM), Cannabidiolic acid (CBDA), Cannabidivarinic acid (CBDVA), Cannabidiorcol (CBD-C1), Cannabidivarin (CBDV), Cannabidiphorol (CBDP)); Cannabigerols (Cannabigerol (CBG), Cannabigerovarin (CBGV), Cannabigerovarinic acid (CBGVA), Cannabigerol monomethylether (CBGM), Cannabigerolic acid monomethylether (CBGAM), Cannabigerolic acid (CBGA); Cannabinols and cannabinodiols (Cannabinolic acid (CBNA), Cannabinodiol (CBND), Cannabinodivarin (CBVD), Cannabinol (CBN), Cannabiorcool (CBN- C1), Cannabivarin (CBV), Cannabinol methylether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBN-C4)); Delta-8-tetrahydrocannabinols (Delta-8-tetrahydrocannabinol (Δ8- THC), Delta-8-tetrahydrocannabinolic acid (Δ8-THCA)); Delta-9-tetrahydrocannabinols (Delta- 9-tetrahydrocannabinol (THC), Delta-9-tetrahydrocannabinol-C4 (THC-C4), Delta-9- tetrahydrocannabiorcol (THC-C1), Delta-9-tetrahydrocannabiorcolic acid (THCA-C1), Delta-9-Attorney Docket No.38383.0001P1 tetrahydrocannabinolic acid-C4 (THCA-C4), Delta-9-tetrahydrocannabivarin (THCV), Delta-9- tetrahydrocannabivarinic acid (THCVA), Delta-9-tetrahydrocannabinolic acid A (THCA-A), Delta-9-tetrahydrocannabinolic acid B (THCA-B), Delta-9-tetrahydrocannabiphorol (THCP)); and Other Cannabinoids (10-Oxo-delta-6a-tetrahydrocannabinol (OTHC), Cannabichromanon (CBCF), Cannabifuran (CBF), Cannabiglendol, Delta-9-cis-tetrahydrocannabinol (cis-THC), Cannbicitran (CBT), Dehydrocannabifuran (DCBF), Tryhydroxy-delta-9-tetrahydrocannabinol (triOH-THC), Cannabiripsol (CBR)). See, e.g., Chief Botanicals, Complete List of Cannabinoids in Cannabis (2013). The 10 most common cannabinoids found in products today include Delta-9- Tetrahydrocannabinol (THC), Delta-8-Tetrahydrocannabinol (D8THC), Cannabidiol (CBD), Cannabinol (CBN), Cannabichromene (CBC), Cannabigerol (CBG), Tetrahydrocannabinolic acid (THCA), Cannabidiolic Acid (CBDA), Tetrahydrocannabivarin (THCV), and Cannabidivarin (CBDV).

[0176] Δ9- tetrahydrocannabinol (Δ9-THC or simply THC) is also known by its International Non-Proprietary Name (INN) as dronabinol. The unsaturated bond in the cyclohexene ring is located between C-9 and C-10 in the more common dibenzopyran ring numbering system. There are four stereoisomers of THC, but only the (–)-trans isomer occurs naturally (CAS-1972-08-03). The fully systematic name for this THC isomer is (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl- 6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol. Two related substances, Δ9- tetrahydrocannabinol-2-oic acid and Δ9-tetrahydrocannabinol-4-oic acid (THCA), are also present in cannabis, sometimes in large amounts. The active isomer Δ8-THC, in which the unsaturated bond in the cyclohexene ring is located between C-8 and C-9, is found in much smaller amounts. Cannabis Drug Profile, European Monitoring Centre for Drugs and Drug Addiction (2023) online website.

[0177] The cannabis plant has more than 200 terpenes, many of which are only present in trace amounts. They are the chemical building blocks of essential oils in plants. Cannabis plants produce terpenes along with cannabinoids in glands called trichomes. Besides giving cannabis its taste and aroma, some terpenoids are believed to also have beneficial effects. Terpenes are simple hydrocarbons, while terpenoids are a modified class of terpenes with different functional groups and having an oxidized methyl group moved or removed at various positions. The most prominentAttorney Docket No.38383.0001P1 terpenes in cannabis plants include but are not limited to myrcene, beta-caryophyllene, limonene, linalool, pinene, humulene, terpinolene, alpha-bisabolol, eucalyptol, geraniol, terpineol, farnesene, borneol, ocimene, nerolidol, guaiol, valencene, delta-3 carene, phytol, sabinene, phellandrene, fenchol, menthol, terpinene, isoborneol, and cymene. Other possible terpenes that might be present include but are not limited to octanol, isopulegol, cedrene, camphene, geranyl acetate, bergamotene, camphor, and pulegone. Liz G., The Complete List of Cannabis-Derived Terpenes (January 2, 2021) Cannabis Trends, Cannabinoids.

[0178] For additional information on the chemical constituents of cannabis see, e.g., Armentano, et al., Clinical Applications for Cannabis & Cannabinoids: A Review of the Recent Scientific Literature (October 31, 2021), NORML, 138 pages; Backes et al., Cannabis Pharmacy: The Practical Guide to Medical Marijuana – Revised and Updated (November 14, 2017) Black Dog & Leventhal, New Edition, 320 pages; Thomas et al., The Analytical Chemistry of Cannabis: Quality Assessment, Assurance, and Regulation of Medicinal Marijuana and Cannabinoid Preparations (Emerging Issues in Analytical Chemistry) Elsevier, 1stEdition, 132 pages; and Kinghorn, Phytocannabinoids: Unraveling the Complex Chemistry and Pharmacology of Cannabis sativa (Progress in the Chemistry of Organic Natural Products Book 103) Springer, 1stEdition, 140 pages. III. Cannabidiol (CBD)

[0179] Botanical cannabinoids and purified CBD show relatively low toxicity and lack any dependence profile while having a broad spectrum of therapeutic properties, such as anticonvulsive, anxiolytic, neuroprotective, antidepressant, anti-inflammatory, and immunomodulating activities (Russo et al 2006).

[0180] The potential therapeutic effects of CBD have been attributed to multiple pharmacological mechanisms with researchers reporting more than 65 discrete molecular targets for CBD (Bih et al 2015, Lee et al 2017, Peng 2022). Cannabidiol is a highly lipophilic cannabinoid-receptor allosteric modulator that interacts with the CNS, resulting in modulation of the endogenous cannabinoid system (ECS), a widespread network of G protein-coupled cannabinoid receptors (CB), synthetic and degradative enzymes, and transporters including anandamide and 2-arachidonoylglycerol, cannabinoid (CB) Type 1 (CB1) or CB Type 2 (CB2) endogenous ligands (Di Marzo & Piscitelli 2015, Mouslech & Valla 2009, Cristino et al 2020). Physiologically,Attorney Docket No.38383.0001P1 cannabinoid receptors of the ECS are present in brain regions involved in motor control, emotional responses, motivated behavior, and cognition. Peripherally these ECS receptors are involved in the modulation of the immune system, autonomic nervous system, and microcirculation (Bergamaschi et al 2011, Iffland & Grotenhermen 2017).

[0181] CBD is a blocker of the equilibrative nucleoside transporter (ENT) (Carrier et al 2006), the orphan G protein-coupled receptor (GPR)55 (Pertwee 2007), and the transient receptor potential cation channel subfamily M member (TRPM)8 channel (Muller 2019). Conversely, CBD enhances the activity of the 5-hydroxytryptamine (5-HT)1A receptor (Russo et al 2005), glycine receptors (Xiong et al 2011) and the transient receptor potential cation channel subfamily A member (TRPA)1 channel (Muller et al 2019). At high micromolar concentrations, CBD activates the nuclear peroxisome proliferator-activated receptor-γ (PPARγ) and the transient receptor potential cation channel subfamily V member (TRPV)1 and TRPV2 channels (Muller et al 2019, Pertwee 2008), also inhibiting cellular uptake and fatty acid amide hydrolase (FAAH)-catalyzed degradation of the endogenous cannabinoid anandamide (Bisogno et al 2001, De Petrocellis et al 2011).

[0190] Epidiolex®, a plant-based, high-purity CBD formulated as a sesame seed oil- basedmedicine was approved by the FDA (25 June 2018), European Medicines Agency (EMA) (19 September 2019), and Therapeutics Goods Administration (TGA) (18 September 2020) as a treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), as well as Tuberous Sclerosis Complex as ani-convulsant, in patients one year and older. Epidiolex® is prescribed for chronic use in humans at up to 25 mg / kg / day (Epidiolex® SBA, Epidiolex® Package Insert), equivalent to a dose of 1750 mg / day assuming 70 kg person.

[0191] Relative to safety pharmacology, purified CBD administered intraperitoneally decreased rat locomotor activity(≥ 60 mg / kg) and CBD as botanical cannabinoid (100 mg / kg) reduced locomotor behavior in Institute of Cancer Research (ICR) mice (Epidiolex®SBA,Epidiolex®Package Insert). CBD inhibited the human Ether-à-go-go-Related Gene (hERG) currents in a concentration-dependent manner (25, 50, and 75% inhibition at 64, 130, and 250 ng / mL CBD, respectively). Oral (po) CBD (10, 50, and 100 mg / kg) decreased heart rate (≥ 50 mg / kg po; 4 h post-dose) and increased systolic blood pressure and R-R, R-H, QRS, andAttorney Docket No.38383.0001P1 QT intervals (100 mg / kg po) in conscious, telemeterized dogs. CBD as botanical cannabinoid (10, 50, or 100 mg / kg po) had no biologically significant effects on respiratory parameters in conscious rats (Epidiolex®SBA).

[0192] Pharmacokinetic study with three CBD formulations (two oral and one transdermal) in healthy dogs demonstrated highest CBD systemic exposure following administration of CBD- infused oil formulation (versus oral microencapsulated oil beads or CBD-infused transdermal cream) (Bartner 2018).

[0193] A study reported in literature concluded that clinically meaningful elevations in CBD exposure are likely in individuals with diminished CYP3A4 function (Stout & Cimino 2014). In another study, CBD administered with rifampin showed that strong induction of the CYP3A4 pathways can cause meaningful reductions in blood, plasma, or tissue CBD levels (Stout & Cimino 2014). Drugs such as phenobarbital, rifampicin, carbamazepine, and phenytoin induce CYP3A4, which causes a reduction in CBD bioavailability (Iffland & Grotenhermen 2017).In vitrostudies showed that CBD most potently inhibited catalytic activity of human CYP3A enzymes, especially CYP3A4 (IC50 = 11.7 µM) and CYP 3A5 (IC50 = 1.65 µM) (Yamaori et al 2011). Other studies suggest a possible weak CYP2C inhibition by CBD, but no other studies were found that yielded the same results (Stout & Cimino 2014). There is evidence that repeated administration of CBD may induce CYP2B isozymes in animal models, which may have implications when CBD-based therapies are administered in combination with other drugs metabolized via those isozymes such as antiepileptic drugs (e.g., valproate and clobazam) (Devinsky et al 2014). Overall, CBD and botanical cannabinoids have been generally found to have a low risk of clinically significant drug interactions.

[0194] Nonclinical toxicology data from Epidiolex®studies showed liver as the primary target organ for purified CBD in 26-week Wistar rat and 39-week Beagle dog studies with findings in both studies of hepatocellular hypertrophy accompanied by increases in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (Epidiolex®SBA).

[0195] Reproductive and developmental studies conducted with purified CBD (Epidiolex®)in rats and rabbits showed drug-related total litter loss in 2 of 20 rats dams at the high-dose (250 mg / kg); and administration of 125 mg / kg / day of Epidiolex in rabbits led to fetal body weight decline (10%),Attorney Docket No.38383.0001P1 and fetal variations (unossified metacarpal, bulging eyes, and non-erupted incisors), and was also associated with evidence of maternal toxicity. In addition, adverse events (AEs) were observed on body weight, attainment of developmental landmarks, learning and memory, and reproductive structure and, possibly, function, primarily at the medium and high doses (150 mg / kg and 250 mg / kg) in rat pre- and postnatal development (PPND) study (Epidiolex®SBA).

[0196] There was no evidence of genotoxicity for purified CBD in a battery ofin vitroandin vivostudies (Epidiolex®SBA).

[0197] Extensive safe use of CBD products in both adult and pediatric participant has been reported, and use of CBD up to 6000 mg / day demonstrated no development of tolerance, with minimal side effects observed in both healthy participant and clinical populations (Iffland, Grotenhermen et al 2017,Larsen et al 2020,Velayudhan et al 2021).

[0198] Furthermore,Epidiolex®, a plant-based, purified CBD formulated as a sesame seed oil- basedliquid solution, is currently approved by FDA, TGA and EMA up to a daily dose of 25 mg / kg / day, equivalent to 1750 mg / day in 70 kg human (Epidiolex®Package Insert).

[0199] CBD has been extensivelyinvestigated in human clinical trials at doses ranging from <10 mg / day to up to a single dose of 6,000 mg / day.

[0200] In early observational studies involving healthy volunteers administered with CBD up to about 300 mg / day, CBD showed a safe and well tolerable profile, including cardiologic and laboratory assessment deemed within normal limits. The main side effect of CBD administration was sedation (Agurell et al 1986,Consroe et al 1979,Ohlsson et al 1986).

[0201] In 2011, the safety and side effects of CBD were comprehensively reviewed (Bergamaschi et al 2011), with a subsequent update completed in 2017 (Iffland, Grotenhermen et al 2017). The reviewed research confirmed CBD's favorable safety profile and lack of toxicity even when used chronically and in doses as high as 1500 mg per day. In addition, the general safety of CBD in humans has not been shown to vary with different routes of administration (oral, inhaled or injected); however, dose, route, and frequency of administration have been shown to be critical factors in an increased risk of AEs.Attorney Docket No.38383.0001P1

[0202] Furthermore, clinical studies involving both acute and chronic administration of CBD have demonstratedno development of tolerance and minimal side effects over a wide range of doses (<10 mg / day up to 1000 mg / day).Specifically, there were no AEs with acute CBD administration and mild to moderate adverse effects with chronic CBD administration across 25 clinical studies, including 927 patients. In most studies reporting on AEs, CBD was administered chronically (4-6 weeks), and the most observed side effects were tiredness, diarrhea and changes of appetite / weight. However, compared to other treatments used for epilepsy and psychotic disorders, CBD administration presented fewer side effects (Larsen et al 2020). IV. Cannabis Hemp Extraction Methods, Extracts, and Compositions The present disclosure provides for cannabinoid extracts of Cannabis sativa L. and pharmaceutical compositions comprising the same. In a preferred embodiment, the Cannabis sativa L is of variety ‘CW1AS1’ strain Methods of Extraction

[0182] A process to obtain a cannabinoid extract comprising terpenoids can comprise steps of drying in an environment wherein the average temperatures do not excess 90°F or more preferably, do not exceed 80°F and extracting with a polar organic solvent, and removing the solvent from the solvent extract and decarboxylating at temperatures that do not exceed 195°F, 190° F, 185° F, or 180 °F.

[0183] In a particular embodiment, the process comprises: a. providing a harvested plant material of Cannabis sativa L., such as the variety ‘CW1AS1’; b. drying the plant material to a moisture content of the plant material of less than 10% or less than 8% in environmental conditions having an average temperature between 50 °F and 90 °F or 50 °F and 80 °F or 60°F to 80°F, c. contacting the dried plant material with a solvent to form a solvent extract comprising cannabinoids and terpenes and an undissolved portion; d. separating the undissolved portion from the solvent extract, such as be filtering; e. removing a substantial portion of solvent from the solvent extract to a level of solvent of less than 5000 ppm in a cannabinoid extract; and f. subjecting the solvent extract to a decarboxylation process to form the cannabinoid extract.Attorney Docket No.38383.0001P1 The cannabinoid extracts described herein are obtained from plant material of Cannabis sativa L. Suitable plant material includes the flowers and leaves of Cannabis sativa L. In some embodiments, the cannabinoid extract comprises at least 85% by weight of flowers and leaves of Cannabis sativa L. In other words, some stem parts can be present but it does not make up a significant portion of the plant material.

[0184] In some embodiments, drying the plant material is in environmental conditions having an average relative humidity less than 65% or less than 60%. Drying the plant material can be in environmental conditions having an average relative humidity, for example, between 20% and 65%, 20% and 60%, 20% and 55%, 20% and 50%, 20% and 45%, 40% and 65%, 40% and 55%, or 50% and 65%. The environmental conditions can have an average relative humidity, for example, of about 20%, 30%, 40%, 50%, 60%, or about 65%.

[0185] The time between drying and contacting with a solvent should be limited to less than 12 months and the temperature during this storage period should be t or below 80°F. In some embodiments, the dried plant material is stored for no more than 6 months at an average temperature at or below 80°F prior to contacting the plant material with solvent. In some embodiments, the dried plant material is stored for no more than 9 months at an average temperature at or below 80°F prior to contacting the plant material with solvent. In some embodiments, the dried plant material is stored for no more than 12 months at an average temperature below 80°F prior to contacting the plant material with solvent. In some embodiments, the dried plant material is stored in a sealed container.

[0186] The solvent is one in which cannabinoids and terpenes, such as BCP, alpha-humulene, and alpha-bisabolol, are soluble, such an alcohol, such as isopropyl alcohol or ethanol. In some embodiments, the solvent comprises, consists of, or consists essentially of an alcohol with 2 to 5 carbons or an alcohol selected from isopropyl alcohol, ethanol, and butanol. In some embodiments, the alcohol consists of or consists essentially of isopropyl alcohol and / or ethanol. In a preferred embodiment, the solvent consists of or consists essentially isopropyl alcohol.

[0187] In order to obtain the cannabinoid extract, the solvent must be substantially removed from the solvent extract and a substantial portion of the CBDA must be decarboxylated to form CBD whilst minimizing the loss of terpenoids. Decarboxylation is the process of removing a carboxylAttorney Docket No.38383.0001P1 group from a carbon chain in cannabinoid acids thereby releasing CO2released. The loss of the carboxyl activates cannabinoids into more potent forms. Solvent removal and decarboxylation both involve adding heat to the solvent extract. Thus, these processes to some extent happen simultaneously with the methods described herein.

[0188] In some embodiments, the substantial portion of the solvent is removed from the solvent extract by heating to solvent extract to a temperature of 170 °F to 195 °F or 180 to 190 °F and spraying the solvent extract in a chamber under a vacuum, wherein the chamber is in fluid communication with a condenser (e.g., a chiller) such that vapor passes to the condenser thereby condensing vapor comprising solvent and separating vaporized solvent from the solvent extract, wherein the condenser is at a temperature of 0°C to 5°C. In some embodiments, the chamber is at a pressure of 30 to 150 Torr more preferably, 30 to 50 Torr.

[0189] The decarboxylation process detailed herein, which is performed in a vessel under vacuum, reduces the temperature required to achieve decarboxylation relative to conventional methods, such as decarboxylation in an oven. In some embodiments, the decarboxylation process comprises heating and mixing the solvent extract in a vessel to a temperature that does not exceed 85 °C, e.g., from about 75° C to 85 °C. The vessel is in fluid communication with a condenser and the extract is heated at ambient pressure until no evaporated solvent condensate is visually identified in the condenser. The condenser is at a temperature that is at least 50°C less than that of the solvent extract.

[0190] In some embodiments, the decarboxylation process comprises heating and mixing the solvent extract in a vessel in fluid communication with a condenser to a temperature of from about 75°C to 85°C until no evaporated solvent condensate is visible in the condenser and incrementally reducing the pressure one or more times while heating, wherein between each pressure reduction no evaporated solvent condensate is visible in the condenser.

[0191] In further embodiments, after the initial heating step and , the decarboxylation process comprises maintaining temperature of from about 75° C to 85 °C and lowering and holding pressure in the vessel to 600 torr until no evaporated solvent condensate is visually identified in the chiller, wherein the chiller temperature is -7°C to 0°C or about -5°C. In some embodiments, the decarboxylation process is performed over a timespan of about 12 hours to about 16 hours.Attorney Docket No.38383.0001P1

[0192] To heat the vessel, the vessel can comprise a heat jacket configured to heat the solvent extract contained within the vessel to the desired temperature or desired temperature range and to maintain the temperature at the desired temperature or within the desired temperature range.

[0193] The extraction method as described above can be used to extract the cannabinoids and terpenes from Cannabis Sativa L., such as from hemp variety ‘CW1AS1’ strain. In other embodiments, said methods can be used with other strains of Cannabis Sativa plants.

[0194] In some embodiments, 150 to 300 kg or 200 to 250 kg of biomass are extracted using the above described method.

[0195] An aspect of the present disclosure is an extract obtained from the foregoing method.

[0196] Other extraction process may also be used to obtain an extract from hemp variety ‘CW1AS1’ strain.

[0197] Solvent reduced oils are also sometimes referred to as an oil, butane hash oil (BHO), CO2 extract, among other names. This type of extract is made by soaking plant material in a chemical solvent capable of solubilizing one or more chemical constituents of the plant (e.g., cannabinoids and / or terpenes). After separating the solvent from plant material, the solvent can be boiled or evaporated off, leaving the extract “oil” behind. Butane Hash Oil is produced by passing butane over cannabis and then letting the butane evaporate. Rick Simpson Oil is produced through iso- propyl, or ethanol extraction of cannabis. The resulting substance is a wax like golden brown extract. Another common extraction solvent for creating cannabis oil is CO2. Persons having skill in the art will be familiar with CO2 extraction techniques and devices, including those disclosed in US Published Patent Application Nos. US 20160279183, US 2015 / 01505455, and US 2018 / 0000857; U.S. Patent Nos. US 9,730,911, US 9,826,689, US 9,867,859, US 9,919,241, US 10,307,446, US 10,308,625, US 10,315,129, US 10,406,186, US 10,570,350, US 10,688,410, US 11,118,131, US 11,241,468, US 11,291,699, and US 11,541,089; and International Published Patent Applications WO 2004 / 016277 and WO 2021 / 084527, all of which are hereby incorporated by reference in their entirety.

[0198] Heat extractions. The present disclosure also teaches extracts produced via heat-based extraction methods, such as those disclosed in US Patent Application Nos. US 2018 / 0078874, USAttorney Docket No.38383.0001P1 2019 / 0151771, US 2019 / 0076753, and U.S. Pat. No. 10,159,908, each of which is hereby incorporated by reference for all purposes in their entirety. In some embodiments, the plants of the present disclosure can be extracted by exposing tissue to a hot air gas stream that volatizes cannabinoids and / or other secondary metabolites of the plant, which are then condensed and recovered in tanks.

[0199] In some embodiments, the present disclosure teaches exposing plants, plant parts or plant cells to vaporizing heat. As used herein, the term “vaporizing heat” refers to heat sufficient to volatize one or more terpene on cannabinoid components of said plant, plant part or plant cell. The boiling points for each of the cannabinoid and terpene constituents of a hemp plant are well known or readily ascertainable. In some embodiments, vaporizing heat comprises 150° F, 155° F, 160° F, 165° F, 170° F, 175° F, 180° F, 185° F, 190° F, 195° F, 200° F, 205° F, 210° F, 215° F, 220° F, 225° F, 230° F, 235° F, 240° F, 245° F, 250° F, 255° F, 260° F, 265° F, 270° F, 275° F, 280° F, 285° F, 290° F, 295° F, 300° F, 305° F, 310° F, 315° F, 320° F, 325° F, 330° F, 335° F, 340° F, 345° F, or 350° F, and all ranges and subranges therebetween. The volatilized components of said plant are captured and isolated to form an extract.

[0200] Tinctures. Tinctures are alcoholic extracts of cannabis. These are usually made by mixing cannabis material with high proof ethanol and separating out plant material. Within the dietary supplement industry “tincture” may also describe an oil dilution of hemp extract.

[0201] In some embodiments, the specialty cannabis of the present disclosure is extracted via methods that preserve the cannabinoid and terpenes. In other embodiments, said methods can be used with any cannabis plants.

[0202] The chemical extraction of specialty cannabis can be accomplished employing polar and non-polar solvents in various phases at varying pressures and temperatures to extract terpenes, cannabinoids, and other compounds of flavor, fragrance or pharmacological value selectively or comprehensively for use individually or combination in the formulation of our products. The solvents employed for selective extraction of our cultivars may include water, carbon dioxide, 1,1,1,2-tetrafluoroethane, butane, propane, ethanol, isopropyl alcohol, hexane, and limonene, in combination or series. It is also possible to extract compounds of interest mechanically by sieving the plant parts that produce those compounds. Measuring the plant part, i.e. trichome gland head,Attorney Docket No.38383.0001P1 to be sieved via optical or electron microscopy can aid the selection of the optimal sieve pore size, ranging from 30 to 130 microns, to capture the plant part of interest. The chemical and mechanical extraction methods of the present disclosure can be used to produce products that combine chemical extractions with plant parts containing compounds of interest.

[0203] The extracts of the present disclosure may also be combined with pure compounds of interest to the extractions, e.g. cannabinoids or terpenes to further enhance or modify the resulting formulation's fragrance, flavor, or pharmacology. Thus, in some embodiments, the present disclosure teaches compositions comprising at least one ingredient extracted from the ‘CW1AS1’ plant. In some embodiments, extracts from the hemp lines of the present disclosure are combined with one or more additional compounds. In some embodiments, extracts of the present disclosure, such as whole hemp extracts, or a purified cannabinoid from said hemp plant, can be combined with an-other cannabinoid or terpene to produce a composition.

[0204] The compositions of the present disclosure encompass many forms. In some embodiments, the present disclosure provides CBD oils and tinctures. In some embodiments, the present disclosure provides CBD capsules. In some embodiments, the CBD oils comprise extracts from ‘CW1AS1’, such as solvent extracted oils, heat extracted oils. In some embodiments, the capsules comprise extracts from ‘CW1AS1.’

[0205] The extracts of the present disclosure may also be combined with pure compounds of interest to the extractions, e.g. cannabinoids or terpenes to further enhance or modify the resulting formulation's fragrance, flavor, or pharmacology. Thus, in some embodiments, the present disclosure teaches compositions comprising at least one ingredient extracted from the ‘CW1AS1’ plant. In some embodiments, extracts from the hemp lines of the present disclosure are combined with one or more additional compounds. In some embodiments, extracts of the present disclosure, such as whole hemp extracts, or a purified cannabinoid from said hemp plant, can be combined with another cannabinoid or terpene to produce a composition.

[0206] The compositions of the present disclosure encompass many forms. In some embodiments, the present disclosure provides CBD oils and tinctures. In some embodiments, the present disclosure provides CBD capsules. In some embodiments, the CBD oils comprise extractsAttorney Docket No.38383.0001P1 from ‘CW1AS1’, such as solvent extracted oils, heat extracted oils. In some embodiments, the capsules comprise extracts from ‘CW1AS1.’ Extract and Pharmaceutical Compositions

[0207] In some embodiments, the pharmaceutical composition of the present disclosure is a botanical drug product (BDP) comprising a cannabinoid extract of the Cannabis sativa L. plant as describe herein.

[0208] The extract can be a full spectrum extract in that it contains the naturally occurring components of the plant that are released from the biomass during the extraction process and retained during the solvent removal process.

[0209] In some embodiments, the extract can be obtained according to the process described herein, particularly with IPA or ethanol as the solvent.

[0210] In some embodiments, cannabinoid extracts of the present disclosure have a high ratio of cannabidiol to THC (detla 9), such as a ratio greater than 22:1 or a ratio greater than 24:1. In particular embodiments, the ratio is, 22:1-50:1 or 22:1-45:1 or 22:1-40:1 or 22:1 to 38:1, and more preferably, the ratio is 24:1 to 40:1 or 24: to 35:1 or 25:1 to 40:1 or 25:1 to 35:1.

[0211] In some embodiments, cannabinoid extracts of Cannabis sativa L. comprise cannabinoids and terpenoids. In particular, the extract comprises particular CBD and THC and one or more of beta-caryophyllene, α-bisabolol, and α-humulene. In a preferred embodiment, the extract comprises beta-caryophyllene, α-bisabolol, and α-humulene.

[0212] The extract can be obtained from a process that preserves terpenes in the air dried plant material from which the extract is obtained from the freshly harvested plant material from which the extract is obtained. For example, as compared to the air dried plant, an extract of the present disclosure can comprise beta-caryophyllene at an amount that is 3% to 25% or 5% to 20% of the amount of beta caryophyllene in the air dried plant material from which the extract is obtained, and / or α-bisabolol at an amount that is 3% to 20% or 5% to 18% of the amount of α-bisabolol in the air dried plant material from which the extract is obtained and / or α-humulene at an amount that is 3% to 30% or 5% to 28% of the amount of α-humulene in the air dried plant material from whichAttorney Docket No.38383.0001P1 the extract is obtained. In some embodiments, less than 55%, less than 50%, or less than 45% of any one of beta caryophyllene, α-humulene, and α-bisabolol is lost between harvest and air drying.

[0213] In some embodiments, the cannabinoid extract of Cannabis sativa L. comprises one or more of the following terpene compounds at the specified concentration: a concentration of beta- caryophyllene is from 15 mg / mL to 70 mg / mL; a concentration of α-bisabolol of from 8 mg / mL to 50 mg / mL; and / or a concentration of α-humulene of from about 4 mg / mL to about 40 mg / mL. In embodiments, the extract further comprises a concentration of CBD from 400 to to 700 mg / mL.

[0214] The extract is diluted in the preparation of the pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises one or more of the following terpene compounds at the specified concentration: a concentration of beta-caryophyllene is from 1 mg / mL to 8 mg / mL; a concentration of α-bisabolol of from 0.7 mg / mL to 8 mg / mL; and / or a concentration of α-humulene of from about 0.3 mg / mL to about 6 mg / mL. In embodiments, the composition further comprises a concentration of CBD from 40 to to 70 mg / mL.

[0215] In some embodiments, the pharmaceutical composition of the present disclosure is a botanical drug product (BDP) comprising a cannabinoid extract of the Cannabis sativa L. proprietary ‘CW1AS1’ hemp cultivar, which is disclosed and claimed in U.S. Patent No. 10,653,085 and U.S. Patent No.10,736,295, both of which are herein incorporated by reference in their entireties. Representative seed of ‘CW1AS1’ has been deposited under NCIMB 43291.

[0216] The extract (also referred to as the botanical drug substance (BDS)) of the present disclosure is a cannabinoid extract containing cannabinoids, carbohydrates, non- cannabinoid / terpene lipids, terpenes, and proteins. This is a full spectrum extract as used herein. The primary cannabinoid is cannabidiol (CBD), along with other minor cannabinoids components including but not limited to cannabichromene (CBC), Δ9-tetrahydrocannabinol (THC), cannabigerol (CBG), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerolic acid (CBGA) and cannabinol (CBN). Total tetrahydrocannabinnoids (i.e., THC and tetrahydrocannabinolic acid [THCA]) are controlled in the extract (FSHE) dried biomass to ≤0.3% (per regulatory requirements for CBD products), and THC is controlled to ≤2% in the BDS and ≤0.3% w / w in the pharmaceutical composition, also referred to herein as the botanical drug product. The BDS is a nonaqueous dark green to black substance, can be semi-solid at roomAttorney Docket No.38383.0001P1 temperature, obtained via extraction of a proprietary strain (i.e., ‘CW1AS1’) of Cannabis sativa L. biomass, particularly bud / flower parts and leaves, such as at least 80% or at least 85% bud / flower parts and stems. The biomass is cultivated and harvested in compliance with good agriculture and collection practices (GACPs). The BDS is primarily composed of cannabinoids, followed by carbohydrates, non-cannabinoid / terpene lipids, terpenes, and proteins. Each of the molecule classes may possess activity and is expected to contribute to the overall pharmacological activity of the BDS. The BDS has low aqueous solubility.

[0217] In some embodiments, the BDS comprises from about 45% to about 65% CBD, from about 1% to about 5% CBC, and from about 0.5% to about 2.5% THC weight / weight% of the BDS. The BDS can comprise, for example, from about 45% to about 60%, about 45% to about 55%, about 45% to about 50%, about 50% to about 65%, about 50% to about 55%, about 55% to about 65%, or about 55% to about 60% CBD weight / weight% of the BDS. The BDS can comprise, for example, from about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 4%, about 2% to about 3%, or about 3% to about 4% CBC weight / weight% of the BDS. The BDS can comprise, for example, from about 0.5% to about 2%, about 0.5% to about 1%, about 1% to about 2.5%, about 1% to about 2%, or about 2% to about 2.5% THC weight / weight% of the BDS. In some embodiments, the BDS comprises about 55% CBD, 2% CBC, and about 1% to about 2% THC weight / weight% of the BDS.

[0218] In some embodiments, the botanical drug product (BDP) Oral Suspension of the present disclosure comprises the cannabinoid extract in a carrier, such as a carrier comprising, consisting of, or consisting essentially of one or more oils and / or oil-like substances. Examples of suitable oils include but are not limited to glyceryl monolinoleate, corn oil, olive oil, sesame oil, soybean oil (e.g., hydrogenated soybean oil), rapeseed oil, coconut oil, sunflower oil, and combinations thereof.

[0219] In some embodiments, the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated and / or unsaturated carbon chain length ranging from 8 to 20 carbons In some embodiments, the carbon chain length is 12 to 20. Such glycerides can be sesame oil, modified sesame oil, corn oil, or modified corn oil. In some embodiments, the glyceride is winterized orAttorney Docket No.38383.0001P1 consists of unsaturated carbon chains. In some embodiments, the glyceride is glyceryl monolinoleate.

[0220] In some embodiments, the pharmaceutical composition comprises a lipid-based formulation or lipid-surfactant based formulation comprising glyceryl monolinoleate. In some embodiments, the pharmaceutical composition comprises the botanical extract in glyceryl monolinoleate. The glyceryl monolinoleate is a blend of long chain mono, di, and triglycerides. In embodiments, the glyceryl monolinoleate is winterized. An example of suitable glyceryl monolinoleate is Maisine CC®, manufactured by Gattefosse. In some embodiments, the glyceryl monolinoleate is a winterized oil composed of mono-, di- and triglycerides of oleic and linoleic acids (C18:1 / C18:2).

[0221] In some embodiments, the oils are purified oils and / or highly refined oils. Examples of specific suitable oils include but are not limited to Refined Olive Oil IV, which can be used as an excipient or API in the formulation of poorly soluble drugs, injectables, syrups, and parenteral nutrition for human and veterinary applications);Refined Sesame Oil IV-1, which can be used as an excipient in the formulation of lipophilic drugs, injectables, and syrups for human and veterinary applications; and Refined Soybean Oil IV, which can be used as an excipient or API in the formulation of poorly soluble drugs, injectables, syrups, and parenteral nutrition for human and veterinary applications. All three of these specialty oils are available from ADM®.

[0222] In order to form the composition, in some embodiments, the extract is diluted with an oil, such as mono, di, and / or tri glycerides described herein, by a factor 3 to 20. In some embodiments, the dilutions factor is 5 to 15 or 8 to 14 or about 11 or about 12.

[0223] In some embodiments, the purified pharmaceutical oils are also used as excipients such as during the formulation of soft gel capsules, syrups, and lotions.

[0224] In some embodiments, the composition comprises a carrier, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons. In some embodiments, the carbon chain length is 12 to 20. In some embodiments, the glyceride is sesame oil, corn oil, or modified corn oil.Attorney Docket No.38383.0001P1

[0225] In some embodiments, the BDP of the present disclosure comprises one or more flavoring agents including but not limited to orange flavoring, citric acid flavoring, cherry flavoring, strawberry flavoring, chocolate flavoring, mint flavoring, and combinations thereof. In some embodiments, the BDP comprises organic chocolate mint flavoring. In some embodiments, the BDP of the present disclosure can be formulated in many different forms and finished formats including but not limited to emulsifications, particle encapsulations, powders, liquids, solids, etc.

[0226] In one embodiment, the oral drug product (i.e., BDP) of the present disclosure consists of BDS of 100 mg to 105 mg / mL, such as 103 mg / mL, in glyceryl monolinoleate, National Formulary (NF), and a flavoring agent, such as an organic mint chocolate flavoring agent. The manufacturing process involves mixing BDS with excipients to yield a fully homogeneous suspension or mixture.

[0227] Glycerol monolinoleate (C21H38O4; MW 354.5 g / mol; PubChem CID 5283469; CAS RN®: 26545-74-4) is a 1-monoglyceride that has octadecadienoyl (linoleoyl) as the acyl group. It is functionally related to linoleic acid. Glycerol monolinoleate is a mixture of monoglycerides, mainly glyceryl monooleate and glyceryl monolinoleate, together with variable quantities of diglycerides and triglycerides. Synonyms include 1-linoleoyl-fac-glycerol, monolinolein, 1- monolinolein, and glycerol 1-monolinolate. Glyceryl monolinoleate is a natural product found in Saposhnikovia divaricate, Hycoscyamus niger, and other organisms. It can be used to enhance absorption of the drug substance, thereby enhancing bioavailability for systemic exposure. For additional information see USPNF Docid: GUID-B60F2346-5660-41F4-97FE- 7721AECF2902_2_en-US.

[0228] In some embodiments, the composition consists of or consists essentially of a cannabinoid extract of Cannabis sativa L. plant of the variety ‘CW1AS1’ strain, a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated and / or unsaturated carbon chain length ranging from 8 to 20 carbons, such as glyceryl monolinoleate, and a flavoring agent.

[0229] In some embodiments of the present disclosure, the compositions of the present disclosure, including the BDP disclosed herein, can be stored under US Pharmacopeia (USP)Attorney Docket No.38383.0001P1 controlled room temperature conditions of about 20°C to about 25°C (about 68°F to about 77°F) with excursions permitted between about 15°C to about 30°C (about 59°F to about 86°F).

[0230] The extract, also referred to herein as the BDS and the pharmaceutical composition, also referred to herein as the BDP as such, the BDP, of the present disclosure contain numerous pharmacologically active compounds also found in cannabis, including THC, CBD and terpenoids. Thus, the extract can be a full spectrum extract. Cannabidiol is the primary naturally occurring cannabinoid in the BDS of the present disclosure along with minor cannabinoid components including cannabichromene (CBC), tetrahydrocannabinol (THC), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), cannabidivarin (CBDV), and cannabinol (CBN).

[0231] In some embodiments, the composition comprises a CBD concentration of from about 5% to about 8% w / w%, a THC concentration of from about 0% to about 0.3% w / w%, a CBC concentration of from about 0 to about 0.5% w / w%, and a CBG concentration of from about 0% to about 0.3% w / w% of the BDP. In some embodiments, the composition comprises a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannabinoids is 5.6-8.4% w / w of the pharmaceutical composition.

[0232] The following references, some of which were relied upon for the following disclosure, provide detailed, background information on methods of preparing pharmaceutical compositions and methods of their administration, including for cannabis-related compositions such as extracts: US Published Patent Application Nos. 20230029180 A1 (01 / 26 / 2023), 20210393719 A1 (12 / 23 / 2021), 20190142756 A1 (05 / 16 / 2019), 20200009060 A1 (01 / 09 / 2020); and US Patent Nos. 6,503,532, 6,635,237, 6,730,330, 6,734,176, 6,946,150, 7,025,992, 7,094,930, 7,344,736, 7,709,536, 7,968,594, 8,211,946, 8,445,023, 8,481,091, 8,512,767, 8,603,515, 8,470,874, 8,652,529, 9,023,400, 9,044,390, 9,186,386, 9,498,444, 9,572,851, 9,789,105, 9,980,996, 10,004,684, 10,064,905, 10,092,611, 10,213,391, 10,238,705, 10,517,911, 10,561,694, 10,568,920, 10,624,940, 10,639,339, 10,729,665, 11,234,944, 11,266,702, 11,318,109,Attorney Docket No.38383.0001P1 11,331,358, 11,311,587, 11,344,591, and 11,478,520.Some of the detailed description in this section are derived from one or more of these references.

[0233] The term “pharmaceutically acceptable” refers to those compounds, materials, compositions and / or dosage forms which are suitable for being in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications, and are commensurate with a reasonable benefit / risk ratio. For example, a pharmaceutically acceptable substance may be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. The pharmaceutically acceptable carrier or excipient preferably meets the requisite toxicological and manufacturing test standards and / or is included in the Inactive Ingredient Guide provided by U.S. Food and Drug Administration.

[0234] In some embodiments, the pharmaceutical compositions disclosed herein may also comprise other conventional pharmaceutically acceptable ingredients, commonly referred to as carriers, excipients, or adjuvants. excipients or adjuvants include, but are not limited to: disintegrants, binders, lubricants, glidants, stabilizers, fillers, diluents, colorants, flavoring agents, and preservatives. For example, useful additives include materials such as agents for retarding dissolution (e.g., paraffin), resorption accelerators (e.g., quaternary ammonium compounds), surface active agents (e.g., cetyl alcohol, glycerol monostearate, and sodium lauryl sulfate), adsorptive carriers (e.g., kaolin and bentonite), preservatives, sweeteners, coloring agents, flavoring agents (e.g., chocolate mint, citric acid, menthol, glycine or orange powder), stabilizers (e.g., citric acid or sodium citrate), binders (e.g., hydroxypropylmethylcellulose), and mixtures thereof. Those of ordinary skill in the art may, by conventional experimentation, select one or more of the above carriers based on the desired properties of the dosage form without undue burden. The amount of each carrier used is within the conventional range in the art.

[0235] The term “pharmaceutically acceptable carrier” as used herein includes any and all solvents, dispersion media, coating agents, surfactants, antioxidants, preservatives (e.g., antibacterial agents or antifungal agents), isotonic agents, absorption delaying agents, salts,Attorney Docket No.38383.0001P1 preservatives, drugs, drug stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavoring agents, dyes, and the like, and combinations thereof, as known to those skilled in the art (see, e.g., Remington’s Pharmaceutical Sciences,18th edition, Mack Printing Company, 1990, 1289-1329). The use of any conventional carrier in therapeutic or pharmaceutical compositions is contemplated herein unless it is incompatible with the active ingredient(s)of the present disclosure.

[0236] ]In some embodiments, the botanical extracts of the present disclosure may be a powdered botanical extract which may optionally be combined with one or more inactive, neutral compounds / ingredients which can be pharmaceutically acceptable excipients or carriers, including, but not limited to, binders, antioxidants, adjuvants, synergists and / or preservatives. In some embodiments, the botanical extract preparations of the present disclosure can further include encapsulating agents known in the art (i.e., phospholipids, cyclodextrins, etc.) to encapsulate the actives. These encapsulating agents can be employed with or without the use of aqueous or organic solvents. In some embodiments, the powdered botanical extract preparations may optionally be combined with one or more additional pharmaceutically active components.

[0237] In some embodiments, where the powdered botanical extracts of the present disclosure are optionally combined with one or more inactive, neutral ingredients or one or more additional pharmaceutically active components, the optional ingredients may be added during the process of preparing the powdered preparation, for example, while the mixture is still in its liquid form and before the solid product has been obtained. Alternatively, the optional ingredients may be added to the powdered preparation after the process of preparing the powdered preparation has been completed, and before further formulation into suitable dosage forms. In some embodiments, the powdered botanical extract of the present disclosure can be further incorporated into different dosage forms in accordance with formulation processes as are known in the art.

[0238] The pharmaceutical compositions of the present disclosure are suitable for delivery to the respiratory tract using a metered dose inhaler (MDI). Polar excipients are used routinely in pharmaceutical compositions for treating respiratory disorders that are delivered using MDIs. They are also sometimes referred to as solvents, co-solvents, carrier solvents and adjuvants. Their inclusion can serve to solubilize a surfactant or the drug in the propellant and / or inhibit deposition of drug particles on the surfaces of the metered dose inhaler that are contacted by theAttorney Docket No.38383.0001P1 pharmaceutical composition as it passes from the container in which it is stored to the nozzle outlet. They are also used as bulking agents in two-stage filling processes where the drug is mixed with a suitable polar excipient. The most used polar excipient is ethanol. If a polar excipient is used, it will typically be present in an amount of from 0.5 to 10% by weight, preferably in an amount of from 1 to 5% by weight based on the total weight of the pharmaceutical composition.

[0239] Some embodiments of the present disclosure are directed to dosage forms that are formulated as solid articles suitable for sublingual or oral administration, such as troches, lozenges, pills, oral dissolving strips, caps, or boluses. These solid dosage forms typically comprise additional excipients. They can be prepared by first mixing the powdered botanical extract of the present disclosure with one or more suitable excipients followed by molding or compressing the blended mixture. Both hard and chewable lozenges and troches are within the scope of the present disclosure. In some embodiments, the oral dosage forms are formulated as capsules in which the powdered botanical extracts are encapsulated in soft or hard gelatin capsules.

[0240] The term “carrier” refers to a substance that serves as a vehicle for improving the efficiency of delivery and the effectiveness of a pharmaceutical composition.

[0241] Some embodiments of the present disclosure are directed to dosage forms that are formulated as topical formulations, including but not limited to creams, ointments, and gel, using formulation methods as are known in the art. In one embodiment, the topical formulation is a transdermal patch, using formulation methods and technologies as are known in the art.

[0242] Some embodiments of the present disclosure are directed to dosage forms that are formulated as solid articles suitable for administration as vaginal ovules or rectal suppositories, using formulation methods as are known in the art.

[0243] Some embodiments of the present disclosure are directed to dosage forms that are formulated as liquids, including but not limited to emulsions, liposomes, dispersions, oils, and tinctures, using formulation methods as are known in the art.

[0244] Some embodiments of the present disclosure are directed to dosage forms that are formulated as beverages and edibles, wherein the powdered botanical extract is incorporated into food and drink products.Attorney Docket No.38383.0001P1

[0245] Some embodiments of the present disclosure are directed to dosage forms that are formulated as smokeable or vaporizable formulations.

[0246] In some embodiments, the dosage forms of the present disclosure can be formulated, as appropriate, to include disintegrants, including but not limited to starch, cellulose derivatives and alginates, cross-linked sodium carboxymethyl cellulose (corscarmellose sodium)(e.g., AC-DI- SOL from FMC), hydroxypropylmethyl cellulose (HPMC), cross-linked polyvinylpyrrolidone (crospovidone), clay, cellulose, gum, cross-linked polymers(e.g.,crospolyvinylpyrrolidone or crospovidone, such as POLYPLASDONE XL from ISP (International Specialty Products, Wayne, N.J.)), croscarmellose calcium, soybean polysaccharide, and guar gum.

[0247] The dosage forms of the present disclosure can be formulated, as appropriate, to include glidants, including but not limited to silicon dioxide, colloidal anhydrous silicon, and other silica compounds, and / or and or lubricants including stearic acid and salts thereof, such as magnesium stearate.

[0248] The term “binder” refers to a substance or compound that promotes, provides, or improves cohesion, i.e., a substance that causes the components of a mixture to cohere to form a solid item that possesses integrity. In some embodiments, typical binders that can be used for formulating dosage forms of the present disclosure include but are not limited to natural, synthetic, or semi- synthetic glycerides, hydrogenated coco-glycerides, mineral oil, gelatins, starches, sucrose and sucrose derivatives, lactose and lactose derivatives, cellulose, methyl cellulose, microcrystalline cellulose (e.g., AVICEL PH from FMC (Philadelphia, Pa.), hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose METHOCEL from Dow Chemical Corp., Midland, Mich.) and other cellulose derivatives, sucrose; dextrose; corn syrup; polysaccharide; gelatin, silicones (e.g., dimethicone, bis-vinyl dimethicone / dimethicone copolymer), isopropyl myristate, isostearyl palmitate, polyvinylpyrrolidone and derivatives, and polyglycols, (e.g., polyethylene glycols (PEGs), polyethylene oxides (POE), methoxpolyethylene glycols, polypropylene glycols, polybutylene glycols or derivatives thereof having a molecular weight that is sufficient to provide the necessary hardness and time for dissolution of the dosage form). Non-limiting examples of some specific polyglycol derivatives that can be used are: (a) PEG-laureates and dilaureates (e.g., PEG-10-, PEG-12-, PEG-20-, PEG-32-laurates, PEG-20- and PEG-32-dilaurates, PEG-20-Attorney Docket No.38383.0001P1 glyceryl-, PEG-30-glyceryl- and PEG-40-glyceryl-laurates, PEG-80-sorbitan laurate); (b) PEG- oleates, dioleates and trioleates (e.g., PEG-12-, PEG-15-, PEG-20-, PEG-32, PEG-200- and PEG- 400-oleates, PEG-20- and PEG-32-dioleates, PEG-20-trioleate, PEG-25-glyceryl trioleate, PEG- 20-glyceryl- and PEG-30-glyceryl-oleates, PEG-40-sorbitan oleate); (c) PEG-stearates and distearates (e.g., PEG-15-, PEG-40-, PEG-100-stearates, PEG-32-distearate and PEG-20-glyceryl stearate) (d) castor, palm kernel, corn and soya oil derivatives of PEG (e.g., PEG-35-, PEG-40- and PEG-60-castor oils, PEG-40-, PEG-50- and PEG-60-hydrogenated castor oils, PEG-40-palm kernel oil, PEG-60-corn oil, PEG-30-soya sterol); (e) other PEG derivatives (e.g., PEG-24- and PEG-30-cholesterol, PEG-25-phytosterol, PEG-6- and PEG-8-caprate / caprylate glycerides, tocopheryl PEG-100 succinate, PEG-15-100 octylphenol products and PEG-10-100 nonylphenol products); (f) other products such as polyglyceryl-10-laurate, POE-9- and POE-23-lauryl ethers, POE-10- and POE-20-oleyl ethers, POE-20-stearyl ether, polysorbate-20 (Tween 20), polysorbate- 80 (Tween 80), polyglyceryl-10-oleate, Tween 40, Tween 60, sucrose monostearate, monolaurate, monopalmitate, and various products of Poloxamer series.

[0249] The term “excipient” refers to a pharmacologically inactive substance that is formulated in combination with a pharmacologically active ingredient of a pharmaceutical composition and is inclusive of, but not limited to, disintegrants, lubricants, flavorings, bulking agents, binders, fillers, diluents, preservatives, antioxidants, and adjuvants, synergists and products used for facilitating drug absorption or solubility or for other pharmacokinetic considerations. See, also, The Handbook of Pharmaceutical Excipients, 4th edition, ed. by Rowe et al., American Pharmaceuticals Association (2003); and Remington: the Science and Practice of Pharmacy, 20th edition, Gennaro (ed.), Lippincott Williams & Wilkins (2003).

[0250] In some embodiments, typical excipients that can be used for formulating dosage forms of the present disclosure include but are not limited to gelatin, sodium saccharin, mannitol, stevioside, peppermint oil, cherry flavor, lemon oil, and raspberry flavor.

[0251] In some embodiments, the dosage forms of the present disclosure may optionally be formulated to further comprise one or several antioxidants. Examples of pharmaceutically acceptable antioxidants include but are not limited to: (1) water-soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite and sodium sulfite;Attorney Docket No.38383.0001P1 (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate and α tocopherol; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid and phosphoric acid. Additional examples of oxidants that could be used according to the present disclosure include but are not limited to α-tocopherol acetate, acetone sodium bisulfite, acetylcysteine, cysteine, tocopherol natural, tocopherol synthetic, dithiothreitol, monothioglycerol, nordihydroguaiaretic acid, propyl gallate, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium sulfite, sodium thiosulfate, thiourea and tocopherols.

[0252] In some embodiments, the dosage forms of the present disclosure may optionally be formulated to further comprise one or several adjuvants or synergists. If adjuvants or synergists are used, non-limiting examples of those that can be used include citric acid, EDTA (ethylenediaminetetraacetate) and salts, hydroxyquinoline sulfate, phosphoric acid, and tartaric acid.

[0253] In some embodiments, the dosage forms of the present disclosure may optionally further comprise one or several preservatives. If preservatives are used, non-limiting examples of those that can be used include benzalkonium chloride, benzethonium chloride, benzoic acid and salts, benzyl alcohol, boric acid and salts, cetylpyridinium chloride, cetyltrimethyl ammonium bromide, chlorobutanol, chlorocresol, chorhexidine gluconate or chlorhexidine acetate, cresol, ethanol, imidazolidinyl urea, metacresol, methylparaben, nitromersol, o-phenyl phenol, parabens, phenol, phenylmercuric acetate / nitrate, propylparaben, sodium benzoate, sorbic acids and salts, o- phenylethyl alcohol, and thimerosal.

[0254] Examples of pharmaceutically acceptable surfactants for use in the present disclosure include but are not limited to polyvinylpyrrolidone, polyethylene glycol surfactants, oleic acid, and lecithin.

[0255] Examples of pharmaceutically acceptable lubricants and pharmaceutically acceptable glidants include, but are not limited to: silica gel, magnesium trisilicate, starch, talc, tricalcium phosphate, magnesium stearate, aluminum stearate, calcium stearate, magnesium carbonate, magnesium oxide, polyethylene glycol, powdered cellulose, and microcrystalline cellulose.Attorney Docket No.38383.0001P1

[0256] Examples of pharmaceutically acceptable fillers and pharmaceutically acceptable diluents include, but are not limited to: powdered sugar, compressible sugar, glucose binding agents, dextrin, dextrose, lactose, mannitol, microcrystalline cellulose, powdered cellulose, sorbitol, sucrose, and talc.

[0257] The optimal dose of each combination partner for treatment can be determined empirically for everyone using known methods and will depend upon a variety of factors, including, but not limited to: the degree of progression of the disease; the age, body weight, general health, gender, and diet of the individual; the time and route of administration; and other medications the individual is taking. Optimal doses may be established using routine testing and procedures that are well known in the art.

[0258] The amount of each combination partner that may be combined with the carrier materials to produce a single dosage form will vary depending upon the individual treated and the mode of administration. In some embodiments, the unit dosage forms containing the combination of agents as described herein will contain a certain amount of each agent of the combination that is typically administered when the agent is administered alone.

[0259] In some embodiments, the drug-carrier complex disclosed herein is administered to a patient in the form of a pharmaceutical composition. In some embodiments, the drug-carrier complex disclosed herein is present in a pharmaceutically effective amount.

[0260] The term “administered in combination with” or “co-administration” as used herein refers to the simultaneous or separate sequential administration in any manner of a solid or liquid oral pharmaceutical dosage form containing the drug-carrier complex disclosed herein and one or more other active agents known to be useful in the treatment of nervous system and / or mental diseases, conditions, disorders, and / or symptoms. The term “other one or more active agent” as used herein includes any compound or therapeutic agent known or proven to exhibit advantageous properties when administered to a patient in need of treatment AdministrationAttorney Docket No.38383.0001P1

[0261] Administration of the extracts or pharmaceutical compositions of the present disclosure can be via any method which delivers a compound of this disclosure systemically and / or locally, including oral routes, transdermal routes, etc. Generally, the compositions of the present disclosure are administered orally, but the following administration methods may also be utilized where necessary and / or appropriate: parenteral administration (e.g., intravenous (IV), intramuscular, subcutaneous (SQ or Sub-Q) injections, or intramedullary), transdermal, via inhalation, topically, via suppository, sublingual administration, and buccal administration.

[0262] In preferred embodiments, extracts and compositions comprising the extracts as described herein can be administered orally and at least a portion of the absorption occurs via buccal absorption, such as via cheek or sublinqually or any other mucus membrane within the mouth. In particular embodiments, the administration is sublingual or directed to the side of the mouth so as to contact the cheeks with the extract or composition. The extracts and the compositions are designed to produce products for human or animal consumption. Modes of administration can be via inhalation (via combustion, vaporization and nebulization), buccal absorption within the mouth, oral administration (e.g., eating / drinking, such as with food or drink), and topical application delivery methods.

[0263] In some embodiments of the present disclosure, the route of administration for the compositions of the present disclosure is oral without further dilution or reconstitution.

[0264] In embodiments, such oral administration may be in a form including but not limited to capsules containing a liquid, tablets, pills, liquid, such as tinctures or sprays, lozenges, etc. In particular embodiments, the dosage form is a liquid or free liquid that is orally administered for buccal absorbtion.

[0265] In some embodiments, the BDP oral suspension is administered 1, 2, or 3 times a day. In a further embodiment, the BDS oral suspension is administered 2 times a day. Each administration is near the time of a meal. Dose

[0266] An aspect of the present disclosure is a dosing regimen that has a starting dose of 25 mg of BDS (equivalent to approximately 13.75 mg of CBD or 0.2 mg / kg assuming a 70kg person)Attorney Docket No.38383.0001P1 with maximum expected dose level up to 618 mg of BDS (equivalent to 340 mg of CBD or 4.85 mg / kg assuming a 70kg person). Another aspect of the present disclosure is a dosing regimen that has a starting dose of 226.6 mg of BDS (equivalent to 125 mg of CBD or 1.8 mg / kg assuming a 70kg person) with maximum expected dose level up to 1823.1 mg of BDS (equivalent to 1000 mg of CBD or 14.3 mg / kg assuming a 70kg person).

[0267]

[0268] The dosing regimens of the present disclosure includes dosages of BDS of about 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg,1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, 1450 mg, 1500 mg, 1550 mg,1600 mg, 1650 mg, 1700 mg, 1750 mg, 1800 mg, 1850 mg, 1900 mg, 1950 mg, and 2000 mg.

[0269] In some embodiments, the BDS dosing regimens of the present disclosure range between about 25 mg to about 50 mg, about 50 mg to about 100 mg, about 75 mg to about 125 mg, about 100 mg to about 150 mg, about 125 mg to about 175 mg, about 150 mg to about 200 mg, about 175 mg to about 225 mg, about 200 mg to about 250 mg, about 225 mg to about 275 mg, about 250 mg to about 300 mg, about 275 mg to about 325 mg, about 300 mg to about 350 mg, about 325 mg to about 375 mg, about 350 mg to about 400 mg, about 375 mg to about 425 mg, about 400 mg to about 450 mg, about 425 mg to about 475 mg, about 450 mg to about 500 mg, about 475 mg to about 525 mg, about 500 mg to about 550 mg, about 525 mg to about 575 mg, about 550 mg to about 600 mg, about 575 mg to about 625 mg, about 600 mg to about 650 mg, about 625 mg to about 675 mg, about 650 mg to about 700 mg, about 675 mg to about 725 mg, about 700 mg to about 750 mg, about 725 mg to about 775 mg, about 750 mg to about 800 mg..

[0270] In embodiments for treating autism in a pediatric, the administered dosage of the BDS is from about 20 mg to about 400 mg per day or to about 650 mg per day. The administered dosage can be, for example, from about 20 mg to about 350 mg, about 20 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 100 mg, about 20 mg to about 50 mg, about 50 mg to about 400 mg, about 50 mg to about 350 mg, about 50 mg to about 300 mg, about 50 mg to about 200 mg, about 50 mg to about 100 mg, about 100 mg to about 400 mg, about 100 mg to about 350 mg, about 100 mg to about 300 mg, about 100 mg to about 200 mg, about 200 mg to about 400Attorney Docket No.38383.0001P1 mg, about 200 mg to about 300 mg, or about 300 mg to about 400 mg. In some embodiments, the administered dosage of the BDS is about 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, or about 650 mg per day.

[0271] In some embodiments, the pharmaceutical composition is administered to provide BDS at an amount from about 40 mg to about 700 mg per day or about 800 mg per day. The administered dosage can be, for example, from about 40 mg to about 650 mg, about 40 mg to about 600 mg, about 40 mg to about 500 mg, about 40 mg to about 400 mg, about 40 mg to about 300 mg, about 40 mg to about 200 mg, about 40 mg to about 100 mg, about 40 mg to about 80 mg, about 80 mg to about 700 mg, about 80 mg to about 650 mg, about 80 mg to about 600 mg, about 80 mg to about 500 mg, about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg, about 100 mg to about 200 mg, about 200 mg to about 650 mg, about 200 mg to about 600 mg, about 200 mg to about 500 mg, about 200 mg to about 400 mg, about 200 mg to about 300 mg, about 300 mg to about 650 mg, about 300 mg to about 600 mg, about 300 mg to about 500 mg, about 300 mg to about 400 mg, about 400 mg to about 650 mg, about 400 mg to about 600 mg, about 400 mg to about 500 mg, or about 500 mg to about 700 mg per day. In some embodiments, the administered dosage of the BDS is from about 100 mg to about 700 mg per day or to about 800 mg per day.

[0272] In some embodiments, the administered dosage of the BDS is about 50 mg, about 100 mg, about 175 mg, about 250 mg, about 300 mg, about 350 mg, about 500 mg, about 600 mg, or about 700 mg per day. about 775 mg to about 825 mg, about 800 mg to about 850 mg, about 825 mg to about 875 mg, about 850 mg to about 900 mg, about 875 mg to about 925 mg, about 900 mg to about 950 mg, about 925 mg to about 975 mg, about 950 mg to about 1000 mg, about 975 mg to about 1025 mg, about 1000 mg to about 1050 mg, about 1025 mg to about 1075 mg, about 1050 mg to about 1100 mg, about 1075 mg to about 1125 mg, about 1100 mg to about 1150 mg, about 1125 mg to about 1175 mg, about 1150 mg to about 1200 mg, about 1175 mg to about 1225 mg, about 1200 mg to about 1250 mg, about 1225 mg to about 1275 mg, about 1250 mg to about 1300 mg, about 1275 mg to about 1325 mg, about 1300 mg to about 1350 mg, about 1325 mg to about 1375 mg, about 1350 mg to about 1400 mg, about 1375 mg to about 1425 mg, about 1400 mg to about 1450 mg, about 1425 mg to about 1475 mg, about 1450 mg to about 1500 mg, about 1475Attorney Docket No.38383.0001P1 mg to about 1525 mg, about 1500 mg to about 1550 mg, about 1525 mg to about 1575 mg, about 1550 mg to about 1600 mg, about 1575 mg to about 1625 mg, about 1600 mg to about 1650 mg, about 1625 mg to about 1675 mg, about 1650 mg to about 1700 mg, about 1675 mg to about 1725 mg, about 1700 mg to about 1750 mg, about 1725 mg to about 1775 mg, about 1750 mg to about 1800 mg, about 1775 mg to about 1825 mg, about 1800 mg to about 1850 mg, about 1825 mg to about 1875 mg, about 1850 mg to about 1900 mg, about 1875 mg to about 1925 mg, about 1900 mg to about 1950 mg, about 1925 mg to about 1975 mg, about 1950 mg to about 2000 mg, about 1975 mg to about 2025 mg, about 2000 mg to about 2050 mg, about 2025 mg to about 2075 mg, about 2050 mg to about 2100 mg, about 2075 mg to about 2125 mg, about 2100 mg to about 2150 mg, about 2125 mg to about 2175 mg, and about2150 mg to about 2200 mg.

[0273] The dose can start low and the titrate to an effective amount for the individual as a maintenance dose. The maintenance dose can fall within the range of 20 mg to about 400 mg per day or to about 650 mg per day or 40 mg to 700 mg per day or 800 mg per day.

[0274] In some embodiments, the BDS is administered as a titrating dose, wherein the initial dose is increased every 3, 4, or 5 days until a maintenance phase. In such embodiments, the effects and tolerability of the titrating dose are observed to determine a maintenance dose.

[0275] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a first daily dose of the composition that is equivalent to about 100-105 mg (such as 103 mg) of the extract to the subject for 4 to 7 days and administering a second daily dose of about 200-210 mg (such as 206 mg) for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

[0276] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a third daily dose of the composition that is equivalent to about 360 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose afterAttorney Docket No.38383.0001P1 the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

[0277] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a fourth daily dose of the composition that is equivalent to about 515 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

[0278] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a fifth daily dose of the composition that is equivalent to about 618 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

[0279] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a first daily dose of the composition that is equivalent to about 53 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 103 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

[0280] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a third daily dose of the composition that is equivalent to about 180 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

[0281] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a fourth daily dose of the composition that is equivalent to about 263 mgAttorney Docket No.38383.0001P1 of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

[0282] In some embodiments wherein the BDS is administered as a titrating dose, the treatment comprises administering a fifth daily dose of the composition that is equivalent to about 314 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

[0283] In terms of CBD, the dosing regimens of the present disclosure includes dosages of CBD of about 25 mg, about 50 mg, about 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, and 1250 mg.

[0284] In some embodiments, the CDB dosing regimens of the present disclosure range between about 25 mg to about 50 mg, about 50 mg to about 100 mg, about 75 mg to about 125 mg, about 100 mg to about 150 mg, about 125 mg to about 175 mg, about 150 mg to about 200 mg, about 175 mg to about 225 mg, about 200 mg to about 250 mg, about 225 mg to about 275 mg, about 250 mg to about 300 mg, about 275 mg to about 325 mg, about 300 mg to about 350 mg, about 325 mg to about 375 mg, about 350 mg to about 400 mg, about 375 mg to about 425 mg, about 400 mg to about 450 mg, about 425 mg to about 475 mg, about 450 mg to about 500 mg, about 475 mg to about 525 mg, about 500 mg to about 550 mg, about 525 mg to about 575 mg, about 550 mg to about 600 mg, about 575 mg to about 625 mg, about 600 mg to about 650 mg, about 625 mg to about 675 mg, about 650 mg to about 700 mg, about 675 mg to about 725 mg, about 700 mg to about 750 mg, about 725 mg to about 775 mg, about 750 mg to about 800 mg, about 775 mg to about 825 mg, about 800 mg to about 850 mg, about 825 mg to about 875 mg, about 850 mg to about 900 mg, about 875 mg to about 925 mg, about 900 mg to about 950 mg, about 925 mg to about 975 mg, about 950 mg to about 1000 mg, about 975 mg to about 1025 mg, about 1000 mg to about 1050 mg, about 1025 mg to about 1075 mg, about 1050 mg to about 1100 mg,Attorney Docket No.38383.0001P1 about 1075 mg to about 1125 mg, about 1100 mg to about 1150 mg, about 1125 mg to about 1175 mg, about 1150 mg to about 1200 mg, about 1175 mg to about 1225 mg, about 1200 mg to about 1250 mg, about 1225 mg to about 1275 mg, and about 1250 mg to about 1300 mg.

[0285] In some embodiments, the pharmaceutical composition is dosed at an amount to provide for CBD dosing of about 0.5 mg / kg, about 0.75 mg / kg, about 1.0 mg / kg, 1.5 mg / kg, 2.0 mg / kg, 2.5 mg / kg, 3.0 mg / kg, 3.5 mg / kg, 4.0 mg / kg, 4.5 mg / kg, 5.0 mg / kg, 5.5 mg / kg, 6.0 mg / kg, 6.5 mg / kg, 7.0 mg / kg, 7.5 mg / kg, 8.0 mg / kg, 8.5 mg / kg, 9.0 mg / kg, 9.5 mg / kg, 10.0 mg / kg, 10.5 mg / kg, 11.0 mg / kg, 11.5 mg / kg, 12.0 mg / kg, 12.5 mg / kg, 13.0 mg / kg, 13.5 mg / kg, 14.0 mg / kg, 14.5 mg / kg, 15.0 mg / kg, 15.5 mg / kg, and 16.0 mg / kg.

[0286] In some embodiments, the pharmaceutical composition is dosed at an amount to provide for a CBD dose between about 0.5 mg / kg to about1.0 mg / kg, such as about 0.75 mg / kg to about 1.25 mg / kg, about 1.0 mg / kg to about 1.5 mg / kg, about 1.25 mg / kg to about 1.75 mg / kg, about 1.5 mg / kg to about 2.0 mg / kg, about 1.75 mg / kg to about 2.25 mg / kg, about 2.0 mg / kg to about 2.5 mg / kg, about 2.25 mg / kg to about 2.75 mg / kg, about 2.5 mg / kg to about 3.0 mg / kg, about 2.75 mg / kg to about 3.25 mg / kg, about 3.0 mg / kg to about 3.5 mg / kg, about 3.25 mg / kg to about 3.75 mg / kg, about 3.5 mg / kg to about 4.0 mg / kg, about 3.75 mg / kg to about 4.25 mg / kg, about 4.0 mg / kg to about 4.5 mg / kg, about 4.25 mg / kg to about 4.75 mg / kg, about 4.5 mg / kg to about 5.0 mg / kg, about 4.75 mg / kg to about 5.25 mg / kg, about 5.0 mg / kg to about 5.5 mg / kg, about 5.25 mg / kg to about 5.75 mg / kg, about 5.5 mg / kg to about 6.0 mg / kg, about 5.75 mg / kg to about 6.25 mg / kg, about 6.0 mg / kg to about 6.5 mg / kg, about 6.25 mg / kg to about 6.75 mg / kg, about 6.5 mg / kg to about 7.0 mg / kg, about 6.75 mg / kg to about 7.25 mg / kg, about 7.0 mg / kg to about 7.5 mg / kg, about 7.25 mg / kg to about 7.75 mg / kg, about 7.5 mg / kg to about 8.0 mg / kg, about 7.75 mg / kg to about 8.25 mg / kg, about 8.0 mg / kg to about 8.5 mg / kg, about 8.25 mg / kg to about 8.75 mg / kg, about 8.5 mg / kg to about 9.0 mg / kg, about 8.75 mg / kg to about 9.25 mg / kg, about 9.0 mg / kg to about 9.5 mg / kg, about 9.25 mg / kg to about 9.75 mg / kg, about 9.5 mg / kg to about 10.0 mg / kg, about 9.75 mg / kg to about 10.25 mg / kg, about 10.0 mg / kg to about 10.5 mg / kg, about 10.25 mg / kg to about 10.75 mg / kg, about 10.5 mg / kg to about 11.0 mg / kg, about 10.75 mg / kg to about 11.25 mg / kg, about 11.0 mg / kg to about 11.5 mg / kg, about 11.25 mg / kg to about 11.75 mg / kg, about 11.5 mg / kg to about 12.0 mg / kg, about 11.75 mg / kg to about 12.25 mg / kg, aboutAttorney Docket No.38383.0001P1 1200 mg / kg to about 12.5 mg / kg, about 12.25 mg / kg to about 12.75 mg / kg, about 12.5 mg / kg to about 13.0 mg / kg, about 12.75 mg / kg to about 13.25 mg / kg, about 13.0 mg / kg to about 13.5 mg / kg, about 13.25 mg / kg to about 13.75 mg / kg, about 13.5 mg / kg to about 14.0 mg / kg, about 13.75 mg / kg to about 14.25 mg / kg, about 14.0 mg / kg to about 14.5 mg / kg, about 14.25 mg / kg to about 14.75 mg / kg, about 14.5 mg / kg to about 15.0 mg / kg, about 14.75 mg / kg to about 15.25 mg / kg, about 15.0 mg / kg to about 15.5 mg / kg, about 15.25 mg / kg to about 15.75 mg / kg, about 15.5 mg / kg to about 16.0 mg / kg, about 15.75 mg / kg to about 16.25 mg / kg, and about 16.0 mg / kg to about 16.5 mg / kg.

[0287] The foregoing doses are administered twice daily. In some embodiments, the dose is titrated. For example, a patient starts at a dose of 2.5 mg / kg and after 4 to 7 days increases the dose to 5 mg / kg and so on until a dose is reached that ameliorates the symptoms.

[0288] In some embodiments, the volume of the pharmaceutical composition, the BDP oral suspension, per dose is from about 0.1 mL to about 6 mL. The volume of BDP oral suspension per dose can be, for example, from about 0.1 mL to about 3 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 1 mL, about 0.25 mL to about 5 mL, about 0.25 mL to about 3 mL, about 0.25 mL to about 3 mL, about 0.25 mL to about 2 mL, about 0.25 mL to about 1 mL, about 0.5 mL to about 5 mL, about 0.5 mL to about 3 mL, about 0.5 mL to about 2 mL, about 0.5 mL to about 1 mL, about 1 mL to about 5 mL, about 1 mL to about 3 mL, or about 3 mL to about 5 mL. In some embodiments, the volume of BDS oral suspension per dose is about 0.25 mL, about 0.5 mL, about 1.0 mL, about 1.5 mL, about 2 mL, or about 3 mL.

[0289] In some embodiments, the volume of BDP oral suspension per dose of the present disclosure includes about 0.25 mL, about 0.5 mL, about 0.75 mL, about 1.0 mL, 1.5 mL, 2.0 mL, 2.5 mL, 3.0 mL, 3.5 mL, 4.0 mL, 4.5 mL, 5.0 mL, 5.5 mL, 6.0 mL, 6.5 mL, 7.0 mL, 7.5 mL, 8.0 mL, 8.5 mL, 9.0 mL, 9.5 mL, 10.0 mL, 10.5 mL, 11.0 mL, 11.5 mL, 12.0 mL, 12.5 mL, 13.0 mL, 13.5 mL, 14.0 mL, 14.5 mL, 15.0 mL, 15.5 mL, 16.0 mL, 16.5 mL, 17.0 mL,17.5 mL, 18.0 mL, 18.5 mL, 19.0 mL, 19.5 mL, and 20.0 mL.

[0290] In some embodiments, the volume of BDP oral suspension per dose is from about 0.5 mL to about 8 mL. The volume of BDS oral suspension per dose can be, for example, from about 0.5 mL to about 6 mL, about 0.5 mL to about 3 mL, about 0.5 mL to about 1 mL, about 1 mL to aboutAttorney Docket No.38383.0001P1 8 mL, about 1 mL to about 6 mL, about 1 mL to about 3 mL, about 3 mL to about 8 mL, or about 3 mL to about 6 mL. In some embodiments, the volume of BDS oral suspension per dose is about 0.5 mL, 1 mL, 1.75 mL, 2.5 mL, 3 mL, 2.5 mL, 5 mL, or about 6 mL.

[0291] In some embodiments, the volume of BDP oral suspension per dose of the present disclosure includes ranges between about 0.25 mL to about 0.5 mL, about0.5 mL to about 1.0 mL, about 0.75 mL to about 1.25 mL, about 1.0 mL to about 1.5 mL, about 1.25 mL to about 1.75 mL, about 1.5 mL to about 2.0 mL, about 1.75 mL to about 2.25 mL, about 2.0 mL to about 2.5 mL, about 2.25 mL to about 2.75 mL, about 2.5 mL to about 3.0 mL, about 2.75 mL to about 3.25 mL, about 3.0 mL to about 3.5 mL, about 3.25 mL to about 3.75 mL, about 3.5 mL to about 4.0 mL, about 3.75 mL to about 4.25 mL, about 4.0 mL to about 4.5 mL, about 4.25 mL to about 4.75 mL, about 4.5 mL to about 5.0 mL, about 4.75 mL to about 5.25 mL, about 5.0 mL to about 5.5 mL, about 5.25 mL to about 5.75 mL, about 5.5 mL to about 6.0 mL, about 5.75 mL to about 6.25 mL, about 6.0 mL to about 6.5 mL, about 6.25 mL to about 6.75 mL, about 6.5 mL to about 7.0 mL, about 6.75 mL to about 7.25 mL, about 7.0 mL to about 7.5 mL, about 7.25 mL to about 7.75 mL, about 7.5 mL to about 8.0 mL, about 7.75 mL to about 8.25 mL, about 8.0 mL to about 8.5 mL, about 8.25 mL to about 8.75 mL, about 8.5 mL to about 9.0 mL, about 8.75 mL to about 9.25 mL, about 9.0 mL to about 9.5 mL, about 9.25 mL to about 9.75 mL, about 9.5 mL to about 10.0 mL, about 9.75 mL to about 10.25 mL, about 10.0 mL to about 10.5 mL, about 10.25 mL to about 10.75 mL, about 10.5 mL to about 11.0 mL, about 10.75 mL to about 11.25 mL, about 11.0 mL to about 11.5 mL, about 11.25 mL to about 11.75 mL, about 11.5 mL to about 12.0 mL, about 11.75 mL to about 12.25 mL, about 12.0 mL to about 12.5 mL, about 12.25 mL to about 12.75 mL, about 12.5 mL to about 13.0 mL, about 12.75 mL to about 13.25 mL, about 13.0 mL to about 13.5 mL, about 13.25 mL to about 13.75 mL, about 13.5 mL to about 14.0 mL, about 13.75 mL to about 14.25 mL, about 14.0 mL to about 14.5 mL, about 14.25 mL to about 14.75 mL, about 14.5 mL to about 15.0 mL, about 14.75 mL to about 15.25 mL, about 15.0 mL to about 15.5 mL, about 15.25 mL to about 15.75 mL, about 15.5 mL to about 16.0 mL, about 15.75 mL to about 16.25 mL, about 16.0 mL to about 16.5 mL about 16.25 mL to about 16.75 mL, about 16.5 mL to about 17.0 mL, about 16.75 mL to about17.25 mL, about 17.0 mL to about 17.5 mL, about 17.25 mL to about 17.75 mL, about 17.5 mL to about 18.0 mL, about 17.75 mL to about 18.25 mL, about 18.0 mL to about 18.5Attorney Docket No.38383.0001P1 mL, about 18.25 mL to about 18.75 mL, about 18.5 mL to about 19.0 mL, about 18.75 mL to about 19.25 mL, about 19.0 mL to about 19.5 mL, about 19.25 mL to about 19.75 mL, about 19.5 mL to about 20.0 mL, about 19.95 mL to about 20.25 mL, and about20.0 mL to about 20.5 mL.

[0235] In some embodiments, the amount of BDS in the BDP is about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL,about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, about 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, about 190 mg / mL, about 195 mg / mL, and about 200 mg / mL. In particular embodiments, the amount is 95 to 115 mg / ml or 100 to 110 mg / ml.

[0292] In some embodiments, the amount of BDS in the BDP ranges from between about 95 mg / mL to about 110 mg / mL, about 100 mg / mL to about 105 mg / mL, about 105 mg / mL to about 110 mg / mL, or about 110 mg / mL to about 115 mg / mL. In some embodiments, the amount of BDS in the BDP ranges from between about 5 mg / mL to about 10 mg / mL, about 10 mg / L to about 15 mg / mL,about 15 mg / mL to about 20 mg / mL, about 20 mg / mL to about 25 mg / mL, about 25 mg / mL toabout 30 mg / mL,about 30 mg / mL to about 35 mg / mL, about 35 mg / mL to about 40 mg / mL, about 40 mg / mL to about 45 mg / mL, about 45 mg / mL to about 50 mg / mL, about 50 mg / mL to about 55 mg / mL, about 55 mg / mL to about 60 mg / mL, about 60 mg / mL toabout 65 mg / mL,about 65 mg / mL to about 70 mg / mL,about 70 mg / mL to about 75 mg / mL, about 75 mg / mL to about 80 mg / mL, about 80 mg / mL to about 85 mg / mL, about 85 mg / mL to about 90 mg / mL, about 90 mg / mL to about 95 mg / mL,about 95 mg / mL to about 100 mg / mL, about 100 mg / mL to about 105 mg / mL, about 105 mg / mL to about 110 mg / mL, about 110 mg / mL to about 115 mg / mL, about 115 mg / mL to about 120 mg / mL,about 120 mg / mL to about 125 mg / mL, about 125 mg / mL to about 130 mg / mL about 130 mg / mL to about 135 mg / mL, about 135 mg / mL to about 140 mg / mL, about 140 mg / mL to about 145 mg / mL, about 145 mg / mL to about 150 mg / mL, about 150 mg / mL to about 155 mg / mL, about 155 mg / mL toabout 160 mg / mL, about 160 mg / mL toAttorney Docket No.38383.0001P1 about 165 mg / mL, about 165 mg / mL to about 170 mg / mL, about 170 mg / mL to about 175 mg / mL, about 175 mg / mL to about 180 mg / mL, about 180 mg / mL to about 185 mg / mL, about 185 mg / mL to about 190 mg / mL, about 190 mg / mL to about 195 mg / mL, and about 195 mg / mL to about 200 mg / mL.

[0293] In some embodiments, the composition comprises a concentration of cannabidiol of at least 45 mg / mL to 75 mg / mL. The composition can comprise a concentration, for example, of cannabidiol of 50 mg / mL to 70 mg / mL, 50 mg / mL to 65 mg / mL of cannabidiol.

[0294] In some embodiments, the composition comprises a ratio of cannabidiol:delta 9- tetrahydrocannabinol of from about 20:1 to about 40:1. The composition can comprise a ratio, for example, of cannabidiol:tetrahydrocannabidiol of from about about 20:1 to about 40:1. In some embodiments, the composition comprises a ratio of cannabidiol:tetrahydrocannabidiol of from about 25:1 to about 40:1. In some embodiments, the composition comprises a ratio of cannabidiol: tetrahydrocannabinol of from about 22:1 to about 40:. The composition can comprise a ratio, for example, of cannabidiol:tetrahydrocannabinol of from about 22:1 to about 35:1, about 23:1 to about 35:1, about 24:1 to about 35:1, about 25:1 to about 35:1, about 23:1 to about 40:1, about 24:1 to about 40:1. In some embodiments, the composition comprises a ratio of cannabidiol:tetrahydrocannabinol of from about 23:1 to about 38:1. In some embodiments, the composition comprises a ratio of cannabidiol:tetrahydrocannabinol of at least 25:1.

[0295] In some embodiments, the composition comprises a tetrahydrocannabinol concentration of less than about 3 mg / mL. The composition can comprise, for example, a tetrahydrocannabinol concentration of less than about 2.8 mg / mL, 2.7 mg / mL, 2.5 mg / mL, 2.3 mg / mL, 2.0 mg / mL, 1.8 mg / mL, 1.7 mg / mL, 1.5 mg / mL, 1.3 mg / mL, 1.0 mg / mL, 0.8 mg / mL, 0.6 mg / mL, 0.3 mg / mL, 0.1 mg / mL, or less than about 0.05 mg / mL. In some embodiments, the composition comprises a tetrahydrocannabinol concentration of from about 1 mg / mL to about 3 mg / mL. VI. Representative Nervous System and Mental Diseases, Conditions, Disorders and / or Symptoms Treated by the Present Disclosure

[0296] In some embodiments, the BDS and BDP of the present disclosure can be used to treat a wide range of nervous, nervous-associated, pain, pain-associated, inflammation, inflammation- associated, mental, and mental -associated diseases, conditions, disorders and / or symptoms.Attorney Docket No.38383.0001P1

[0297] Nervous system diseases, also known as nervous system or neurological disorders, refer to over 600 medical conditions affecting the nervous system. Examples of nervous system diseases, disorders, conditions, and / or symptoms that can be treated according to the present disclosure include but are not limited to Acute Spinal Cord Injury, Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Ataxia, Bell's Palsy Brain Tumors, Cerebral Palsy, Cerebral Aneurysm, Epilepsy, Seizures, Lennox-Gastaut syndrome (LGS), Dravet syndrome, and Tuberous Sclerosis Complex (TSC), Guillain-Barré Syndrome, Headache Head Injury, Hydrocephalus, Lumbar Disk Disease (Herniated Disk), Meningitis, Motor Neurone Disease (MND), Multiple Sclerosis, Muscular Dystrophy, Seizure Disorder, Neurofibromatosis, Neurocutaneous Syndromes, Parkinson's Disease, Stroke (Brain Attack), Cluster Headaches, Tension Headaches, Migraine Headaches, Encephalitis, Sciatica, Shingles, Septicemia, Types of Muscular Dystrophy and Neuromuscular Diseases, Myasthenia Gravis, Huntington’s Disease, Charcot-Marie-Tooth Disease, Polyneuropathy, Moyamoya Disease, Multiple System Atrophy, Neoplasm, Chronic Inflammatory, Acute Motor Axonal Neuropathy, Angelman Syndrome, Progressive multifocal leukoencephalopathy (PML), Canavan Disease, Medical Medullary Syndrome, Demyelinating Polyradiculoneuropathy, Spina Bifida, Autism Spectrum Disorder, Strokes, 16P11.2 Deletion Syndrome, Prader-Willi Syndrome, Sotos Syndrome, 22q11 Deletion Syndrome, Rett Syndrome, 1P36 Deletion Syndrome, and Sturge-Weber Syndrome.

[0298] Autoimmune and inflammatory diseases that can be treated according to the present disclosure include but are not limited to Ankylosing Spondylitis, Antiphospholipid Antibody Syndrome, Autoimmune Encephalitis, Chronic Recurrent Multifocal Osteomyelitis, Gout, Henoch-Schonlein Purpura, Juvenile Dermatomyositis, Juvenile Idiopathic Arthritis, Juvenile Lupus (SLE), Juvenile Scleroderma, Juvenile Vasculitis, Kawasaki Disease, Lupus (Systemic Lupus Erythematosus), Mixed Connective Tissue Disease, Myositis, Poststreptococcal Inflammatory Syndromes, Psoriatic Arthritis, Reactive Arthritis, Rheumatoid Arthritis, Scleroderma, Sjogren's Syndrome, Spondyloarthritis / Spondyloarthropathy, Systemic Juvenile Idiopathic Arthritis, Undifferentiated Connective Tissue Disease, Uveitis, and Vasculitis.

[0299] The compositions and treatments of the present disclosure can also be used to treat pain, including but not limited to temporary, acute, chronic, or permanent pain. Acute pain is pain thatAttorney Docket No.38383.0001P1 may come from inflammation, tissue damage, injury, illness, or recent surgery. It usually lasts less than a week or two. The pain usually ends after the underlying cause is treated or has been resolved. Chronic pain is pain that persists for months or even years. The pain may come from inflammation, tissue damage, injury, illness, or recent surgery. The pain may be associated with headaches including but not limited to the most common types of chronic headaches such as migraines, cluster headaches, and tension headaches. The pain may be low back pain. Other pain disorders that can be treated according to the present disclosure include but are not limited to neuralgias and neuropathies that affect nerves throughout the body, pain due to damage to the central nervous system (the brain and spinal cord), as well as pain where no physical cause can be found-- psychogenic pain. Common types of pain that can be treated according to the present disclosure include but are not limited to arthritis (.e.g., osteoarthritis, rheumatoid arthritis), muscle pain, bone pain, joint pain, back pain, neck pain, musculoskeletal pain, cancer pain (e.g., near a tumor), headaches, including migraines, testicular pain (orchialgia), lasting pain in scar tissue, muscle pain all over (such as with fibromyalgia), multiple sclerosis, neurogenic pain (e.g., from damage or pressure to the nerves or other parts of the nervous system), AIDS, gall bladder disease, problems with the CNS (e.g., diabetes, shingles, sciatica), and organ pain because of injuries, infections, or health problems such as inflammatory bowel disease, irritable bowel syndrome, pelvic pain, and stomach ulcers. Many of these types of pain can be chronic and a person can have more than one kind of pain at the same time (e.g., fibromyalgia can cause pain in muscles and nerves).

[0300] Mental illness is a general term for a group of illnesses that may include symptoms that can affect a person’s thinking, perceptions, mood, and / or behavior. Mental illness can make it difficult for someone to cope with work, relationships, and other demands. Examples of mental and / or psychiatric diseases, disorders, conditions and / or symptoms that can be treated according to the present disclosure include but are not limited to Schizophrenia, Bipolar Affective Disorder, Psychosis, Depression, Dissociation and Dissociative Disorders, Personality Disorder, Paranoia, Anxiety Disorders, Eating Disorders, Mood Disorders, Obsessive-Compulsive Disorders, Post- Traumatic Stress (PTS) Disorders, Dissociative Disorders, Panic Disorders, Substance Use Disorders, behavioral and emotional disorders in children and adults, and Schizoaffective disorder. In some embodiments, the compositions and treatments of the present disclosure can be used toAttorney Docket No.38383.0001P1 treat schizophreniform disorder (acute schizophrenic episode); schizoaffective disorder; bipolar I disorder (mania, manic disorder, manic-depressive psychosis); bipolar II disorder; major depressive disorder with psychotic feature (psychotic depression); delusional disorders (paranoia); shared psychotic disorder (shared paranoia disorder); brief psychotic disorder (other and unspecified reactive psychosis); psychotic disorder not otherwise specified (unspecified psychosis); paranoid personality disorder; schizoid personality disorder; and schizotypal personality disorder. See, e.g., US Patent No.9,017,737.

[0301] Disorders that can be treated according to the present disclosure include but are not limited to antisocial personality disorder, anxiety disorder, Asperger symptom / disorder, attention deficit disorder, autistic disorder, bipolar disorder, body dysmorphic disorder, borderline personality disorder, central auditory processing disorder, chromosome disorder, compulsive personality disorder, conversion disorder, cruise-associated diarrheal disorder, cumulative trauma disorder, delusional disorder, dependent personality disorder, depersonalization disorder, depressive disorder, developmental disorder, dissociative identity disorder, dysthymic disorder, eating disorder, anorexia nervosa, bulimia nervosa, binge-eating disorder, EBV-associated lymphoproliferative disorder, endometrial disorder, expressive disorder, expressive language disorder, factitious disorder, functional disorder, gender identify disorder, generalized anxiety disorder, genetic disorders, hearing disorder, histrionic personality disorder, identity disorder, internet addiction disorder, iodine deficiency disorder, language disorder, late luteal phase dysphoric disorder, lymphoproliferative disorder, major depressive disorder, Matha Stewart disorder, Mendelian disorder, mental disorder, motor speech disorder, movement disorder, multiple autoimmune disorder, multiple personality disorder, musculoskeletal disorder, myeloproliferative disorder, narcissistic personality disorder, neurodegenerative disorder, neurogenic communication disorder, neurotic disorder, non-Mendelian disorder, obsessive- compulsive disorder (OCD), obsessive-compulsive personality disorder, Pan-ethnic disorder, panic disorder, partial syndrome eating disorder, passive-aggressive personality disorder, post- translation lymphoproliferative disorder, post-traumatic stress disorder (PTSD), Prader-Willi syndrome, premenstrual dysphoric disorder, psychotic disorder, reactive attachment disorder of infancy or early childhood, reading disorder, S-100-positive T-cell lymphoproliferative disorder,Attorney Docket No.38383.0001P1 schizoid personality disorder, seasonal affective disorder, seizure disorder, sexual pain disorder, shared psychotic disorder, silicone-reactive disorder, single gene disorder, sleep disorder, sleep terror disorder, smell disorder, social anxiety disorder, somatization disorder, speech disorder, swallowing disorder, taste disorder, thought disorder, throat disorder, thyroid disorder, urea cycle disorder, urologic disorder, voice disorder, treatment-resistant depression, and X-linked disorder. This list is adapted from McGraw-Hill Concise Dictionary of Modern Medicine (2002) The McGraw Hill Companies, Inc.

[0302] Autism spectrum disorder (ASD) is a neurological and developmental disorder that affects how people interact with others, communicate, learn, and behave. Although autism can be diagnosed at any age, it is described as a “developmental disorder” because symptoms generally appear in the first 2 years of life. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a guide created by the American Psychiatric Association that health care providers use to diagnose mental disorders, people with ASD often have difficulty with communication and interaction with other people; restricted interests and repetitive behaviors; and symptoms that affect their ability to function in school, work, and other areas of life. Autism is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience. People of all genders, races, ethnicities, and economic backgrounds can be diagnosed with ASD. Although ASD can be a lifelong disorder, treatments and services can improve a person’s symptoms and daily functioning. The American Academy of Pediatrics recommends that all children receive screening for autism. The compositions of the present disclosure can be used to treat or ameliorate one or more symptoms associated with autism and orphan conditions that share similar symptomatology. Examples of such symptoms include but are not limited to the following: stereotypic behavior, irritability, social anxiety, social withdrawal, inappropriate speech, hyperactivity / non-compliance, seizures, lethargy, depressive symptoms / depression. Adapted from a list provided by the National Institute of Mental Health (February 2023).

[0303] Thus, cannabinoid extract and pharmaceutical compositions described herein can be used to treat autism spectrum disorder (ASD) or one or more symptoms associated therewith. It is estimated that 1 in 36 children may have ASD (Maenner et al., 2020). ASD is characterized byAttorney Docket No.38383.0001P1 deficits in social communication, irritability, repetitive behaviors, impulsivity, temper tantrums, and high caregiver burden (Lecavalier et al., 2006).

[0304] Currently, the only Food and Drug Administration (FDA)-approved therapeutics used for the treatment of ASD symptoms are aripiprazole and risperidone, both of which are indicated for irritability in pediatric ASD (Abilify®Package Insert, Risperdal®Package Insert). These therapeutics for this chronic developmental disorder are effective but are associated with considerable adverse effects (AEs) as a result of long-term use, such as weight gain, metabolic syndrome, risk of the onset of type 2 diabetes, prolactin elevation, development of breast tissue, and extrapyramidal / movement-related side effects (Abilify®Package Insert, Risperdal®Package Insert). The anticonvulsant divalproex sodium (VPA), although not approved for the treatment of ASD, significantly reduces irritability and repetitive behaviors in individuals with ASD (Hollander et al 2006, Hollander et al 2010, King et al 2013). Although VPA is efficacious for pediatric epilepsy and some ASD symptoms, it also has significant AEs, including weight gain, sedation, and nausea (Depakote®Package Insert).

[0305] Thus, described herein are methods of treating autism spectrum disorder (ASD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein. In some embodiments, treating ASD in a subject comprises treating one or more symptoms of ASD selected from anxiety, irritability, lethargy / social withdrawal, stereotypic behavior, hyperactivity / noncompliance, inappropriate speech, social avoidance, and sleep disturbances. In some embodiments, treating ASD in a subject comprises improving one or more deficits associated with ASD selected from cognition deficits, sensory sensitivity, social deficits, and speech and language deficits.

[0306] In some embodiments, the subject is a human. In some embodiments, the human is less than 18 years of age or 5 to 17 years of age. In some embodiments, the human is at least 13 years of age or 13 to 30 years of age.

[0307] Also described herein are methods of treating epilepsy in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition described herein. In some embodiments, the subject is a human.Attorney Docket No.38383.0001P1

[0308] These AE profiles of currently approved and off-label therapeutics affect patient compliance in maintaining therapy and suggest that there is a large, unmet medical need for additional treatment options that do not have a significant AE profile. EXAMPLES

[0309] The present disclosure is further illustrated by the following examples that should not be construed as limiting. The contents of all references, patents, and published patent applications cited throughout this application, as well as the Figures, are incorporated herein by reference in their entirety for all purposes. Example 1: Drying and Extraction of Cannabis sativa L. plants to form Botanical Drug Substance (BDS)

[0310] After manual harvesting of Cannabis sativa L. plants, the plants are handled gently to reduce trichome loss and transported to a drying facility. The plants are dried using natural drying without additional heat applied. The moisture level is ensured to be 10% or lower as measured using Ohaus MB90 or a MB120 Moisture Analyzer.

[0311] The plants are spaced evenly to provide adequate airflow. Large plants may be cut into smaller pieces to hang dry. Fans and vents are ensured to exchange wet and dry air in and out of the facility, and the plant materials are kept clean and isolated from contaminants.

[0312] The plants are dried to 7% moisture or below. The stems should snap cleanly before removal of flowers from stalks, or more drying is required. Following drying to 7% moisture or below, the hemp plants are hand processed to separate the flowers and leaves from the stalks, branches, and other undesired plant material. The hemp is then ran through a brush separator to remove stem material and to particle size hemp and homogenize the hemp biomass.

[0313] Extraction

[0314] The extraction process extracts CBD and other cannabinoids from hemp cultivars of Cannabis sativa L. using isopropyl alcohol. Flower and leaves of a hemp plant of the variety ‘CW1AS1’ strain is mixed with isopropyl alcohol using a CUP-15 (Delta Separations / Prospiant) centrifuge. The cannabinoids are extracted from the physical biomass and brought into theAttorney Docket No.38383.0001P1 solution. After centrifugation, the solution or miscella retrieved from the centrifuge is filtered with a 50-micron bag and a 25-micron bag through a filtration system. The miscella is then pumped into a storage drum, and the alcohol is substantially evaporated from the extract with spray evaporation. Alcohol recovered from the evaporation system can be used for further solvent extractions. The extract isolated from the alcohol is collected.

[0315] Decarboxylation - Reactor Method

[0316] Decarboxylation can be performed using a decarboxylation reactor. As many cannabinoids contain a carboxyl group, decarboxylation activates these cannabinoids to more effective forms after removal of the carboxyl group. The extract placed into a 20 L vessel that is heat jacketed and heated to a temperature 180 to 190°F. Chiller columns are in fluid communication with the reactor configured to receive evaporated products from the reactor, and the vessel is placed under vacuum. A mixer is applied to the extract solution. Further evaporation of remaining alcohol solvent occurs, and application of heat converts the cannabinoids into decarboxylated cannabinoids.

[0317] A representative chemical analysis of the extract is shown in Table 1. Table 1: Chemical Analysis Component Amount Cannabidiol 6.49% by weight Δ9-Tetrahydrocannabinol 0.24% by weight Cannabichromene 0.37% by weight Cannabigerol 0.20% by weight (-)-α-bisabolol 5700 ppm Camphene < 50 ppm (1S)-(+)-3-Carene < 50 ppm β-Caryophyllene 5100 ppm p-Cymene < 50 ppm Eucalyptol 140 ppm α-Humulene 2300 ppm (-)-Isopulegol < 50 ppm (R)-(+)Limonene 67 ppm Linalool 72 ppm beta-Myrcene < 50 ppm (E)-b-Ocimene < 50 ppm (Z)-b-Ocimene < 50 ppmAttorney Docket No.38383.0001P1 Component Amount α-Pinene < 50 ppm β-Pinene < 50 ppm α-Terpinene < 50 ppm β-Terpinene < 50 ppm γ-Terpinene < 50 ppm Terpinolene < 50 ppm Example 2: Formulation of BDS Oral Suspension (BDP)

[0318] The BDP manufacturing process consists of compounding a solution of a cannabinoid extract of CW1AS1, Glycerol Monolinoleate, NF, and flavoring agent in a large mixing kettle. The mixture is heated to 45-75 °C followed by mixing for 30 minutes. The homogenized solution is filled into bottles followed by capping and secondary packaging.

[0319] A summary of the manufacturing process operating parameters is provided in Table 2. Table 2: Process Operating Parameters Process Step Operating Parameter Range Compounding Temperature 45-75 ℃ Time No more than 30 minutes Homogenization Mixing speed 700-800 rpms Temperature 45-75 °C Time No more than 30 minutes Filling Frequency 400 bottles / hour Example 3: Summary of Nonclinical Pharmacokinetics

[0320] CBD exposure following oral dosing was assessed in two in vivo genetic toxicity studies (i.e., comet assay and mouse micronucleus) to confirm exposure. In Study 842-489-5825 (comet assay), male rats administered a single oral dose of the BDS of the present disclosure at 2000 mg / kg body weight (corresponding to approximately 145 mg / kg total cannabinoids) resulted in mean CBD plasma concentration of 1177 ng / mL at 2 hours, 1487 ng / mL at 4 hours, and 1795 ng / mL at 6 hours. In Study 842-474-5814 (mouse micronucleus), male mice administered single oral dose of the BDS of the present disclosure of 2000 mg / kg body weight (corresponding toAttorney Docket No.38383.0001P1 approximately 145 mg / kg total cannabinoids) resulted in mean CBD plasma concentration of 602.3 ng / mL at 2 hours, 408.6 ng / mL at 4 hours, 350.7 ng / mL at 6 hours, and 32.2 ng / mL at 24 hours after treatment. Example 4: Summary of Nonclinical Toxicology

[0321] Four good laboratory practice (GLP) toxicology studies and one non-GLP dose range finding (DRF) were performed to assess repeat-dose toxicity (i.e., 14-day repeat-dose rat and 90- day repeat-dose rat) and genotoxicity (i.e., Ames, comet assay, and mouse micronucleus), which have been reported in literature (Dziwenka et al 2020). The BDS contained ~55% CBD, ~2% CBC, and 1 to 2%THC.

[0322] A non-GLP 14-day DRF oral toxicity study was conducted in 40 Sprague-Dawley CD®IGS rats (20 males and 20 females) at dose levels of 0 (vehicle control [olive oil]), 1000, 2000, and 4000 mg / kg / day of botanical extract (i.e., corresponding to the BDS of the present disclosure) via oral gavage, corresponding to ~63, ~125 and ~251 mg total cannabinoids / kg body weight (Study 48149). Clinical signs directly attributable to test article administration were observed in the 4000 mg / kg / day group: hypoactivity, hyperactivity, reduced food consumption, and piloerection. Test article-related changes in serum chemistry values on Day 15 were observed in this dose group and consisted of increased blood urea nitrogen and creatinine. Test article-related decreases in mean weekly body weights, daily body weight gain, food consumption, and food efficiency were observed in the 1000, 2000, and 4000 mg / kg / day groups. Test article-related microscopic observations consisted of hepatocyte hypertrophy in the 2000 and 4000 mg / kg / day groups that correlated with an increase in liver weights, and vacuolation of the adrenal cortex in 1000, 2000, and 4000 mg / kg / day groups that correlated with dose-dependent increased adrenal weights. Based on these data, an oral dose <1000 mg / kg / day is expected to be tolerated in a rat study of longer duration.

[0323] A 90-day GLP repeat-dose toxicology study was performed with male and female Sprague-Dawley rats divided into four main test and four recovery groups (i.e., 10 and 5 / sex / group for the main and recovery study, respectively) (Study 48150). Dose levels of 200 (low-dose), 400 (mid-dose), and 800 mg / kg / day (high-dose) of botanical extract of the present disclosure in olive oil and vehicle control (olive oil) were administered by oral gavage once a day for 93 and 94 daysAttorney Docket No.38383.0001P1 to males and females, respectively, with a weekly dose adjustment based on the body weight changes. The same study design was applied for the recovery groups, followed by a recovery period (i.e., 31 days for the male rats and 30 days for the female rats). Dose-dependent decreases in mean weekly body weights were observed in the male main test groups (low-, mid-, and high- dose) and test article recovery groups, correlating with significant decreases in mean daily body weight gain and food consumption. A significant decline in food efficiency (measured as food consumption measurements coincidence with body weight changes) occurred in the high-dose recovery group. Body weight decrements of less than 10%, with evidence of a faster recovery considered non-adverse, occurred in the low and mid-doses (main and recovery groups), while declines greater than 10% considered adverse were observed in high doses treated groups. Based on these results, the no observed adverse effect level (NOAEL) was determined to be 800 mg / kg / day (app. ~ 55 mg / kg / day total cannabinoids) for females and 400 mg / kg / day (~ 27 mg / kg / day total cannabinoids) for males.

[0324] The BDS of the present disclosure did not show evidence of bacterial mutagenicity in a bacterial reverse mutation test (Ames) up to 5000 µg (Study 51956). The BDP did not show genotoxicity activity up to a dose of 2000 mg / kg in a mouse micronucleus test (Study 842-474- 5814) or in the examined rat stomach or liver tissues in an in vivo alkaline comet assay (Study 843- 489-5825). Example 5: Non-Interventional PK Study A non-interventional PK study was conducted with Farm Bill 2018-compliant product containing the same cannabinoid extract of the present disclosure and a similar drug product composition to the BDP of the present disclosure. There were no serious adverse events (SAEs) or withdrawals due to safety during the study, and overall data showed CBD absorption, which correlated with patterns observed in other human CBD PK studies. Example 6: A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study

[0325] The present study is a double-blind, randomized, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the BDP of the present disclosure (i.e., anAttorney Docket No.38383.0001P1 oral suspension of the BDS of the present disclosure) in fasting and fed healthy participants. See Fig.1 for an example of the study design (i.e., schematic) for the clinical protocol.

[0326] The BDP of the present disclosure is a botanical cannabinoid drug substance in a suspension intended for oral delivery. The BDS of the present disclosure is an oral suspension of 103 mg / mL of the BDS in glyceryl monolinoleate, National Formulary (NF), and an organic chocolate mint flavoring agent. The placebo is the suspension vehicle with no drug substance and is identical in appearance to the BDP of the present disclosure.

[0327] Food effect will be evaluated in one cross-over SAD fasting dose cohort after a minimum 14-day washout period. Approximately 64 participants will be enrolled.

[0328] Participants will undergo study-specific screening within 28 days prior to dose administration. Prior to any screening procedures being performed, participants will sign the study- specific consent form in the presence of a suitably trained study site staff member.

[0329] The study is comprised of two parts, Part A (SAD) and Part B (MAD). Up to 8 participants will be randomized (6 participants receiving the active drug and 2 participants receiving the placebo) in each cohort of Parts A and B. Participants in Part A will receive a single dose of the BDP of the present disclosure or placebo on Day 1 while those in Part B will receive a split dose of the BDP of the present disclosure or placebo, where one dose will be administered as two equal doses taken twice daily, (BID; administered approximately every 12 hours [± 30 minutes]) for 6 consecutive days (Day 1-Day 6), and 1 morning dose on Day 7.

[0330] Cohorts will be dosed sequentially in an ascending fashion. Safety Review Committee (SRC) meetings will be held after safety and tolerability data up to at least Day 7 (Part A) and up to at least Day 9 (Part B) are available for all participants from a single cohort and remainder of timepoints of the preceding cohort (when applicable), in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. A new cohort will not be dosed until the clinical portion of the preceding dose level has been completed, appropriate data has been reviewed by the SRC and authorization to proceed with the next dose level has been given by the SRC.Attorney Docket No.38383.0001P1

[0331] Part A and Part B each have four planned dose level cohorts (A1-A4 and B1-B4). Part A will include 1 cohort (A-X), which will enter a cross-over dosing scheme, where the participants will return to the clinical site on Day 14 to receive the BDP of the present disclosure or placebo following a high-fat, high-calorie breakfast on the morning on Day 15 after overnight fasting period. There will be an additional +2-day window between treatments allowed. In addition, based on the safety data accumulated from previous cohorts, optional Cohorts A5 / B5 and A6 / B6 may be employed if maximum tolerated dose (MTD) or maximum planned dose level has not been achieved in A4 / 5 and B4 / 54 for each study Part A and B, respectively.

[0332] Parts A and B of the study will be completed sequentially but with partial overlapping. Part B may be initiated when safety and tolerability are known and deemed acceptable for the first two cohorts in Part A (Cohorts A1-A2) at least.

[0333] A staggered dosing schedule will be used for dosing each cohort in Part A and will include 2 sentinel participants (1 active and 1 placebo). The 2 sentinel participants will be dosed initially, and the remaining 6 participants will be dosed at least 24 hours later, contingent on the resulting safety profile and once deemed safe to move forward in the opinion of Investigator in consultation with the SRC (if required).

[0334] All participants will fast overnight, and no food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose on Day 1 (Part A and Part B) and Day 7 (Part B). Additionally, no fluids (except for water given with the study drugs) will be allowed for 1 hour before dosing until 1-hour post-dose. No food will be allowed from at least 2 hours before until at least 1 hour after dosing for all other doses (Part B).

[0335] In the fed cross-over period for one cohort in Part A (A-X), after a fasting period of at least 10 hours, participants will be administered the BDP of the present disclosure 30 minutes after starting a Food and Drug Administration (FA)-compliant high-fat, high-calorie breakfast (approximately 50% calories from fat, approximately 800-1000 kcals). Participants will be required to consume entire meal in 30 minutes or less. No food will be allowed at least 4 hours post-dose. Except for water given with the study drug and fluids provided with the high-fat, high- calorie meal, no liquids will be allowed for 1 hour before dosing until 1-hour post-dose.Attorney Docket No.38383.0001P1

[0336] The anticipated dosing regimen is a starting dose of 226.6 mg BDS (equivalent to 125 mg CBD) with maximum expected dose level up to 1823.1 mg BDS (equivalent to 1000 mg CBD).

[0337] The role of the BDP of the present disclosure as adjuvant therapy is being evaluated in conditions where the available treatments are clinically insufficient or have a significant AE profile. Thus, the BDP of the present disclosure is being developed for the treatment of symptoms of CNS-associated diseases, with the first indication being ASD.

[0296] As an initial trial in the clinical development ofBDP of the present disclosure, this study is designed as a Phase 1, double-blinded, placebo-controlled, randomized, single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) ofBDP of the present disclosure in healthy participants.

[0297] The essential safety, tolerability, PK, and PD data ofBDP of the present disclosure will be collected in this study. The study includes an assessment of the potential interaction of the BDS of the present disclosure with food in healthy participants and the design follows the methodology described FDA Guidance for IndustryAssessing the Effects of Food on Drugs in INDs and NDAs – Clinical Pharmacology Considerations(June 2022).

[0298] Rationale for Starting Dose and Dose Range.The no observable adverse effect levels (NOAELs) determined in the 90-day pivotal rat toxicity study and twoin vivogenetic toxicity studies are shown inTable 1, along with the corresponding maximum plasma CBD exposure from the latter two studies. Following FDA Guidance for IndustryEstimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers(July 2005) the NOAEL dose levels observed in the rat toxicity study are equivalent to a minimum human equivalent dose (HED) of 4.4 and 8.9 mg / kg / day total cannabinoids for males and females, respectively, and 4.3 and 8.5 mg / kg / day CBD for males and females, respectively.

[0299] For the genetic toxicity studies in mice and rats, the observed NOAEL dose levels correspond to HEDs of 11.3 / 10.5 and 24.3 / 20.9 mg / kg / day (total cannabinoid basis / CBD), respectively.Attorney Docket No.38383.0001P1

[0300] The recommended starting dose is determined based on theBDS of the present disclosure as used in nonclinical studies, the established safe profile of CBD-containing products in both adult and pediatric participants, as well as the maximum approved dose of Epidiolex®. Recognizing that the documented clinical safety data are not specific tothe BDS of the present disclosure,this study utilizes a conservatively established safe starting dosing regimen of226.6 mgBDS, equivalent to 125 mg CBD (1.8 mg / kg assuming 70kg person), which is a 14-fold lower dose than maximum approved daily dose level for Epidiolex®. In addition, the proposed BDS dose (i.e., 1.8 mg / kg as calculated above) is 2.8-fold lower than the recommended starting dosage for Epidiolex®of 5 mg / kg / day.

[0301] The maximum planned dose to be evaluated in this study will be 1823.1 mgBDS, equivalent to 1000 mg CBD, a dose that is well below the maximum approved daily dose for Epidiolex®in a 70-kg person. Table1- NOAEL and Corresponding HED from GLP Toxicology Studies NOAEL (mg / kg) Max. HED(mg / kg)bRationale Plasma Study Route Sex Olive CBD Total st Total for Oil TeCaCBD THCNOAEL Exposure Canna CBD THC Productnnabinoidsat a binoids NOAEL 90-Day Oral M 400 27.3 26.4 0.88 >10% ND 4.4 4.3 0.14 repeat-dose decrease toxicology in body in rats weight (Study considered 48150)cadverse F 800 54.6 52.8 1.76 Highest ND 8.8 8.5 0.28 dose tested Mouse Oral M 2000 145 129.6 4.10 Highest 602 11.8 10.5 0.33 micronucle dose ng / mL us (Study tested (2 h post- 842-474- dose) 5814)dRat Comet Oral M 2000 145 129.6 4.10 Highest 1795 23.4 20.9 0.66 Assay dose ng / mL (Study 842- tested (6 h post- 489-5825)ddose) THC:Δ9-Tetrahydrocannabinol; CBD: cannabidiol; F: female; HED: human equivalent dose; M: male; ND: not determined; NOAEL: no observed adverse effect levelaStudies 842-474-5814 and 842-489-5825 included limited pharmacokinetic samplingAttorney Docket No.38383.0001P1bBased on conversion of animal doses to human equivalent doses in FDA Guidance:Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers.cBatch A00569: Total cannabinoid = 62 mg / mL; THC = 2.0 g / mL; CBD = 60.0 mg / mL (density 0.909 g / mL).dBatch A00895E: Total cannabinoid = 72.4 mg / g; THC = 2.05 mg / g; CBD = 64.8 mg / g

[0302] Rationale for the Study Population.Healthy adult participants have been selected for the study because healthy participants with no concomitant diseases and using no concomitant medications represent a homogenous populationallowing for proper evaluation of the PK, PD, safety, and tolerability of a drug without confounding factors.

[0303] No animal reproductive studies have been conducted with the BDS of the present disclosure, and nonclinical studies with purified CBD use during pregnancy have demonstrated detrimental effects on the fetus, such as reduced fetal body weight and increased developmental delays. In addition, studies have shown cannabinoids can be detected in breast milk. Because the risk to the developing human fetus followingBDS exposure is unknown at this time and following the current recommendation from FDA that strongly advises against the use of CBD during pregnancy and lactation, only males and non-pregnant, non-lactating females will be included in the study. As a precaution for female participants, a serum pregnancy test will be performed at different times during the study. Females of childbearing potential and males with partners of childbearing potential will only be included if they agree to use appropriate methods of contraception.

[0304] Risk Assessment.As this is a Phase 1 study, a complete understanding of the risk involved with administering the BDS of the present disclosure is unknown. However, CBD is the primary cannabinoid component of the BDS and the associated CBD doses to be delivered via the BDS of the present disclosure and evaluated in this study are well below CBD dose levels for which safety and tolerability have been established in nonclinical and clinical studies; therefore, the risk of treatment-related AEs is deemed to be low.

[0305] The most common AEs reported by participants undergoing CBD clinical trials and patients receiving Epidiolex® for the treatment of epilepsy were diarrhea (~31%), elevated transaminases (~25%), drowsiness (~25%), weight loss (up to 31% at highest dose level) and loss of appetite.Attorney Docket No.38383.0001P1

[0306] Although these AEs have been reported to occur predominantly in higher doses than planned to be evaluated in this study, or when certain concomitant medications were taken, relevant precautions will be taken in this study.

[0307] Participants will be screened for inclusion and exclusion criteria to ensure only participants with no concomitant diseases and no concomitant medications will be included. Additionally, participants will be monitored for transaminase levels at several timepoints during the study, and suicide risk assessment will be performed at screening and subsequent timepoints using the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire to ensure participants' safety.

[0308] All treatment periods will be conducted at the clinical site, and participants will be confined for an appropriate time to allow safety monitoring. Real-time review of safety data will be performed, with safety monitoring to be adjusted as required if any risks become apparent. A Safety Review Committee (SRC) will be established to oversee the study and ensure the safety of study participants.

[0309] A sentinel group of 2 participants (1 active and 1 placebo) will be used for each cohort with the sentinel group being dosed at least 24 hours prior to dosing the remaining subjects of the cohort, and contingent on the results of ongoing safety evaluation.

[0310] Additionally, following dose administration to all participants in each cohort, SRC meetings will be held after safety and tolerability data up to at least Day 7 are available for all participants from a single cohort and remainder of timepoints of the preceding cohort (when applicable), in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. Cohort drug administrations will be separated by the minimum days required to ensure interim safety data review.

[0311] With the current study design including the evaluation of higher single dose levels in Part A prior to starting with repeated dose administration in Part B, the SAD cohorts effectively play a rolelike the one of sentinel participants for the MAD cohorts; therefore, sentinel participants will not be necessary in the MAD cohorts.

[0312] The primary objective of the study is toevaluate the safety and tolerability ofthe BDP of the presentdisclosure(i.e., the BDS in oral suspension) following oral administration of a singleAttorney Docket No.38383.0001P1 ascending dose (SAD) and multiple ascending doses (MAD) in healthy adult participants.Secondary objectives include (1) characterizingthe pharmacokinetic (PK) characteristics in plasma ofthe BDP’s cannabinoids and metabolites following single and multiple oral doses in healthy adult participants in fasted conditions;(2) evaluating food effect on the safety, tolerability, and PK profile of the cannabinoids and metabolites following a single dose administration in healthy adult participants;and (3) evaluating PD effects following single and multiple doses of the BDS of the present disclosure.

[0313] Primary endpointsfor safety and tolerability.Incidence, severity and relationship of Adverse events (AEs); incidence of Serious adverse events (SAEs); incidence of AEs of special interest (AESI) – abnormal clinically significant LFTs values (AST, ALT, total bilirubin and eGFR) for this drug due to the Cannabidiol (CBD) – major active pharmaceutical ingredient (API); changes from baseline in clinical parameters (including hematology, serum chemistry and urinalysis); vital signs measurements (blood pressure [BP], heart rate [HR], respiratory rate [RR], and body temperature [BT]);12-lead electrocardiogram (ECG) recordings; physical examination findings; changes in suicidal ideation and behavior (assessed by the Columbia Suicide Severity Rating Scale [C-SSRS]); and use of concomitant medications.

[0314] Secondaryendpoints for pharmacokinetics.FortheBDP of the present disclosure, PK parameters are evaluated for primary cannabinoids and metabolites. The parameters include the following:

[0315] Single Dose Parameters: minimal plasma concentration (Cmin),maximum plasma concentration (Cmax), time of maximum serum concentration (Tmax), Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-last),Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) [including percent of area under the curve obtained by extrapolation (AUCExtrap)],terminal rate constant (lz),half-life (t1 / 2),Apparent clearance (Cl / F),Apparent volume of distribution (Vz / F),and concentration at last time point (CTlast).

[0316] Multiple Dose Parameters: Cmin, Cmax, Tmax,area under the concentration-time curve from time zero to the end of the dosing interval (tau) at steady state(AUC0-tau),lz, t1 / 2, apparent volumeAttorney Docket No.38383.0001P1 of distribution at steady state (Vd / F,ss), and apparent clearance at steady state (Cl / F,ss) (as data allows).

[0317] PK parameters forthe BDP’s primary cannabinoids and metabolites, including cumulative amount excrete renally (Aer), fraction of unchanged drug excreted (fe%), and renal clearance (CLr [Ae0-t / AUC0-t])

[0318] Secondary endpoints forpharmacodynamics.Pharmacodynamic effects of the BDP of the present disclosure will be assessed using the Drug EffectsQuestionnaire(DEQ);andcognitive and psychomotor effects ofthe BDP of the present disclosurewill be assessed using the Digit SymbolSubstitutionTest (DSST) and the Paced Auditory Serial Addition Test (PASAT).

[0319] Study DesignOverview.This study is a Phase 1, double-blind, randomized, placebo- controlled, SAD and MAD study to assess safety, tolerability, PK, and PD ofthe BDP of the present disclosurein fasting and fed healthy participants. Food effect will be evaluated in Part A, in one cross-over SAD fasting dose cohort after a 14-day washout period. Approximately 64 participants will be enrolled.

[0320] The study is comprised of two parts, Part A (SAD) and Part B (MAD). Parts A and B of the study will be completed sequentially but with partial overlapping. Part B may be initiated when safety and tolerability are known and deemed acceptable for the first two cohorts in Part A (Cohorts A1-A2) at least.

[0321] Cohorts will be dosed sequentially in an ascending fashion. Safety Review Committee (SRC) meetings will be held after safety and tolerability data up to at least Day 7 (Part A) and up to at least Day 9 (Part B) are available for all participants from a single cohort and remainder of timepoints of the preceding cohort (when applicable), to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. A new cohort will not be dosed until the clinical portion of the preceding dose level has been completed, appropriate data has been reviewed by the SRC and authorization to proceed with the next dose level has been given by the SRC. Cohort drug administrations will be separated by the minimum days required to ensure interim safety data review.

[0322] Part A and Part B each have four planned dose level cohorts (A1-A4 and B1-B4). Part A will include 1 cohort (A-X), which will enter a cross-over dosing scheme, where the participantsAttorney Docket No.38383.0001P1 will return to the clinical site on Day 14 to receivethe BDP of the present disclosureor placebofollowing an FDA-compliant high-fat, high-calorie breakfast (vegetarians and vegans are allowed as long as an equivalent amount of fat and calories are consumed) on the morning on Day 15 after overnight fasting period. In addition, based on the safety data accumulated from previous cohorts, optional Cohorts A5 / B5 and A6 / B6 may be employed ifmaximum tolerated dose (MTD)or maximum planned dose level has not been achieved in A4 / 5 and B4 / 54 for each study Part A and B, respectively.

[0323] A staggered dosing schedule will be used for dosing each cohort in Part A and will include 2 sentinel participant (1 active and 1 placebo). The 2 sentinel participants will be dosed initially, and the remaining 6 participants will be dosed at least 24 hours later, based on the contingent on the resulting safety profile and once deemed safe to move forward in the opinion of Investigator in consultation with the SRC (if required).

[0338] An adaptive design based on safety data will be used. The planned dose range of the BDS of the present disclosure is anticipated to be 226.6 mg (equivalent to 125 mg CBD) to 1823.1 mg (equivalent to 1000 mg CBD). See Table 2.

[0325] Table2-Clinical Dosing and Equivalent Levels of Total Cannabinoids, Cannabidiol and Δ9-Tetrahydrocannabinol Dose Cannabinoid Equivalents (mg) Volume BDS (mg BDS)Total CannabinoidsaCBDbΔ9-THCc Oral Suspension (mL)226.6 145.51254.8 2.2 1823.1 1163.6100038.5 17.7 Δ9-THC: Δ9-Tetrahydrocannabinol; CBD: cannabidiolaBased-on target concentration of 62% total cannabinoidsbBased on target concentration of 60% cannabidiol

[0339] cBased on potential maximum concentration of 2.7% Δ9-tetrahydrocannabinol

[0326] The rationale of having the following adaptive features is based on the hypothesis-forming approach of this clinical study. The following categories will be adapted as presented inTable 3.

[0327] Table3- Adaptive Features and BoundariesAttorney Docket No.38383.0001P1 Adaptive study Adaptive Features Boundaries design category Dose level for the SAD dose levels Doses are intended to escalate and will not exceed a 3-fold SAD cohorts increase from the previous cohort. Doses may be adjusted to an intermediate (lower) or equivalent dose, on the basis of safety and tolerability data reported in the previous cohort(s). Dose level for the MAD dose levels The first MAD dose must be lower or equal to an already MAD cohorts dosed SAD cohort(s) of which safety and tolerability data are available. Doses are intended to escalate and will not exceed a 3-fold increase from the previous cohort. Doses may be adjusted to an intermediate (lower) or equivalent dose, on the basis of safety and tolerability data reported in the previous cohort(s). The highest daily dose level tested in MAD cohort(s) will not exceed the maximum safe dose level tested in SAD cohort(s) on any given administration day. The quantity of The quantity of SAD and The planned number of different dose level cohorts is 4 for SAD and MAD MAD cohorts may be the SAD and 4 for the MAD. However, based on data cohorts adapted (i.e., decreased or accumulated from previous cohorts, it may be decided to increased). decrease or increase the number of cohorts in either part of the study by two. If additional cohorts are added to either part of the study, the dose level of any additional cohort will not be higher than the MTD (if established) in that part of the study. Overlap between The MAD portion of this A MAD dose level cannot be higher than the last dose level SAD and MAD clinical study may overlap tested in SAD. with the SAD. MAD: multiple ascending dose; MTD: maximum tolerated dose; SAD: single ascending dose

[0328] Study Description.Participants will undergo study-specific screening within 28 days prior to dose administration. Prior to any screening procedures being performed, participants will sign the study-specific consent form in the presence of a suitably trained study site staff member.

[0329] The study is comprised of two parts, Part A (SAD) and Part B (MAD). Up to 8 participants will be randomized (6 participants receivingthe BDP of the present disclosure and 2 participants receiving placebo) in each cohort of Parts A and B. Participants in Part A will receive a single doseAttorney Docket No.38383.0001P1 of the BDP of the present disclosure or placebo on Day 1 while those in Part B will receive a split dose of the BDP of the present disclosure or placebo, where one dose will be administered as two equal doses taken twice daily (twice daily [BID]; administered approximately every 12 hours [± 30 minutes]) for 6 consecutive days (Day 1-Day 6), and 1 morning dose on Day 7.

[0330] All participants will fast overnight, and no food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose on Day 1 (Part A and Part B) and Day 7 (Part B). Additionally, no fluids (except for water given with the study drugs) will be allowed for 1 hour before dosing until 1-hour post-dose.No food will be allowed from at least 2 hours before until at least 1 hour after dosing for all other doses (Part B). Participants will be advised not to take unusual diets (e.g., low sodium) throughout the study duration. Part A will include 1 cohort (A-X), which will enter a cross-over dosing scheme, where the participants will return to the clinical site on Day 14 to receivethe BDP of the present disclosureor placebo30 minutes after starting a Food and Drug Administration (FDA)-compliant high-fat, high-calorie breakfast (approximately 50% calories from fat, approximately 800-1000 kcals). Participants will be required to consume entire meal in 30 minutes or less. No food will be allowed at least 4 hours post-dose. Except for water given with the study drug and fluids provided with the high-fat, high-calorie meal, no liquids will be allowed for 1 hour before dosing until 1-hour post-dose.

[0331] Participants in Part A will be admitted to clinic on Day-1 and stay until Day 3. Blood samples for PK analysis will be drawn on Day 1 (within 45 minutes before dosing [pre-dose]), and post-drug administration completion at approximately 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60 and 72 hours (outpatient). A blood sample will also be collected at approximately 168 hours post-dose at the Day 7 study visit. Blood samples for PK analysis for the cross-over fed dose cohort will be collected at these same timepoints as the fasted cohort. Urine will be collected over the intervals 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, and 24-48 hours post-dose on Day 1 and Day 2. The volume of urine collected at each interval will be documented. Safety electrocardiograms (ECGs) for on-site interpretation will be recorded at screening, Day -1, Day 1 at pre dose (within 1.5 hours), 30 min, 1, 2 hrs (± 10 min), 24 hours (+1 hour) and 48 hours (+1 hour) post dose and on Day 7 (Part A). Identical timepoints will apply for fed period (cohort A-X). Participants will beAttorney Docket No.38383.0001P1 discharged after their final 48-hour PK blood draw and completion of safety assessments. Participants will return to the clinic on approximately Day 7 (± 2 days) for a final safety evaluation.

[0332] When all participants in the Cohorts A1-A2 (at least) have been dosed and safety results were reviewed by SRC and deemed to be safe, Part B may start while the remaining cohorts in Part A are progressing. The starting dose of the Part B will be adaptive as described inTable3and will follow similar dose escalation decisions described above for the Part A; however, the dose to be administered in Part B will not exceed the higher dose levels tested in Part A.

[0333] Participants in Part B (B1-B4) will be admitted to clinic on Day -1 and stay until Day 9. Blood samples for PK analysis will be drawn on Day 1 (within 45 minutes before dosing [pre- dose] and post-morning drug administration completion at approximately 0.5, 1, 2, 3, 4, 5, 6, 8, 12 (trough level to be drawn prior to administration of second daily dose), pre-morning dose on Days 2-6, and on Day 7 (within 45 minutes before dosing [pre-morning dose]) and post-morning drug administration completion at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 96 hours. Urine will be collected over the intervals 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, and 24-48 hours post-dose on Day 7 and Day 8. Safety ECGs for on-site interpretation will be recorded at screening period, Day -1, pre-dose on dosing days: Day 2, Day 3, Day 5, Day 7, Day 9, Day 11 and EOS. Electrocardiograms taken on Days 2, 3, 5, 7 and 9 should be taken at the same time of day as the first study drug dose was given on Day 1 (+ 1 hour). Participants will be discharged after their PK blood draw on Day 9 and completion of safety assessments. Participants will return to the clinic on Day 11 for 96-hour PK sample and Day 14 (± 2 days) for a final evaluation.The anticipated dosing regimen is a starting dose of226.6 mgof the BDS of the present disclosure (equivalent to 125 mg CBD) with maximum expected dose level up to1823.1 mgof the BDS of the present disclosure (equivalent to 1000 mg CBD).

[0334] Safety and Tolerability.Safety and tolerability will be evaluated by monitoring the occurrence of AEs, changes in physical examination findings, ECGs, vital signs measurements, clinical laboratory test results, changes in suicidality (assessed with the C-SSRS), and use of concomitant medications.Attorney Docket No.38383.0001P1

[0335] Cohort / Dose Escalation Stopping Rules.Doses will be administered in an escalating manner following satisfactory review of the available safety and tolerability data from previous cohort(s) by the SRC.The individual members of the SRC and the decision-making process will be outlined in an SRC charter.

[0336] If any of the following events occur in the sentinel group, dosing within that cohort will be temporarily halted: the occurrence of any SAE considered at least possibly related to the study drug or the occurrence of any ≥Grade 3 AE considered at least possibly related to the study drug.

[0337] If any of the following safety concerns are observed, dosing of all participants at the given dose level or higher will be suspended / halted and all available data will be evaluated by the SRC. Dose continuation (remaining participants within a cohort or remaining dosing for a participant) or escalation should not proceed for any of, but not limited to, the following reasons are met:if ≥1 drug-related (i.e., possibly related) SAE occurs in a cohort; if ≥3 participants experience a ≥ Grade 2 drug-related (i.e., possibly related) AE in a cohort; if ≥3 participants experience clinically significant changes in vital signs considered to be drug-related (i.e., possibly related) in a cohort; or if ≥3 participants experience changes in ECGs (QTc greater than 500 msec with an increase from baseline greater than 60 msec) considered to be drug-related (i.e., possibly related) in a cohort.

[0338] Dose escalation will be discussed during the SRC meeting and may be stopped depending on the Investigator or Sponsor’s decision, based on but not limited to the following: if ≥2 participants experience clinically significant abnormalities in physical examination, ECG, or vital signs considered to be drug-related (i.e., possibly related) in a cohort; or the occurrence of any ≥Grade 3 organ-specific laboratory parameters (e.g., liver and / or kidney tests) considered at least possibly related to the study drug.

[0339] Clinical Trial Stopping Rules.if ≥2 drug-related SAEs occur in a cohort; or the occurrence of any death attributable to the study treatment.

[0340] Maximum Tolerated Dose and Recommended Phase 2 Dose.The MTD will be determined according to the safety and tolerability review occurring during the SAD and MAD parts of the study. MTD is defined as the highest dose level reached per the stopping rules.Attorney Docket No.38383.0001P1

[0341] If MTD is reached at the lowest dose in the SAD or MAD; in that case, the Investigator and Sponsor will determine if an additional lower dose cohort should be evaluated based on the safety, PK, and PD data. If MTD is not reached in the A4 / B4, the Investigator, and Sponsor will determine if an additional cohort should be evaluated, or the Recommended Phase 2 Dose (RP2D) determined based on the available safety, PK, and PD data. If additional cohorts are going to be evaluated, the dose to be administered in the given cohorts will not exceed the maximum dose of 2150.0 mgof the BDS of thepresent disclosure as currently outlined in the protocol.Observations made at previous dose cohort levels will also be considered (i.e., data in its aggregate form will be used to define the presence of possible trends that may not be apparent from an assessment of individual data).

[0342] Blinding.Thefollowing controls will be employed to maintain the double-blind status of the study during each cohort:

[0343] For Parts A and B, the participants and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the participant’s treatment assignment (BDP or placebo).

[0344] Designated pharmacy personnel at the clinical site not directly involved with the clinical aspects of the trial will prepare and dispense the study medication and will be aware of the randomization code. The study drug and placebo will have the same visual appearance in order to avoid compromising the study blinding.

[0345] Sealed individual randomization envelopes will be available to the Investigator or designee. This randomization information may be opened and the randomization for an individual participant made available to the Investigator (or designee), only in the event of a medical emergency or an adverse reaction that necessitates identification of the test material for the welfare of that participant.

[0346] Whenever possible, the Investigator or designee should consult with the Sponsor prior to breaking the blind. Except in a medical emergency, the Investigator (or designee) and blindedAttorney Docket No.38383.0001P1 site clinical staff will remain at least until the clinical phase of the study is completed (i.e., when reporting and evaluation of all AEs have been completed, for all cohorts).

[0347] Randomization.For each cohort in Part A and Part B, participants eligible for participation will be randomized (on Day 1) to receive either the active study drug or matching placebo in a 3:1 ratio, for a total of 6 participants receiving the BDP of the present disclosure and 2 participants receiving the matching placebo in each dose level. For each dose level in Part A, a staggered dosing schedule will be used and will include 2 sentinel participants randomized in a 1:1 ratio (1 active and 1 placebo) dosed initially, and the remaining 6 participants (5 active and 1 placebo) dosed at least 24 hours later. One randomization scheme will be produced for each cohort separately.

[0348] For the one cohort in Part A- fed arm, participants will be administered each treatment according to the 2-period, block randomization scheme.

[0349] Randomization will be performed by a computer-generated randomization schedule. The participant and the study team (except for necessary pharmacy staff) will remain blinded to the treatment arm at least until the clinical phase of the study is completed (i.e., when reporting and evaluation of all AEs have been completed, for all cohorts.

[0350] Number and Identification of Participants.Approximately 64 participants will be enrolled. Each participant will be assigned a randomization number at the time of randomization. The participant will retain that same randomization number for the remainder of the study. If a participant is a screen failure, they may be rescreened.

[0351] Inclusion criteria. Participants to be included in this study must meet the following inclusion criteria: (1) Provide signed ethics committee (EC)-approved consent form prior to any study procedures, can understand and comply with the requirements of the study, and are able to communicate with the Investigator; (2) Males and females, aged 18 and 65 years (inclusive), with body mass index (BMI) of 18-32.0 kg / m2and body weight ≥50.0 kg at screening; (3) No known allergic reaction to cannabis products and formulation components (glyceryl monolinoleate (NF), and organic chocolate mint flavoring agent); (4) Medically healthy with no clinically significant medical history (fully resolved childhood asthma and mild asthma that does not require a relieverAttorney Docket No.38383.0001P1 more than once per month, and does not require a preventer or any additional therapies is not considered clinically significant and permissible), physical examination, laboratory profiles, vital signs, or ECG, as deemed by the Investigator; (5) Must have hepatic and renal clinical laboratory test results (ALT, AST, total bilirubin [including direct and indirect bilirubin results], and estimated glomerular filtration rate [eGFR]) within a laboratory defined normal range; (6) Male participants who are not vasectomized for at least 6 months prior to dosing and who are sexually active with a female partner of childbearing potential must be willing to use one of the acceptable contraceptive methods from the first dose and for 90 days after the last dose; (7) Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized at least 6 months prior to the first study drug administration) must be willing to use one of the acceptable contraceptive methodsthroughout the study and for at least 3 months after the last study drug administration;(8) Refrain from donating sperm for the duration of the study and for at least 90 days after the last dose of investigational product (IP); (9) Females must have a negative serum pregnancy test (SPT) at screening and urinary pregnancy test (UPT) at check-in on Day -1;(10) Agree to frequent blood sampling during the course of the study with adequate venous access; (11) Agree to be confined for parts of the study in the Phase 1 unit and follow study procedures; (12) Agree to comply with the study-specified diet while confined in the Phase 1 unit. Participants in the Part A - cohort which enter the fed cross-over design (A-X) must agree to complete consumption of a standardized high-fat breakfast during the fed period on Day 15; (13) Negative drug and alcohol tests at screeningand at admissions on Day -1 and willing to abstain from alcohol / illegal drug use from the screening visit until the End of Study (EOS) visit;and,(14) Able to read, understand, provide signed informed consent, communicate adequately, and comply with the requirements for the entire study.

[0352] Exclusion criteria.Participants must not meet any of the following exclusion criteria to be eligible for the study:(1)Use of any medications or over the-counter (OTC) products within 10 days or 5 half-lives (whichever is longer) prior to administration of study medication (including analgesics [note: except paracetamol up to 2 g per day], antibiotics, hormonal contraceptives[except oral contraceptives or implantthat are permitted; stable doses of oral contraceptives for birth control in women of childbearing potential (WOCBP) (minimum of 3Attorney Docket No.38383.0001P1 months without issue as deemed by the Investigator) will be allowed. No other hormonal treatment will be allowed.], natural food supplements, vitamins, garlic as a supplement);(2)Use of an investigational drug or participation in an investigational study within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing;(3)Use of known inhibitors or inducers of hepatic drug metabolism (e.g., rifampin, carbamazepine, phenytoin, norethindrone, barbiturates [e.g., phenobarbital], dexamethasone, antidepressants [e.g., fluoxetine, paroxetine], proton pump inhibitors, ketoconazole) 1 month before the start of the study (Day 1);(4)Hypersensitivity or any significant allergic rection to the investigational compound / compound class being used in this study or any ingredients of this medication;(5)Medical history or any clinically significant disorder (as determined by the Investigator and Sponsor) including but not limited to: clinically significant allergies, asthma (fully resolved childhood asthma with no reoccurrences in adulthood is permissible),, angioedema, pulmonary, bronchospasm, ulcer disease, gastrointestinal (GI), GI bleeding, coagulation defects, hypertension, edema, heart failure, hypokalemia, cardiovascular disease, significant dermatologic diseases or conditions; hematological, neurological, psychiatric, hepatic, or renal disorders; condition that would significantly influence the immune response; or history of infections of unexplained frequency or severity;(6)Personal diagnosis or first-degree relative diagnosis of psychosis / schizophrenia;(7)Presence of current psychiatric condition, suicide ideations or psychiatric condition requiring pharmacological management within the last 6 months;(8)History or presence of any condition that, in the opinion of the Investigator, could interfere with the study conduct or observation (to be confirmed by medical history);(9)Has used any tobacco / nicotine- containing products (e.g., cigarettes, vaporizers, cigars, pipe tobacco, smokeless tobacco, nicotine gum, lozenges, patches) on more than 5 occasions within 1 month of the Screening visit; (10)History of significant drug abuse within 1 year prior to screening or use of drugs such as cannabis within 2 months prior to the screening visit or drugs such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening;(11)History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week for female participants and 21 units for male participants (1 unit = 150 mL of wine, 375 mLAttorney Docket No.38383.0001P1 of mid strength beer, or 30 mL of distilled alcohol 40%);(12)History of or risk for seizures (one- off febrile seizure as a child is permissible);(13)History or positive screening results to hepatitis B surface antigen or C virus Ab tests, or to human immunodeficiency virus (HIV) Ag / Ab combination, or has known immune deficiency disease at screening;(14)Surgical (history of stomach or intestinal surgery or resection) or medical condition (evidence of prior chronic GI disease such a cholecystitis, cholecystectomy, Gilbert’s syndrome) that would interfere with gastric motility, pH, or absorption of study drug;(15)Laboratory values outside normal ranges based on the laboratory reference values and are clinically significant or ≥ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE; v5.0) (repeat testing is allowed once) at screening and Day -1;(16)Presence of out-of-range cardiac interval (PR ≥120 msec, PR ≤220 msec, QRSD <120 msec and QTcF ≤450 msec for males and females) on the ECG at Screening and Day -1 or other clinically significant ECG abnormalities, unless deemed non-significant by the Investigator;(17)Presence of clinically significant vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 resp / min) at screening and Day -1;(18)Use of Δ9- tetrahydrocannabinol (THC)- or cannabidiol. (CBD)-containing products within 60 days of start of study (Day 1);(19)Serious illness in the 30 days preceding the beginning of treatment on Day 1 (i.e., that resulted in hospitalization);(20)Receipt of treatment for any type of internal cancer within the 5 years prior to enrollment (fully treated and resolved basal cell carcinoma and or squamous cell carcinoma are permissible);(21)Females who are pregnant, plan to become pregnant during the study, or are breastfeeding a child;(22)Positive alcohol breath testor urine drug screenat screening or at admissions on Day -1;(23)Blood or plasma donation (500 mL) within the past month, or receipt of blood transfusion within 1 month prior to Day 1;and (24)Employee, family member, or student of the Investigator or clinical site(s).

[0353] ParticipantWithdrawal and Replacement.Participants will be informed that they have the right to withdraw from the study at any time for any reason, without prejudice to their medical care. Over the course of the study the Investigator also has right to withdraw any participant from the study for one of thefollowingreasons:intolerance / unacceptable AEs;death;needs for medication which may interfere with study measurements;non-compliance with protocol requirements or non-Attorney Docket No.38383.0001P1 adherence to study drug;significant protocol deviation;unwillingness to continue in the study;participant lost to follow-up;and any other reason based upon the medical judgment of the Investigator.

[0354] If a participant is withdrawn from the study for any reason, whether related to the study drug or not, or if a participant voluntarily withdraws before or after receiving the study drug, such participant will be considered an early termination participant. The reason for study withdrawal is to be documented in the participant’s source documents and electronic case report form (eCRF). The Investigator will make every effort to ensure that early termination participants who have received the study drug complete all scheduled safety assessments, including all follow-up visit assessments in the relevant treatment period. A PK blood sample may be collected at the time of withdrawal if deemed required by the Investigator.

[0355] Participants who withdraw prior to dosing may be replaced.In the event that the number of drop-outs exceeds initial expectations, participants who withdraw or are withdrawn from the study after dosing for reasons other than safety and tolerability may be replaced after consultation between the Investigator and the Sponsor.

[0356] Additionally, reasonable efforts will be made to contact participants who are lost to follow- up. These efforts must be documented in the participant’s notes.

[0357] Study Plan and Procedures.The various schedule of assessments and study activities that will be conducted during the study are described in

[0358] Table4

[0358] for Part A (SAD) and for Part B (MAD),and Table6and Table7,provide the PK sampling schedules for Part A and Part B, respectively.

[0359] Table4- Schedule of Assessments Part A (Single Ascending Dose)Attorney Docket No.38383.0001P1 Treatment Screening Day (visit window) SAD Cohort(s) Fed SAD Cohort OnlykExamination 7 (±2 21 (±2 4 days) / days) / -28 to 14 (±2 15 (±2 16 (±2 17 (±2 18 (±2 -2-1 1 2 3EOS / days)idays)idays)idays)idays)iEOS / Early Early Term TermiInformed consent X Demographics andmedical historyXInclusion / exclusion X X Prior medications X XVital signsaX X X X X XX X X X XHeight / weight, BMI X XjX X Physicalexaminationb X X X X X X XSafety ECGcX X X X X X X X X X X Blood collection forlaboratory testsX X X X X X X X XSerology testing for Hepatitis B and C X and HIV Serum pregnancytestXBlood collection forPKdX X X X X X X X X XAlcohol breath test X XXUrine collectioneX X X X XX X X XCheck-in / randomizationf X X X XColumbia Suicide Severity Rating X X X X X Scale Drug EffectsQuestionnaireg X X X XDigit SymbolSubstitution Testg X XAttorney Docket No.38383.0001P1 Treatment Screening Day (visit window) SAD Cohort(s) Fed SAD Cohort OnlykExamination 7 (±2 21 (±2 4 days) / days) / -28 to 14 (±2 15 (±2 16 (±2 17 (±2 18 (±2 -2-1 1 2 3EOS / EOS / days)idays)idays)idays)idays)iEarly Early Term TermiPaced AuditorySerial Addition Testg X XUrine pregnancy test X X X X Drug administration X X ConcomitantmedicationsX X X X X X X X X XAdverse eventshX X X X X X X X X X X Medical historyhX X High-fat, High-calorie breakfasti XDischarge X X AE: adverse events; BMI: body mass index; ECG: electrocardiogram; EOS: end of study; HIV: human immunodeficiency virus; ICF: informed consent form; PK: pharmacokinetic; SAD: single ascending dose a. Vital signs will be collected with the participant supine and after they have been resting for 5 minutes. Vital signs will be taken at screening, Day -1, Day 1: pre-drug administration (within 1 hour), and at 15 minutes, 1 hour, 4 hours, and 12 hours post-dose (± 10 minutes up to and including 12 hour); Day 2: 24 hours post-dose (± 30 minutes); Day 3 and 7. Vitals should be collected prior to blood draws. Additional vital signs may be taken at any time during study as needed.The same timepoints for vitals will occur in the fasting and fed assessments of one SAD cohort. b. A full physical examination to be conducted at screening, with symptom-directed physical examinations thereafter. c. Electrocardiograms will be taken during Screening Period, Day -1, Day 1 at pre dose (within 1.5 hours), 30 min, 1, 2 hrs (± 10 min), 24 hours (+1 hour) and 48 hours (+1 hour) post dose and on Day 7. Identical timepoints will apply for fed period (cohort A-X). d. The same timepoints for blood sample collection for PK analysis will occur in the fasting and fed SAD cohorts. SeeTable 6for PK sample collection times and windows.Note, 72 hour blood draw is outpatient. e. Urine collection will occur for 1) drug and cotinine screen at screening and Day -1and Day 14 (for fed portion of the study); 2) urine will be collected over the intervals 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, and 24- 48 hours post-dose on Day 1 to Day 2 and Day 15 to Day 16 for the fed cohort for PK analysis; 3) immunoassay (IA) drug testing to detect the presence of THC on Day 7and Day 21 for the fed cohort. The volume of urine collected at each interval will be recorded. f. Randomizationoccurson Day 1. g. The Drug Effects Questionnaire and cognitive / psychomotor assessments will be completed pre-morning dose on Day 1 and at 1 hour (+10 minutes), 2 hours (+10 minutes), 4 hours (+10 minutes), 6 hours (+10 minutes),8 hours (+10 minutes) and 12 hours (+10 minutes) post-dose. The Drug Effects Questionnaire (only) will also be completed on Day 3 prior to discharge. h. Adverse events are collected upon signing the ICF through the last study visit; those that occur before dosingAttorney Docket No.38383.0001P1 will be recorded as medical history instead of as an AE, however, if their condition deteriorates at any time during the study, it will be recorded as an AE. i. Food effect will be evaluated in one cross-over SAD fasting dose cohort after a minimum 14-day washout period (vegetarians and vegans are allowed as long as an equivalent amount of fat and calories are consumed). Participants will be dosed 30 minutes after they start high-fat, high-calorie breakfast. The confinement, assessments (Day 14-17), and discharge (Day 17) and EOS (Day 21) will be identical to those scheduled for the fasting period. j. Height will be measured at screening only. k. Apply for participants in fasted / fed cohort (A-X) only.

[0360] Table5- Schedule of Assessments Part B (Multiple Ascending Dose)Attorney Docket No.38383.0001P1 Treatment Screening Day (visit window) Examination 14 (±2 days) / -28 to -2-1 1 2 3 4 5 6 7 8 9 11EOS / Early Term Informed consent X Demographics andmedical historyXInclusion / exclusion X X Prior medications X XVital signsaX X X X X X X X X XX XX Height / weight,BMIX X XPhysicalexaminationb X X X XSafety ECGcX X X X X X X X X X Blood collectionfor laboratory testsX X X X X XSerology testing for Hepatitis B and X C and HIV Serum pregnancytestXBlood collectionfor PKdX X X X X X X X X XAlcohol breath test X X X Urine collectioneX X X X X X Check-in / Randomizationf X XColumbia Suicide Severity Rating X X X X X X X X X Scale Drug EffectsQuestionnaireg X X XDigit SymbolSubstitution Testg X X XPaced Auditory Serial Addition X X X TestgAttorney Docket No.38383.0001P1 Treatment Screening Day (visit window) Examination 14 (±2 days) / -28 to -2-1 1 2 3 4 5 6 7 8 9 11EOS / Early Term Urine pregnancy XtestXDrugadministrationh X X X X X X XConcomitant XmedicationsX X X X X X X X X XMedical historyiX X Adverse eventsiX X X X X X X X X X X Discharge X AE: adverse event; BMI: body mass index; ECG: electrocardiogram; EOS: end of study; HIV: human immunodeficiency virus; ICF: informed consent form; : PK: pharmacokinetic a. Vital signs will be collected with the participant supine and after they have been resting for 5 minutes. Vital signs will be taken at screening, Day -1, Days 1 and 7 (at pre-morning dose [within 1 hour], 4 hours [± 10 minutes], and 8 hours [± 10 minutes] post-first dose of the day) and on Days 2-6 (within 1 hour prior to each post-morning dose), at 24 hours, 48 hours and 96 hours [± 30 minutes] post-administration on Day 7 and at the EOS visit (Day 14). Additional vital signs may be taken at any time during study as needed. b. A full physical examination to be conducted at screening, with symptom-directed physical examination thereafter. c. Electrocardiograms will be taken during Screening Period, Day -1, pre-dose on dosing days: Day 2, Day 3, Day 5, Day 7, Day 9, Day 11 and EOS. Electrocardiograms taken on Days 2, 3, 5, 7 and 9 should be taken at the same time of day as the first study drug dose was given on Day 1 (+1 hour). d. SeeTable 7for PK sample collection times and windows. e. Urine collection will occur for 1) drug and cotinine screen at screening and Day -1; 2) urine will be collected over the intervals 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, and 24-48 hours post-dose on Day 7 to Day 8 for PK analysis; 3) immunoassay (IA) drug testing to detect the presence of THC onDay 9 discharge and Day 14. The volume of urine collected at each interval will be recorded. f. Randomization may occuron Day 1 due to pending repeat tests. g. The Drug Effects Questionnaire and cognitive / psychomotor assessments will be completed pre-morning dose on Days 1, 3, and 7 and at 1 hour (+10 minutes), 2 hours (+10 minutes), 4 hours (+10 minutes), 6 hours (+10 minutes), 8 hours (+10 minutes) and 12 hours (+10 minutes) post-dose. The Drug Effects Questionnaire (only) will also be completed on Day 9 prior to discharge. h. Participants will receive a split dose with twice daily dosing (approximately every 12hours [± 30 minutes]) for6 days, then only 1 morning dose on the seventh day. i. Adverse events are collected upon signing the ICF through the last study visit; those that occur before dosing will be recorded in medical history instead of as an AE, however, if their condition deteriorates at any time during the study, it will be recorded as an AE.

[0361] Table6- Single Ascending Dose Group Pharmacokinetic Sampling ScheduleAttorney Docket No.38383.0001P1 Study Day SAD PK Time Point (post-dose) * Pre-dose (within 45 minutes before dosing) 0.5 h (± 5 min) 1 h (± 5 min) 2 h (± 5 min) Day 1 3 h (± 5 min) (Fed: Day 15 ±2 days) 4 h (± 5 min) 5 h (± 5 min) 6 h (± 5 min) 8 h (± 5 min) 12 h (± 10 min) Day 2 24 h (± 30 min) (Fed: Day 16 ±2 days) Day 3 48 h (± 30 min) (Fed: Day 17 ±2 days) 60 h (± 30 min) Day 4 72 h (± 30 min) (Fed: Day 18 ±2 days) Day 7 168 h (± 30 min) (Fed: Day 21 ±2 days) PK: pharmacokinetics; SAD: single ascending dose *Actual time of blood draw will be recorded. The same timepoints for blood sample collection for PK analysis willoccur in the fasting and fed SAD cohorts. The fed cohort will have a 14-day wash-out period and will then follow this schedule (e.g., ‘Day 1’ begins on Day 15 ±2 days; ‘Day 2’ begins on Day 16 ±2 days; etc.)

[0362] Table7- Multiple Ascending Dose Group Pharmacokinetic Sampling Schedule MAD PK Time MAD PK Time Study Day Point Study Day Point (post-first dose) ** (post- dose) ** Pre-morning dose Pre-morning dose (within 45 minutes (within 45 minutes before dosing) before dosing) 0.5 h (± 5 min) 0.5 h (± 5 min) 1 h (± 5 min) 1 h (± 5 min) Day 1 2 h (± 5 min) Day 7 2 h (± 5 min) 3 h (± 5 min) 3 h (± 5 min) 4 h (± 5 min) 4 h (± 5 min) 5 h (± 5 min) 5 h (± 5 min) 6 h (± 5 min) 6 h (± 5 min) 8 h (± 5 min) 8 h (± 5 min)Attorney Docket No.38383.0001P1 12 h prior to second dose (± 10 min)12 h (± 10 min)Pre-morning dose 24 h (± 30 min) Day 2 (within 15 minutes Day 8 before dosing) 36 h (± 30 min) Pre-morning dose Day 3 (within 15 minutes Day 9 48 h (± 30 min) before dosing) Pre-morning dose Day 4 (within 15 minutes Day 11 96 h (± 30 min) before dosing) Pre-morning dose Day 5 (within 15 minutes before dosing) Pre-morning dose Day 6 (within 15 minutes before dosing) PK: pharmacokinetics; MAD: multiple ascending dose; Sample times during MAD cohorts may be adjusted based on emerging data from SAD cohorts *Timing expressed relative to Day 7 morning dose **Actual time of blood draw will be recorded.

[0363] Clinical Evaluations.Unused biological samples collected during completion of study procedures as outlined below may be stored and used for future research. The coded samples may be used up to 5 years after the clinical study ends. A participant may contact the Investigator to have his or her unused samples destroyed at any time during the storage period. However, if the link between the participant and the samples has been removed, unused sample destruction may not be possible. Results from the future use studies will not be shared with participants.

[0364] Screening Evaluations.Screening evaluations will commence once a participant has provided informed consent. Screening evaluations will permit the review of baseline health status and to determine eligibility.

[0365] Baseline Demographics.Participant demographics will be recorded, including year of birth, sex, race and ethnicity, smoking status.

[0366] Medical, Surgical and Medication History.A complete medical history will include evaluation for past or present cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, metabolic, lymphatic, hematologic, immunologic, dermatologic,Attorney Docket No.38383.0001P1 psychiatric, and genitourinary disorders, medication and surgical history and review of any other pre-existing conditions. Medical history will also include alcohol and caffeine consumption and smoking history.

[0367] Body Weight and Height.Body weight (kilograms), wearing light clothes, no shoes, and height (centimeters) will be measured at the screening visit to allow the calculation of BMI (rounded to one decimal place).

[0368] Viral Serology.HIV antibodies, hepatitis B surface antigen and hepatitis C antibody will be measured at screening.

[0369] Safety and Tolerability Assessments.Safety and tolerability will be evaluated by performing physical examinations, vital signs measurements, ECG measurements, clinical laboratory safety tests, C-SSRS, concomitant medication and AE monitoring.

[0370] Physical Examination.Full physical examinations will be performed at screening, with symptom-directed physical examinations thereafter. The physical examination will include examination of the following: general appearance, head, ears, eyes, nose, throat, neck (including thyroid), skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes and nervous system. Any findings made during the physical examination must be noted regardless if they are part of the participant’s medical history. Additional symptom-directed physical examinations may also be performed at any time through the study as clinically indicated.

[0371] Vital Signs Measurements.Vital signs measurements will include systolic and diastolic blood pressure (mm Hg), pulse rate (beats / minute), respiratory rate (breaths / minute) and body temperature (tympanic; °C).

[0372] Wherever possible, vital signs will be recorded after the participant has rested comfortably (supine position) for at least 5 minutes and using consistent methods between participants. Testing for any out-of-range values may be repeated at the discretion of the Investigator. The Investigator (or a qualified observer at the investigational site) will interpret the vital signs using one of the following categories: within normal limits, abnormal not clinically significant (NCS), or abnormal clinically significant (CS). All CS findings will be recorded as AEs. The following normal ranges for vital sign parameters will be applied:Systolic BP: 90 toAttorney Docket No.38383.0001P1 140 mmHg; Diastolic BP: 40 to 90 mmHg; Heart rate: 40 to 100 beats / minute; Respiratory rate: 10 to 22 breaths / minute; and Temperature: 35.5 to 37.5 °C.

[0373] 12-lead Electrocardiogram.A 12-lead ECGs will be performed in triplicate, approximately 1 minute apart (a maximum of 2 minutes between traces is acceptable) after the participant has rested comfortably in the supine position for 5 minutes at screening, Day -1, Day 1 at pre dose (within 1.5 hours), 30 min, 1, 2 hrs (± 10 min), 24 hours (± 1 hour) and 48 hours (± 1 hour) post dose and on Day 7 (Part A). Identical timepoints will apply for fed period (cohort A- X). For Part B electrocardiograms will be taken during Screening Period, Day -1, pre-dose on dosing days: Day 2, Day 3, Day 5, Day 7, Day 9, Day 11 and EOS. Electrocardiograms taken on Days 2, 3, 5, 7 and 9 should be taken at the same time of day as the first study drug dose was given on Day 1 (± 1 hour).

[0374] The following ECG parameters will be assessed: heart rate, PR interval, RR interval, QRS duration, QT interval and QTcF. The mean value for the triplicate will be utilized. Testing for any out-of-range values may be repeated once at the discretion of the Investigator. The Investigator (or a qualified observer at the investigational site) will interpret the ECG using one of the following categories: within normal limits, abnormal NCS, or abnormal CS. All CS findings will be recorded as AEs.

[0375] The following ranges for normal 12-lead ECG parameters will be applied: Heart rate: 40 to 100 beats / minute; PR interval: ≥120 to ≤220 msec; QRS duration: <120 msec; and QTcF interval: ≤ 450 msec (for both genders). Clinical Laboratory Safety Tests.Blood and urine samples will be collected according to the clinical site SOPs at the times specified inTable 4 for Part A (SAD) and for Part B (MAD), and analyzed and assessed by a certified local laboratory, using their reference’s ranges. The clinical laboratory assessments to be performed are listed inTable 8 below.Attorney Docket No.38383.0001P1

[0376] Table8- Clinical Laboratory Evaluations Serum Chemistry Hematology Aspartate aminotransferase (AST) Hematocrit Alanine aminotransferase (ALT) Hemoglobin MCH Alkaline phosphatase MCHC Gamma-glutamyl transferase (GGT) MCV Sodium Platelet count Potassium RBC count Reticulocyte count Chloride WBC count Calcium Differential WBC Magnesium Phosphorus Glucose Serum ureaCoagulationUric acid Activated partial thromboplastin time (APTT) Total Bilirubin Prothrombin time Creatinine International normalized ratio (INR) Total protein Albumin Urinalysis Total Cholesterol Microscopic examination*Triglycerides Specific gravity Creatinine phosphokinase (CPK) pH FSH Protein Glucose Serology Ketones Hepatitis B Blood Hepatitis C Urobilinogen Human immunodeficiency virus (HIV) Bilirubin Nitrites Leucocytes IA THC** Additional testing may be performed if clinically indicated. *Only performed if positive dipstick. **Performed at the end of the studyAttorney Docket No.38383.0001P1

[0377] The Investigator must review the laboratory report, and all out-of-range (abnormal) laboratory values must be evaluated and commented on by the Investigator for clinical significance. Laboratory safety results will be interpreted as normal, abnormal NCS, or abnormal CS. All CS findings will be recorded as AEs.

[0378] In the event of an unexplained CS abnormal laboratory test result, the test should be repeated andfollowed until it has returned to the normal range and / or an adequate explanation of the abnormality is found.

[0379] In the event of a positive drug of abuse urine test, the test could be repeated once based on the Investigator opinion. Columbia Suicide Severity Rating Scale.Columbia Suicide Severity Rating Scale will be administered as perTable 4 for Part A (SAD) andTable 5 for Part B (MAD). The C-SSRS is a questionnaire designed for the assessment of suicidal ideation and behavior in adolescents and adults. The questionnaire must be administered by the Investigator or other individual that is suitably qualifiedfor education or training. When administered, all responses recorded on the scale must be provided by the participant either verbally or by gesture. The baseline version of the C-SSRS will be used during screening to assess lifetime suicidality. At all other protocol- specified timepoints, the C-SSRS – Since Last Visit version will be used to assess the participant’s suicidality since the last assessment. Any changes from baseline assessment should be reported as an AE on the eCRF. Pregnancy Test.A serum pregnancy test (β-human chorionic gonadotropin) will be performed at screening for all female participants of childbearing potential to confirm negative pregnancy results and urine pregnancy test subsequently as perTable 4 for Part A (SAD) andTable 5 for Part B (MAD).

[0380] Prior / Concomitant Medications.All medications, including prescription drugs, herbal products, vitamins, minerals, and OTC drugs, taken within 30 days (or 5 half-lives, whichever is longer) prior to the start of the study will be recorded as prior medications. All medications taken after the first dose of the study drug and through the EOS visit will be recorded as concomitant therapy. Any changes in concomitant medications also will be recorded in the participant’sAttorney Docket No.38383.0001P1 eCRF. Information regarding the total daily dose, route of administration, start and discontinuation dates, and indication are to be recorded on the participant’s eCRF.

[0381] Except for medication which may be required to treat AEs and contraceptive medications, no other treatment or medication other than the study drugs will be allowed from the first dosing until all study activities and evaluations have been completed. If any concomitant medications are taken, a record of all medications taken during the course of the study will be made. Information regarding the total daily dose, route of administration, start and discontinuation dates, and indication are to be recorded on the participant’s eCRF.

[0382] Adverse Events.Adverse events will be recorded and evaluated as detailedelsewhere herein.

[0383] Blood Collection and Processing.Blood will be collected for determination of plasma concentrations of the following BDS cannabinoids and metabolites, including Cannabidiol (CBD),Cannabichromene (CBC),Cannabigerol (CBG), Cannabidiolic acid (CBDA), Δ9- Tetrahydrocannabinol (THC),7-hydroxy-CBD (7-OH-CBD), 7-carboxy-CBD (7-COOH-CBD), 11-hydroxy-THC (11-OH-THC), and 11-carboxy-THC (11-COOH-THC).

[0384] Pharmacokinetics Sampling and Timing.Blood samples will be drawn according toTable 6 and Table 7.

[0385] SAD: A total of 10 blood samples will be collected from each participant on Day 1, one blood sample on each Day 2, 4, and 7 (total of 3 samples across these days) and two blood samples on Day 3. The participants in the fed cohort will have follow the same schedule of blood samples collected in the fasting cohort.

[0386] MAD: A total of 10 blood samples will be collected from each participant on each Day 1 and 7 (total of 20 samples across Day 1 and 7) and one blood sample on each day for Days 2-6, 9 and 11 (total of 7 samples across these days); and two samples on Day 8.

[0387] The actual times of sample collection will be documented in the eCRF. Pharmacodynamic Assessments.Pharmacodynamic assessments will be administered as perTable 4 for Part A (SAD) and Table 5 for Part B (MAD) and include the following questionnaires:Attorney Docket No.38383.0001P1

[0388] Drug Effects Questionnaire (DEQ).Participative effects before and after dosing will be self-reported using the DEQ. The is a validated instrument commonly used in psychoactive drug research consisting of 20 itemsare each rated using a unipolar 100 mm visual analog scale, with anchors of “not at all” on one end and “extremely” on the other. Participants are instructed to rate how they were feeling “right now” on six items related to the investigational study product: feeling the effect, liking any of the effects, disliking any of the effects, feeling any good effects, feeling any bad effects and likelihood of taking the study product again. Additionally, participants rate how much they are experiencing the following 14 adjectives: “sick,” “heart racing,” “anxious,” “relaxed,” “paranoid,” “tired / drowsy,” “alert,” “irritable,” “energetic,” “restless,” “hungry,” “dazed,” “distracted” and “euphoric / happy.”

[0389] Digit Symbol Substitution Test (DSST).The DSST measures psychomotor ability and detects working memory impairment.Participants are presented with a sheet of paper that contains numbers 1-9 on the top of the page, each paired with a unique symbol. On the bottom of the page are numbers with blanks beneath them, and participants are instructed to write in the correct symbol beneath each number as quickly as possible. Task duration is 90 seconds. DSST outcomes include: number of trials attempted, number correct, and percentage of attempted trials completed correctly.

[0390] Paced Auditory Serial Addition Test (PASAT).The PASAT measures working memory and higher order cognition.The PASAT is presented on audiocassette tape or compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds or every 2 seconds and the participant must add each new digit to the one immediately prior to it. The test result is the number of correct sums given (out of 60 possible).

[0391] Description, Identification and Storage.Both of the IP,BDP (i.e., BDS in oral suspension) and matching placebo will be supplied in glass bottles. The IP will be stored at 20-25 °C (with excursions permitted between 15 to 30°C) in the study site pharmacy, which is locked with restricted access and with monitoring for temperature excursions.

[0392] BDP:Oral suspension of 103 mg / mL BDS inglycerylmonolinoleate(NF),and an organic chocolate mint flavoring agent in a fully homogeneous solution.Attorney Docket No.38383.0001P1 Example 7: A Maximum Tolerated Dose and 7-Day Dose Range Finding Study

[0340] The objectives of this study were to determine the maximum tolerated dose (MTD) and to evaluate and characterize the toxicokinetics and toxicity of the test article, the BDP of the present disclosure, when administered via oral (gavage) once or for up to 7 consecutive days to dogs.

[0341] The study design are shown in Table 4 and Table 5: Table 4: Study Design for MTD and 7-Day Dose Range Finding Dose Level Dose Dose Main Study Group Test (mg / kg / ), Volume Concentration No. Article No. of No. of BDSa(mL / kg) (mg / mL) Males Females 1 BDP 10 5 2 2BDP 30 5 61b 1b3 BDP 50 5 10 4 BDP 100 5 20aThe first day of dosing for each dose level was designated as Day 1.bthe same animals were administered up to 3 additional doses of the BDS (CBD), with a 5-day washout period between each dose level, as warranted. The proposed dose levels were increased or decreased based on the responses to the preceding dose level(s) until the dose-limiting toxicity was observed (MTD). Doses did not exceed 100 mg / kg (limit dose). Table 5: Study Design for MTD and 7-Day Dose Range Finding Dose Level Dose Dose Main Study Group Test (mg / kg / day), Volume Concentration No. Article No. of No. of BDS (mL / kg) (mg / mL) Males Females 5 Vehicle 10 5 0 2 2 6 BDP 30 5 2 2 2 7 BDP 50 5 6 2 2 8 BDP 100 5 10 2 2

[0342] The following parameters and endpoints were evaluated in this study: mortality, clinical signs, body weights, food consumption, clinical pathology parameters (hematology, coagulation, and clinical chemistry), toxicokinetic (TK) parameters of cannabidiol (CBD) and other analytes, (±)-cannabichromene (CBC), 7-hydroxy-cannabidiol (7OHCBD), 7-carboxy-cannabidiol (7COOHCBD), delta-9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11OHTHC), and 11- carboxy-THC (11COOHTHC) on Day 1 and Day 7, and macroscopic examination.Attorney Docket No.38383.0001P1

[0343] Following a single or repeated once daily oral gavage dosing to beagle dogs at dose levels 10, 30, 50 or 100 mg / kg, the BDP was well tolerated at all dose levels and all animals survived to study completion.

[0344] In both the Maximum Tolerated Dose (MTD) and Dose Range Finding (DRF) phases at >10 mg / kg, all animals exhibited transient clinical observations of decreased activity starting 2 hours post dose. At >30 mg / kg all animals exhibited transient clinical observations of incoordination, salivation, abnormal pupils and / or eye color and / or vomitus starting 4 hours post dose. All clinical observations resolved prior to the start of the next dose.

[0345] In the 7-day DRF phase, administration of the BDP at 0 (control), 10, 30, or 50 mg / kg / day to male and female beagle dogs for 7 days was associated with alterations in clinical chemistry parameters in males at 50 mg / kg / day (decreases in sodium) and females at >30 mg / kg / day (increases in alkaline phosphatase [ALP], decreases in globulin, total protein, calcium, glucose, and sodium).

[0346] For all other parameters (body weights, food consumption, additional clinical pathology parameters, and macroscopic examination), there were no toxicologically significant changes considered to be related to administration of the BDP.

[0347] Following once daily oral administration of the BDP to male dogs, mean Cmax, AUCtlastand AUC0-24hrvalues of CBD and other analytes (CBC, 7OHCBD, 7COOHCBD, delta-9-THC, 110HTHC, and 11COOHTHC) increased with increasing dose in a generally dose-proportional manner from 10 to 30 mg / kg / day, with no apparent increase from 30 to 50 mg / kg / day on Days 1 and 7. In females, mean Cmax, AUCtlastand AUC0-24hrvalues of CBD and the other analytes displayed minimal to no increase with increasing dose on Day 1, but appeared to increase with increasing dose in a less than dose-proportional manner on Day 7. Systemic exposure (Cmax and AUC values) to CBD in male and female dogs did not appear to change consistently following repeated administration of the BDP. Systemic exposure to all analytes in males and females were lower than CBD with changes not being dose proportional with the BDP.

[0348] In conclusion, oral administration of the BDP up to 100 mg / kg was generally well tolerated. The single dose MTD was considered to be 100 mg / kg based on the occurrence ofAttorney Docket No.38383.0001P1 clinical observations. Also, dose levels of 10, 30 or 50 mg / kg / day administered daily to dogs for 7 days was well tolerated. Example 8: A 4-Week Study by Oral Gavage Administration in Beagle Dogs with a 2-Week Recovery Period

[0349] The objectives of this study were to determine potential toxicity of the BDP of the present disclosure (i.e., an oral suspension of the BDS of the present disclosure), when given via oral (gavage) daily for up to 4 weeks to dogs and to evaluate the potential reversibility of any findings following a 2-week recovery period. The doses and concentrations were based on the content of cannabidiol (CBD) present. In addition, the toxicokinetic (TK) characteristics were determined. The study design was as shown in Table 6: Table 6: Study Design Dose Level Dose Dose Main Study Recovery Study Group Test (mg / kg / day), Volume Concentration No. Article No. of No. of No. of No. of BDSa(mL / kg) (mg / mL) Males Females Males Females 1 Vehicle05 0 4 4 2 2 2 BDP105 2 4 4 - - 3 BDP 30 5 6 4 4 - - 4 BDP 50 5 10 4 4 2 2 - = Not Applicable a Dose based on the content of CBD in BDS

[0350] The following parameters and endpoints were evaluated in this study: mortality, clinical signs, body weights, body weight gains, food consumption, ophthalmology, electrocardiographic

[0351] examinations (ECGs), clinical pathology parameters (hematology, coagulation, clinical

[0352] chemistry, and urinalysis), organ weights, and macroscopic and microscopic examinations. In addition, TK parameters were determined on Days 1 and 28 for CBD, (±)- cannabichromene (CBC), 7-hydroxy-cannabidiol (7OHCBD), 7-carboxy-cannabidiol (7COOHCBD), delta-, 11-hydroxy-THC (11OHTHC), and 11-carboxy-THC (11COOHTHC).

[0353] All dose formulation results were within approximately 4% of the target BDS concentration as measured by the primary CBD component. The analytical data demonstrated acceptable performance of the method for all reported results and that dose formulations were prepared at the intended target concentration and were homogeneous. Vehicle control samples were below the limit of quantitation (<0.2000 mg / mL). Following a repeated once daily oralAttorney Docket No.38383.0001P1 gavage dosing to beagle dogs at dose levels 10, 30, or 50 mg / kg / day, the BDS was well tolerated at < 50 mg / kg / day for up to 4 Weeks.

[0354] There was no test article-related mortality. A single control male at 0 mg / kg / day was euthanized early on Day 6 based on clinical observations (severely increased lung sounds, audible breathing (wheezing), severe pallor, severely decreased activity, salivation, low heart rate, and cold to touch) post dose. Clinical pathology changes were consistent with an acute phase response and supportive of microscopic findings of mixed cell inflammation and foreign material within the lungs. The cause of moribundity leading to early euthanasia of this dog was gavage injury / aspiration and was not considered BDP related.

[0355] At > 10 mg / kg / day, animals exhibited non-adverse, BDS-related, transient clinical observations of salivation (including controls), decreased activity, incoordination, abnormal pupils, vomitus, and / or hunched posture starting 4 to 6 hours post dose. All clinical observations resolved prior to the start of the next dose.

[0356] Abnormal feces (liquid / soft / mucoid), decreased appetite, and / or thin body conditions were observed in most males and females across all dose groups (> 10 mg / kg / day), including control animals. Veterinary intervention was required (food enrichment, gastrointestinal (GI) blend canned food) each day of the study until the feces and / or body conditions of the animal normalized. Thin body condition and loss of body weight (up to approximately -23.5% in males and up to -12.0% in females compared to controls) were likely secondary to fecal changes and decreased appetite (up to -91.1% in males and up to -96.1% in females compared to controls).

[0357] The magnitude and timing of the observations varied throughout the dosing period. However, these observations fully resolved or trended toward resolution during the recovery period and were therefore not considered adverse.

[0358] BDP-related changes were observed in hematology parameters in males and / or females and included mildly lower mean reticulocyte counts at > 30 mg / kg / day accompanied by minimally to mildly lower erythrocyte mass (red blood cell count [RBC], hemoglobin concentration, and / or hematocrit) at 50 mg / kg / day. Minimally to mildly lower mean lymphocyte, eosinophil, basophil, and total white blood cell counts were noted at 50 mg / kg / day. Minimally to mildly higher mean platelet (PLT) counts were observed at > 10 mg / kg / day. BDP-related minimally shortened meanAttorney Docket No.38383.0001P1 activated partial thromboplastin times (APTT) were observed in males at > 10 mg / kg / day and females at 50 mg / kg / day. BDP-related changes in chemistry parameters were observed in males and / or females as mildly to moderately higher mean alkaline phosphatase (ALP) at ≥ 10 mg / kg / day and minimally higher gamma glutamyl-transferase (GGT) at ≥ 30 mg / kg / day.

[0359] Minimally lower mean total calcium at > 30 mg / kg / day, minimally to mildly lower mean albumin and resultant total protein concentrations at 50 mg / kg / day were evident. Following a 2- week recovery interval, lower albumin and total protein concentrations persisted in females at 50 mg / kg / day. All remaining BDP-related alterations in clinical pathology parameters had partially to fully resolved at 50 mg / kg / day.

[0360] Non-adverse BDP-related microscopic findings were noted in the liver and thymus. In the liver, minimal to mild hepatocellular hypertrophy was present in all BDP dose groups in both sexes. Hepatocellular hypertrophy correlated with higher mean liver / gallbladder weights and higher hepatobiliary clinical chemistry parameters at > 10 mg / kg / day. BDP-related decreased lymphoid cellularity of thymus in all dose groups of both sexes was considered an indirect effect secondary to stress. This correlated with lower mean thymus weights at > 30 mg / kg / day in males and all dose groups in females and lower mean lymphocyte counts in females at 50 mg / kg / day.

[0361] Mean prostate gland weights in males at > 10 mg / kg / day and mean spleen weights in males at > 30 mg / kg / day and females at 50 mg / kg / day were lower than controls and considered BDS-related. Prostate gland and spleen weight differences lacked microscopic correlates. At the end of the recovery phase, minimal hepatocellular hypertrophy was observed in one male and both females at 50 mg / kg / day and there were no organ weight differences, indicative of partial recovery. Decreased lymphoid cellularity in the thymus was also reduced in incidence and severity, supportive of partial recovery.

[0362] Following once daily oral administration of the BDP to male and female dogs, mean Cmax, AUCtlast, and AUC0-24hrvalues of CBD increased with increasing dose in a generally dose proportional manner from 10 to 50 mg / kg / day. TK values for other analytes (CBC, 7OHCBD, 7COOHCBD, THC, 110HTHC, and 11COOHTHC) increased with increasing dose in a generally dose proportional manner from 10 to 30 mg / kg / day, with no apparent increase from 30 to 50 mg / kg / day on Days 1 and 28. Systemic exposure (Cmax and AUC values) to CBD in male andAttorney Docket No.38383.0001P1 female dogs did not appear to change consistently following repeated administration of the BDS. Systemic exposure (Cmax and AUC values) to the metabolites of both CBD and THC was less than the corresponding parent substance on Days 1 and 28 and ranged from < LLOQ (lower limit of quantitation) to up to approximately 41% lower than the parent compound. Systemic exposure to the analytes appeared to be independent of sex.

[0363] For all other parameters (ophthalmology, electrocardiographic examinations (ECGs), clinical pathology parameters (urinalysis), and macroscopic examinations), there were no toxicologically significant changes considered to be related to administration of the BDP.

[0364] In conclusion, following repeated once daily oral gavage dosing to beagle dogs at dose levels of 10, 30 or 50 mg / kg / day, the disclosed BDS was tolerated at < 50 mg / kg / day for up to 4 weeks, and there were no test article-related deaths. Transient clinical observations of salivation (including controls), decreased activity, incoordination, abnormal pupils, vomitus, and / or hunched posture were noted at > 10 mg / kg / day. BDP-related changes in hematology and clinical chemistry parameters in males and / or females starting at > 10 mg / kg / day (increases in ALP, GGT and / or

[0365] PLT, decreases in albumin, total protein, calcium, reticulocytes, RBC mass and lymphocyte counts). Non-adverse BDS-related microscopic findings were present in the liver and thymus were observed in males and females and correlated with clinical pathology findings.

[0366] The no-observed-adverse-effect-level (NOAEL) for males and females for the BDS was considered to be 50 mg / kg / day based on the CBD content, the highest dose level tested, and was associated with a mean plasma CBD Cmax of 3850 ±1470 ng / mL and AUC0-24h, of

[0367] 47700 ±18900 hr•ng / mL in males and females combined on Day 28. Example 9: A Phase 2 Study to Investigate the Safety, Tolerability, and Effectiveness of the BDP in Adolescents and Adults with Autism Spectrum Disorder

[0368] This is a multicenter open-label study to investigate the safety, tolerability, and effectiveness of the BDP disclosed herein with ASD. Subjects will be enrolled to receive the BDP. This study will utilize a flexible-dose design, with doses individualized to each subject based on safety and tolerability. Doses will be titrated up from the starting dose over an approximately 3-week Titration Period, with dose adjustments taking place approximately every 4 days.Attorney Docket No.38383.0001P1

[0369] Doses will be administred orally for buccal absorptoion, preferably sublingually but this can depend on the patient’s level of cooperation.

[0370] Subjects will begin dosing with 0.5 mL of the BDP (51.5 mg BDS; equivalent to 28.4 mg CBD and 1.1 mg THC) administered twice daily for a total daily dose of 1.0 mL (equivalent to 56.8 mg CBD and 2.2 mg THC) and titrated up to a maximum dose of 3.0 mL (309 mg BDS; equivalent to 170.4 mg CBD and 6.5 mg THC) twice daily for a total daily dose of 6.0 mL (equivalent to 340.8 mg CBD and 13.1 mg THC).

[0371] The Titration Period will be followed by one more week of dosing (Maintenance Period) for a total Treatment Period of 4 weeks, and a 2-week Safety Follow-up Period. Safety and efficacy assessments will take place during each clinic visit. Assessments made during the Titration Period will be conducted by telephone or videoconference.

[0372] Dose Titration Guideline. All subjects will receive the BDP beginning with a 3-week Titration Period to reach a safe and tolerable dose according to the following schedule in Table 7: Table 7: Dose Titration Amount of Titration Period Study Medication Day 1 Day 5 Day 9 Day 13 Day 17 Day 21 Day 22-29 Per dose 0.5 mL 1.0 mL 1.75 2.5 mL 3.0 mL Check-in to confirm Maintenance mL maintenance dose Per day 1.0 mL 2.0 mL 3.5 mL 5.0 mL 6.0 mL Check-in to confirm Maintenance maintenance dose

[0373] This table is a guideline only for the Investigator; the actual titration will depend on the individual subject’s response to treatment, i.e., decisions to increase each subject’s dose will be based on tolerability and safety.

[0374] The BDP should be taken twice per day (BID), in the morning and evening (approximately every 12 ± 2 hours) within one hour after eating a meal (e.g., breakfast and dinner).

[0375] The Titration Period is expected to take up to 3 weeks, with dose adjustments to be made approximately every 4 days. Some subjects may reach a dose limit based on safety and tolerability (based on Investigator judgment) in less than 3 weeks at which point they would remain at that dose through Week 4 of the study.Attorney Docket No.38383.0001P1

[0376] During titration, if a subject is unable to tolerate an increased dose, they should be reverted to the previous tolerable dose and remain at that dose until AEs subside, in consultation with the Investigator. Subjects can attempt to increase the dose again during the Titration Period in consultation with the Investigator.

[0377] Subjects should titrate until they achieve at least one of the following: experience unacceptable / intolerable side effects, as judged by the Investigator, or reach the maximum allowed daily dose.

[0378] If at any point after reaching a stable tolerable dose a subject experiences intolerable AEs, the Investigator may decrease the dose or temporarily pause dosing until tolerability is achieved. Subjects whose dose has been decreased can have their dose increased again in consultation with the Investigator provided there is adequate tolerance. Subjects who fail to tolerate dose adjustments may be withdrawn from the study by the Investigator in consultation with the Sponsor.

[0379] Inclusion Criteria. To, subjects must meet ALL of the following inclusion criteria prior to enrollment: Males or females 13-30 years of age at Screening, Diagnosis of ASD confirmed by Mini International Neuropsychiatric Interview (MINI), ABC-I score of ≥18 at Screening and Baseline, CGI-S of irritability associated with ASD score of >4 at Screening and Baseline. Description of Investigational Product. The IP is a BDP containing FSHE-L. proprietary CW1AS1 hemp cultivar in an oral solution consisting of Glyceryl Monolinoleate NF (Macine CC®), and a mint chocolate flavoring agent. The BDS is primarily composed of cannabinoids (~48%) followed by carbohydrates (~40%), non-cannabinoid / terpene lipids (~6%), terpenes (~5%), and proteins (~1%). While efficacy is expected to be derived from the cannabinoids, each of the molecule classes may possess activity and is expected to contribute to the overall pharmacological activity of the BDS. The BDP is a brown oil-based solution consisting of 103 mg / mL BDS in Glyceryl Monolinoleate, NF and a chocolate mint flavoring.

[0394] Placebo:Vehicle identical in appearance tothe BDP of the present disclosure consisting of glyceryl monolinoleate(NF), and an organic chocolate mint flavoring.

[0395] Storage Conditions.Storage conditions are provided in Table 9.

[0396] Table9- Storage conditionsAttorney Docket No.38383.0001P1 Investigational Product Storage Conditions Storage Temperature BDP (i.e., BDS in Oral Upright position 20℃ to 25℃ (with excursions Suspension) permitted between 15°C to 30°C) PlaceboUpright position 20℃ to 25℃ (with excursionspermitted between 15°C to 30°C) Drug Accountability and Handling.Individual doses for each participant and period will be dispensed at the clinical site pharmacy, as per the appropriate SOP and according to the randomization scheme, in appropriate bottles / containers indicated with at least the protocol number, the randomization number and the participant screening number.

[0398] At the end of the study, there will be a final reconciliation of the study drug received, dispensed, consumed, and returned.

[0399] Treatment Compliance.The following measures will be employed to ensure treatment compliance:all doses will be administered by a qualified site personnel;anddetails of all doses administered in the study will be documented in the source documents and recorded.

[0400] Study Drug Administration.For all treatment periods in study Part A, IP will be administered to each participant, and a mouth check will be performed to ensure the consumption of the medication.

[0401] All participants will fast overnight, and no food will be allowed from at least 10 hours before dosing until at least 4 hours post-dose on Day 1 (Part A and Part B) and Day 7 (Part B). Additionally, no fluids (except for water given with the study drugs) will be allowed for 1 hour before dosing until 1-hour post-dose, participants will be advised not to take unusual diets (e.g.,low sodium) throughout the study duration.

[0402] In the fed cross-over period for one cohort in Part A, after a fasting period of at least 10 hours, participants will be administered BDP (i.e., BDS in Oral Suspension) 30 minutes after startingan FDA-compliant high-fat, high-calorie breakfast (approximately 50% calories from fat, approximately 800-1000 kcals). Participants will be required to consume entire meal in 30 minutes or less. No food will be allowed at least 4 hours post-dose. Except for fluids provided with theAttorney Docket No.38383.0001P1 high-fat, high-calorie meal, no liquids will be allowed for 1 hour before dosing until 1-hour post- dose.

[0403] Contraception.Male participants who are not vasectomized for at least 6 months prior to dosing, and whoare sexually activewith a female partner of childbearing potentialmustbe willing to use one of the following acceptable contraceptive methods from the first dose and for 90 days after the last dose: simultaneous use of condom and established use of oral, injected or implanted hormonal contraceptive (atleast 4 weeks prior to screening); and, simultaneous use of condom and placement of intrauterine device (IUD) or intrauterine system (IUS).There are no contraceptive requirements if any of following conditions apply: sexual partner is surgically sterile; partner of non-childbearing potential; same sex relationship; and, abstinence from heterosexual intercourse as usual and preferred lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.

[0404] Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomised at least 6 months prior to the first study drug administration) must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 3 months after the last study drug administration: simultaneous use of intrauterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration; or intrauterine contraceptive device with hormone release system placed at least 12 weeks prior to first study drug administration; or oral hormonal contraceptives (minimum 12 week use without issue), and a condom for the male partner.

[0405] Females of non-childbearing potential must be: post-menopausal (absence of menses for at least 12 months prior to the first study drug administration) with confirmation of the post-menopausal status by documented FSH level ≥40 mIU / mL; or surgically sterile (complete hysterectomy or bilateral oophorectomy at least 3 months prior to the first study drug administration). Women with tubal ligation will be required to undergo apregnancy tests and partner to use a condom (ie. they will be treated as WOCBP).Attorney Docket No.38383.0001P1

[0406] Concomitant Medications.Any medication or vaccine that the participant is receiving at the time of enrollment (within 30 days before the time of randomization) or receives during the study must be recorded on the eCRF along with the following: reason for use; dates of administration, including start and end dates; and, dosage information, including dose and frequency.

[0407] If the use of any concomitant treatment becomes necessary (e.g., for treatment of an AE), the treatment and administration details must be recorded in the source documents and the eCRF. In addition, the medical monitor must be notified of all prohibited medications administered to any participant to assess the participant’s eligibility to continue in the study.

[0408] Medications taken by participants before dosing will be documented as prior medications, and medications taken by participants after dosing through the last study day will be documented as concomitant medications.

[0409] Drugs, Nicotine and Alcohol.Participants must have a negative drug of abuse urine test and alcohol breath test at screening and at each treatment period admission.Participants will be required to abstain from: (1)use of cannabis within 2 months prior to the screening and throughout the study; use of cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening and throughout the study; (2) habitual use of any nicotine-containing products (e.g., cigarettes, vaporizers, cigars, pipe tobacco, smokeless tobacco, nicotine gum, lozenges, patches) from 3 months prior to the screening visit and throughout the study; including no more than 5 occasions within 1 month of the Screening visit; (3) alcohol-based products from 24 hours prior to each treatment period admission and 24 hours prior to study visit on Day 7 (and Day 21 for fed cohort) in study part A and 24 hours prior to study visit on Day 14 in study Part B until after the last PK blood sample collection of each period; and, has used any tobacco / nicotine-containing products (e.g., cigarettes, vaporizers, cigars, pipe tobacco, smokeless tobacco, nicotine gum, lozenges, patches) on more than 5 occasions within 1 month of the Screening visit.Attorney Docket No.38383.0001P1

[0410] Dietary Restriction, Physical Exercise.Participants should follow the following dietary restrictions during the study:(1) food or beverages containing grapefruit, Seville orange,starfruit, pomegranate, pineapple, or pomelo from14days prior to study drug administration on Day 1 until completion of the EOS visit; (2) foodor beverages containing xanthine derivatives or xanthine- related compounds(coffee, black / green tea, chocolate)or energy drinks from 48 hours prior to each admission and each follow-up visit; (3) food containing poppy seeds from 24 hours prior to screening and admission of each treatment period; (4) food, beverages or supplements containing St John’s Wort from 10 days prior to study drug administration on Day 1 until completion of the EOS visit; and, (5) participants should not engage in heavy exercise (e.g., marathon runners, weightlifters) within48 hours prior to each admission and each follow-up visit.

[0411] Definition of Adverse Event.An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

[0412] The occurrence of an AE may come to the attention of study personnel during confinement at clinical trial unit (CTU), outpatient study visits, or upon review of participant data by a study monitor. Participants will be questioned regarding their physical and mental health during each in- clinic visit and will be reminded to inform a study team member immediately should any AEs arise. Any medical condition that is present at the time that the participant is screened will be considered part of their medical history and not reported as an AE. However, if their condition deteriorates at any time during the study, it will be recorded as an AE. It is the responsibility of the Investigator to document all AEs that occur during the study. AEs should be reported on the appropriate page of the eCRF.

[0413] Definitionof Serious Adverse Event.An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (i.e., the participant is at immediate risk of death at the time the event occurred; it does not refer to an event which might hypothetically have causedAttorney Docket No.38383.0001P1 death had it been more severe);requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability / incapacity; is a congenital anomaly / birth defect; or is a medically important event or reaction.

[0414] Medical and scientific judgment should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life- threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also usually be considered serious. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in hospitalizations, or the development of drug dependency or drug abuse.

[0415] The following hospitalizations / admissions do not need to be reported as SAEs:hospitalization for social reason (e.g., caregiver relief); hospitalization for surgery / procedure planned prior to study entry; hospital visits less than 24 hours (e.g., held for observation or treatment, but duration of stay less than 24 hours); and / or treatment at hospital or center for minor procedures (e.g. laser eye surgery).

[0416] Definition of a Suspected Unexpected Serious Adverse Reaction.A suspected unexpected serious adverse reaction (SUSAR) is an AE that meets all the following criteria:is serious; there is a least a reasonable possibility of a causal relationship between the event and the investigational product; and is considered unexpected (as assessed using the current IB as occurring with a class of drug or are anticipated from the pharmacological properties of the drug but are not specifically mentioned as occurring with study drug).

[0417] Assessment of Severity.The Investigator will make a clinical judgment to evaluate the severity for each AE and SAE reported during the study. The severity of each AE and SAE will be graded using the Common Terminology Criteria for Adverse Events (Version 5.0) 5-point scale as specified inTable 10.

[0418] Table10- Severity of Adverse EventsAttorney Docket No.38383.0001P1 Severity Grade DescriptionMild IAsymptomatic or mild symptoms: clinical or diagnostic observations only;intervention not indicated.Moderate IIMinimal, local or non-invasive intervention indicated; limiting age- appropriateinstrumental activities of daily living (ADL).Severe IIISevere or medically significant but not immediately life-threatening: hospitalizationor prolongation of hospitalization indicated; disabling; limiting self-care ADL.Life-threateningIV Life-threatening consequences; urgent intervention indicated.Death V Death related to AE.

[0419] If an AE / SAE has multiple aspects (symptoms), the aspect with the highest severity will be graded.The term severe is a measure of severity. Thus, a severe AE is not necessarily serious. For example, itching for several days may be rated as severe, but may not be clinically serious. Any changes to the severity of an AE will be recorded as a comment in the eCRF.

[0420] Assessment of Relationship to Study Drug.The Investigator will assess the relationship between a study drug and each AE / SAE occurrence based on the medical judgment. Alternative causes, such as a natural history of underlying medical conditions, concomitant therapy and other risk factors, and the temporal relationship of the event to the study drug will be investigated. The causal relationship of the study drug to an AE will be ratedrelationship categories: Definitely, possibly, unlikely, and unrelated. The definitions for the relationship categories are as follows:

[0421] Table11- Adverse Event Relationship Categories Category of Casual RelationshipDefinition^ ^ ^Cannot be reasonably explained by an alternative explanation, e.g. concomitant drug(s), concomitant disease(s). Definitely ^ ^ ^The relationship in time to study drug is very suggestive with improvement on cessation of study drug or reduction in dose. ^ ^ ^Reappears upon rechallenge (if rechallenge occurs) and follows a known patternof response to the study drug. ^ ^ ^Follows a reasonable temporal sequence from the administration of the drug. Possibly ^ ^ ^May have been produced by the participant’s clinical state, environmental or toxic factors, or other modes of therapy administered to the participant.Attorney Docket No.38383.0001P1 ^ ^ ^Does not follow a reasonable temporal sequence from the administration of the Unlikely investigational product. ^ ^ ^May have been produced by the participant’s clinical state, environmental or other modes of therapy administered to the participant. ^ ^ ^Clearly and incontrovertibly due only to extraneous causes (disease, environment, Unrelated etc.). ^ ^ ^Do not meet the criteria for medication relationship listed under unlikely, possible, or probable.

[0422] Recording of Adverse Events.Adverse events and medical history will be collected and documented from the time of signing the Participant information and informed consent form (PICF) and throughout the study until the EOS. Any medical condition that is present at the time that the participant is screened until the drug administration will be considered part of their medical history and not reported as an AE. However, if their condition deteriorates at any time following the drug administration, it will be recorded as an AE.

[0423] Adverse events will be recorded and evaluated for their seriousness, severity, and relationship to the study drug. All AEs, regardless of seriousness, severity, or presumed relationship to the study drug, will be assessed by the Investigator (or medically qualified sub- Investigator). When an AE / SAE occurs, the Investigator must review all documentation (e.g., hospital progress notes, laboratory, and diagnostic reports) relative to the event and record all relevant information using medical terminology in the eCRF and / or other sources. Whenever possible, diagnoses should be given when signs and symptoms are due to a common etiology (e.g., cough, runny nose, sneezing, sore throat, and head congestion) may be reported as “upper respiratory infection”. Investigators must record in the eCRF the date of onset of the event, their opinion concerning the relationship of the event to the study drug, the severity of the event, whether the event is serious or nonserious, actions taken to manage the event, the outcome of the event, and date of resolution where applicable. All details of any treatments initiated due to the AE should also be recorded in the participants’ notes and the eCRF. Adverse events will be followed up until complete resolution or until the Investigator or designee judges safe to discontinue follow-up.Attorney Docket No.38383.0001P1

[0424] The following data should be documented for each AE: description of the symptom event; classification of ‘serious’ or ‘not serious’;severity; date of first occurrence and date of resolution (if applicable); action taken (no action, medication required, tests required, hospitalization required or prolonged, study drug administration interrupted / withdrawn and / or other – specify); causal relationship; and outcome of event (refer toTable12).

[0425] Table12- Event Outcome Categories Category of Event OutcomeDefinitionThe participant has fully recovered, or by medical or surgical treatment the condition has Recovered returned to the level observed at the first trial-related activity after the participant signed the informed consent. The participant has recovered from the condition, but with lasting effect due to a disease, Recovered with injury, treatment or procedure. If a sequela meets an SAE criterion, the AE must be sequelae reported as an SAE.Not recoveredThe condition of the participant has not improved, and the symptoms are unchanged, or theoutcome is not known at the time of reporting.This term is only applicable if the participant died from a condition related to the reported AE. Outcomes of other reported AEs in a participant before he / she died should be assessed Fatal as “recovered”, “recovering”, “recovered with sequelae” or “not recovered”. An AE with fatal outcome must be reported as an SAE. Unknown This term is only applicable if the participant is lost to follow-up.

[0426] Statistical Methods and Determination of Sample Size.This section describes the general framework to be used for the analysis and presentation of data in this study. The information described in this section may be revised during the study to accommodate protocol amendments and to make changes to adapt to unexpected issues in study execution and data that could affect planned analyses. Unless specified otherwise, statistical analyses will be performed using SAS®software Version 9.3 or higher.

[0427] Determination of Sample Size.The sample size for this study was not based on statistical power calculations, but is consistent with typical sample sizes used for similar studies to assess safety and PK.Attorney Docket No.38383.0001P1

[0428] Definition of Analysis Populations.The Safety Population will consist of all participants who receivedthe BDP of the present disclosure or placebo and have at least 1 post-dose safety assessment. The PK Population will consist of all participants who received the BDP of the present disclosure and have evaluable PK data.

[0429] General Statistical Methodology.Data listings will be provided for all participants. For continuous data, summary statistics will include the number of participants, arithmetic mean, arithmetic standard deviation, median, minimum, and maximum.

[0430] Pharmacokinetic Parameters.The PK parameters for the study are defined inTable 13.Descriptive statistics will be presented for all plasma concentrations and PK parameters in the PK population forBDS and metabolites. The descriptive statistics will consist of N, geometric mean, geometric coefficient of variation (CV)%, arithmetic mean, arithmetic standard deviation (SD), median, minimum, and maximum.

[0431] Table13- Pharmacokinetic Parameters Parameter Definition Single Dose Parameters Cmin Minimal plasma concentration Cmax Maximum observed plasma concentration TmaxTime of maximum serum concentration (Tmax)Attorney Docket No.38383.0001P1 Parameter Definition AUC0-last The area under the plasma concentration-time curve from time 0 to the last quantifiable time point AUC0-inf The area under the plasma concentration-time curve from time zero to extrapolated to infinity (AUC0-inf) [including percent of area under the curve obtained by extrapolation AUCExtrap]^zTerminal rate constant t1 / 2 The terminal half-life Cl / F Apparent clearance Vz / F Apparent volume of distribution CTlastTime of the last observable concentration (CTlast) Multiple Dose Parameters Cmin Minimal plasma concentration Cmax Maximum observed plasma concentration Tmax Time of maximum serum concentration (Tmax) AUC0-tau The area under the concentration-time curve from time zero to the end of the dosing interval (tau) at steady state^zTerminal rate constant t1 / 2 The terminal half-life V / Fss Apparent volume of distribution at steady state Cl / Fss Apparent clearance at steady state (Clss) Additional PK parameters may be calculated as data allows, such as metabolite / parent ratio.

[0432] Pharmacokinetics of BDP cannabinoids and metabolites will be assessed for relationship to dose level of BDS for single and multiple dose administration, using a power model, (i.e., regression model of log [PK parameter] vs log [dose]). Comparison of fed vs fasted at one single dose level will be performed by analysis of variance of logarithmic transformed parameters, with terms for fed status and participant. Accumulation will be assessed by comparing exposure parameters for Day 1 and Day 7 in multiple dose cohorts.

[0433] Safety and Tolerability Analysis.All AEs will be listed. Adverse Events will be summarized by treatment, severity, and relationship to the study drug. The frequency of AEs (the number of AEs, the number of participants experiencing an AE, and the percentage of participants experiencing an AE) will be summarized by treatment, Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC), and preferred term (PT). The summary and frequency AE tables will be presented for all causalities and for those consideredAttorney Docket No.38383.0001P1 related to the study drug (those that have a relationship of possibly related or definitely related). Serious AEs will be tabulated.

[0434] Clinical blood and urine laboratory parameters will be summarized by treatment. In addition, all blood and urine laboratory data outside the clinical reference ranges will be listed by parameter and treatment. Values for any laboratory or urine values outside the clinical reference ranges will be listed and flagged on the listings.

[0435] All vital signs measurements will be listed. The vital signs data will be summarized by treatment, together with changes from baseline.

[0436] The ECG data (PR, QT, QRS duration, QTcF and heart rate) will be obtained. All ECG parameters will be listed. The ECG data will be summarized by treatment, together with changes from screening.

[0437] Changes in C-SSRS scores will be summarized descriptively by treatment group. Clinically significant changes in suicidal ideation and behavior (such as a “Yes” response to C- SSRS suicidal ideation question 4 or 5, or an actual attempt, interrupted attempt, or aborted attempt) will be reported as AEs.

[0438] All concomitant medications will be listed, including the name, dose, start and stop dates if applicable, frequency of dosing and reason for use.

[0439] Subjective and cognitive / psychomotor performance outcomes will be summarized for each cohort and time point using descriptive statistics (i.e., number of participants, mean, standard deviation [SD], median, minimum, and maximum). Details regarding statistical analysis of PD outcomes will be provided in an SAP.

[0440] The Investigator must complete a participant identification and enrollment log to identify each participant during and after the study easily. This document will be reviewed by the study monitor for completeness.

[0441] Any log identifying the study participant's identity will be treated as confidential and filed by the Investigator in the Investigator Site File. To ensure participant confidentiality, no copy willAttorney Docket No.38383.0001P1 be made. All reports and communication relating to the study will only identify participants assigned randomization numbers.

[0442] The Investigator must also complete a participant screening log, which reports on all participants who were seen to determine eligibility for inclusion in the study.

[0443] In compliance with local regulations and ICH GCP guidelines, it is required that the Investigator and institution permit authorized representatives of the Sponsor, the regulatory agency(s), and the HREC direct access to review the source documentation for verification of study-related procedures and data.

[0444] Source documentation must be available to substantiate participant identification, eligibility, and participation; proper informed consent procedures; protocol-specified medical history; dates of visits; adherence to protocol procedures; record of safety and efficacy parameters, adequate reporting and follow-up of AEs; administration of concomitant medication; study drug receipt / dispensing / return records; study drug administration information; and date of participant completion, discontinuation from treatment, or withdrawal from the study, and the reason if appropriate.

[0445] Direct access includes examining, analyzing, verifying, and reproducing any records and reports that are important to the evaluation of the study. The Investigator is obligated to inform the participant and obtain their consent to permit named representatives to have access to his / her study-related records without violating the confidentiality of the participant.

[0446] No amendments to the protocol may be implemented without prior approval from the Sponsor, the relevant HREC and the appropriate regulatory authorities, as applicable, except where necessary to eliminate an immediate hazard to participants, or when the change involves only logistical or administrative aspects of the study.

[0447] Administrative amendments to the protocol will be classed as corrections of a typographical error, clarification of confusing wording, and other minor modifications, including but not limited to name, address, and contact information changes that have no impact on the safety of the participants or the science of the study. Administrative amendments will be submitted to the HREC for information only.Attorney Docket No.38383.0001P1

[0448] In all other instances, an amendment to the protocol must be submitted to HREC for approval (and the appropriate regulatory authorities, as appliable). If a protocol amendment requires changes to the PICF, the revised PICF, prepared by the Investigator, must be approved by the HREC.

[0449] No deviations to the protocol are permitted except in instances when issue relating to the safety of study participant arise which requires a deviation from the protocol. If there is a need for such a deviation the Investigator must notify the Sponsor and the responsible HREC of the facts and circumstance causing the deviation as soon as is reasonably practical, but in any event no later than 5 working days after the change is implemented. The nature and reasons for the protocol deviations will be recorded in the participant’s eCRF. The Sponsor may not reimburse the Investigator for cases in which the study procedures and evaluations are conducted such that they result in major protocol violations.

[0450] Following closure of the study, the clinical research organization (CRO) will maintain all study records in a safe and secure location (except for those required by local regulation to be maintained elsewhere). Example 10: An Open-Label, Safety, Tolerability, and Effectiveness Study of the BDP disclosed herein in Children and Adolescents with Autism Spectrum Disorder (ASD)

[0380] This open-label Phase 2 study is being conducted to evaluate the safety, tolerability, and effectiveness of the BDP disclosed herein in pediatric patients with ASD. As described above, the BDP is a cannabinoid extract of CW1AS1 strain in Macine CC oil. The extract was obtained via the solvent extraction and decarboxylation process described herein using isopropyl alcohol.

[0381] . The BDP will be studied for its effectiveness to treat irritability, repetitive behaviors, and improve cognition, sociability, and quality of life for ASD patients.

[0382] Doses will be administred orally for buccal absorptoion, preferably sublingually but this can depend on the patient’s level of cooperation.

[0383] Dose Titration Guideline. Approximately 20 subjects will be enrolled to receive one of two different doses (N = 10 per dose group) of open-label BDP for a total of up to 12 weeks. Within each dose group, enrolled subjects will include 5 subjects <12 years old and 5 subjects ≥12Attorney Docket No.38383.0001P1 years old. Group 1 will be enrolled and completed prior to enrolling any subjects in Group 2 to ensure that a maximum daily dose of up to 3.0 mL is safe and well tolerated. Safety and tolerability data from Group 1 to be reviewed before deciding to proceed to Group 2. Subjects will be dosed BID, approximately 12 ± 2 hours apart within one hour after eating a meal (e.g., breakfast and dinner), and will begin with a 3-week Titration Period according to the following schedule: Table 8: Dose Titration Titration Period Dose Day Day Day 22-85 Group Day 1 Day 5 Day 9 13 17 Day 21 (9 weeks) Group 1 (N = 10) Per Dose 0.25 0.5 mL 0.75 1.0 mL 1.5 mL Check-in to confirm Maintenance mL mL maintenance dose Per Day 0.5 mL 1.0 mL 1.5 mL 2.0 mL 3.0 mL Check-in to confirm Maintenance maintenance dose Group 2 (N = 10) Per Dose 0.5 mL 1.0 mL 1.75 2.5 mL 3.0 mL Check-in to confirm Maintenance mL maintenance dose Per Day 1.0 mL 2.0 mL 3.5 mL 5.0 mL 6.0 mL Check-in to confirm Maintenance maintenance dose

[0384] Overall Design. This is a single-site, open-label study to evaluate the safety, tolerability, and effectiveness of the BDP disclosed herein in children and adolescents aged 5-17 years old with ASD. Approximately 20 subjects will be enrolled to receive one of two different doses of the BDP (N = 10 per dose group). Each dose group will be comprised of 5 subjects <12 years old and 5 subjects ≥12 years old. The BDP will be administered with food.

[0385] The following dose levels will be evaluated:Attorney Docket No.38383.0001P1

[0386] The first 10 subjects (Group 1) will begin with 0.25 mL (i.e., 25.75 mg BDS; equivalent to 14.2 mg CBD and 0.55 mg THC) administered BID for a total daily dose of 0.5 mL and will titrate up to a maximum dose of 1.5 mL (i.e., 154.5 mg BDS; equivalent to 85.2 mg CBD and 3.25 mg THC) BID for a total daily dose of 3.0 mL.

[0387] The subsequent 10 subjects (Group 2) will begin with 0.5 mL (i.e., 51.5 mg BDS; equivalent to 28.4 mg CBD and 1.1 mg THC) administered BID for a total daily dose of 1.0 mL, and will titrate up to a maximum dose of 3.0 mL (i.e., 309 mg BDS; equivalent to 170.4 mg CBD and 6.5 mg THC) BID for a total daily dose of 6.0 mL.

[0388] Doses will be titrated up from the starting dose over an approximately 3-week Titration Period, with upward dose adjustments to take place approximately every 4 days, based on assessments of safety and tolerability and in the judgment of the Investigator. Assessments made during the Titration Period will be conducted by telephone or videoconference.

[0389] The Titration Period will be followed by an approximately 9-week Maintenance Period (for a total Treatment Period of 12 weeks), and a 2-week Follow-up Period. If at any point during the Maintenance Period a subject experiences intolerable adverse effects, the Investigator may decrease the dose until tolerability is achieved. In-person clinic visits are scheduled to take place on Days 29 ± 3 days, 57 ± 3 days, and 85 ± 3 days and the final safety follow-up visit will take place on Day 99 ± 3 days by telephone or videoconference.

[0390] Inclusion Criteria. To be eligible for the study, subjects must meet ALL of the following inclusion criteria prior to enrollment:

[0391] Male or female pediatric outpatients aged between 5 to 1 years inclusive at Screening.

[0392] Diagnosis of ASD confirmed by the Autism Diagnostic Observation Schedule™, Second Edition (ADOS-2).

[0393] ABC-I score of ≥ 18 at Screening and Baseline.

[0394] CGI-S of irritability associated withAttorney Docket No.38383.0001P1 ASD score of > 4 at Screening and Baseline. Further Numbered Embodiments of the Disclosure Other subject matter contemplated by the present disclosure is set out in the following numbered embodiments: 1. A pharmaceutical composition comprising an oral suspension of a full spectrum hemp extractderived from Cannabis sativa hemp variety ‘CW1AS1’, wherein representative seed of the variety has been deposited under NCIMB No.43291. 2. The pharmaceutical composition ofembodiment1, wherein the pharmaceutical composition further comprisesglyceryl monolinoleate. 3. The pharmaceutical composition ofembodiment 1 or 2, wherein the pharmaceutical composition further comprises a flavoring agent. 4. A method of treating a nervous system or mental disease, disorder, condition, or symptom by administeringan effective amount of the pharmaceutical composition ofembodiment 1, 2, or 3 to a subject in need thereof. 5. The method of claim 4, wherein the disease, disorder, condition, or symptom is a primary indication. 6. The method ofembodiment 4, wherein the disease, disorder, condition, or symptom is a secondary indication. 7. The method ofembodiment 4, wherein the nervous system disease, disorder, condition, or symptom is a CNS-associated disease, disorder, condition, or symptom. 8. The method ofembodiment 7, wherein the CNS-associated disease, disorder, condition, or symptom is autism. 9. The method ofembodiment 4, wherein the nervous system disease, disorder, condition, or symptom is epilepsy. 10.The method ofembodiment 4, wherein the mental disease, disorder, condition, or symptom is anxiety and / or irritability associated with autism.Attorney Docket No.38383.0001P1 11. The method of claim 4, wherein the full spectrum hemp extract in the pharmaceutical composition ranges from about 200 mg to about 2000 mg per dose. INCORPORATION BY REFERENCE

[0395] All references, articles, publications, patents, patent publications, and patent applications cited herein within the above text and / or cited below are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world. U.S. PATENT DOCUMENTS

[0396] 10,653,085 Joel Stanley and Keri Reel

[0397] 10,736,295 Joel Stanley and Keri Reel OTHER PUBLICATIONS

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Claims

Attorney Docket No.38383.0001P1 CLAIMS What is claimed is:

1. A method of treating one or more symptoms of autism spectrum disorder (ASD) or a seizure disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a cannabinoid and terpene extract of Cannabis sativa L. of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291, and a carrier, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons.

2. The method of claim 1, wherein the extract is a solvent reduced oil obtained from a process comprising isopropyl alcohol solvent extraction.

3. The method of claim 1 or 2, wherein the carbon chain length is 12 to 20.

4. The method of claim 1 or 2, wherein the glyceride is sesame oil, corn oil, and / or modified corn oil.

5. The method of claim 1 or 3, wherein the composition comprises: a. beta-caryophyllene at an amount that is 3% to 25% of the amount of beta caryophyllene in the air dried plant material from which the extract is obtained, and / or b. α-bisabolol at an amount that is 3% to 20% of the amount of α-bisabolol ne in the air dried plant material from which the extract is obtained and / or c. α-humulene at an amount that is 3% to 30% of the amount of α-humulene in the air dried plant material from which the extract is obtained, and / or d. a concentration of cannabidiol of 5 to 8% w / w of the composition.Attorney Docket No.38383.0001P1 6. The method of any one of claims 1 to 5, wherein the composition comprises a ratio of cannabidiol: delta 9 tetrahydrocannabinol of from 20:1 to 40:1 or from about 25:1 to about 40:

1.

7. The method of any one of claim 1 to 6, wherein a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannabinoids is 5.6-8.4% w / w of the pharmaceutical composition.

8. The method of any of claims 1-7, wherein the composition is not an emulsion.

9. The method of any of claims 1-8, wherein the Cannabis sativa plant is of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

10. The method of any of claims 1-9, wherein the cannabinoid composition comprises a tetrahydrocannabinol concentration of 1 to 3 mg / mL.

11. The method of any of claims 1-10, wherein the pharmaceutical composition consists of or consists essentially of a cannabinoid extract of Cannabis sativa plant, the carrier, and a flavoring agent.

12. The method of any one of claims 1 to 11, wherein the carrier is a winterized oil composed of mono-, di- and triglycerides of oleic and linoleic acids.

13. The method of any one of claims 1 to 12, wherein one or more symptoms of ASD is treated 14. The method of any one of claims 1 to 13, wherein the symptom of ASD is selected from irritability, anxiety, lethargy / social withdrawal, stereotypic behavior, hyperactivity / noncompliance, inappropriate speech, or social avoidance or wherein the symptom is irritability.Attorney Docket No.38383.0001P1 15. The method of any one of claims 1 to 14, wherein the subject is a human.

16. The method of any one of claims 15, wherein the human subject is less than 18 years of age or 5 to 17 years of age.

17. The method of any one of claims 15 wherein the human subject is at least 13 years of age or 13 to 30 years of age.

18. The method of claim 16, wherein a daily dose of the pharmaceutical composition comprises from 20 mg to 400 mg of the cannabinoid extract.

19. The method of claim 16 or 17, wherein a daily dose of the pharmaceutical composition comprises from about 100 mg to about 700 mg of the cannabinoid extract.

20. The method of claims 16 or 17, comprising administering a first daily dose of the composition that is equivalent to about 103 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 206 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

21. The method of claim 20, comprising administering a third daily dose of the composition that is equivalent to about 360 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

22. The method of claim 21, comprising administering a fourth daily dose of the composition that is equivalent to about 515 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration ofAttorney Docket No.38383.0001P1 the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

23. The method of claim 22, comprising administering a fifth daily dose of the composition that is equivalent to about 618 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

24. The method of claim 16, comprising administering a first daily dose of the composition that is equivalent to about 53 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 103 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

25. The method of any of claims 24, comprising administering a third daily dose of the composition that is equivalent to about 180 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

26. The method of any of claims 25, comprising administering a fourth daily dose of the composition that is equivalent to about 263 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days ofAttorney Docket No.38383.0001P1 administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

27. The method of any of claims 26, comprising administering a fifth daily dose of the composition that is equivalent to about 314 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

28. The method of claims 16 or 17, comprising administering a first daily dose of the composition that is between 100 to 700 mg of the extract to the subject for 7 to 60 days and administering a second daily dose for 7 to 60 days that is more than or less than the first daily dose after the 7 to 60 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 7 to 60 days of administering the second daily dose, resuming administration of the first daily dose after the 7 to 60 days of the second daily dose and optionally wherein a daily dose is administered twice daily, or administering a third daily dose that is more or less than the second daily dose after the 7- 60 days of the second daily dose, optionally wherein the first, second or third daily dose is a maintenance dose.

29. The method of any one of claims 1 to 28, wherein the seizure disorder is treated.

30. A method of making a cannabinoid extract, comprising: a. providing a harvested plant material of Cannabis sativa; b. drying the plant material to a moisture content of the plant material of less than 10% or less than 8% in environmental conditions having an average temperature between 50°F and 90°F or 60°F and 80°F,Attorney Docket No.38383.0001P1 c. contacting the dried plant material with a solvent to form a solvent extract comprising cannabinoids and terpenes and an undissolved portion; d. separating the undissolved portion from the solvent extract; e. removing a substantial portion of solvent from the solvent extract and decarboxylating at least detla 9-THCA and CBDA to form a cannabinoid extract comprising no more than 5000 ppm of the solvent.

31. The method of claim 30, wherein drying the plant material is in environment conditions having average relative humidity between 0% and 65%.

32. The method of claim 30 or 31, wherein the solvent comprises, consists of, or consists essentially of an alcohol with 2 to 5 carbons or an alcohol selected from isopropyl alcohol and ethanol or wherein the solvent consists of or consists essentially of isopropyl alcohol.

33. The method of claim 32, wherein detla 9-THCA in the cannabinoid extract is not more than 2% or not more than 1% w / w of the cannabinoid extract and CBDA in the cannabinoid extract is not more than 2% or not more than 1% w / w of the cannabinoid extract.

34. The method of any one of claim 30 to 33, wherein the solvent is isopropyl alcohol and the substantial portion of the solvent is removed from the solvent extract by heating to solvent extract to a temperature of 170 °F to 195 °F or 180 to 190 °F and spraying the solvent extract in a chamber under a vacuum, wherein the chamber is in fluid communication with a condenser (e.g, a chiller) such that vapor passes to the condenser thereby condensing vapor comprising isopropyl alcohol and separating vaporized isopropyl alcohol from the solvent extract, wherein the condenser is at a temperature of 0°C to 5°C.

35. The method of any one of claims 30 to 34, wherein the decarboxylation process comprises heating and mixing the solvent extract in a vessel that is in fluid communication withAttorney Docket No.38383.0001P1 a condenser, wherein the solvent extract is heated to a temperature of from about 75°C to 85°C until no evaporated solvent condensate is visible in the condenser and incrementally reducing the pressure one or more times while heating, wherein before each pressure reduction, no evaporated solvent condensate is visible in the condenser.

36. The method of claim 35, wherein the pressure is incrementally reduced to 5-15 torr and held until no solvent is visible in the condenser and / or held for 1-2 hours, thereby obtaining the cannabinoid extract.

37. The method of claim 35 or 36, wherein the condenser temperature is -7°C to 0°C or about -5°C.

38. The method of any one of claims 30 to 37, wherein at least a portion of decarboxylation occurs during removing the solvent from the solvent extract.

39. The method of any one of claim 35 to 38, wherein the vessel comprises a heat jacket configured to heat the solvent extract contained within the vessel.

40. The method of any of claims 30 to 39, wherein removing the undissolved portion from the solvent extract comprises filtering the undissolved portion from the extraction portion.

41. The method of any one of claims 30 to 40, wherein the dried plant material that is contacted with the solvent comprises at least 85% by weight of flowers and leaves of the dried plant material.

42. The method of any one of claims 30 to 41, wherein the dried plant material is stored for no more than 12 months at an average temperature not to exceed 80°F prior to contacting the plant material with solvent.

43. The method of any one of claims 30 to 42, wherein the dried plant material is stored for no more than 9 months at an average temperature not to exceed 80°F prior to contacting the plant material with solvent.Attorney Docket No.38383.0001P1 44. The method of any one of claims 30 to 43, wherein the dried plant material is stored for no more than 6 months at an average temperature not to exceed 80°F prior to contacting the plant material with solvent.

45. The method of any one of claims 30 to 44, wherein the dried plant material is stored in a sealed container.

46. The method of any one of claims 30 to 45, wherein the Cannabis sativa plant material is of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

47. An extract obtained from a method according to any one of claims 30 to 46.

48. A pharmaceutical composition comprising an extract according to claim 47.

49. The pharmaceutical composition according to claim 48, wherein the composition comprises a carrier, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons, optionally, wherein the carbon chain length is 12 to 20, optionally wherein the glyceride is sesame oil, corn oil, modified corn oil, 50. The pharmaceutical composition according to claim 48 or 49, wherein the composition is not an emulsion.

51. The pharmaceutical composition according to any one of claims 48 to 50, wherein the composition consists of or consists essentially of the extract, the carrier, and a flavoring agent.

52. The pharmaceutical composition according to claim any one of claims 48 to 51, wherein a concentration of cannabidiol is 5-8% w / w of the composition.Attorney Docket No.38383.0001P1 53. The pharmaceutical composition according to any one of claims 48 to 52, wherein a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, and a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannabinoids is 5.6-8.4% w / w of the pharmaceutical composition.

54. The pharmaceutical composition according to any one of claims 48 to 53, wherein the carrier is a winterized oil composed of mono-, di- and triglycerides of oleic and linoleic acids and / or wherein the oil is obtained from corn.

55. The pharmaceutical composition according to any one of claims 48 to 54, wherein the composition comprises: a. beta-caryophyllene at an amount that is 3% to 25% percent of the amount of beta caryophyllene in the air dried plant material from which the extract is obtained, and / or b. α-bisabolol at an amount that is 3% to 20% percent of the amount of α-bisabolol ne in the air dried plant material from which the extract is obtained and / or c. α-humulene at an amount that is 3% to 30% percent of the amount of α-humulene in the air dried plant material from which the extract is obtained, and / or d. a concentration of cannabidiol of 5 to 8% w / w of the composition..

56. The pharmaceutical composition according to any one of claims 48 to 55,, wherein the composition comprises a ratio of cannabidiol:tetrahydrocannabinol of from 20:1 to 40:1 or from about 25:1 to about 40:

1.

57. A method of treating one or more symptoms of autism spectrum disorder (ASD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 48 to 56.Attorney Docket No.38383.0001P1 58. The method of claim 57, wherein the symptom of ASD is anxiety and / or irritability.

59. The method of claim 57 or 58, wherein the subject is a human.

60. The method of any one of claims 59, wherein the human subject is less than 18 years of age or 5 to 17 years of age.

61. The method of any one of claims 59, wherein the human subject is at least 13 years of age or 13 to 30 years of age.

62. The method of claim 60, wherein a daily dose of the pharmaceutical composition comprises from 20 mg to 400 mg of the cannabinoid extract.

63. The method of claim 60 or 61, wherein a daily dose of the pharmaceutical composition comprises from about 100 mg to about 700 mg of the cannabinoid extract.

64. The method of claims 60 or 61, comprising administering a first daily dose of the composition that is equivalent to about 103 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 206 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

65. The method of claim 64, comprising administering a third daily dose of the composition that is equivalent to about 360 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.Attorney Docket No.38383.0001P1 66. The method of claim 65, comprising administering a fourth daily dose of the composition that is equivalent to about 515 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

67. The method of claim 66, comprising administering a fifth daily dose of the composition that is equivalent to about 618 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

68. The method of claim 60, comprising administering a first daily dose of the composition that is equivalent to about 53 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 103 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

69. The method of any of claims 68, comprising administering a third daily dose of the composition that is equivalent to about 180 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

70. The method of any of claims 69, comprising administering a fourth daily dose of the composition that is equivalent to about 263 mg of the extract to the subject for 4 to 7 daysAttorney Docket No.38383.0001P1 after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

71. The method of any of claims 70, comprising administering a fifth daily dose of the composition that is equivalent to about 314 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.

72. A method of treating epilepsy in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition comprising an extract obtained from the method according to any of claims 48 to 56.

73. The method of claim 72, wherein the subject is a human.

74. A pharmaceutical composition is a lipid-based formulation or lipid-surfactant based formulation, wherein the formulation comprises a cannabinoid extract of Cannabis sativa and a carrier, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons, wherein the composition comprises: a. beta-caryophyllene at an amount that is 3% to 25% percent of the amount of beta caryophyllene in the air dried plant material from which the extract is obtained, and / or b. α-bisabolol at an amount that is 3% to 20% percent of the amount of α-bisabolol ne in the air dried plant material from which the extract is obtained and / orAttorney Docket No.38383.0001P1 c. α-humulene at an amount that is 3% to 30% percent of the amount of α-humulene in the air dried plant material from which the extract is obtained, and / or d. a concentration of cannabidiol of 5 to 8% w / w of the composition.

75. The pharmaceutical composition of claim 74, wherein the extract comprises the concentration of α-bisabolol of from 8 mg / mL to 50 mg / mL of the extract or wherein the extract comprises the concentration of humulene of from 4 mg / mL to 40 mg / mL of the extract.

76. The pharmaceutical composition of claim 74 or 75, wherein the extract comprises the concentration of beta-caryophyllene is from 15 mg / mL to 70 mg / mL of the extract.

77. The pharmaceutical composition of any one of claims 74 to 76, wherein the composition comprises a ratio of cannabidiol:delta 9 tetrahydrocannabinol of from 20:1 to 40:1 or from about 25:1 to about 40:

1.

78. The pharmaceutical composition of any one of claim 74 to 77, wherein a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannabinoids is 5.6-8.4% w / w of the pharmaceutical composition.

79. The pharmaceutical composition of any of claims 74 to 78, wherein the composition is not an emulsion.

80. The pharmaceutical composition of any of claims 74 to79, wherein the Cannabis sativa L. is of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

81. The pharmaceutical composition of any of claims 74 to 80, wherein the cannabinoid composition comprises a tetrahydrocannabinol concentration of 1 to 3 mg / mL.Attorney Docket No.38383.0001P1 82. The pharmaceutical composition of any of claims 74 to 81, wherein the composition comprises a concentration of α-humulene of from about 2 mg / mL to about 3.5 mg / mL.

83. The pharmaceutical composition of any of claims 74 to 82, wherein the pharmaceutical composition consists of or consists essentially of a cannabinoid extract of Cannabis sativa L., the carrier, and a flavoring agent.

84. The pharmaceutical composition of any one of claims 74 to 83, wherein the carbon chain length of the glyceride is 12 to 20 or wherein the glyceride is sesame oil, corn oil, modified corn oil, or combination thereof, or wherein the carrier comprises, consists or consists essentially of a winterized oil composed of mono-, di- and triglycerides of oleic and linoleic acids.

85. A method of treating one or more symptoms of autism spectrum disorder (ASD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any of claims 74 to 84.

86. The method of claim 85, wherein the symptom of ASD is anxiety and / or irritability.

87. The method of claim 85 or 86, wherein the subject is a human.

88. The method of claim 87, wherein the human subject is less than 18 years of age or 5 to 17 years of age.

89. The method of claim 87, wherein the human subject is at least 13 years of age or 13 to 30 years of age.

90. The method of any of claims 88, wherein a daily dose of the pharmaceutical composition comprises from 20 mg to 400 mg of the cannabinoid extract.Attorney Docket No.38383.0001P1 91. The method of any of claims 88 or 89, wherein a daily dose of the pharmaceutical composition comprises from about 100 mg to about 700 mg of the cannabinoid extract.

92. The method of claims 88 or 89, comprising administering a first daily dose of the composition that is equivalent to about 103 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 206 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

93. The method of claim 92, comprising administering a third daily dose of the composition that is equivalent to about 360 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

94. The method of claim 93, comprising administering a fourth daily dose of the composition that is equivalent to about 515 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

95. The method of claim 94, comprising administering a fifth daily dose of the composition that is equivalent to about 618 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.Attorney Docket No.38383.0001P1 96. The method of claim 87, comprising administering a first daily dose of the composition that is equivalent to about 53 mg of the extract to the subject for 4 to 7 days and administering a second daily dose of about 103 mg for 4 to 7 days after the 4 to 7 days of administering the first daily dose, and optionally continuing administration the second daily dose as a maintenance dose after the 4 to 7 days of administering the second daily dose or resuming administration of the first daily dose after the 4 to 7 days of the second daily dose and optionally wherein a daily dose is administered twice daily.

97. The method of any of claims 96, comprising administering a third daily dose of the composition that is equivalent to about 180 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the second daily dose, and optionally continuing administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose or resuming administration of the second daily dose as a maintenance dose after the 4 to 7 days of administering the third daily dose.

98. The method of any of claims 97, comprising administering a fourth daily dose of the composition that is equivalent to about 263 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the third daily dose, and optionally continuing administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose or resuming administration of the third daily dose as a maintenance dose after the 4 to 7 days of administering the fourth daily dose.

99. The method of any of claims 98, comprising administering a fifth daily dose of the composition that is equivalent to about 314 mg of the extract to the subject for 4 to 7 days after the 4 to 7 days of administering the fourth daily dose, and optionally continuing administration of the fifth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose or resuming administration of the fourth daily dose as a maintenance dose after the 4 to 7 days of administering the fifth daily dose.Attorney Docket No.38383.0001P1 100. A method of treating a seizure disorder in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of any of claims 74 to 84.

101. The method of claim 100, wherein the subject is a human.

102. A cannabinoid extract of Cannabis sativa L. comprising: CBD to delta 9-THC ratio of at least 20:1 to 40:1; a concentration of CBD from 400 to 1000 mg / mL or 500 mg / mL to 800 mg / mL, and one ore more of the following: a concentration of beta-caryophyllene is from 15 mg / mL to 70 mg / mL; a a concentration of α-bisabolol of from about 8 mg / mL to about 50 mg / mL; a concentration of α-humulene of from about 4 mg / mL to about 40 mg / mL.

103. The extract of claim 102, wherein the extract is of variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

104. A pharmaceutical composition comprising a cannabinoid extract of claim 102 or 103 and an oil-based carrier, wherein the composition comprises a concentration of cannabidiol (CBD) of 5 to 8% w / w of the composition or wherein the extract is diluted at a factor of about 3 to 20 or 8 to 14 or about 11 or 12 to make the composition.

105. The pharmaceutical composition of claim 104, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons.

106. The pharmaceutical composition of claim 105, wherein the carbon chain length is 12 to 20.

107. The pharmaceutical composition of claim 105 or 106, wherein the glyceride is sesame oil, corn oil, and / or modified corn oil.

108. The pharmaceutical composition of claim 105 or 106, werein the glyceride is glyceryl monolinoleate, preferably Macine CC oil.Attorney Docket No.38383.0001P1 109. The pharmaceutical composition of any one of claims 104 to 108, wherein the composition comprises a ratio of CBD: delta 9 THC of from 25:1 to 40:

1.

110. The pharmaceutical composition of any one of claims 104 ot 109, wherein the cannabinoid composition comprises a tetrahydrocannabinol concentration of 1 to 3 mg / mL.

111. The pharmaceutical composition of any one of claims 104 to 110, wherein the extract is diluted by a factor of about 8 to 14 to make the composition.

112. The pharmaceutical composition of any one of claims 104 to 111, wherein the extract concentration of beta-caryophyllene is from 8 mg / mL to about 40 mg / mL.

113. The pharmaceutical composition of any one of claims 104 to 112, wherein the extract concentration of α-bisabolol is from about 4 mg / mL to about 40 mg / mL.

114. The pharmaceutical composition of any one of claims 104 to 113, wherein the extract concentration of α-humulene is from about 3 mg / mL to about 30 mg / mL.

115. The pharmaceutical composition of any one of claim 104 to 114, wherein a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannibinoids is 5.6-8.4% w / w of the pharmaceutical composition.

116. The pharmaceutical composition of any one of claims 104 to115, wherein the composition is not an emulsion.

117. The pharmaceutical composition of any one of claims 104 to 116, wherein the Cannabis sativa plant is of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

118. The pharmaceutical composition of any one of claims 104 to 117, wherein the pharmaceutical composition consists of or consists essentially of a cannabinoid extract of Cannabis sativa plant, glyceryl monolinoleate, and a flavoring agent.

119. A method of treating one or more symptoms of autism spectrum disorder (ASD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any of claims 104 to 118.

120. The method of claim 119, wherein the symptom of ASD is anxiety and / or irritability.

121. The method of claim 119 to 120, wherein the subject is a human.

122. The method of claim 121, wherein the human subject is less than 13 years of age.Attorney Docket No.38383.0001P1 123. The method of claim 121, wherein the human subject is at least 13 years of age.

124. The method of any of claims 122, wherein a daily dose of the pharmaceutical composition comprises from 20 mg to 400 mg or 20 mg to 700 mg of the cannabinoid extract.

125. The method of any of claims 123, wherein a daily dose of the pharmaceutical composition comprises from about 40 mg to about 700 mg or 800 mg of the cannabinoid extract.

126. The method of any of claims 122 or 123, comprising administering a first dose of about 25 mg or about 50 mg of the cannabinoid extract and increasing the dose after 4 to 10 days.

127. A method of treating epilepsy in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of any of claims 104 to 118.

128. The method of claim 127, wherein the subject is a human.

129. A cannabinoid extract of Cannabis sativa L. comprising: CBD to delta 9-THC ratio of at least 20:1 to 40:1; and terpenes comprising beta-caryophyllene, α-bisabolol, and α-humulene, wherein beta-caryophyllene, α-bisabolol, and α-humulene are at least 90%, at least 95%, or at least 98% by weight of the terpenes in the extract.

130. The extract of claim 129, wherein the extract is of variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

131. A pharmaceutical composition comprising a cannabinoid extract of claim 129 or 130 and an oil-based carrier, wherein the composition comprises a concentration of cannabidiol (CBD) of 5 to 8% w / w of the composition or wherein the extract is diluted at a factor of about 3 to 20 or 8 to 14 or about 11 or 12 to make the composition.

132. The pharmaceutical composition of claim 131, wherein the carrier comprises, consists of, or consists essentially of a mono, di, or tri glyceride or any combination thereof, wherein the fatty acids of the glycerides have a saturated or unsaturated carbon chain length ranging from 8 to 20 carbons.

133. The pharmaceutical composition of claim 132, wherein the carbon chain length is 12 to 20.

134. The pharmaceutical composition of claim 132 or 133, wherein the glyceride is sesame oil, corn oil, and / or modified corn oil.Attorney Docket No.38383.0001P1 135. The pharmaceutical composition of claim 132, werein the glyceride is glyceryl monolinoleate, preferably Macine CC oil.

136. The pharmaceutical composition of any one of claims 131 to 135, wherein the composition comprises a ratio of CBD:THC of from 25:1 to 40:

1.

137. The pharmaceutical composition of any one of claims 131 ot 136, wherein the cannabinoid composition comprises a tetrahydrocannabinol concentration of 1 to 3 mg / mL.

138. The pharmaceutical composition of any one of claims 131 to 137, wherein the extract is diluted by a factor of about 8 to 14 to make the composition.

139. The pharmaceutical composition of any one of claims 131 to 138, wherein the extract concentration of beta-caryophyllene is from 15 mg / mL to about 70 mg / mL.

140. The pharmaceutical composition of any one of claims 131 to 139, wherein the extract concentration of α-bisabolol is from about 8 mg / mL to about 50 mg / mL.

141. The pharmaceutical composition of any one of claims 131 to 140, wherein the extract concentration of α-humulene is from about 4 mg / mL to about 40 mg / mL.

142. The pharmaceutical composition of any one of claim 131 to 141, wherein a concentration of delta 9-THC is 0-0.3% w / w / of the pharmaceutical composition, a concentration of cannabichromene is 0-0.5% w / w of the pharmaceutical composition, a concentration of cannabigerol is 0 to 0.3% w / w of the pharmaceutical composition and / or wherein a concentration of total cannibinoids is 5.6-8.4% w / w of the pharmaceutical composition.

143. The pharmaceutical composition of any one of claims 131 to 142, wherein the composition is not an emulsion.

144. The pharmaceutical composition of any one of claims 131 to 143, wherein the Cannabis sativa plant is of the variety ‘CW1AS1’ strain, wherein a representative seed of the variety has been deposited under NCIMB No.43291.

145. The pharmaceutical composition of any one of claims 131 to 144, wherein the pharmaceutical composition consists of or consists essentially of a cannabinoid extract of Cannabis sativa plant, glyceryl monolinoleate, and a flavoring agent.

146. A method of treating one or more symptoms of autism spectrum disorder (ASD) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any of claims 131 to 145.

147. The method of claim 146, wherein the symptom of ASD is anxiety and / or irritability.Attorney Docket No.38383.0001P1 148. The method of claim 146 to 147, wherein the subject is a human.

149. The method of claim 148, wherein the human subject is less than 13 years of age.

150. The method of claim 148, wherein the human subject is at least 13 years of age.

151. The method of any of claims 149, wherein a daily dose of the pharmaceutical composition comprises from 20 mg to 400 mg or 20 mg to 700 mg of the cannabinoid extract.

152. The method of any of claims 150, wherein a daily dose of the pharmaceutical composition comprises from about 40 mg to about 700 mg or 800 mg of the cannabinoid extract.

153. The method of any of claims 149 or 150, comprising administering a first dose of about 25 mg or about 50 mg of the cannabinoid extract and increasing the dose after 4 to 10 days.

154. A method of treating epilepsy in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of any of claims 131 to 145.

128. The method of claim 154, wherein the subject is a human.

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