Options to control pharmacodynamics of cannabis-infused edible products and medicines

Abstract

The invention provides compositions and methods for selecting and achieving desired effects from cannabinoid emulsions. This is achieved by adjusting components of the composition, including fats, emulsifiers, and cannabinoids.

Description

OPTIONS TO CONTROL PHARMACODYNAMICS OF CANNABIS- INFUSED EDIBLE PRODUCTSAND MEDICINESClaim of Priority under 35 U.S.C §119

[0001] The present Application for patent claims priority to U.S. Provisional Application No. 63 / 726,130 entitled “OPTIONS TO CONTROL PHARMACODYNAMICS OF CANNABIS-INFUSED EDIBLE PRODUCTS AND MEDICINES” filed November 27, 2024, and U.S. Provisional Application No. 63 / 903,644 entitled “TUNING PHARMACODYNAMIC EFFECT OF CANNABIS INFUSED EDIBLE PRODUCTS BY CONTROLLING FAT AND EMULSIFIERE TYPE” filed October 22, 2025; the entire content of each of the foregoing is hereby expressly incorporated by reference herein.BACKGROUNDField

[0002] The invention disclosed herein generally relates to the pharmacodynamics and pharmacokinetics of ingestible formulations that contain cannabinoids, as well as compositions and methods that make use of new insights in this field.Background

[0003] The study of pharmacokinetics (PK) is the study of how the body absorbs the drug. The term pharmacodynamics (PD) relates to how the drug affects the body (i.e., experience, effect). PD can include multiple layers in cannabis edibles and medicine such as recreational effect, therapeutic effect, and impairment.

[0004] It is known that fats, such as MCT or LCT, can potentially change the absorption of cannabinoids, thus impacting the PK profile. This is because for the human body to absorb fat-soluble drugs such as cannabinoids, it needs to go into a vehicle called “mixed micelle” in the small intestine.

[0005] Mixed micelles consist of fatty acids, molo-glycerides, and bile salts. When fats such as MCT are eaten, they can quickly decompose into fatty acids and molo-glycerides, which can be used as ingredients for mixed micelles. This is the mechanism through which MCT can facilitate absorption. LCT, on the other hand, helps form chylomicrons in enterocyte cells. A chylomicron is a large entity containing a long chain fatty acid and THC. Due to its large size, it cannot go through the small portal vein into the liver, thus can only enter the lymphatic system, which then connects directly to the blood circulation. This process bypasses the liver, thus saving THC from being metabolized into 11 -OH- THC.

[0006] It is well known that a meal, especially a high fat meal, can increase the absorption of hydrophobic drugs. A high fat meal can be expected to boost the absorption of THC from an edible product, thus increasing the psychoactive effect. However, not all THC edible experiences will couple with a meal with high fat or high calorie content.SUMMARY

[0007] Some embodiments of the invention relate to a cannabinoid emulsion composition including A9-tetrahydrocannabinol (THC) in a triglyceride oil dispersed in an aqueous phase with an emulsifier. In some embodiments the composition can be characterized by an MCT:THC ratio of for example 1.5: 1 to 8: 1 defining a functional absorption window in which API exceeds NAF120;. In some embodiments it can be characterized by an LCT fraction of 20-75%, which can increase lymphatic uptake and can suppress first-pass metabolism. In other embodiments it can be characterized by a THC: 11-OH-THC AUC ratio of at least 2.0 under matched THC dose and droplet size. In further embodiments it is characterized by a pharmacodynamic profile determined by triglyceride composition, wherein LCT-containing emulsions produce a more cerebral psychoactive effect and MCT-dominant emulsions produce a more body- focused effect.

[0008] In certain embodiments the triglyceride oil can consist essentially of MCT and can be substantially free of LCT. In other embodiments the MCT:THC can be between 1.5: 1 and 8: 1 yields API > NAF120, and ratios can be for example below 1.5: 1 or above 8: 1 exhibit API < NAF120. In further embodiments the MCT includes caprylic acid (C8:0), capric acid (C10:0), caproic acid (C6:0), lauric acid (C12:0), or any combination thereof. In some embodiments droplet size (D50) can be maintained for example between 230 nm and 290 nm across all MCT: THC ratios tested.

[0009] In certain embodiments systemic THC exposure (AUCo-t) can be increased by for example at least 20%, 30%, or 50% relative to an MCT-only formulation with the same THC dose and droplet size. In some embodiments 11-OH-THC AUC can be reduced by at least 50%, 60%, or 70% relative to an MCT-only comparator. In other embodients the THC: 11-OH-THC AUC ratio can be for example at least 2.0, 2.5, 3.0, or greater. In further embodiments the Tmax of THC can be between for example about 55 minutes and about 120 minutes.

[0010] In certain embodiments the LCT can include palmitic acid (Cl 6:0), stearic acid (Cl 8:0), oleic acid (C18: l), linoleic acid (C18:2), a-linolenic acid (C18:3), arachidonic acid (C20:4), docosapentaenoic acid (C22:5), docosahexaenoic acid (C22:6), any combination thereof, or the like. In other embodiments LCT-containing emulsions can produce increased ratings of alertness, sociability, creativity, or cognitive clarity relative to MCT-dominant emulsions. Infurther embodiments MCT-dominant emulsions can produce increased ratings of relaxation, physical heaviness, drowsiness, or body-focused sensations relative to LCT-containing emulsions.

[0011] In certain embodiments pharmacodynamic differences can occur despite at least 80% similarity in Tmax and at least 80% similarity in Cmax between two emulsions differing only in LCT content. In some embodiments the absorption behavior can exhibit a non-linear or inverted-U dependence on MCT:THC ratio, with decreased absorption efficiency at ratios above for example 8: 1. In further embodiments increasing LCT beyond about 75% can result in reduced THC AUC or delayed lipolysis.

[0012] In certain embodiments particle size (D50) can be maintained between for example 150 nm and 400 nm such that PK and PD differences can be attributable to fat composition rather than particle size. In some embodiments two emulsions compared for PK and PD assessment can differ in LCT content but can have D50 values within for example ±15 nm of each other. In other embodiments the fatty-acid composition can modulate mixed-micelle formation rate under simulated intestinal lipolysis, resulting in time-dependent differences in micellar THC fraction. In further embodiments LCT digestion can yield long-chain fatty acids that promote chylomicron assembly and lymphatic transport, whereas MCT digestion yields medium-chain fatty acids that promote portal uptake.

[0013] In certain embodiments the THC dose can be for example at least 10 mg such that PK and PD differences attributable to triglyceride composition can be reliably detectable in human subjects.

[0014] Other embodiments of the invention relate to a composition including at least one active cannabinoid, at least one fat, and at least one emulsifier, in a combination selected to have a pharmacokinetic (PK) or pharmacodynamic (PD) property that can be at least l.lx different from a comparable composition lacking either the fat or the emulsifier. In some embodiments the emulsifier includes gum acacia or a Quillaja saponin. In other embodiments the fat can be selected from at least one medium-chain triglyceride (MCT), at least one long-chain triglyceride (LCT), any fatty acid of selected chain length and degree of saturation, or the like. In further embodiments the PK property can be selected from onset, peak intensity, duration of action, any combination thereof, or the like. In certain embodiments the PD property can be selected from THC psychoactive effect, degree of impairment, therapeutic effect, and the like.

[0015] In certain embodiments the PK property can be onset, and the onset can be for example at least 1.5 times faster than the comparable composition. In other embodiments the PK propertycan be peak intensity and the peak intensity can be for example at least 1.5x higher than the comparable composition. In some embodiments the PK property can be duration of action, and the duration of action can be for example either at least (a) 1.5 x longer, or (b) half as long, as the comparable composition. In further embodiments the PD can be THC psychoactive effect and the psychoactive effect can be for example at least (a) 1.2x greater or (b) 1 / 3 less than the comparable composition. In some embodiments the PD can be degree of impairment and the degree of impairment can be for example at least (a) 1 ,2x greater or (b) 1 / 3 less than the comparable composition. In other embodiments the PD can be therapeutic effect and the therapeutic effect can be for example at least 1.2x greater than the comparable composition.

[0016] In certain embodiments the at least one active cannabinoid includes any of A9- tetrahydrocannabinol (A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol, A6a,10a-tetrahydrocannabinol, A7-tetrahydrocannabinol, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabicyclol (CBL), cannabitriol (CBT), cannabielsoin (CBE), cannabinodiol (CBND), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabigerovarin (CBGV), cannabichromevarin (CBCV), and cannabielsoin varin (CBEV). Acidic precursors such as A9-tetrahydrocannabinolic acid A (THCA-A), A9-tetrahydrocannabinolic acid B (THCA-B), A8-tetrahydrocannabinolic acid, Alo-tetrahydrocannabinolic acid, cannabidiolic acid (CBDa), cannabigerolic acid (CBGa), cannabichromenic acid (CBCa), cannabinolic acid (CBNa), cannabicyclolic acid (CBLa), cannabitriolic acid (CBTa), cannabielsoic acid (CBEa), cannabinodiolic acid (CBNDa), tetrahydrocannabivarinic acid (THCVa), cannabidivarinic acid (CBDVa), cannabigerovarinic acid (CBGVa), cannabichromevarinic acid (CBCVa). Hexahydrocannabinol (HHC), hydrogenated cannabidiol (H4-CBD), hydrogenated cannabigerol (H4-CBG), hydrogenated cannabinol (H4-CBN), hexahydrocannabivarin (HHC-V), hydrogenated cannabidiol varin (H4-CBDV), hydrogenated cannabigerovarin (H4-CBGV),11-hydroxy-THC (11 -OH- THC), 8-hydroxy- THC, 11-hydroxy-CBD, 7-hydroxy-CBD, 11-hydroxy-CBG, 8-hydroxy-CBN, 11-oxo-CBN, 9-hydroxy-HHC, 10-hydroxy-HHC, dihydroxy-THC isomers, cannabinol-quinone, cannabinodiol (CBND), cannabichromanon (CBCN), cannabifuran (CBF), cannabicoumaronone, cannabiripsol, A9-THCV, A8-THCV, CBDV, CBGV, CBCV, CBLV, CBNDV, CBTv, CBEv, CBV, tetrahydrocannabiorcol (THCC), tetrahydrocannabutol (THCB), tetrahydrocannabihexol (THCH), THCP (tetrahydrocannabiphorol), CBDP (cannabidiphorol), CBGP (cannabigerophorol), CBCP (cannabichromephorol), CBNP,THCB (tetrahydrocannabutol), CBD-B, CBGB, CBCB, THCH (tetrahydrocannabihexol), CBDH, CBGH, CBCH, cannabiorcol (CBO), cannabiripsol (CBR), cannabicitran (CBT), cannabifuran (CBF), cannabimovone (CBM), cannabiripsin, cannabioxepane, cannabiglendol, dronabinol, nabilone, HU-210, HU-211, CP-55,940, WIN-55,212-2, JWH series cannabinoids, and pharmaceutically acceptable salts, esters, ethers, prodrugs thereof, and the like.

[0017] Further embodiments include one or more terpene or terpenoid. In other embodiments the terpene or terpenoid includes at least one of myrcene, P-caryophyllene, a-humulene, limonene, a-pinene, P-pinene, linalool, terpinolene, geraniol, nerol, borneol, isopulegol, eucalyptol (1,8-cineole), camphene, sabinene, ocimene, valencene, farnesene, bisabolol, guaiol, cedrol, phytol, terpineol, perillyl alcohol, carvone, pulegone, citronellol, menthol, thymol, carvacrol, P-elemene, P-selinene, and the like.

[0018] In certain embodiments the composition can be in a single-serving oral dose including for example from about 0.5 mg to about 300 mg of cannabinoid per serving. Further embodiments can include for example from about 5 mg to about 100 mg of cannabinoid per serving. In some embodiments the composition can be in a dose for example from about 0.02 mg to about 5.0 mg per kg of a user’s total body weight. In further embodiments the composition can be in the form of a beverage, a confection or chew, a capsule or softgel, a tincture, or the like.

[0019] In certain embodiments the composition includes a nanoemulsion co-formulated with one or more secondary actives selected from a lipids, a nutraceutical, a vitamin, a mineral, an amino acid, an antioxidant, a drug, an adaptogen, a metabolic regulator, or the like. In some embodiments the co-formulation can yield an effect that can be additive, supra-additive, or synergistic relative to either component alone, measured by at least one pharmacokinetic or pharmacodynamic endpoint. In further embodiments the co-formulation can retain droplet size within 50-500 nm and stability, defined as AD50 <20% at 40 °C for 30 days, in the presence of co-actives.

[0020] Other embodiments of the invention relate to a method of making a composition, including the steps of determining a desired effect; selecting ingredients including at least one active cannabinoid, at least one fat, and at least one emulsifier suited to the desired effect; and processing the ingredients from the selecting step under conditions suitable to yield a stable emulsion capable of achieving the desired effect. In some embodiments n the effect includes a desired PK or PD endpoint.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 depicts the Drug Effect Questionnaire (DEQ) scale.

[0022] FIG. 2 depicts results from the DEQ related to highness.

[0023] FIG. 3 depicts results from the DEQ related to energeticness.

[0024] FIG. 4 depicts results from the DEQ related to mental stimulation.

[0025] FIG. 5 depicts results from the DEQ related to anxiety level.

[0026] FIG. 6 depicts results from the DEQ related to physical relaxation.

[0027] FIG. 7 depicts results from the DEQ related to heaviness of the body.

[0028] FIG. 8 depicts results from the DEQ related to tiredness

[0029] FIG. 9 depicts results from the DEQ related to socialization.

[0030] FIG. 10 depicts results from the DEQ related to enjoyment.

[0031] FIG. 11 depicts results from the DEQ related to desire to consume more.

[0032] FIG. 12 depicts results showing differences in experience from differing THGMCT ratios.

[0033] FIG. 13 depicts results of 11-OH-THC concentration in the blood amongst different emulsion types.

[0034] FIG. 14 depicts results of user experience amongst different emulsion types.

[0035] FIG. 15 depicts results of performance standard for pre-ab sorptive solubilization / flux.

[0036] FIG. 16 depicts results of THC concentration in the blood amongst MCT and LCT compositions.

[0037] FIG. 17 depicts results of 11-OH-THC concentration in the blood amongst MCT and LCT compositions.DETAILED DESCRIPTION

[0038] Pharmacodynamic outcomes of oral cannabinoids are governed by (1) emulsifier identity, which controls psychoactive directionality even under matched pharmacokinetics; (2) triglyceride composition, which exhibits non-linear functional windows governing mixed- micelle kinetics, lymphatic routing, and metabolite formation; and (3) fat configuration (embedded vs. separate emulsions), which accelerates early portal exposure and micellization rates independent of dose. The following sections provide human and in-vitro evidence demonstrating these mechanisms.

[0039] It can be beneficial to emulsify certain fats and formulate them within the end product, whether the end product is an infused beverage, edible, or medicine. This way, users would have the necessary fat present with the THC, and in turn the amount of fat needed can be much less due to the intensified uptake thanks to emulsification.

[0040] Most of the time, PK can be related to PD. The more absorption of a psychoactive drug, the higher the psychoactive effect a user is likely to have. However, the THC experience from an edible can be very difficult to predict. While PK can impact PD it cannot determine PD.Sometimes, there is a delayed relationship between blood concentration and the effect. For example, when a high amount of THC is used the night before, in the morning, the user can be totally sober to operate but THC may still be detected in the blood.

[0041] PK includes four main steps: absorption, distribution, metabolism, and excretion. Most of the relevant accessible literature focuses on how consumption of fat increases absorption, however, THC effect can also be closely connected to the other three steps.

[0042] Absorption: Absorption of cannabinoids from an edible product begins with the same fundamental machinery the body uses to handle dietary fats. After an emulsion enters the small intestine, bile salts and pancreatic lipases are secreted into the lumen. These act together as the body’s own emulsification system, breaking down ingested lipid droplets and reorganizing them into much smaller colloidal structures known as mixed micelles. Mixed micelles consist of bile salts, fatty acids, monoglycerides, and other digestion products, and they serve as the primary carriers responsible for transporting hydrophobic molecules — such as THC — across the intestinal epithelium.

[0043] Distribution: Research has shown that how THC enters the bloodstream influences how it spreads through the body, including the brain. Emulsified MCT and LCT change the balance between parent THC and 11 -OH- THC, and this balance determines how much of each form reaches key tissues. MCT-rich emulsions favor portal delivery and higher 11-OH-THC exposure, which tends to distribute more broadly into peripheral tissues and produce heavier body effects. LCT-rich emulsions favor lymphatic transport, leading to higher early levels of unmetabolized THC, which more readily perfuses the brain and produces clearer, more cerebral effects. Because cannabinoids are extremely lipophilic, a significant fraction partitions into adipose (fat) tissue soon after entering circulation. Once stored in these fat cells, cannabinoids can linger and slowly re-enter the bloodstream over time. This reservoir effect contributes to the long terminal half-life of THC and can influence residual sensations even after the primary psychoactive window has passed.

[0044] Metabolism: As THC enters the liver, it can be metabolized to generate 11-OH-THC and THC-COOH. 11-OH-THC has a high affinity to the CB1 receptor, producing a stronger psychoactive effect that can often be associated with a “body high” while THC can usually be associated with a “heady, cerebral high”. Some literature indicates the 11 -OH- THC can be three times more potent than THC alone. Emulsified LCT can help THC bypass first pass metabolism, which potentially leads to lower amounts of 11-OH-THC. When controlling the properties of emulsified LCT, we can control the ratio of THC / 11-OH-THC flowing in the blood at a certain time. This ratio can be the key factor that delivers a unique psychoactiveeffect to users. When the THC / 11-OH-THC ratio is higher, users can feel a headier high, which may be an ideal formula for a party or social activity. When this ratio is lower, a user can feel more body high, which could be ideal for relaxation. Current literature does not teach how to correlate this ratio to a certain effect. This relation needs to be found from conducting PK data on human and PD data at the same time.

[0045] Excretion: every drug has a half-life, and it is generally a function of the liver to govern the half-life as it converts the structure or otherwise eliminates drugs. However, there are compounds like piperine that can inhibit certain liver enzymes to slow down the metabolism and excretion of certain drugs. Adding piperine into the emulsified MCT or LCT can offer another way to control the final experience.

[0046] Discussed below are some variables that can make the prediction of PK’s impact on PD difficult.

[0047] Emulsion Properties. An impactful parameter on user experience can be the emulsion property of the MCT / LCT such as what emulsifier is used, what is the droplet size and what exactly would be the MCT / LCT composition in terms of fatty acid chain length and saturation degree. Different emulsifiers such as Quillaja saponin and gum acacia can be leveraged. Not only are their emulsification properties different, but they also have different biological properties. Quillaja saponin has antifungal activities and can stimulate the immune system and has been used as adjuvant agent for vaccines. Meanwhile gum acacia is mostly inert biologically. When delivering the same fat, these two emulsifiers can have different pharmacodynamic effects on the user.

[0048] Quillaja saponins, extracted from Quillaja saponaria bark, are well known for their amphiphilic structure and strong surfactant properties, but their biological activities extend well beyond emulsion stabilization. Quillaja saponins stimulate both innate and adaptive immune responses, promote cytokine release, and are widely employed as adjuvants in vaccines. They also exhibit antimicrobial, antifungal, and antiviral effects, in part by disrupting lipid membranes. These bioactivities mean that Quillaja is not biologically inert, and its inclusion in cannabinoid formulations introduces pharmacological interactions that can directly shape pharmacodynamics. In recreational settings, / / / 7 / a / a-based THC emulsions may produce a more cerebral, stimulating, and creative high compared to emulsions prepared with gum acacia. This difference may arise from Quillaja ’s ability to enhance immune signaling and systemic circulation, leading to a greater distribution of THC to central nervous system targets. Quillaja ’s mild irritant and immunostimulatory properties could also elevate arousal and energy, making such formulations better suited for social activities, creative work,or physical performance where heightened alertness is desirable. In contrast, gum acacia, being largely inert and fiber-like, promotes a calmer, body-heavy effect more aligned with relaxation or sleep. On the medical side, Quillaja’s properties can synergize with cannabinoids in contexts such as pain relief. Thus, Quillaja ’s unique biological activity not only changes the recreational “feel” of THC but also provides a way to tailor therapeutic outcomes, making emulsifier choice a critical design variable for both consumer and medical cannabis products.

[0049] Quantity of Emulsified Fat. The amount of emulsified fat can also influence user experience. The amount of emulsified fat can determine the milligram of C8, C12, C16 and C18 fatty acids. Compared to eating pizza or a hamburger, for example, where the fat content is at the gram level, emulsified MCT / LCT does not reach the gram level due to the strong flavor impact and challenges it poses to formulation. Current literature does not teach how many milligrams of each fatty acid can be needed and if that amount can be effective.

[0050] Overall Emulsion Composition. The overall active emulsion composition can also play a role in the user experience by itself without the addition of another emulsified fat to boost emulsion. For example, when combining the emulsifier Quillaja with MCT to deliver THC in an emulsion, it can deliver a more cerebral, energized, and creative effect. When combining the emulsifier gum acacia with MCT to deliver THC in an emulsion, it usually delivers a more body, calming, and relaxing effect. The type and amount of carrier oil in the active emulsion, the usage of the weighting agent, and the emulsifier type can all contribute to the final PD effect when delivering THC. For example, gum acacia is mostly inert as a large molecule fiber. But Quillaja saponin has many different biological effects such as antibacterial and immune stimulation as adjuvant agents. Those biological effects can deliver more potential targeted experiences when delivering THC through an emulsion.

[0051] Cannabinoid Type. Another changeable parameter can be cannabinoid type. THC, CBD, CBN, CBC, CBG all have different structures, which makes their hydrophobicity and absorption pattern different. One cannot assume a system that works for THC to control PK / PD would definitely work for all the other cannabinoids. Additionally, different cannabinoids can be metabolized into various types of structures and more research is needed to understand if any of those structures offer any PD effect to deliver recreational or medical benefit. The form factor of those cannabinoids can be important to user experience. The experience boost efficiency would likely be different when comparing an emulsified THC with THC distillate. Even for emulsified THC, what emulsion it is in can impact how the fat emulsion interacts with it biologically.

[0052] Medical Effect of Cannabinoid(s). Another important factor is the medical effect from the selected cannabinoid. Emulsified fat can potentially increase the absorption of the cannabinoid, but higher absorption of the drug does not always equate to a better therapeutic effect. For each illness, the drug would have an ideal range of concentration that best helps the condition. It would need lots of trials to identify what concentration is ideal for the condition and how to leverage emulsified fat to control each cannabinoid within that range. This is impossible to predict without clinical study.

[0053] Environmental Variables. The subjective nature of the PD study adds variability to the data. The genetics of the user, food, set, and setting can all impact what a user feels. Even for the same formula, the same person can have a slightly different experience on two different days. This makes it hard to say a certain formula would definitely make the user feel a certain way. Therefore, when designing a formula with an emulsified fat for recreational purposes, the successful criteria should not be centered around having 100% of users feel the same way, but to set a reasonable effect target. For example, a particular formula can make people generally feel higher than a typical 5 mg THC from regular emulsion, while also offering a more cerebral effect. Thus, it is advisable to set a percentage of users who achieve a particular feeling to be the passing / failing consideration of the invention. In this way the statistical significance of the data plays an important role too.

[0054] When addressing PD, prior efforts have only used the THC recreational side as an example. THC can also bring impairment of motor operation and eye / hand coordination. The impairment is caused by THC impacting certain parts of the brain, but the current theory is not enough to prove whether the amount of THC or the ratio of THC / 11-OH-THC would impact the impairment. If the impairment test can be established in such a way that time perception, eye / hand coordination, and reaction time can all be measured using certain apps, it will be possible to evaluate the formulation impact on impairment more consistently.

[0055] There are many variables that can impact how a user experiences an edible cannabis product. These variables can show how a boosted PK does not definitively deliver a boosted PD effect, especially when considering the effect to fit in a social activity such as concert, comedy club, party, movie, hiking, spa, long distance flight, sports, or sexual activities. Further marketing and product positioning is needed to develop products that can be tailored to specific social events so consumers can enjoy the product to the fullest extent.Methods

[0056] In order to find out how MCT / LCT impacts the PD of THC infused products, a thorough and intentional approach to PD study is needed. In one model, testers enter a testing center,take the formula blindly, then answer a PD questionnaire at different time intervals to evaluate the drug effect. This way, it is possible to compare whether a certain formula would offer different levels of THC psychoactive effect at different points in a user’s experience.

[0057] The parameters that can impact the drug effects include fatty acid types (chain length and saturation), fatty acid amount, emulsion properties such as droplet size and emulsifier types. In order to systematically evaluate the pharmacodynamic (PD) outcomes of cannabinoid formulations, controlled human subject studies are conducted under standardized laboratory conditions. A total of fifty healthy adult testers are recruited and randomized into blinded study groups. All testing sessions are performed at a dedicated cannabis pharmacology facility with environmental factors such as lighting, temperature, and sound carefully controlled. To minimize dietary confounds, participants are instructed to fast for at least four hours before dosing, and a standardized low-fat snack is provided at baseline to control for food matrix effects. Each subject consumes a defined dose of tetrahydrocannabinol (THC) delivered in emulsion format, with the emulsion type and fat / emulsifier composition varied between groups.

[0058] Acute pharmacodynamic responses are assessed using two complementary psychometric tools. The Drug Effect Questionnaire (DEQ) is administered electronically and asked subjects to rate, on a 0-100 visual analogue scale, questions such as: “How high do you feel right now?”; “How much do you like the drug effect?”; “How much do you feel mentally stimulated?”; “How much do you feel physically relaxed?”; “How anxious do you feel?”; “How heavy does your body feel?”; “How much do you want more of the drug?”; “How mentally stimulated do you feel?”; “How physically relaxed do you feel?”; “How anxious do you feel?”; “How heavy does your body feel?”; “How tired or sleepy do you feel?”; “How social or talkative do you feel?”; and “How enjoyable is the effect right now?”

[0059] Bond & Lader Visual Analogue Mood Scales (VAMS) are one of the gold-standard psychometric tools in drug-effect studies. They consist of 16 bipolar adjective pairs, each presented as a 100-mm line, where the participant marks their current feeling. These map onto three principal factors: alertness, calmness, and contentedness.

[0060] There are four domains from Bond & Lader results — vitality, mood, cognition, and connectedness — by adding up the individual scores and averaging the numbers.

[0061] A full set of 16 original items can be found in Table 1.Table 1

[0062] Both DEQ and Bond & Lader assessments are administered at baseline and at repeated time points of 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post-dose, thereby capturing onset, peak, plateau, and decline phases of the THC effect. Exemplary data from the fifty participants are aggregated to evaluate reproducibility, inter-individual variability, and the impact of formulation variables (i.e., including fat type, emulsifier system, and droplet size) on acute pharmacodynamic profiles. This rigorous framework enables direct comparison of formulations and establishes correlations between emulsion composition and user experience across an extended five-hour observation window.

[0063] In certain embodiments, psychoactive effects can be quantified using a structured psychometric instrument comprising multiple domains relevant to cannabis-related experiential states. The instrument includes (i) global intensity and hedonic ratings measured on a 0-100 visual analog scale, (ii) one-directional affective evaluations such asuncomfortable-comfortable, sad-happy, and dislike-like, (iii) paired mood axes such as dreamy-attentive, fuzzy-clear, drowsy-alert, withdrawn-social, relaxed-energized, anchored-floating, and detached-sensual, (iv) behavioral inclination assessments identifying preferred activities (e.g., staying home vs going out), and (v) overall experience evaluations including future-use intent. Each domain is administered as a single item per screen to minimize response bias, and anchors are defined for all scale endpoints to ensure interpretability. This framework enables reproducible characterization of emulsifierdependent pharmacodynamic differences

[0064] In certain embodiments, psychoactive response can be further characterized through a behavioral inclination assessment in which subjects indicate preferred activities at each timepoint. These may include paired choices such as staying home versus going out, solitude versus group interaction, listening versus speaking, resting versus moving, or engaging in creative versus passive consumption activities. Such activity preferences serve as externalized behavioral markers of underlying pharmacodynamic states. It was observed that Quillaja- stabilized emulsions tend to shift activity inclination toward social engagement, external interaction, creativity, or active environments, whereas gum-acacia-stabilized emulsions tend to shift inclination toward rest, solitude, quiet settings, or introspective activities. The activitybased domain may be presented as single forced-choice items to reduce context bias and may incorporate temporal tracking to capture state changes over the duration of the psychoactive experience.Example 1

[0065] When delivering THC in an emulsion using the same amount of MCT as carrier oil, Quillaja saponin and gum acacia emulsifiers can bring different experiences to users. Quillaja saponin THC emulsion usually offers a cerebral, energized high that is more suitable to couple with outdoors, creative and social activities. Gum acacia THC emulsion usually offers a body, relaxing, calming high that is more suitable to couple with indoor, chilling and sleep-inducing activities.

[0066] In a PD study, fifty testers were given two different emulsion formulas in a blind fashion on two separate days. The two formulas contained lOmg THC, one made with gum acacia, one made with Quillaja. The Drug Effect Questionnaire (DEQ) was developed electronically and was asked repeatedly at time points of 5, 10, 15, 30, 45, 60, 90 and 120 mins. Questions include “how high you feel now”, “how energized you feel”, “how mentally stimulated you feel”, “how anxious you feel”, “how physically relaxed you feel”, “heaviness in the body you feel”, “how tired you feel”, “how much social vs being with yourself’, “how enjoyable youfeel” and “how much do you want more of it”? The scale is from 0-100 and testers can drag the button and offer answers with intuition. See FIG. 1.

[0067] FIG. 2 -11 show the average results from testers. “04.1” is the emulsion made with Quillaja and “05” is the emulsion made with gum acacia. The data show gum acacia THC emulsion generally makes users feel more physically relaxed, heaviness in the body and tired, which is more ideal for being with the self-environment. While Quillaja saponin THC emulsion generally makes people feel more energized, mentally stimulated and anxious, which is more ideal for social environments. Those specific effects are non-obvious just from the emulsifier physical difference, especially when both emulsions delivered a similar onset profile as the intensity of the high is relatively equal.

[0068] This result enables the design of specific experiences by delivering THC in different vehicles, especially in the beverage format using emulsions. It also shows how complex it can be when designing a particular experience for users.

[0069] In an additional blinded human evaluation involving twelve participants, a comparison was made betweenoral emulsions formulated with gum acacia against emulsions formulated with Quillaja saponins, each delivering the same THC dose and exhibiting matched droplet size and onset characteristics. Across participants, the O / / / 7 / a / a-stabilized emulsions consistently produced higher ratings in cognitive-clarity domains, including feelings of being more mentally quick-witted, attentive, playful, or socially inclined. Correspondingly, participants receiving the Quillaja emulsions showed a greater inclination toward outward-facing or mentally engaging activities, such as conversing, participating in group settings, or performing creative or expressive tasks. In contrast, the gum-acacia-stabilized emulsions produced higher ratings in somatic and relaxation-associated domains, including physical heaviness, calmness, sensual immersion, and stronger perceived overall intensity. Participants receiving gum-acacia formulations showed a greater preference for quiet, restorative, or sedentary activities, such as resting, listening, introspection, or remaining in a calm environment. These divergent psychoactive and behavioral profiles were observed despite comparable pharmacokinetic parameters, thereby further supporting that emulsifier identity alone can direct distinct and reproducible pharmacodynamic and activity-related outcomes in humans. It was unexpectedly found that emulsifiers are not inert; they shape the psychoactive effect even when dose and PK are matched. Quillaja produces more energizing, cerebral experiences, while gum acacia yields calmer, body-focused effects. These reproducible differences show that emulsifier choice alters cannabinoid distribution and neural engagement in ways not taught by existing literature.

[0070] It was further observed that the difference in psychoactive effect between / / / 7 / a / a-stabilized emulsions and gum-acacia-stabilized emulsions becomes more distinguishable at moderate to high THC doses. In certain embodiments, the divergence in reported psychoactive domains is detectable at doses of at least 10 mg THC, and may become increasingly apparent at higher doses such as 20 mg, 30 mg, 40 mg, 50 mg, 60mg, 70mg, 80mg, 90mg, lOOmg, 150mg, 200mg or up to 300 mg THC. At lower doses (e.g., below 5 mg THC), the psychoactive response may be less pronounced, making emulsifier-dependent differences more difficult to resolve in blinded testing.Example 2

[0071] When adjusting the oil phase within an emulsion that consists of THC and MCT, their ratio can play a role in the THC experience. When keeping everything else the same (i.e., emulsifier ratio, water ratio, droplet size and tested THC potency), the more MCT is in the THC emulsion, even with similar onset, which is mainly determined by the droplet size, the ramp to the peak is much faster and the peak effect is higher. It contributes to a much higher overall absorption of THC in the body. See FIG. 12.

[0072] This phenomenon is universal when applied with different emulsifiers and when those emulsions are infused into beverages, gummies or all other product form factors.Table 2Example 3

[0073] Using MCT or LCT in the active THC emulsion can also play a significant role in impacting the final THC effect. MCT and LCT can both help absorb THC in the small intestine, but LCT can potentially help THC bypass the liver. Each exact emulsion formula may deliver a specific ratio of THC / 11 -OH- THC, which may impact the final experience of the THC.

[0074] Previously, the rate of absorption and bypassing the liver from THC emulsions using LCT was unknown, making the prediction impossible. From this study, it was found that, when used at the same ratio, both LCT and MCT THC emulsions offer a similar onset and ramp. However, users report a more cerebral high from the LCT THC emulsion and a more body high from MCT THC emulsion. This can be used as a tool to design specific experiences.Example 4

[0075] Droplet size of the emulsion is directly connected to the onset time. Quillaja and gum acacia based THC emulsion were tested at different droplet size ranges to evaluate the average onset. A smaller droplet size can offer a quicker onset. It was further demonstrated that in a beverage format, in order to get an onset below 15 minutes, the average emulsion droplet size needs to be smaller than 1000 nm.Added MCT Boost Emulsion

[0076] Gum acacia and Quillaja based active THC emulsion were used as the control and a pharmacodynamic study was performed with 20mg THC in 2 oz of water. The overall onset, intensity and mood state was recorded as the baseline.

[0077] MCT boost emulsion was added separately into the 2 oz of water together with the 20mg THC, which was emulsified with MCT, water and Quillaja or gum acacia. The amount of MCT was studied at 125mg and 250mg, to evaluate the impact of MCT amount to the overall experience.

[0078] The experience was recorded, see Table 4 below. These results indicated that when MCT was emulsified with different emulsifiers and when combined with active emulsion, the combination of emulsifiers between active emulsion and blank boost emulsion plays a significant role. There are no “best” or “worst” experience in terms of the recreational THC effect because each specific effect can be tailored to a special activity that can enhance thatactivity. Cannabis beverage or edible brands can use the table as a guide to craft their target experiences. By adding MCT boost to the active THC emulsion, the experience differs from the original control. This can create significant product diversity and market potential.Table 4Example 6

[0079] A LCT boost emulsion was added into the MCT containing active THC emulsion. LCT boost would have a similar effect in terms of onset, ramp and intensity but it will deliver a more cerebral THC effect to the users.Example 7Combining Different Cannabinoids

[0080] Examples 1-6 discussed herein all use THC as the only cannabinoid input while changing only the composition of the emulsion. However, when adding other cannabinoids, the experience can be dramatically shifted. For example, CBD would make the THC experience more mellow, THCv would make the THC experience more focused, and CBN would make the THC experience more sedative, which can be used to induce sleep.

[0081] Determining which emulsion ratio to use in order to deliver certain cannabinoids can be difficult. For example, CBD / CBN tends to make users calm and relaxed, if it is delivered in a Quillaja emulsion with LCT, there can be a conflicting effect that could make the experience more heady. CBD / CBN can be best delivered in the gum acacia formula. Using similar logic, when delivering THC / THCv to a user, if a cerebral and energized high effect are the main target, then Quillaja and LCT can be the best consideration. This example seeks to determine the synergistic effect between cannabinoids type, target effect and the delivery composition.Example 8Table 5

[0082] Three oil-in-water THC emulsions were prepared with i entica carrier oil to THC ratios, differing only in the emulsifier employed. In each case, THC (1 g) was combined with medium-chain triglycerides (MCT, 3 g) as the oil phase. The aqueous phase contained eitherQuillaja saponin (Sample A, 0.5 g), gum acacia (Sample B, 4 g), or polysorbate 80 (Sample C, 3 g), with water added to balance total weight. Each mixture was homogenized by a single pass through a high-pressure homogenizer operating at -25,000 psi. Droplet size distributions are measured by laser diffraction, yielding comparable median diameters (D50 = 255-270 nm using laser diffraction or Dynamic Light Scattering) across all three emulsions.

[0083] In certain embodiments, the compositions comprise oil-in-water cannabinoid emulsions in which the oil phase contains THC dissolved in a triglyceride carrier (c.g, MCT and / or LCT), and the aqueous phase contains either Quillaja saponin or gum acacia as the primary emulsifier, wherein the relative amounts are selected from broad ranges that preserve pharmacokinetic equivalence while enabling pharmacodynamic modulation. For Quillaja systems, the weight ratio of emulsifier to total oil (surfactant-to-oil ratio, SOR) is from about 0.05: 1 to about 1.5: 1, preferably 0.10: 1 to 0.60: 1, and more preferably 0.15: 1 to 0.40: 1; Quillaja concentration in the finished beverage is typically about 0.02-3 wt%, preferably 0.05-1.0 wt%. For gum acacia systems, the SOR is from about 0.10: 1 to about 3.0: 1, preferably 0.25: 1 to 1.5:1, and more preferably 0.40: 1 to 1.0: 1; gum acacia concentration is about 0.5-15 wt%, preferably 1-8 wt%. Across both emulsifier types, the THC: carrier-oil weight ratio is from about 1 :2 to about 1 : 15, preferably 1 :3 to 1: 10; total oil (THC plus carrier) is about 0.05-6 wt%, preferably 0.1-3 wt% of the finished matrix; water constitutes the balance with optional co-solvents (e.g., ethanol, propylene glycol) below about 5 wt%. Emulsions are processed to a volume-weighted median droplet size (Dv50) of about 150-400 nm, preferably 180-320 nm, with span <2.0, while maintaining pH about 2.5-7.5 and ionic strength up to about 150 mM; in some embodiments the MCT:LCT ratio is tuned from 100:0 to 0: 100, preferably 80:20 to 20:80, without loss of the disclosed pharmacodynamic directionality. These ratio ranges are applicable to beverages and semi-solids (e.g., gummies after dilution), and encompass solids contents of about 2-20 wt% (beverages) or 70-85 °Brix (confections) while preserving the observed / / / 7 / a / a-leaning alertness profile and gumacacia-leaning calmness profile under otherwise equivalent dosing conditions. See FIG. 13.Example 9

[0084] A randomized, double-blind, crossover pharmacokinetic study was conducted in ten healthy adult participants. Following an overnight fast, subjects received a single oral dose of 10 mg THC formulated in one of the emulsions, with a minimum 7-day washout period between treatments. Venous blood samples are collected at 0, 15, 30, 60, 120, 180, 240, and 300 minutes post-dose. Plasma concentrations of THC and its primary psychoactive metabolite, 11-hydroxy-THC (11-OH-THC), were quantified using validated liquid chromatographytandem mass spectrometry (LC-MS / MS).

[0085] Plasma THC and 11-hydroxy-THC (11-OH-THC) concentration-time profiles were obtained from ten participants following oral administration of 10 mg THC formulated in Quillaja, gum acacia, or polysorbate 80 emulsions. All three emulsions exhibited comparable absorption and elimination patterns, with subtle but non-significant differences observed in peak amplitude and late-phase disposition.

[0086] For THC, mean plasma concentrations rose rapidly, reaching maximal levels between 2.7 and 3.2 ng / mL at 60 minutes post-dose. / / / 7 / a / a-based emulsions achieved the highest Cmax (3.2 ng / mL), gum acacia the lowest (2.7 ng / mL), and polysorbate 80 an intermediate profile (3.0 ng / mL). After 180 minutes, the polysorbate 80 curve slightly exceeded the Quillaja curve, illustrating a late-phase crossover. Despite these small differences, statistical testing confirmed equivalence of AUC0-300 and Cmax values within a ±20% margin.

[0087] For 11-OH-THC, all three emulsions exhibited delayed peaks at approximately 120 minutes, with maximal concentrations ranging from 1.42 to 1.50 ng / mL. The polysorbate 80 formulation yielded slightly higher values at peak and in the elimination tail, whereas gum acacia produced marginally lower values throughout. Quillaja occupied an intermediate position.

[0088] Importantly, the ratio of THC: 11-OH-THC was highly consistent across emulsions, averaging ~3.0 at 15 minutes and converging to ~1.1 by 300 minutes. No significant differences are detected at any time point (p > 0.30, paired analysis). This demonstrates that, although minor formulation-driven variations in PK exist, the overall systemic exposure to THC and 11-OH- THC — and their ratio over time — can be essentially equivalent across Quillaja, gum acacia, and polysorbate 80 emulsions.

[0089] These results establish that the three emulsions generate similar pharmacokinetic profiles, with only minor, non-clinically meaningful differences in magnitude or timing. Consequently, the distinct pharmacodynamic effects described below cannot be attributed to altered cannabinoid absorption or metabolism, but instead arise from the biological properties of the emulsifier itself.

[0090] Table 6 - Average blood PK exemplary data of 10 testers on THC and 11-OH-THC from3 emulsion types.

[0091] Contrary to expectation, despite nearly identical pharmacokinetic profiles and comparable onset (-30-33 min), peak intensity (-70-72 VAS units), and duration of action (-270 min), the three emulsions produced distinct subjective outcomes as measured by validated psychometric tools.

[0092] VAS on “How high do you feel” showed no significant difference, see FIG. 14

[0093] In some embodiments, the threshold is defined functionally as the lowest cannabinoid dose at which the difference in Bond and Lader alertness composite scores between Quillaja and gum acacia formulations was at least 10 visual analogue scale units with statistical significance of p<0.05. Thus, Quillaja emulsions yielded a reproducible increase in alertness, attentiveness, and sociability relative to gum acacia emulsions at doses at or above the defined threshold,while gum acacia emulsions yielded a reproducible increase in calmness, relaxation, and sedation at the same threshold, all under conditions in which pharmacokinetics remain equivalent.

[0094] In certain embodiments, the pharmacodynamic effect attributed to emulsifier identity exhibited a dose-dependent threshold. In a randomized blinded study using oral doses of 5 milligrams, 10 milligrams, and 20 milligrams of A9-tetrahydrocannabinol per serving with fifty participants per arm for pharmacodynamic assessments, it was observed that formulations prepared with Quillaja saponin produced significantly greater scores in domains of alertness, attentiveness, clear-headedness, energy, and cognitive proficiency compared to otherwise identical formulations prepared with gum acacia, but only at the 10 milligram and 20 milligram doses. Statistical analysis of Bond and Lader composite scores and item-level exemplary data demonstrated that the differences between Quillaja and gum acacia emulsions at 10 milligrams and 20 milligrams reached p<0.01 with effect sizes exceeding 0.7, while at 5 milligrams no statistically significant divergence between emulsifiers was detected in either alertness or calmness domains (p>0.10). Subjective intensity measures such as drug-liking and “how high” ratings are similar across emulsifiers at all three dose levels, indicating that the divergence related to the quality of the experience rather than the magnitude of intoxication.

[0095] Pharmacokinetic profiles were substantially equivalent across emulsifiers at each dose, with area-under-the-curve and Cmax values for both THC and 11-OH-THC falling within ±20 percent of each other and with THC: 11-OH-THC ratios remaining aligned over time. These results demonstrated that emulsifier identity can modulate pharmacodynamic outcomes only above a minimum effective dose threshold, which in certain studies corresponded to doses of at least 8-12 milligrams THC for an adult subject weighing 60-80 kilograms. Below this threshold, no reproducible effect of emulsifier identity is detected. The conclusion is Quillaja and gum acacia THC emulsion’s mood impact was only apparent when consumed THC is over lOmg.

[0096] Surprisingly, despite the three emulsions yielding essentially equivalent pharmacokinetic profiles for tetrahydrocannabinol (THC) and 11-hydroxy-THC, the Bond and Lader Visual Analogue Mood Scales demonstrated that the choice of emulsifier produced reproducible, directional, and statistically significant changes in pharmacodynamic outcomes across multiple domains, including vitality, mood, cognition, and connectedness. In formulations prepared with Quillaja saponin, test subjects consistently reported higher values in measures associated with alertness, energy, and cognitive clarity. Mean scores for items such as alertversus drowsy, energetic versus lethargic, clear-headed versus fuzzy, quick-witted versus mentally slow, and attentive versus dreamy were significantly shifted toward the alert, energetic, and cognitively sharp anchors, with average values between approximately 65 and 70 on a 0-100 scale. These participants also recorded elevated ratings in domains of friendliness and sociability, indicating that / / / 7 / a / a-based emulsions unexpectedly enhanced vigilance, mental acuity, and prosocial orientation, producing a psychoactive profile that is activating, cerebral, and suited for daytime or social use.

[0097] Table 7 - 50 people average exemplary data with 20mg THC on the delta of mood change against time 0 exemplary data from Bond & Lader questionnaire.

[0098] In contrast, formulations prepared with gum acacia produced the opposite effect. Subjects consuming gum acacia emulsions scored substantially higher on anchors associated with drowsiness, lethargy, dreaminess, and withdrawal, with mean values between approximately 70 and 85, while scoring lower in alertness, attentiveness, and clear-headedness, with average values between approximately 25 and 35. Gum acacia emulsions thereby produced a profile characterized by sedation, calmness, tranquility, and social withdrawal, consistent with a body-heavy, introspective, and sleep-promoting effect. Participants described increased relaxation and reduced cognitive sharpness, demonstrating that gum acacia is not an inert stabilizer but rather a determinant of pharmacodynamic outcomes in cannabinoid formulations.

[0099] By comparison, formulations prepared with polysorbate 80 produced no reproducible directional effect. Scores across all Bond and Lader domains clustered near neutral midpoints of 45-55 with larger standard deviations, reflecting an absence of systematic bias toward either arousing or calming poles. The polysorbate emulsions thus served as a control, establishing that not all emulsifiers affect psychoactive outcomes and underscoring the unexpected nature of the pharmacodynamic divergence observed with Quillaja and gum acacia.

[0100] These findings are unexpected in light of prior art, which treats emulsifiers solely as functional stabilizers without pharmacological consequence. The present results demonstrate that emulsifier identity can be used as a deliberate design lever to modulate pharmacodynamic profiles independently of pharmacokinetic exposure. Quillaja saponin, in particular, yields a formulation that enhances alertness, vigilance, attentiveness, quick-wittedness, clearheadedness, proficiency, friendliness, and sociability. Gum acacia yields a formulation that enhances calmness, tranquility, relaxation, dreaminess, fuzziness, lethargy, and social withdrawal. Polysorbate 80 yields a formulation that maintains neutrality without directional effect. The ability to direct cannabinoid pharmacodynamics toward stimulation and clarity or toward sedation and calmness through emulsifier selection alone is entirely non-obvious, andprovides a novel and powerful method for engineering predictable recreational and therapeutic outcomes in cannabis products.

[0101] These unexpected results enable the purposeful design of socially contextual cannabis products. / / / 7 / a / a-based THC emulsions are well suited for social, creative, and active scenarios where energy, focus, and mental clarity are valued. Examples include concerts, comedy shows, collaborative brainstorming sessions, outdoor festivals, hiking excursions, long-distance travel, dance parties, athletic training, gaming tournaments, and co-working environments. In such contexts, the ability of Quillaja to heighten alertness and sociability provides a clear advantage.

[0102] Conversely, gum acacia-based THC emulsions are more appropriate for relaxation and restorative use, where calmness and body heaviness are desired. Ideal settings include at-home movie nights, meditation retreats, yoga classes, spa treatments, sleep preparation, long-haul flights, quiet reading, intimate gatherings, recovery after exercise, and stress relief after work. The sedative tilt of gum acacia formulations makes them uniquely suited for winding down or deep relaxation.

[0103] The ability to steer user experience simply through emulsifier choice — without altering THC dose, onset, or duration — was entirely unexpected. Prior art considered emulsifiers inert stabilizers; this invention demonstrates they are active determinants of mood and experience, opening a new design space for both recreational and therapeutic cannabis products.

[0104] In additional embodiments of Example 1, the results are confirmed across variations in emulsion process parameters. The pharmacokinetic equivalence and pharmacodynamic divergence between Quillaja, gum acacia, and polysorbate emulsions are observed consistently when the volume-weighted median droplet diameter (Dv50) ranged from about 150 nm to about 400 nm, with distribution span less than 2.0, and across formulations adjusted to pH values between 2.5 and 7.5 and ionic strengths up to about 150 mM. The divergent pharmacodynamic profiles are also observed under both fasted and fed conditions, confirming that the effect of emulsifier identity is independent of gastric state.

[0105] In some embodiments, objective neurocognitive and impairment assessments are performed in addition to Bond and Lader and Drug Effect Questionnaire ratings. These included computerized simple reaction time and choice reaction time tasks, eye-hand coordination tests, and a temporal reproduction task. Consistent with the mood profiles, Quillaja emulsions produced improved scores on attention and coordination tasks, gum acacia emulsions produced reduced performance consistent with sedative effects, and polysorbate emulsions showed neutral or baseline performance. These findings establish that the subjective reportsof alertness versus calmness are corroborated by measurable functional outcomes in psychomotor performance.

[0106] In further embodiments, the pharmacodynamic divergence persisted across a range of tetrahydrocannabinol doses. When doses as low as 1 mg and as high as 50 mg are tested, the same directionality of effect is observed: Quillaja emulsions produced greater alertness and attentiveness, gum acacia emulsions produced greater calmness and sedation, and polysorbate emulsions remained neutral, provided the dose is at or above the functional threshold described herein.

[0107] In some embodiments, the emulsions additionally comprise co-actives that modulate absorption or metabolism, such as piperine, quercetin, curcumin, or other enzyme modulators, and the divergent pharmacodynamic effects of Quillaja and gum acacia are preserved under these conditions, confirming that emulsifier identity functions as an independent lever to modulate outcomes.

[0108] In still further embodiments, the invention is not limited to beverage emulsions but applies to multiple oral delivery formats. The same pharmacokinetic equivalence and pharmacodynamic divergence were observed when the emulsions were incorporated into gummies, capsules, softgels, oral thin films, powdered beverage mixes, and semi-solid confections, demonstrating that the principle of emulsifier-dependent pharmacodynamics is not dependent on product form.

[0109] Together, these additional embodiments establish that the effect of emulsifier identity on pharmacodynamic outcomes in tetrahydrocannabinol formulations is robust to changes in droplet size, pH, ionic strength, fed versus fasted state, dose level, co-active inclusion, and finished product form, thereby underscoring the generality and non-obviousness of the discovery.

[0110] In certain embodiments, it has been discovered that the divergent pharmacodynamic outcomes of / / / 7 / a / a-stabilized versus gum acacia-stabilized A9-tetrahydrocannabinol (THC) emulsions manifest in a dose-dependent manner. At THC doses below approximately 5 mg, no statistically significant differences are observed between emulsions, and all formulations produced comparable subjective ratings and pharmacokinetic profiles. At doses of about 10 mg and above, however, clear divergence emerged. Specifically, Quillaja emulsions produced statistically significant increases in measures of alertness, attentiveness, and coordination, while gum acacia emulsions produced statistically significant increases in calmness, relaxation, and sedation, each as compared to matched pharmacokinetic profiles. At doses of 10-15 mg, divergence is most robust, with Quillaja emulsions producing at least 20percentage point increases on Bond & Lader scales for “attentive over dreamy,” “clear-headed over muzzy,” “well-coordinated over clumsy,” “alert over drowsy,” and “energetic over lethargic,” relative to gum acacia emulsions. These differences persisted at doses up to at least 50 mg and are maintained across repeated administrations.[OHl] In further embodiments, the invention is not limited to absolute dose levels but may be defined functionally in terms of validated pharmacodynamic measures. For example, the divergence between Quillaja and gum acacia emulsions may be defined as the occurrence of at least a 15-20 percent improvement on Bond & Lader attentiveness or alertness scales, or a corresponding 15-20 percent increase in positive Drug Effect Questionnaire (DEQ) responses, when measured under conditions of pharmacokinetic equivalence, such that Cmax and Tmax values of THC and 11-OH-THC are aligned within ±20%.

[0112] In still further embodiments, the divergence is observed when emulsions are prepared under defined formulation conditions, including droplet size distributions between approximately 200 and 300 nm as measured by laser diffraction, THC: carrier oil ratios of approximately 1 :3, and pH between about 3.0 and 7.0. Under these conditions, Quillaja emulsions consistently produced an “uplifting” pharmacodynamic profile, whereas gum acacia emulsions produced a “chilling and relaxing” pharmacodynamic profile, with polysorbate emulsions producing neutral or baseline effects.

[0113] In certain embodiments, the invention encompasses the use of Quillaja emulsions for enhancing daytime or social functioning, including productivity, focus, creativity, and energy in contexts such as work, study, or recreational group activities, while gum acacia emulsions may be selected for evening or calming uses, including relaxation, stress reduction, and sleep preparation. The ability to “dial” pharmacodynamic outcomes by emulsifier identity and ratio, while maintaining pharmacokinetic equivalence, represents a novel method for tailoring cannabinoid experiences.

[0114] In some embodiments, claims may be defined by exclusion of conditions in which the divergence does not occur, such as doses below 5 mg THC, emulsions with droplet sizes outside 150-400 nm, or emulsions in which Cmax or Tmax values diverge by more than 20% between emulsifiers.

[0115] In further embodiments, the invention is not limited to any specific emulsifier ratios per se, but rather to the functional discovery that Quillaja emulsions produce a stimulatory / alertness profile while gum acacia emulsions produce a calming / sedation profile, under conditions of matched pharmacokinetics. Accordingly, claims may be formulated in functional terms, for example: “A method of enhancing alertness in a human subject, comprising administering aA9-tetrahydrocannabinol emulsion stabilized with Quillaja saponin, wherein said emulsion produces at least a 15% increase in attentiveness over dreamy relative to a gum acacia- stabilized comparator at the same THC dose and pharmacokinetic profile,” or conversely, “A method of inducing relaxation in a human subject, comprising administering a A9- tetrahydrocannabinol emulsion stabilized with gum acacia, wherein said emulsion produces at least a 15% increase in calmness and sedation relative to a / / / 7 / a / a-stabilized comparator.”

[0116] In certain embodiments, the divergence between / / / 7 / a / a-stabilized and gum acacia- stabilized A9-tetrahydrocannabinol (THC) emulsions is further characterized across a wide dose range, including microdoses, standard use doses, and high doses up to at least 300 mg THC per administration.

[0117] At doses below about 5 mg, no statistically significant pharmacodynamic differences are observed between emulsions, and subjective and objective measures remained comparable to baseline and to each other. At doses of about 10 mg, divergence emerged, with Quillaja emulsions producing measurable increases in alertness, attentiveness, and energy, while gum acacia emulsions produced increased calmness and relaxation, each as compared to pharmacokinetically matched controls.

[0118] At doses of about 20-30 mg, the divergence intensified, with Quillaja emulsions producing at least 20-25 percentage point improvements in Bond & Lader scores for attentiveness, alertness, and coordination relative to gum acacia emulsions, while gum acacia emulsions produced at least 20-25 percentage point increases in calmness, sedation, and relaxation relative to Quillaja emulsions.

[0119] At doses of about 40-60 mg, the divergence remained statistically significant, with Quillaja emulsions producing at least 25-30 percentage point improvements on measures of attentiveness and energy, and gum acacia emulsions producing at least 25-30 percentage point improvements in calmness and sedation, relative to each other.

[0120] At doses of about 75-100 mg, divergence persisted but individual variability increased. Quillaja emulsions at these levels produced sustained increases in clear-headedness and alertness in a majority of subjects, whereas gum acacia emulsions continued to produce strong sedative effects.

[0121] At doses of about 150 mg, the divergence is still present but with diminishing margins, such that group mean differences narrowed to approximately 10-15 percentage points on Bond & Lader scales.

[0122] At very high doses of about 200-300 mg, divergence is not consistently observed, and bothQuillaja and gum acacia emulsions produced overlapping pharmacodynamic profilesdominated by intoxication, sedation, and impairment, with no reproducible differentiation between emulsifiers.

[0123] Accordingly, in certain embodiments, the divergence in pharmacodynamic outcomes between Quillaja and gum acacia emulsions is most pronounced at THC doses between about 10 and about 100 mg, is reproducible up to at least 150 mg, and diminishes at doses above about 200 mg. In some embodiments, the functional window of divergence is defined compositionally by the use of Quillaja versus gum acacia as emulsifiers, and functionally by the dose range of 10-150 mg THC, wherein Quillaja emulsions produce at least a 15-30 percentage point improvement in attentiveness or alertness, and gum acacia emulsions produce at least a 15- 30 percentage point improvement in calmness or sedation, each relative to the other under conditions of pharmacokinetic equivalence.

[0124] In further embodiments, claims may be drafted to encompass administration of THC at doses of about 10-20 mg, 20-40 mg, 40-60 mg, 75-100 mg, or 100-150 mg, wherein the divergent pharmacodynamic outcomes disclosed herein are observed, while explicitly excluding doses below about 5 mg or above about 200 mg in which such divergence is not consistently observed.

[0125] In certain embodiments, the emulsifier type itself is shown to impart distinct and reproducible pharmacodynamic profiles under otherwise matched conditions of THC dose, droplet size, and carrier oil. Nanoemulsions are prepared as described herein with A9-tetrahydrocannabinol (THC) 10 mg, carrier oil comprising medium-chain triglycerides, and emulsifiers consisting of either Quillaja saponin or gum acacia. Droplet sizes are maintained between 240-280 nm with narrow distributions. Fifty healthy adult participants are enrolled in a double-blind, crossover design. Pharmacokinetics are matched across arms, with THC and 11 -OH- THC AUC and Cmax values falling within ±10% between the two emulsifier types, thereby ensuring that any differences in subjective pharmacodynamics could not be attributed to differential systemic exposure.

[0126] Bond & Lader visual analogue scales and Drug Effects Questionnaire (DEQ) results demonstrated a clear divergence. Emulsions stabilized with Quillaja saponin reproducibly increased alertness, attentiveness, and clear-headedness, with participants reporting significantly higher scores on “attentive vs dreamy,” “clear-headed vs muzzy,” “energetic vs lethargic,” and “well-coordinated vs clumsy.” These profiles corresponded to an uplifting, stimulating, and focus-enhancing experience.

[0127] By contrast, emulsions stabilized with gum acacia yielded a pharmacodynamic profile that is more relaxing, sedative, and body-oriented. Participants reported significantly higher scoreson “calm vs excited,” “drowsy vs alert,” “dreamy vs attentive,” and “contented vs discontented.” DEQ ratings reflected greater “relaxation” and “body heaviness,” consistent with a soothing, restful pharmacological effect. Importantly, these differences are not explained by differences in pharmacokinetics, as both emulsifiers yielded comparable THC and metabolite concentrations, but are instead attributable to the emulsifier identity.

[0128] Accordingly, in some embodiments, the invention is defined such that emulsions prepared with Quillaja saponin preferentially elicit an alert, uplifting, and energizing pharmacodynamic profile, while emulsions prepared with gum acacia preferentially elicit a calming, sedative, and body-relaxing pharmacodynamic profile, under otherwise identical dosing conditions. In further embodiments, gum acacia may be selected when the desired consumer or patient experience is relaxation, sedation, sleep facilitation, or reduction of agitation, while Quillaja may be selected when the desired experience is mental clarity, sociability, or activity engagement.

[0129] In certain embodiments, subjective pharmacodynamic (PD) outcomes are assessed using validated visual-analogue and semantic-differential instruments derived from the Bond & Lader Mood Rating Scale and the Drug Effects Questionnaire, supplemented with additional custom items designed to capture social connectedness, bodily awareness, and affective tone characteristic of cannabinoid responses.

[0130] Participants (n = 50) completed ratings at baseline and serially over 300 minutes post-dose following administration of / / / 7 / a / a-stabilized and gum-acacia-stabilized THC nanoemulsions (10 mg THC each; equivalent PK exposure). The scales used included conventional Bond & Lader bipolar pairs — such as alert-drowsy, clear-headed-muzzy, well- coordinated-clumsy, energetic-lethargic, contented-discontented — together with customized items developed to evaluate social and somatic experiential domains as shown in Table 8.Table 8 Exemplary Customized Effects Questionnaire

[0131] Each item is rated on a continuous 100-mm visual-analogue line anchored by the bipolar adjectives. Mean peak scores and area-under-effect-curve (AUEC0-300) values are computed for each dimension and compared between emulsifier types.

[0132] Surprisingly, the / / / 7 / a / a-stabilized emulsions produced significantly higher scores (p < 0.05) toward Empathetic, Inspired, Sensual, Active, Optimistic, and Playful poles, corresponding to enhanced social connectedness, body energy, and positive affect. Conversely, gum-acacia emulsions produced higher scores toward Indifferent, Satiated, Sedated, and Serious poles, consistent with a calmer, introspective, and physically relaxed state. The Hungry-Satiated pair further differentiated formulations, with Quillaja increasing appetite drive (+18 mm VAS) and gum acacia maintaining satiety (-12 mm VAS), despite equivalent plasma THC and 11- OH-THC exposure.

[0133] These findings demonstrate that even under matched pharmacokinetic conditions, emulsifier identity alone can direct subjective experience along distinct multidimensional axes, including social engagement (Empathetic / Inspired / Sensual), somatic activation (Active / Hungry), and mood valence (Optimistic / Playful). Accordingly, in some embodiments, the invention encompasses cannabinoid emulsions configured to modulate connectedness, bodily activation, or mood polarity as measured by the foregoing scales, wherein the Quillaja- stabilized emulsions elicit statistically greater positive-valence and engagement scores relative to gum-acacia-stabilized counterparts.

[0134] In certain embodiments, the pharmacodynamic differentiation between / / / 7 / a / a-stabilized and gum-acacia-stabilized cannabinoid emulsions can be further characterized throughfunctional experience domains representative of consumer or patient use scenarios. These domains correspond to specific affective, cognitive, and physiological patterns reproducibly measured using the expanded Bond & Lader and DEQ-derived scales described herein.

[0135] The invention therefore encompasses cannabinoid emulsions formulated and selected to preferentially elicit one or more of the following experiential categories, each defined by characteristic emotional and behavioral descriptors: Social Activation (PARTY-TRICK type):

[0136] A Ow / G / a-stabilized emulsion configured to promote heightened social connectedness, verbal fluency, energy, playfulness, optimism, and empathic engagement under conditions of matched cannabinoid exposure. Users report increased alertness, laughter, and sociability, suitable for activities involving group interaction or celebratory environments.Shared Immersion (BONFIRE type):

[0137] A Ow / G / a-stabilized emulsion producing sustained engagement, curiosity, affection, and creative insight during social or intimate settings such as meals, dating, or collaborative discussions. The formulation enhances attentiveness and warmth while maintaining cognitive clarity.Focused Immersion (ZONE-IN type):

[0138] A Ow / G / a-stabilized emulsion configured for activities requiring creative focus, sensory enhancement, and flow-like absorption, such as concerts, art, or media consumption. The profile is characterized by increased clear-headedness, altered sensory vividness, and productive introspection without sedation.Restorative Relaxation (RELIEF type):

[0139] A gum-acacia-stabilized emulsion designed to induce calmness, comfort, physical ease, and pleasant relaxation following stress or exertion. Users experience contentment, mellow affect, and soothing bodily sensations with minimal cognitive impairment, supporting leisure and self-care contexts.Evening Transition (UNWIND type):

[0140] A gum-acacia-stabilized emulsion formulated to assist transition into rest by promoting tranquility, physical stillness, and reduced mental stimulation. The resulting state includes mild sedation and lowered arousal while maintaining emotional stability, facilitating pre-sleep routines.Sleep Induction (NIGHT-CAP type):

[0141] A gum-acacia-stabilized emulsion configured to support sleep initiation and maintenance, producing somnolence, muscle relaxation, and attenuated sensory responsiveness. Usersreport tiredness, ease of sleep onset, and absence of anxiety or restlessness within approximately 60-120 minutes post-dose.

[0142] Accordingly, / / / 7 / a / a-stabilized emulsions are characterized by energizing, socially and cognitively activating pharmacodynamic effects-aligning with the PARTY-TRICK, BONFIRE, and ZONE-IN domains-while gum-acacia-stabilized emulsions produce relaxing, restorative, and sedative effects corresponding to the RELIEF, IJNWIND, and NIGHT-CAP domains. These contrasts persist even under equivalent pharmacokinetic parameters (THC AUC and Cmax within ± 15 % of matched comparators), confirming that emulsifier identity functions as an independent determinant of experiential directionality.

[0143] In some embodiments, each domain can be quantified by composite PD indices derived from specific item clusters (e.g., Empathetic-Indifferent, Active- Sedated, Optimistic-Pessimistic, Playful-Serious), wherein Quillaja formulations yield statistically higher positive-valence and activation scores (p < 0.05) and gum-acacia formulations yield higher relaxation and tranquility scores (p < 0.05).

[0144] Accordingly, the invention encompasses cannabinoid emulsions tailored to distinct behavioral and experiential use-cases, wherein emulsifier selection and formulation ratio provide predictable modulation of mood, energy, and connectedness profiles independent of pharmacokinetic exposure.

[0145] In certain embodiments, the emulsions described herein are not limited to Neutral cannabinoids such as A9-tetrahydrocannabinol (A9- THC), AMetrahydrocannabinol (A8-THC), Alo-tetrahydrocannabinol, A6a, lOa-tetrahydrocannabinol, A7-tetrahydrocannabinol, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabicyclol (CBL), cannabitriol (CBT), cannabielsoin (CBE), cannabinodiol (CBND), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabigerovarin (CBGV), cannabichromevarin (CBCV), and cannabielsoin varin (CBEV). Acidic precursors such as A9-tetrahydrocannabinolic acid A (THCA-A), A9- tetrahydrocannabinolic acid B (THCA-B), A8-tetrahydrocannabinolic acid, A10- tetrahydrocannabinolic acid, cannabidiolic acid (CBDa), cannabigerolic acid (CBGa), cannabichromenic acid (CBCa), cannabinolic acid (CBNa), cannabicyclolic acid (CBLa), cannabitriolic acid (CBTa), cannabielsoic acid (CBEa), cannabinodiolic acid (CBNDa), tetrahydrocannabivarinic acid (THCVa), cannabidivarinic acid (CBDVa), cannabigerovarinic acid (CBGVa), cannabichromevarinic acid (CBCVa). Hydrogenated cannabinoids such as Hexahydrocannabinol (HHC), hydrogenated cannabidiol (H4-CBD), hydrogenated cannabigerol (H4-CBG), hydrogenated cannabinol (H4-CBN), hexahydrocannabivarin(HHC-V), hydrogenated cannabidiol varin (H4-CBDV), hydrogenated cannabigerovarin (H4- CBGV). Oxidized / hydroxylated cannabinoids such as 11-hydroxy-THC (11-OH-THC), 8- hydroxy-THC, 11-hydroxy-CBD, 7-hydroxy-CBD, 11-hydroxy-CBG, 8-hydroxy-CBN, 11- oxo-CBN, 9-hydroxy-HHC, 10-hydroxy-HHC, dihydroxy-THC isomers, cannabinolquinone. Degradation products such as Cannabinodiol (CBND), cannabichromanon (CBCN), cannabifuran (CBF), cannabicoumaronone, cannabiripsol. Varin class cannabinoids such as A9-THCV, A8-THCV, CBDV, CBGV, CBCV, CBLV, CBNDV, CBTv, CBEv, CBV, tetrahydrocannabiorcol (THCC), tetrahydrocannabutol (THCB), tetrahydrocannabihexol (THCH). Propyl, butyl, pentyl, and hexyl homologues such as THCP (tetrahydrocannabiphorol), CBDP (cannabidiphorol), CBGP (cannabigerophorol), CBCP (cannabichromephorol), CBNP, THCB (tetrahydrocannabutol), CBD-B, CBGB, CBCB, THCH (tetrahydrocannabihexol), CBDH, CBGH, CBCH. Rare cannabinoids such as Cannabiorcol (CBO), cannabiripsol (CBR), cannabicitran (CBT), cannabifuran (CBF), cannabimovone (CBM), cannabiripsin, cannabioxepane, cannabiglendol. And Synthetic and semi-synthetic analogs such as Dronabinol, nabilone, HU-210, HU-211, CP-55,940, WIN- 55,212-2, JWH series cannabinoids, and pharmaceutically acceptable salts, esters, ethers, and prodrugs thereof.

[0146] In certain embodiments, the emulsions may further comprise one or more terpenes or terpenoids, including but not limited to myrcene, P-caryophyllene, a-humulene, limonene, a- pinene, P-pinene, linalool, terpinolene, geraniol, nerol, borneol, isopulegol, eucalyptol (1,8- cineole), camphene, sabinene, ocimene, valencene, famesene, bisabolol, guaiol, cedrol, phytol, terpineol, perillyl alcohol, carvone, pulegone, citronellol, menthol, thymol, carvacrol, P-elemene, and P-selinene. In some embodiments, mixtures of these terpenoids, such as naturally occurring terpene fractions derived from cannabis or other botanical sources, are incorporated into the emulsions together with cannabinoids.

[0147] In certain embodiments, the dose of the active cannabinoid is not limited to 50 milligrams but may be selected from a broad continuum to accommodate different product formats, subject populations, and target effects while preserving the disclosed pharmacokinetic equivalence between emulsifier systems. In some embodiments, a single-serving oral dose comprises from about 0.5 mg to about 300 mg of cannabinoid per serving, more typically from about 2 mg to about 200 mg, and in particular implementations from about 5 mg to about 100 mg. In weight- normalized terms, the dose may be from about 0.02 mg / kg to about 5.0 mg / kg, more typically from about 0.05 mg / kg to about 2.0 mg / kg, and in some embodiments from about 0.1 mg / kg to about 1.0 mg / kg, calculated on total body weight. The dose may be delivered as a beverage(for example, from about 0.5 mg / 100 mL to about 100 mg / 100 mL), as a confection or chew (for example, from about 1 mg / unit to about 50 mg / unit), as a capsule or softgel (for example, from about 5 mg to about 100 mg per unit), or as a tincture (for example, from about 1 mg / mL to about 50 mg / mL), with the Quillajadotal-o ratio maintained within the disclosed ranges to achieve the pharmacodynamic outcomes.

[0148] In some embodiments, the dose is administered as a single acute serving; in other embodiments, the daily dose is divided into two to four administrations separated by at least 2 hours to control peak concentration while preserving the Quillaja-dependent potentiation. The total daily dose may therefore range from about 0.5 mg / day to about 600 mg / day, more typically about 5 mg / day to about 200 mg / day, with cumulative exposure (AUC) remaining within the ±20 percent equivalence margin across emulsifiers. In multi-day regimens, the compositions may be administered once daily for 1-14 days, or once daily for 2-8 weeks in chronic use studies, with steady-state exposure remaining equivalent between Quillaja and gum acacia comparators under otherwise identical conditions.

[0149] The foregoing ranges apply to cannabidiol as well as to other cannabinoids described herein. For A9-tetrahydrocannabinol and other higher-potency intoxicating cannabinoids, lower absolute ranges may be employed in some embodiments, for example about 0.25 mg to about 20 mg per serving, more typically about 1 mg to about 10 mg per serving, or about 0.01-0.3 mg / kg, while maintaining the same Quillajadotal-o ratio window to modulate pharmacodynamic outcomes independent of pharmacokinetics. For minor or less potent cannabinoids such as cannabigerol or cannabinol, higher absolute ranges may be used, for example about 5 mg to about 200 mg per serving, without departing from the principles disclosed herein.

[0150] The formulations are incorporated into multiple product formats including beverages, gummies, capsules, tablets, softgels, oral films, and powdered beverage mixes. The ratiodependent potentiation of effects is observed across all formats, demonstrating that the effect is not dependent on finished product form.

[0151] In some embodiments, co-actives that modulate metabolism such as piperine, quercetin, and curcumin are included. The ratio-dependent potentiation by Quillaja remained intact under these conditions, confirming that the effect is not attributable to minor differences in metabolic rate but is a direct consequence of emulsifier identity and level.Example 10Adjusting MCT / THC ratio to tune PK

[0152] THC (1.00 g) is dissolved in MCT oil at the masses indicated below and dispersed as an oil- in-water nanoemulsion with Quillaja saponin (QS) in purified water. Oil phase: THC + MCT only; no LCT is used in this example. Aqueous phase contained QS at the amounts shown, adjusted to pH 6.0 ± 0.2 with citrate buffer. Emulsification is performed by high-pressure homogenization (single pass, 25,000 psi) followed by 5 min recirculation at 10,000 psi to tighten the distribution. Median droplet diameter (D50) is measured by laser diffraction and is reported for each sample; span is 1.6-1.9 for all. Compositions. All emulsions are assayed by LC-MS / MS to confirm identical THC content per mL and negligible free THC crystallinity before use.Table 9

[0153] In certain embodiments, A9-tetrahydrocannabinol (THC) nanoemulsions are prepared with a constant emulsifier system (Quillaja saponin) and matched droplet sizes, while varying the ratio of medium-chain triglycerides (MCT) to THC over more than a 40-fold range. The objective is to determine whether a finite MCT:THC window exists in which the Absorption Potential Index (API) exceeds the Non- Absorbed Fraction at 120 minutes (NAF120), indicating superior pre-ab sorptive solubilization and epithelial flux; and, conversely, whether API falls below NAF120 outside that window. All experiments are conducted underpharmacotechnical controls such that emulsifier identity, processing conditions, and median droplet size remained substantially constant across samples.

[0154] A pH-stat lipolysis model is employed to simulate intestinal digestion (FaSSIF; 37 °C; bile salts 15 mM, lecithin 3.75 mM; pancreatic lipase 2000 U / mL with colipase; CaCL 5 mM) at pH 6.5 with automated NaOH titration. At 5, 10, 20, 30, 60, 90, and 120 min, aliquots are withdrawn and ultracentrifuged (40,000 g, 40 min, 37 °C) to separate mixed-micelle + vesicle (supernatant) from oil + precipitate (pellet). THC in each phase is quantified by LC-MS / MS.

[0155] For two-stage coupling, the clarified supernatant from each timepoint is immediately applied to the apical side of Caco-2 monolayers (day 21 post-seeding; TEER > 500 (1 cm2; HBSS buffer; 37 °C). Apparent permeability Papp(t) is determined from basolateral appearance over 20 min per fraction (sink maintained with 3% BSA). The Absorption Potential Index (A) is defined as the time-integrated product of micellar availability and permeability: A = API = Jo120fmic(t) • Papp(t) dt where is the fraction (0-100%) of dose present in mixed- micelles / vesicles at time ttt. API is normalized to an arbitrary unit scale for presentation (mean of windowed samples ~ 85 a.u.).

[0156] The Non-Absorbed Fraction at 120 min (B = NAF120) is defined as: B = NAF120= % THC in (oil + precipitate) at 120 mins

[0157] Caco-2 integrity (Lucifer yellow rejection), medium osmolality, and bile salt carry-over are controlled and did not differ materially among samples. Each condition n = 6 independent runs; results summarized as means with SD; ANOVA with Tukey correction, a = 0.05.

[0158] Under otherwise matched emulsifier and particle-size conditions, the measured API exhibits a pronounced inverted-U dependence on MCT:THC ratio, while NAF120 exhibits a complementary U-shape. The observed values (means) were:Table 10

[0159] Across replicates, the window within which API exceeded NAF 120 is bounded by MCT:THC ratios from about 1.5 to about 8.0 (Samples E-I), with peak API observed at ratios 4-6 (Samples G-H). Outside this window — z.e., at ratios < 1.5 (Samples A-D) or > 8.0 (Samples J-K) — the inequality reversed and API fell below NAF 120, indicating inferior solubilization / flux at both extremes. Differences between “window” and “non-window” sets are statistically significant for both API (p < 0.001) and NAF120 (p < 0.001). Median droplet sizes (240-269 nm) showed no correlation with API or NAF 120 (|r| < 0.15), confirming that effects are composition-driven rather than particle-size artifacts.

[0160] The exemplary data demonstrate that MCT is not a linear “more is better” lever. At low MCT:THC, insufficient lipid digestion and mixed-micelle formation leaves THC in oil / precipitate (high NAF120, low API). At intermediate MCT:THC (~ 1.5-8), lipolysis efficiently generates absorbable colloids with favorable viscosity / partitioning, maximizing the API while minimizing NAF 120. At very high MCT:THC (> 8), increasing lipid load and phase behavior (e.g., coalescence, viscosity, core-solubilization) decrease epithelial flux and increase re-precipitation, raising NAF 120 and lowering API. This non-monotonic pattern is unexpected relative to prevailing assumptions that more lipid monotonically increases oral absorption.

[0161] Accordingly, in some embodiments, the invention provides a functional absorption window for / / / 7 / a / a-stabilized THC nanoemulsions, defined compositionally as an MCT:THC ratio between about 1.5 and about 8.0, and defined functionally as the set of ratios at which: API > NAF120 (p < 0.05 vs. ratios outside the window). See FIG. 15.

[0162] In further embodiments, ratios below about 1.5 or above about 8.0 are explicitly excluded, as they fail the criterion (API < NAF 120) and therefore do not meet the performance standard for pre-ab sorptive solubilization / flux.

[0163] The API>NAF120 inequality within 1.5-8 is preserved under: (i) FaSSIF vs FeSSIF media; (ii) bile salt ±20% concentration; (iii) lipase activity ±20%; (iv) pH 6.0-6.8; (v) droplet D50 spanning 230-290 nm; and (vi) Quillaja levels 0.13-1.30 g as listed, with identical THC dose and total solids. Caco-2 monolayer TEER remained >500 (1 cm2before and after exposure; no cytotoxicity is observed at test dilutions.

[0164] Example 2 showed that MCT oil can potentially increase the absorption of cannabinoids such as THC but the ratio of MCT: THC plays an important role. When this ratio is below 1.5, the API < NFA120, which indicates less cannabinoids would be absorbed, indicating an inefficient PK profile. When this ratio is between 1.5 to 8, API > NFA120, indicating MCT could offer more assistance to help with PK and absorption. What is surprising to find out is this relationship is not linear, when MCT / THC ratio is above 8, API becomes lower than NFA120 again, indicating there could be some competing or over-saturating factors during the uptake. This unexpected result may guide future product development to optimize cannabinoids PK profile.Example 11

[0165] In certain embodiments, the effect of medium-chain triglyceride (MCT) configuration on cannabinoid pharmacokinetics is evaluated. The purpose of this example is to determine whether delivering the same absolute amounts of A9-tetrahydrocannabinol (THC) and MCT in two different configurations, while holding emulsifier identity, droplet size, and total doses constant, would produce divergent pharmacokinetic outcomes. The underlying hypothesis is that when MCT oil is supplied as a separate emulsion co-administered with a THC emulsion, the pharmacokinetic profile of THC is enhanced relative to a comparator in which the same total MCT dose is embedded in the same droplets with THC.Table 11

[0166] All emulsions in this study are prepared with Quillaja saponin as the sole emulsifier using high-pressure homogenization at 25,000 psi. The aqueous phase is adjusted to pH 6.0 ± 0.2. Droplet size is confirmed by laser diffraction to be within 240 to 270 nm with span less than 2.0 for all samples. The compositions used included the following: Sample C, containing 1 gTHC, 1 g MCT, 0.2 g Quillaja, and 5 g water, produced a potency of 138.9 mg THC per gram and 138.9 mg MCT per gram with droplet size 269 nm. Sample F, containing 1 g THC, 2 g MCT, 0.3 g Quillaja, and 5 g water, produced a potency of 120.5 mg THC per gram and 241.0 mg MCT per gram with droplet size 250 nm. Sample G, containing 1 g THC, 4 g MCT, 0.5 g Quillaja, and 7 g water, produced a potency of 80.0 mg THC per gram and 320.0 mg MCT per gram with droplet size 256 nm. Sample H, containing 1 g THC, 6 g MCT, 0.7 g Quillaja, and 9 g water, produced a potency of 59.9 mg THC per gram and 359.3 mg MCT per gram with droplet size 264 nm. Sample X contained no THC, 2 g MCT, 0.2 g Quillaja, and 5 g water, producing a potency of 0 mg THC per gram and 277.8 mg MCT per gram with droplet size 251 nm. All emulsions had density approximated as 1 g per mL.

[0167] Three experimental pairs are constructed such that each pair delivered 100 mg THC and the same total amount of MCT, with the only difference being whether the MCT is embedded with the THC in the same emulsion (Configuration A) or supplied partly as a separate MCT emulsion co-administered with the THC emulsion (Configuration B). In Pair 1, the total MCT load is 200 mg. In Configuration A, 0.83 mL of Sample F is administered, providing 100 mg THC and 200 mg MCT. In Configuration B, 0.72 mL of Sample C is co-administered with 0.36 mL of Sample X, yielding 100 mg THC and a total of 200 mg MCT, with 100 mg of the MCT embedded with THC and 100 mg supplied as a separate emulsion. In Pair 2, the total MCT load is 400 mg. In Configuration A, 1.25 mL of Sample G is administered, providing 100 mg THC and 400 mg MCT. In Configuration B, 0.72 mL of Sample C is co-administered with 1.08 mL of Sample X, yielding 100 mg THC and a total of 400 mg MCT, with 100 mg embedded and 300 mg separate. In Pair 3, the total MCT load is 600 mg. In Configuration A, 1.67 mL of Sample H is administered, providing 100 mg THC and 600 mg MCT. In Configuration B, 0.83 mL of Sample F is co-administered with 1.44 mL of Sample X, yielding 100 mg THC and a total of 600 mg MCT, with 200 mg embedded and 400 mg separate.Table 12Obtaining the same THC / MCT amount by different configurations where MCT is introduced either from the active emulsion or active emulsion + a separate MCT emulsion, both under Quillaja.

[0168] By construction, each pair provided the same dose of THC and the same total dose of MCT, while maintaining Quillaja as the emulsifier and droplet size within a narrow range. The only difference is whether MCT is fully embedded with THC or partly provided as a separate MCT emulsion. This experimental structure enables direct attribution of any pharmacokinetic divergence to the configuration of MCT rather than to dose, emulsifier identity, or particle size.

[0169] Early Portal Exposure Advantage (EPEA). In certain embodiments, the effect of MCT configuration on early portal delivery of A9-tetrahydrocannabinol (THC) is quantified in a controlled animal model. Male Sprague-Dawley rats (250-320 g) are fasted overnight, instrumented under isoflurane with indwelling jugular venous catheters for systemic sampling and a temporary portal venous catheter for 0-60 minute sampling, and recovered to consciousness before dosing. A crossover design is employed with a seven-day washout; each subject received both configurations for its assigned pair in random order. Oral dosing is by gavage at 10 mL / kg. All emulsions are stabilized with Quillaja saponin, are prepared by high- pressure homogenization (25,000 psi single pass with a 10,000 psi polish), and exhibits median droplet diameters between 240 and 270 nm with distribution span below 2.0. Dose solutions are matched for THC concentration per mL, Quillaja percentage, osmolality, and total caloric load. For each of the three compositional pairs described above (Pair 1 = 100 mg THC with 200 mg total MCT; Pair 2 = 100 mg THC with 400 mg total MCT; Pair 3 = 100 mg THC with 600 mg total MCT), two configurations are compared at identical THC and total MCT masses: Configuration A, in which all MCT is embedded within the THC emulsion droplets; and Configuration B, in which the THC emulsion is co-administered together with a separate MCT-only emulsion such that the combined MCT mass equaled that of Configuration A. Co-administration occurred within five minutes, with the THC emulsion delivered first; a timing-control arm confirmed that staggering the MCT emulsion by more than sixty minutes abrogated the effect.

[0170] Portal blood is sampled at -5, 10, 20, 30, 45, and 60 minutes relative to the THC dose; systemic blood is sampled to 360 minutes for full pharmacokinetics. Plasma is stabilized with antioxidant and esterase inhibitors and stored at -80 °C. THC and 11-hydroxy-THC are quantified by validated LC-MS / MS (lower limit of quantitation < 0.1 ng / mL; accuracy within ±10%; precision CV < 10%). For each animal, the early portal exposure is computed as thetrapezoidal AUCo-eo(THC) in portal plasma. The Early Portal Exposure Advantage (EPEA) is defined for each pair as the ratio EPEA = AUCo-eo(B) / AUCo-eo(A). Because THC doses and total MCT doses are identical within each pair, the ratio isolates configuration as the operative variable. Results are analyzed with a mixed-effects model appropriate for 2^2 crossover (sequence, period, treatment as fixed effects; subject as random); log-AUC is analyzed and back-transformed to obtain geometric mean ratios and 90% confidence intervals; multiplicity-adjusted two-sided p-values are reported with a = 0.05.

[0171] Across n = 6 animals per configuration per pair, Configuration B reproducibly increased early portal THC exposure relative to Configuration A. For Pair 1 (200 mg MCT), the mean AUCo- eo is 950 ± 180 ng min / mL for Configuration A and 1,350 ± 210 ng min / mL for Configuration B, corresponding to an EPEA of 1.42 with a 90% confidence interval of 1.20-1.66 (p = 0.006). For Pair 2 (400 mg MCT), the mean AUCo-eo is 900 ± 170 ng min / mL for Configuration A and 1,300 ± 200 ng min / mL for Configuration B, yielding an EPEA of 1.44 (90% CI 1.23- 1.68; p = 0.004). For Pair 3 (600 mg MCT), the mean AUCo-eo is 820 ± 160 ng min / mL for Configuration A and 1,150 ± 190 ng min / mL for Configuration B, yielding an EPEA of 1.40 (90% CI 1.18-1.63; p = 0.008). Normalizing AUCo-eo to dose (ng min mL^ mg"1) produced the same directionality and magnitude; therefore, the effect is independent of absolute THC mass within the tested range. The advantage is preserved under fed conditions (standard chow provided thirty minutes prior to dosing), with geometric mean EPEA values of 1.31-1.36 across the three pairs and all comparisons remaining statistically significant.Table 13Crossover rats; portal sampling 0-60 min; n=6 / arm / pair; Quillaja and droplet sizes matched; same THC (100 mg human-equivalent) and same total MCT per pair.

[0172] The observed divergence in early portal exposure is mechanistically consistent with two findings measured in companion in-vitro digestion experiments: first, when MCT is administered as a separate emulsion, the time to reach 50% mixed-micelle association (tso,mic) during pH-stat lipolysis is reduced by approximately thirty-five to forty percent relative to the embedded configuration; second, the mixed-micelle fraction derived from theseparate MCT stream accelerates solubilization and apical-to-basolateral flux of THC released from the THC emulsion, thereby increasing the amount of THC that appears in the portal circulation during the first hour. Because total MCT mass, emulsifier identity, droplet size distribution, and THC dose are controlled and matched, the increase in AUCo-eo can be attributed to configuration of the same lipid mass rather than to more lipid, smaller particles, or higher drug load.

[0173] In some embodiments, the invention is defined functionally by the Early Portal Exposure Advantage. Under otherwise matched conditions of dose, emulsifier, particle size, and prandial state, co-administration of a separate O / / / 7 / a / a-stabilized MCT emulsion together with a O / / / 7 / a / a-stabilized THC emulsion produces an early portal exposure ratio EPEA > 1.30, equivalently an increase in AUCo-eo(THC) of at least thirty percent relative to an embedded-MCT comparator. In certain embodiments, the lower bound of the 90% confidence interval for EPEA is at least 1.20. In further embodiments, the EPEA threshold is met for total MCT loads between about 200 mg and about 600 mg at a THC dose of about 100 mg (or the human-equivalent thereof), persists in both fasted and fed states, and is observed when coadministration occurs within five minutes; in still further embodiments, delaying the separate MCT emulsion by more than sixty minutes removes the advantage, thereby defining a temporal window for achieving the effect. In additional embodiments, EPEA is accompanied by a reduction in time to 50% micellarization such that tso,mic(B) < 0.65 x tso,mic(A), and by a reduction in systemic Tmax and an increase in systemic Cmax, each in the expected direction but not required for the definition of the anchor.

[0174] Accordingly, the EPEA anchor provides an objective, quantitative basis to claim that configuration — not merely quantity — of MCT determines the rate and extent of early portal delivery of THC. The discovery that a separate MCT emulsion confers a reproducible >30% increase in portal AUC over the first hour at identical THC and MCT doses is unexpected in view of prior teachings that emphasize lipid quantity alone, and it enables method claims that specify the configuration, timing, and magnitude thresholds described herein.

[0175] Lipolysis Acceleration Index (LAI). In certain embodiments, the effect of MCT configuration on the kinetics of intestinal lipid digestion and mixed-micelle formation is quantified using a pH-stat in-vitro lipolysis model coupled with phase separation and quantitative analysis of cannabinoid partitioning. The objective of this assay is to determine whether, at identical total doses of THC and MCT and under matched emulsifier and droplet-size conditions, coadministration of a separate MCT emulsion together with a THC emulsion (Configuration B) accelerates the appearance of THC in absorbable colloidal phases relative to a comparator inwhich all MCT is embedded in the same droplets as THC (Configuration A). The primary kinetic endpoint is the time to 50% mixed-micelle association (tso,mic). The Lipolysis Acceleration Index (LAI) is defined for each compositional pair as the ratio LAI = tso,mic(B) / tso,mic(A); values less than unity indicate acceleration in Configuration B. A prespecified functional criterion of tso,mic(B) < 0.65 x tso,mic(A) is adopted as the threshold for a configuration-dependent kinetic advantage.

[0176] Formulations are identical to those described for the Early Portal Exposure Advantage (EPEA) study. Briefly, nanoemulsions are stabilized with Quillaja saponin and prepared by high-pressure homogenization to median droplet diameters between 240 and 270 nm (span < 2.0), with THC and total MCT doses matched within each pair (Pair 1 : 100 mg THC with 200 mg total MCT; Pair 2: 100 mg THC with 400 mg total MCT; Pair 3: 100 mg THC with 600 mg total MCT). Configuration A contained the entire MCT dose embedded within the THC emulsion. Configuration B consisted of a THC emulsion containing only the MCT required to solubilize THC, co-administered with a separate MCT-only emulsion such that the combined MCT mass equaled that of Configuration A. For Configuration B, the two emulsions are mixed with simulated intestinal media immediately prior to lipolysis initiation to emulate co-dosing.

[0177] Lipolysis is conducted at 37 °C in FaSSIF (sodium taurocholate 15 mM; lecithin 3.75 mM) at pH 6.5 under pH-stat titration with 0.2 N NaOH to maintain constant pH while pancreatic lipase (2000 U / mL) and colipase are added along with CaCL (5 mM). At predetermined timepoints (5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes), aliquots are withdrawn and immediately subjected to temperature-controlled ultracentrifugation (40,000 g, 40 minutes, 37 °C) to resolve an upper oil phase and precipitate (pellet) from a clear supernatant comprising mixed micelles and vesicles. THC concentrations in each phase are quantified by LC-MS / MS, and the fraction in mixed micelles as a function of time, fmic(t), is computed as the percentage of dose detected in the supernatant relative to total recovered THC. The tso,miC for each replicate is obtained by fitting fmic(t) to a standard sigmoidal or Weibull model with goodness-of-fit criteria pre-specified (R2> 0.95; residual structure inspected). Each condition is run with n = 6 independent vessels; assay controls verified constant bile salt / lecithin concentrations and absence of lipase inhibition by formulation excipients; recovery of THC across phases exceeded 95% in all runs.Table 14

[0178] t5o,miC (min) time to reach 50 / o of dose m mixed micelles during pH-stat lipolysis (FaSSIF, 37 °C; bile / lecithin; lipase+colipase). Same formulations; n=6 independent runs / arm; supernatant quantified by LC-MS / MS.

[0179] Across the three compositional pairs, co-administration of a separate MCT emulsion produced a reproducible acceleration of mixed-micelle appearance relative to the embedded-MCT comparator. For Pair 1 (200 mg MCT total), Configuration A exhibits a mean tso,miC of 24.5 ± 3.1 min, whereas Configuration B exhibits 15.8 ± 2.4 min, yielding LAI = 0.65 and a 36% reduction in tso,miC (two-sided p = 0.002). For Pair 2 (400 mg MCT total), Configuration A yielded 28.0 ± 3.5 min and Configuration B 17.5 ± 2.6 min, LAI = 0.63, corresponding to a 38% acceleration (p = 0.001). For Pair 3 (600 mg MCT total), Configuration A yielded 31.5 ± 4.0 min and Configuration B 19.0 ± 2.8 min, LAI = 0.60, corresponding to a 40% acceleration (p = 0.001). The acceleration effect is preserved when the assay is repeated in FeSSIF to model fed-state conditions; absolute times increased modestly as expected, but LAI values remained between 0.60 and 0.68 with all comparisons statistically significant. Sensitivity analyses varying bile salt concentration by ±20%, lipase activity by ±20%, and initial droplet diameter within 230-290 nm did not materially alter the direction or magnitude of LAI; no correlation is observed between small shifts in D50 and tso,miC (|r| < 0.2).

[0180] Mechanistically, the observed acceleration is consistent with immediate digestion of the MCT-only emulsion in Configuration B, rapidly generating mixed micelles enriched in medium-chain fatty acids that accept THC as it is released from the THC emulsion droplets, thereby reducing the time required to achieve 50% micellar association. In contrast, when the entire MCT load is embedded with THC (Configuration A), interfacial crowding and coresolubilization phenomena increase local viscosity and delay interfacial lipase access, producing slower release of THC into the micellar phase and a longer tso,miC. Because total MCT mass, emulsifier identity, particle size distribution, and THC dose are matched, the acceleration can be attributed to configuration of the same lipid mass rather than to dose escalation or particle-size artifacts.

[0181] In some embodiments, the invention is defined functionally by the Lipolysis Acceleration Index under the stated in-vitro conditions. Under otherwise matched dose, emulsifier, particle size, and media conditions, co-administration of a separate O / / / 7 / a / a-stabilized MCT emulsion together with a O / / / 7 / a / a-stabilized THC emulsion produces tso,mic(B) < 0.65 x tso,mic(A), equivalently an acceleration in mixed-micelle formation of at least 35% relative to an embedded-MCT comparator. In certain embodiments, the upper bound of the 90% confidence interval for LAI does not exceed 0.80, thereby ensuring that the acceleration is both statistically and practically significant. In further embodiments, the LAI criterion is met across total MCT loads of about 200 mg to about 600 mg at a THC dose of about 100 mg (or humanequivalent thereof), persists in both fasted and fed simulated intestinal media, and is achieved when co-administration of the separate MCT emulsion occurs within five minutes of the THC emulsion; in still further embodiments, pre-mixing the two emulsions into a single bottle prior to lipolysis, or staggering the MCT emulsion by more than sixty minutes, abolishes the acceleration and yields LAI values approaching unity, thereby defining a temporal and configurational window for the effect.

[0182] Accordingly, the LAI anchor provides an objective and quantitative kinetic basis for claiming that configuration — not merely quantity — of MCT governs the rate of formation of absorbable colloidal carriers for THC during intestinal digestion. Together with the Early Portal Exposure Advantage, the LAI establishes that separating MCT into its own emulsion confers a reproducible and material improvement in pre-ab sorptive processes that translate into earlier portal appearance and, in related in-vivo studies, faster systemic onset.

[0183] In certain embodiments, the distribution of MCT between the cannabinoid emulsion and the separate MCT emulsion is varied across a wide range. In some embodiments, the cannabinoid emulsion contains less than about 10% of the total MCT dose, with the balance of 90% or more supplied as the separate MCT emulsion. In some embodiments, the cannabinoid emulsion contains less than about 20% of the total MCT dose, with the balance of 80% or more supplied as the separate MCT emulsion. In some embodiments, the cannabinoid emulsion contains less than about 30% of the total MCT dose, with the balance of 70% or more supplied as the separate MCT emulsion. In some embodiments, the cannabinoid emulsion contains less than about 40% of the total MCT dose, with the balance of 60% or more supplied as the separate MCT emulsion. In certain embodiments, the cannabinoid emulsion contains from about 10% to about 40% of the total MCT dose, with the balance of about 60% to about 90% supplied as the separate MCT emulsion. In additional embodiments,the cannabinoid emulsion contains from about 5% to about 50% of the total MCT dose, with the balance of about 50% to about 95% supplied as the separate MCT emulsion.

[0184] In further embodiments, the cannabinoid emulsion may contain a majority of the MCT, such as from about 50% to about 90% of the total MCT dose, with the remainder of about 10% to about 50% supplied as the separate MCT emulsion. In some embodiments, the cannabinoid emulsion contains at least about 60%, 70%, 80%, or 90% of the total MCT dose, with the balance of about 40%, 30%, 20%, or 10% respectively provided by the separate emulsion. In still further embodiments, the cannabinoid emulsion contains essentially all of the MCT (100%) and the separate emulsion contributes essentially none, which configuration corresponds to the embedded comparator. Conversely, in other embodiments, the cannabinoid emulsion contains essentially none of the MCT (0%), and the separate MCT emulsion contributes substantially all of the MCT dose, which configuration represents the extreme of complete separation.

[0185] Accordingly, in some embodiments, the cannabinoid emulsion may contain less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of the total MCT dose, with the balance correspondingly supplied by the separate MCT emulsion. The effect described herein of improved early portal exposure and accelerated lipolysis is observed across these ranges, and is particularly robust when the cannabinoid emulsion contains from about 10% to about 40% of the total MCT and the separate emulsion contains from about 60% to about 90% of the total MCT.

[0186] In certain embodiments, the separate MCT emulsion is formulated at a potency of from about 15% to about 45% MCT by weight of the total emulsion. In some embodiments, the separate MCT emulsion contains at least about 15%, 20%, 25%, 30%, 35%, 40%, or 45% MCT by weight. In some embodiments, the separate MCT emulsion contains between about 15% and about 25% MCT by weight, between about 20% and about 30% MCT by weight, between about 25% and about 35% MCT by weight, between about 30% and about 40% MCT by weight, or between about 35% and about 45% MCT by weight. In certain embodiments, the separate MCT emulsion contains about 15%, 20%, 25%, 30%, 35%, 40%, or 45% MCT by weight. In further embodiments, the separate MCT emulsion contains less than about 20% MCT by weight, less than about 25% MCT by weight, less than about 30% MCT by weight, less than about 35% MCT by weight, less than about 40% MCT by weight, or less than about 45% MCT by weight. In still further embodiments, the separate MCT emulsion contains more than about 15%, more than about 20%, more than about 25%, more than about 30%, more than about 35%, more than about 40%, or more than about 45% MCT by weight.

[0187] Accordingly, in some embodiments the separate MCT emulsion is defined as having an MCT potency of about 15-45% by weight, with useful sub-ranges including 15-25%, 20-30%, 25- 35%, 30-40%, and 35-45%. This range provides emulsions that are fluid, physically stable, and deliverable by oral dosing, while ensuring sufficient lipid load to accelerate lipolysis and enhance portal exposure of THC and other cannabinoids when co-administered with the cannabinoid emulsion.

[0188] In certain embodiments, the separate MCT emulsion can be prepared with any suitable emulsifier, including but not limited to Quillaja saponin, gum acacia, polysorbates, lecithins, saponins of other botanical origin, whey proteins, modified starches, or combinations thereof. The invention is not limited to a single emulsifier class, provided that the emulsifier is present at a level sufficient to stabilize the MCT droplets and yield a physically stable emulsion suitable for oral delivery.

[0189] In some embodiments, the ratio of emulsifier to MCT, expressed as weight of emulsifier relative to weight of MCT oil, is maintained within certain ranges. In some embodiments, the emulsifier-to-MCT ratio is from about 0.06 to about 0.35 (w / w). In certain embodiments, the ratio is at least about 0.06, 0.08, 0.10, 0.12, 0.15, 0.20, 0.25, 0.30, or 0.35. In further embodiments, the ratio is less than about 0.35, less than about 0.30, less than about 0.25, less than about 0.20, less than about 0.15, less than about 0.12, less than about 0.10, or less than about 0.08.

[0190] In other embodiments, the emulsifier-to-MCT ratio is from about 0.35 to about 4.0 (w / w). In certain embodiments, the ratio is at least about 0.35, 0.40, 0.50, 0.75, 1.0, 1.5, 2.0, 3.0, or 4.0. In further embodiments, the ratio is less than about 4.0, less than about 3.0, less than about 2.0, less than about 1.5, less than about 1.0, or less than about 0.75.

[0001] Accordingly, in some embodiments, the emulsifier-to-MCT ratio may be selected from the ranges of about 0.06-0.35, 0.35-1.0, 1.0-2.0, 2.0-3.0, or 3.0-4.0. In further embodiments, the ratio may be explicitly set at about 0.06, 0.08, 0.10, 0.12, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, 0.50, 0.75, 1.0, 1.5, 2.0, 3.0, or 4.0. In still further embodiments, the emulsifier-to-MCT ratio may be defined as less than about 0.35 or greater than about 0.35, thereby encompassing both the low-emulsifier regime and the high-emulsifier regime.Example 12

[0191] In certain embodiments, the pharmacokinetics of A9-tetrahydrocannabinol (THC) are examined in human volunteers following oral administration of nanoemulsions formulated exclusively with medium-chain triglycerides (MCT) or exclusively with long-chain triglycerides (LCT) as the lipid carrier. Both emulsions are stabilized with Quillaja saponin,prepared under identical high-pressure homogenization conditions, and exhibit median droplet diameters of approximately 240-270 nm with narrow distributions. THC content and dosing are equivalent across both arms (10 mg), with Quillaja concentration, osmolality, and excipient profiles matched.Table 15

[0192] The resulting pharmacokinetic outcomes demonstrated that pure MCT and pure LCT systems yield markedly different profiles despite equivalent THC dose and droplet size. In the MCT condition, plasma THC exhibits a faster onset and earlier peak, with mean Tmax at approximately 55 minutes and Cmax of 2.9 ng / mL. By contrast, in the LCT condition, plasma THC rose more slowly, with Tmax delayed to approximately 115 minutes, but ultimately achieved a higher Cmax of 4.3 ng / mL, corresponding to a -48% increase in peak concentration relative to the MCT comparator. Similarly, the overall exposure as measured by AUCo-sh is increased by approximately 40-50% in the LCT condition relative to MCT. See FIG. 16 and FIG. 17.

[0193] The profile of the primary active metabolite 11-hydroxy-THC (11-OH-THC) is inverted relative to THC. In the MCT arm, 11-OH-THC concentrations rose to a mean Cmax of 2.3 ng / mL with Tmax near 85 minutes. In the LCT arm, metabolite formation is markedly suppressed, with Cmax limited to -0.6 ng / mL and overall AUC reduced by approximately 70% relative to the MCT condition. Thus, while MCT promoted earlier portal delivery and consequently higher first-pass metabolism to 11-OH-THC, LCT promoted lymphatic routing and reduced hepatic metabolism, thereby yielding higher systemic THC concentrations and markedly lower metabolite concentrations.

[0194] The THC: 11-OH-THC AUC ratio illustrates this shift clearly: under pure MCT conditions the ratio is approximately 1.2, whereas under pure LCT conditions the ratio increased to approximately 3.0, representing a 2.5-fold difference at matched THC dose. This change inparent-to-metabolite ratio is particularly significant because THC and 11-OH-THC are believed to contribute differently to the overall pharmacodynamic profile. The exemplary data therefore establish that the identity of the triglyceride carrier — MCT versus LCT — fundamentally alters not only the extent and timing of THC exposure but also the balance between THC and its active metabolite, producing divergent pharmacokinetic and pharmacodynamic outcomes despite otherwise identical formulations.

[0195] In certain embodiments, subjective pharmacodynamic (PD) responses are evaluated in parallel with pharmacokinetic sampling for the MCT-dominant and LCT-dominant emulsions described above. Fifty healthy adult participants (n = 25 per arm in a crossover design) ingested 10 mg THC formulated either with pure MCT (Sample A) or pure LCT (Sample B). PD assessments are performed every 20-30 minutes for five hours using a visual analogue “Drug Effects Questionnaire” (DEQ) and Bond & Lader visual analogue mood scales.

[0196] The PD exemplary data reflected the distinct PK signatures of the two formulations. Sample A (MCT-dominant). Participants reported a faster onset of effects, with a median subjective onset time of approximately 30 minutes, corresponding to the early rise in plasma THC. Maximum subjective intensity is reached at ~70 minutes and corresponded to the peak in 11 - OH- THC. Bond & Lader factor analysis indicated higher scores on the Calmness and Contentedness dimensions, with significant increases in item pairs such as “drowsy vs alert,” “dreamy vs attentive,” and “lethargic vs energetic.” DEQ ratings for “feel drug” and “like drug” rose quickly and peaked early, but also declined more rapidly. Participants often described the experience as heavier, sedative, and body-centered, consistent with the higher proportion of 11 -OH- THC exposure. So MCT dominant THC emulsion tends to offer a quick onset, quick offset and deeper sedative effect coming from 11-OH-THC.

[0197] Sample B (LCT-dominant). Participants reported a slower onset of effects, with a median onset near 50 minutes. Subjective peak intensity is achieved later (-110-120 minutes) but is rated as more sustained, in line with the higher and prolonged THC concentrations. Bond & Lader factors shifted toward Alertness and Vitality, with higher scores for “attentive vs dreamy,” “clear-headed vs muzzy,” “energetic vs lethargic,” and “well-coordinated vs clumsy.” DEQ ratings for “feel drug” rose more gradually but plateaued higher and lasted longer, with significant elevations still present at 4-5 hours. Participants described the experience as clearer, more cerebral, and more energizing, consistent with the THC-dominant PK profile and reduced formation of 11-OH-THC. LCT dominant THC emulsion tends to offer a slower onset, longer duration but cerebral or heady high due to the less concentration of 11-OH-THC.Table 16

[0198] In certain embodiments, oral nanoemulsions containing A9-tetrahydrocannabinol (THC) are prepared with Quillaja saponin under identical high-pressure homogenization conditions (single pass, 25,000 psi). The triglyceride phase is systematically varied as a binary mixture of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) across eleven compositions (0, 10, 20 up to 100% LCT). All formulations are matched for THC dose (10 mg), excipient profile, aqueous osmolality, and median droplet diameter (D50 240-270 nm, span <2.0). Healthy adult participants received a single dose in a randomized crossover with >7-day washouts. Plasma THC and 11-hydroxy-THC (11 -OH- THC) are quantified by LC- MS / MS to 5 h post-dose. The primary prespecified endpoint is the exposure ratio AUCo- sh(THC) / AUCo-sh(l 1-OH-THC); supporting endpoints included Cmax for each analyte andthe THC Dominance Index (TDI) defined as AUCo-sh(THC) / [AUCo-sh(THC)+AUCo- 5h( 11-OH-THC)].

[0199] Under these matched conditions, the relationship between %LCT and the THC: 11-OH-THC balance is non-linear and threshold-dependent, rather than a simple monotonic slider. When LCT constituted <20% of total triglycerides ( / .< ., >80% MCT), the parent-to-metabolite balance is essentially indistinguishable from the pure-MCT reference. Specifically, at 0-20% LCT the exposure ratio remained <1.52 (pure MCT 1.21; 20% LCT 1.52) and 11-OH-THC exposure persisted near the MCT level (AUCo-sh 6.2-7.0 ng h / mL). Thus, small LCT admixtures did not measurably alter first-pass metabolism.

[0200] A switch-like change emerged once LCT reached the 20-75% range. In this window the 11- OH-THC pathway is drastically suppressed while parent THC exposure rose. Representative values are: 50% LCT yielded AUCo-5h(THC) 12.0 ng h / mL and AUCo-5h( 11-OH-THC) 3.0 ng h / mL, producing an exposure ratio of 4.00 and TDI 0.80; 60% and 70% LCT further increased the ratio to 4.36 and 4.77 (AUCo-sh(l 1-OH-THC) 2.8 and 2.6 ng h / mL, respectively). Compared to the pure-MCT condition (ratio 1.21), the parent-to-metabolite ratio increased 3-4* in this mid-LCT window, establishing a THC-dominant systemic profile.

[0201] At >80% LCT an unexpected rebound in 11 -OH- THC exposure is observed: 80% LCT gave AUCo-sh(l l-OH-THC) 4.6 ng h / mL with a reduced exposure ratio of 2.63; 90% LCT rose further to 5.9 ng h / mL with ratio 1.86, approaching the MCT-like balance despite high LCT content. At 100% LCT, the system returned to the characteristic LCT profile described elsewhere — high parent THC exposure with suppressed metabolite (AUCo-sh 12.5 vs 4.2 ng h / mL, ratio 2.98).

[0202] This exemplary dataset establishes three surprising features that are not predicted by prior teachings that “more LCT increases absorption.” First, the no-effect zone: <20% LCT produces essentially the same metabolite burden as pure MCT (exposure ratio <1.52; 11-OH- THC AUC within -10-15% of MCT). Second, a threshold window (20-75% LCT) in which 11-OH-THC exposure is suppressed by approximately 50-60% while THC exposure increases, driving the exposure ratio to >2.5 and commonly >4.0 under otherwise matched dose, emulsifier, and droplet size. Third, a non-monotonic rebound at >80% LCT in which metabolite exposure climbs back toward MCT levels, followed by re-emergence of the LCT- dominant profile at 100% LCT. The net effect is a switch-plus-plateau behavior of the THC: 11-OH-THC ratio with respect to %LCT, rather than a linear progression.

[0203] Accordingly, in some embodiments the invention is defined functionally such that, under the stated manufacturing and dosing conditions, (i) when LCT is 20-75% of total triglyceridesthe AUCo-5h(THC):AUCo-sh(l 1-OH-THC) ratio is at least 2.5 (illustratively 4.00-4.77) with AUCo-sh(l 1-OH-THC) reduced by >50% relative to MCT >80%; (ii) when LCT is <20%, the ratio is <1.5 and 11-OH-THC exposure remains within the MCT reference band; and (iii) when LCT is >80%, the ratio declines toward <2.7 with partial restoration of 11-OH-THC exposure, while at 100% LCT the ratio is approximately 3.0 with low 11-OH-THC Cmax (~0.6 ng / mL). These inequalities demonstrate that composition, not droplet size or dose, controls the parent-to-metabolite balance, and that the LCT effect exhibits a threshold and non-monotonicity that a skilled formulator would not anticipate.

[0204] In certain embodiments, the compositions described herein exhibit non-linear and nonmonotonic functional relationships between formulation variables (such as emulsifier type, emulsifier-to-oil ratio, and lipid chain-length composition) and measurable pharmacokinetic or pharmacodynamic outcomes. Contrary to conventional understanding that bioavailability or performance scales linearly with surfactant concentration or lipid chain length. Thresholds, inflection points, and reversals have been discovered that define distinct functional domains of performance. These behaviors are surprising and not predictable from the prior art.

[0205] When the emulsifier-to-oil ratio (w / w) is systematically varied, performance does not increase linearly. In certain embodiments at low ratios (<0.05), emulsions are physically unstable and show poor cannabinoid absorption (AUCo-sh(THC) < 6 ng h / mL). In some embodiments at moderate ratios (0.06-0.35), bioavailability improves dramatically (AUCo-sh(THC) > 10-12 ng h / mL, droplet D50 - 200 nm). However, when the ratio is increased beyond 0.35-4.0, the AUC and Cmax decrease again (by 20-40%), despite smaller droplet sizes and higher apparent emulsifier content. This “bell-shaped” response demonstrates that excessive emulsifier content can hinder absorption — an unexpected phenomenon that contradicts the assumption that more surfactant uniformly enhances solubilization and uptake.

[0206] Likewise, varying the proportion of long-chain triglyceride (LCT) to medium-chain triglyceride (MCT) yields a non-monotonic pharmacokinetic pattern. In some examples below 20% LCT, the parent-to-metabolite ratio (THC : 11-OH-THC) remains similar to MCT control (~ 1.2). In other examples between 20-75 % LCT, 11-OH-THC formation is suppressed by > 50 %, and the ratio increases sharply to > 4.0, defining an optimal window for lymphatic uptake and reduced hepatic conversion. In further examples above 75 % LCT, the effect reverses: 11-OH-THC exposure rises again (AUCo-sh - 4-6 ng h / mL), and overall absorption plateaus or declines due to delayed lipolysis and impaired gastric emptying. Such reversal behavior, seen as an inverted-U curve, is not anticipated by conventional lipid absorption models, which predict monotonic increases with chain length.

[0207] A further unexpected observation is that the described LCT window is selective for unsaturated Cl 8 species (Cl 8 : 1, Cl 8 : 2). Substitution with saturated C16 : 0 triglycerides eliminates the ratio shift and returns the profile to MCT-like behavior. This demonstrates that unsaturation and chain length jointly define functionality, not chain length alone. The skilled formulator would not predict that changing two carbons or adding a double bond could reverse the metabolic routing of cannabinoids.

[0208] Thermal stability testing revealed another non-monotonic outcome. When stored at ambient temperature (25 °C), emulsions remained stable for > 12 months with constant droplet size and predictable PK. When stored at 40 °C, modest droplet growth (< 10 %) is observed and PK remained stable. However, at 60 °C, droplet growth accelerated (> 25 %) and bioavailability decreased disproportionately (AUCo-sh reduced by > 40 %), despite droplet diameters remaining below 400 nm. This decoupling between droplet size and absorption efficiency is unexpected, suggesting that thermally induced interfacial reorganization, rather than droplet size per se, governs performance.

[0209] In mixed systems containing both Quillaja saponin and gum acacia, it was observed that certain blend ratios (e.g., 70:30 Quillaja. gum) produced enhanced bioavailability (AUC $ 25 %) and balanced pharmacodynamic effects — combining the alertness of Quillaja with the calmness of gum. Yet other ratios (e.g., 90: 10 or 10:90) yielded lower performance or unstable emulsions. This demonstrates non-additive, composition-specific synergy between natural emulsifiers, a behavior not predicted by standard colloid theory.

[0210] A further surprising result is that these inflection behaviors persist across doses from 5 mg to 4000 mg total cannabinoids. Typically, enzymatic saturation or dose linearity would alter such relationships; the persistence of the same optimal windows across low and high doses indicates an intrinsic physicochemical rather than purely pharmacological origin.

[0211] Another unexpected finding is that within the optimal compositional windows (emulsifier: oil = 0.06-0.35; LCT = 40-75 %), inter-subject coefficient of variation (CV%) for AUC and Cmax decreases by > 25-40 % relative to either MCT-dominant or LCT-dominant controls. This variability suppression is unanticipated, as heterogeneity in human digestion typically increases with lipid complexity.

[0212] In certain embodiments, subjective pharmacodynamic (PD) effects are assessed in parallel with pharmacokinetic sampling using a randomized, double-blind, crossover design with healthy adult participants. Each subject received a 10 mg oral THC nanoemulsion prepared as described herein with Quillaja saponin and D50 240-270 nm. The triglyceride phase is varied to yield LCT fractions of 0, 10, 20, 40, 60, 80, 90, and 100% (balance MCT). PD isevaluated at baseline and every 20-30 minutes for five hours using (i) a 100-mm visual analogue Drug Effects Questionnaire (DEQ) for “overall enjoyment,” “feel drug,” “like drug,” and “take again,” and (ii) Bond & Lader visual analogue subscales aggregated into prospectively defined composites: Heady / Clear (attentive, clear-headed, quick-witted, proficient), Social / Outgoing (friendly, social), and Active / Energetic (alert, energetic, well- coordinated). For each measure, the prespecified summary is peak change from baseline (Apeak) and time-weighted average over 0-3 h (TWAAo-sh). Mixed-effects models for crossover are employed with treatment, period, and sequence as fixed effects and subject as random; multiplicity is controlled by Holm adjustment. A clinically meaningful difference is defined a priori as >10 mm on a 100-mm VAS sustained for >30 minutes or a TWAA difference >6 mm h.

[0213] Under otherwise matched conditions of dose, emulsifier identity, and particle size, formulations containing 20-80% LCT produced a reproducible and statistically significant enhancement on four prospectively defined endpoints — overall enjoyment, Heady / Clear, Social / Outgoing, and Active / Energetic — relative to MCT-dominant comparators (<10% LCT) and to >90% LCT. Illustratively, within the 20-80% LCT window, DEQ overall enjoyment Apeak increased by +12 to +18 mm (least-squares mean difference vs MCT baseline +12.8 mm; 95% CI +8.1 to +17.5; p<0.001) and TWAAo-sh increased by +7.4 mm h (95% CI +4.2 to +10.6; pO.OOl). The Heady / Clear composite Apeak increased by +10 to +16 mm with a corresponding Active / Energetic Apeak increase of +9 to +14 mm; both remained elevated through 3 h with TWAAo-sh differences of +6-9 mm h (all adjusted p<0.01). The Social / Outgoing Apeak increased by +8 to +13 mm (adjusted p<0.01) with an associated responder rate (>10-mm improvement) of 62-71% in the 20-80% LCT arms versus 28-34% under MCT-dominant control (risk ratio 2.1-2.3).

[0214] The effect exhibits threshold and non-monotonic behavior consistent with the pharmacokinetic switching observed for the THC: 11-OH-THC balance. When LCT is <10- 20%, PD scores did not differ from the pure-MCT condition (all Apeak and TWAA differences <5 mm; p>0.10). When LCT is 20-80%, PD enhancements met both statistical and clinical significance criteria across the four endpoints and correlated with a parentdominant PK profile defined by AUCo-sh(THC): AUCo-sh(l 1-OH-THC) > 2.5. When LCT is >90%, PD advantages attenuated despite persistent THC exposure, with overall enjoyment and Active / Energetic returning toward MCT-like values (Apeak difference <5 mm; p>0.10), consistent with the observed rebound in 11 -OH- THC and delayed onset.

[0215] In some embodiments, the invention is defined functionally such that, under the stated manufacturing and dosing conditions, formulations comprising 20-80% LCT produce (i) DEQ overall enjoyment Apeak > +10 mm and TWAAo-sh > +6 mm h relative to an MCT- dominant comparator, (ii) Heady / Clear composite Apeak > +8 mm and Active / Energetic Apeak > +8 mm, and (iii) a Social / Outgoing responder rate >60% with an absolute increase of >25 percentage points versus MCT-dominant control; and that the foregoing PD improvements co-occur with a parent-to-metabolite exposure ratio > 2.5. In further embodiments, PD improvements are not observed when LCT <20% or when LCT >90%, thereby defining a 20-80% LCT targeting range for products intended to yield a clearer, more social, and more active recreational profile without increasing dose.

[0216] In certain embodiments, the invention relates to the discovery that not all long-chain triglycerides are equivalent in their effect on cannabinoid pharmacokinetics. LCTs are a heterogeneous class of triglycerides composed of fatty acyl chains of sixteen carbons or more, often including saturated, monounsaturated, and polyunsaturated moieties (for example, C16:0 palmitic acid; C18:0 stearic acid; C18:l oleic acid; C18:2 linoleic acid; C20:4 arachidonic acid, among others).

[0217] Surprisingly, it is observed that only certain subclasses of LCTs confer the lymphatic bypass and parent-dominant profile described herein. Specifically, emulsions prepared with triglycerides enriched in C18: l (oleic acid) and C18:2 (linoleic acid) consistently produced the pharmacokinetic advantages of increased systemic THC AUC, reduced 11-OH-THC exposure, and increased parent-to-metabolite ratios (>2.5). By contrast, formulations prepared with LCTs predominantly comprising C16:0 (palmitic acid) or other saturated C16 triglycerides failed to demonstrate the same effect, yielding pharmacokinetic outcomes similar to MCT controls (THC: 11 -OH- THC ratio <1.5, no significant reduction in 11-OH- THC AUC).Table 17

[0218] This specificity is unexpected because prior art treats LCTs as a uniform class with interchangeable effects on lipid digestion and drug transport. The present results demonstrate that only LCTs containing unsaturated Cl 8 fatty acyl chains (Cl 8: 1 and Cl 8:2) are effective in promoting lymphatic transport of cannabinoids and shifting the metabolite balance, whereas saturated C16 triglycerides do not confer this advantage.

[0219] Accordingly, in some embodiments the invention is defined functionally such that the carrier oil comprises at least one triglyceride with a fatty acyl chain selected from Cl 8: 1 and Cl 8:2, and that the proportion of such unsaturated C18 species constitutes at least 50% of the total triglyceride fraction in order to achieve a parent-dominant systemic profile. In further embodiments, when the carrier oil comprises predominantly C16:0 triglycerides, the pharmacokinetic profile remains indistinguishable from MCT comparators and fails to meet the parent-to-metabolite ratio criteria described herein.

[0220] In certain embodiments, the effect of lipid chain-length composition on hepatic first-pass conversion is mapped across a continuous series of eleven arms in which long-chain triglyceride (LCT) content is varied from 0% to 100% in 10% increments, with the balance constituted by medium-chain triglycerides (MCT). All arms comprised / / / 7 / a / a-stabilized nanoemulsions manufactured under identical high-pressure homogenization conditions to yield median droplet diameters of approximately 240-270 nm with narrow distributions. A9- tetrahydrocannabinol (THC) dose is constant at 10 mg, and excipient profiles, osmolality, and Quillaja levels are matched. Pharmacokinetic sampling over 5-6 hours quantified parent THC and the primary metabolite 11-hydroxy-THC (11 -OH- THC); the exposure ratio AUCo- t(THC):AUCo-t(l l-OH-THC) served as the functional readout of hepatic conversion versus lymphatic bypass. Under these matched conditions, the relationship between %LCT and the parent-to-metabolite balance proved thresholded and non-monotonic, not a simple linear slider: <20% LCT behaved like pure MCT; a switch-like window from 20-75% LCTsuppressed 11-OH-THC and elevated parent THC; >80% LCT exhibits a partial rebound of 11-OH-THC before returning to the characteristic pure-LCT signature (high THC, low metabolite) at 100% LCT. Representative exposure ratios by arm are summarized below and align with the detailed values already reported for the pure-MCT, mid-LCT, and pure-LCT conditions.

[0221] Parent: metabolite exposure ratio AUCo-t(THC):AUCo-t(l 1-OH-THC) by %LCT (10% steps) 0% LCT (100% MCT): 1.21; 10%: 1.35; 20%: 1.52; 30%: 2.02; 40%: 2.48; 50%: 4.00; 60%: 4.36; 70%: 4.77; 80%: 2.63; 90%: 1.86; 100%: -3.0. These values reflect the documented noeffect zone (<20% LCT), the mid-LCT suppression of 11-OH-THC with 3-4 x ratio increases (20-75% LCT), and the >80% LCT rebound with a final return to the LCT-dominant phenotype at 100% LCT, where 11-OH-THC Cmax remains low (~0.6 ng / mL) and THC exposure is elevated relative to MCT.

[0222] Accordingly, in some embodiments the invention is defined functionally such that, under the stated manufacturing and dosing conditions: (i) when LCT is <20% of total triglycerides the exposure ratio is <1.5 and 11-OH-THC exposure remains within the MCT reference band; (ii) when LCT is 20-75% of total triglycerides the exposure ratio is >2.5 (illustratively 4.00-4.77) with >50-60% reduction in 11-OH-THC AUC at matched THC dose; and (iii) when LCT is >80% the ratio declines toward <2.7 with partial restoration of 11-OH-THC, while at 100% LCT the system exhibits the characteristic LCT profile (elevated THC exposure, suppressed metabolite). These inequalities demonstrate that lipid chain-length composition — specifically the MCT :LCT ratio — governs the THC: 11-OH-THC balance, enabling deliberate PD steering via composition rather than changes to dose or droplet size.

[0223] In further embodiments, the inclusion of long-chain triglycerides (LCT) in the triglyceride phase of the emulsion not only governs the pharmacokinetic conversion of tetrahydrocannabinol (THC) but also exerts comparable influence across a broad class of cannabinoids and terpenes. When the proportion of LCT is maintained between about twenty and seventy-five percent of the total triglyceride content, a substantial fraction of absorbed lipid droplets enters the intestinal lymphatic system rather than the portal circulation. This lymphatic diversion partially bypasses hepatic first-pass metabolism, resulting in enhanced systemic exposure of the parent compound and reduced formation of oxidative and conjugated metabolites. The same principle applies to multiple cannabinoids beyond THC, including cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromene (CBC), cannabigerovarin (CBGV), cannabicyclol (CBL), tetrahydrocannabiphorol (THCP), and cannabidiphorol (CBDP). Eachof these cannabinoids undergoes characteristic Phase I and Phase II transformations, such as hydroxylation and subsequent oxidation or glucuronidation, yielding metabolites including 7- hydroxy- and 7-carboxy-CBD, 6'-hydroxy-CBG, 11-hydroxy-CBN, 11-hydroxy-THCV, 8- hydroxy-CBC, and related glucuronides and carboxylic derivatives. When formulated in emulsions with an LCT fraction between about twenty and seventy-five percent, plasma analyses demonstrate that the parent-to-metabolite exposure ratio for each cannabinoid increases by approximately two- to four-fold relative to emulsions containing medium-chain triglycerides (MCT) alone. These results mirror the relationship observed between THC and 11-hydroxy-THC and confirm that lipid-chain composition can be used as a generalizable variable to regulate hepatic bypass and systemic pharmacokinetics across multiple cannabinoids.

[0224] This metabolic modulation also extends to terpenes that commonly co-exist with cannabinoids in full-spectrum or broad-spectrum extracts. Representative terpenes such as myrcene, limonene, P-caryophyllene, linalool, a- and P-pinene, humulene, ocimene, terpinolene, and nerolidol each undergo oxidation through cytochrome P450-mediated pathways to form hydroxylated or oxidized derivatives such as myrcenol, perillyl alcohol, caryophyllene oxide, linalool oxide, verbenone, pinocarvone, humulene oxide, ocimenone, terpineol, and nerolic oxide. The presence of LCT in the emulsion substantially suppresses this oxidative turnover, decreasing the formation of these metabolites by approximately twenty to sixty percent while increasing parent-terpene bioavailability by thirty to one hundred percent. The Quillaja- stabilized emulsions containing both cannabinoids and terpenes thus retain higher levels of the native volatile and aromatic constituents, prolonging their biological and sensory contributions to the overall pharmacodynamic profile.

[0225] Without being bound by theory, it is believed that LCT-rich emulsions enhance chylomicron- mediated transport of cannabinoids and terpenes into the lymphatic circulation, thereby minimizing exposure to hepatic cytochrome P450 and UDP-glucuronosyltransferase enzymes responsible for oxidative and conjugative metabolism. The net result is a controlled modulation of the parent-to-metabolite ratio that can be tuned through the MCT:LCT composition of the carrier oil. Accordingly, in some embodiments, the invention provides a composition and method for governing the rate of hepatic bypass and metabolic conversion of cannabinoids and terpenes by adjusting the long-chain triglyceride fraction, such that an LCT content of approximately twenty to seventy-five percent produces optimal diversion to the lymphatic pathway and a predictable shift in the pharmacodynamic effects associated with each active compound.Example 13

[0226] In certain embodiments, a long-chain triglyceride (LCT) emulsion is formulated as an independent component and co-administered with a cannabinoid emulsion. The LCT emulsion may be prepared with any pharmaceutically acceptable emulsifier, including Quillaja saponin, gum acacia, polysorbates, lecithins, proteins, or combinations thereof. Droplet diameters are typically controlled between 200-300 nm under high-pressure homogenization (25,000 psi, single pass). The cannabinoid emulsion is independently formulated with Quillaja saponin and contains at least one cannabinoid selected from A9- tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and pharmaceutically acceptable derivatives or salts thereof.

[0227] The key experimental condition is that the separately prepared LCT emulsion is introduced into the dosing mixture such that the LCT accounted for between 10% and 90% of the total carrier oil present in the cannabinoid emulsion system. In other words, if the cannabinoid emulsion itself contained 100 mg of carrier oil, an additional 11-900 mg of LCT from the separate emulsion is incorporated such that the combined system achieved the specified fraction of LCT relative to total oil. THC dose is maintained at 10 mg across all conditions.

[0228] Pharmacokinetic sampling in healthy adult participants demonstrated that, across the range of 10-90% LCT supplementation, systemic cannabinoid exposure increased and the proportion of parent THC relative to 11-OH-THC increased. For example, at 10% LCT supplementation, AUCo-eh(THC) increased by approximately 20% relative to a cannabinoid emulsion without separate LCT; at 50% supplementation, AUCo-eh(THC) increased by approximately 45% with a simultaneous 60% reduction in 11-OH-THC AUC; and at 90% supplementation, THC exposure is increased by approximately 35% with 11-OH-THC exposure reduced by approximately 40%. The parent-to-metabolite exposure ratio (AUCo-6h(THC):AUCo-eh(l l- OH-THC)) rose from ~1.2 under control conditions to >2.5 across the 10-90% LCT supplementation window.

[0229] This finding is unexpected because prior art emphasizes that bioavailability enhancement is achieved by embedding lipids directly in the cannabinoid emulsion; here, separating the LCT into its own emulsion, even while keeping droplet sizes and total oil load constant, produced a statistically significant improvement in systemic exposure and a shift away from hepatic first-pass metabolism. The functional advantage is described herein as the LCT Supplementation Advantage, defined as: when a separately emulsified LCT fraction accounts for between 10-90% of total carrier oil, systemic cannabinoid exposure (AUCo-eh) increasesby at least 20% relative to an otherwise identical emulsion lacking separate LCT, and the THC: 11-OH-THC ratio is increased by at least 1.5-fold.

[0230] As used herein, the term carrier oil refers to any pharmaceutically or nutritionally acceptable lipid or lipid mixture that can be incorporated into an emulsion for the delivery of cannabinoids. In some embodiments, the carrier oil comprises medium-chain triglycerides (MCTs), including but not limited to triglycerides of the carrier oil comprises medium-chain triglycerides (MCTs), including caproic (C6:0), caprylic (C8:0), capric (Cl 0:0), and lauric (C12:0) fatty acids; or long-chain triglycerides (LCTs), including myristic (C14:0), palmitic (C16:0), stearic (C18:0), oleic (C18: l), linoleic (C18:2), a-linolenic (C18:3), arachidonic (C20:4), eicosapentaenoic (EP A, C20:5), docosapentaenoic (DPA, C22:5), docosahexaenoic (DHA, C22:6), or mixtures thereof. In certain embodiments, the carrier oil may further include structured lipids, mixed triglycerides containing both medium- and long-chain fatty acids, diglycerides, monoglycerides, phospholipids, or combinations thereof. In still further embodiments, the carrier oil may be derived from natural sources such as coconut oil, palm kernel oil, olive oil, soybean oil, sunflower oil, com oil, safflower oil, canola oil, flaxseed oil, marine oils, algal oils, or purified fractions thereof, or may be synthetically or semi- synthetically manufactured. Accordingly, the term carrier oil is not limited to a particular fatty acid chain length, saturation pattern, or source, provided that the oil is capable of forming an emulsion suitable for oral administration and supporting the delivery of cannabinoids.

[0231] As used herein, the term emulsifier refers to any amphiphilic compound capable of stabilizing oil-in-water dispersions of carrier oil and cannabinoids by reducing interfacial tension and preventing coalescence. In certain embodiments, the emulsifier comprises natural saponins such as Quillaja saponin, yucca saponin, or glycyrrhizin. In other embodiments, the emulsifier comprises natural gums such as gum acacia (gum arabic), gum ghatti, or gum tragacanth. In further embodiments, the emulsifier comprises food-grade surfactants such as polysorbates (e.g., polysorbate 20, 40, 60, or 80), sorbitan esters (spans), lecithins (soy, sunflower, egg), or proteins such as whey protein isolate, caseinate, pea protein, or rice protein. Additional emulsifiers may include modified starches, cellulose derivatives (e.g., hydroxypropyl methylcellulose), or synthetic polymers such as polyvinyl alcohol or poloxamers. In certain embodiments, combinations of emulsifiers are used, such as saponin-polysorbate mixtures, gum-protein mixtures, or other blends to achieve desired droplet sizes, zeta potentials, or stability profiles. The emulsifier may be present at any concentration sufficient to stabilize the droplets, for example, an emulsifier-to-oil weight ratio between 0.01 and 4.0, as described herein.

[0232] Accordingly, the invention is not limited to a particular carrier oil or emulsifier, but encompasses any oil phase and any emulsifier or emulsifier blend that supports formation of stable cannabinoid-containing emulsions suitable for oral administration and capable of achieving the pharmacokinetic and pharmacodynamic profiles described herein.

[0233] In certain embodiments, emulsions of cannabinoids in carrier oil and water are prepared by a multistep emulsification process. The process generally involves (i) preparation of an aqueous phase containing one or more emulsifiers, (ii) preparation of an oil phase containing cannabinoids dissolved or dispersed in a carrier oil, (iii) blending of the aqueous and oil phases to form a coarse emulsion, and (iv) size reduction and stabilization of droplets by high-energy homogenization.

[0234] In some embodiments, the aqueous phase is prepared by dissolving or dispersing the chosen emulsifier(s) in water or buffer, optionally containing salts, buffers, sweeteners, flavors, preservatives, or other excipients. The emulsifier concentration may range from 0.01% to 20% (w / w), with typical concentrations between 0.1% and 5%. The aqueous phase may be prepared at ambient temperature, elevated temperature (20-80 °C), or under cooling conditions, depending on the solubility of the emulsifier.

[0235] The oil phase is prepared by dissolving or suspending the cannabinoid or cannabinoids in the carrier oil. Carrier oils may include medium-chain triglycerides, long-chain triglycerides, structured lipids, diglycerides, or combinations thereof. The oil phase may be prepared at ambient or elevated temperatures (20-80 °C), and may optionally include antioxidants, viscosity modifiers, or other lipid-soluble additives. The cannabinoid concentration in the oil phase may range from 0.01% to 50% (w / w), depending on solubility and desired potency.

[0236] The oil and aqueous phases are combined under agitation using low- or moderate-shear mixing equipment such as overhead stirrers, rotor-stator homogenizers, blenders, or static mixers. This produces a coarse emulsion with droplet diameters typically between 1-100 pm. The oil-to-water ratio may range from 1 : 100 to 1 : 1, with typical food and pharmaceutical emulsions between 1 : 10 and 1 :2.

[0237] The coarse emulsion is then processed through a high-pressure homogenizer, microfluidizer, or equivalent device to reduce droplet size into the submicron or nanometer range. The homogenization pressure may vary broadly depending on equipment and formulation. In some embodiments, homogenization is conducted at low pressures between 100-500 bar. In other embodiments, pressures are between 500-5,000 bar. In further embodiments, pressures between 5,000-40,000 psi (350-3,000 bar) are used to achieve droplet sizes below 300 nm. The number of passes through the homogenizer may range from one to twenty or more, withtypical processes using two to ten passes. In some embodiments, an initial pass at lower pressure (e.g., 500-2,000 bar) is used to precondition the coarse emulsion, followed by one or more passes at higher pressure (e.g., 5,000-40,000 psi).

[0238] In other embodiments, droplet size reduction may be achieved by ultrasonication, high-shear rotor-stator homogenization, membrane emulsification, microchannel emulsification, or combinations thereof. The resulting emulsions generally exhibit median droplet diameters (D50) between 50 nm and 1 pm, with preferred embodiments between 100 and 400 nm, and span (D90-D10) / D50 less than 2.0. Zeta potential may range between -10 and -60 mV depending on emulsifier type and concentration.

[0239] In some embodiments, the emulsions described herein may be incorporated into any ingestible, topical, or inhalable format suitable for delivering cannabinoids. The invention is not limited to a particular product form, but encompasses all carriers and delivery vehicles in which a cannabinoid-containing emulsion may be dispersed or embedded.

[0240] In certain embodiments, the emulsion is incorporated into beverages, including but not limited to carbonated soft drinks, flavored waters, juices, teas, coffees, sports drinks, energy drinks, powdered drink mixes, alcoholic beverages, or non-alcoholic beers, wines, and spirits. In other embodiments, the emulsion is incorporated into confectionery products, including gummies, jellies, fruit chews, chocolates, hard candies, lozenges, chewing gums, and mints.

[0241] In further embodiments, the emulsion is incorporated into baked goods such as cookies, brownies, snack bars, crackers, or breads, or into savory edibles such as sauces, condiments, spreads, dressings, dips, soups, or prepared meals.

[0242] In some embodiments, the emulsion is formulated into capsules, tablets, or powders, including hard-shell or soft-gel capsules, orally disintegrating tablets, or sachets of dry powder that can be reconstituted into beverages.

[0243] In other embodiments, the emulsion is incorporated into topical or transdermal products, including lotions, creams, balms, salves, gels, sprays, shampoos, conditioners, lip balms, or transdermal patches, in which the emulsion may be dispersed in an aqueous or oil-based carrier for application to the skin, scalp, lips, or nails.

[0244] In additional embodiments, the emulsion is incorporated into cosmetics or personal care products, including foundations, primers, serums, toners, cleansers, moisturizers, sunscreens, deodorants, perfumes, or oral-care products such as toothpastes, mouth rinses, or breath sprays.

[0245] In still further embodiments, the emulsion is incorporated into inhalable or vaporization formats, including e-liquids, aerosolized sprays, or dry-powder inhalers, provided that theemulsion is suitably processed (e.g., spray-dried, lyophilized, or reconstituted) to yield particles or droplets compatible with pulmonary delivery.

[0246] Accordingly, the invention encompasses any consumer or pharmaceutical product form in which a cannabinoid-containing emulsion can be delivered, including beverages, foods, dietary supplements, cosmetics, topicals, pharmaceuticals, and inhalables, without limitation to a particular format or matrix.

[0247] In certain embodiments, the emulsions described herein are characterized by well-defined droplet size distributions and electrokinetic stability parameters that ensure predictable pharmacokinetic and pharmacodynamic performance. The term droplet size as used herein refers to the volume-weighted median diameter (D50) or droplet size mean (z-average) of the dispersed oil phase measured by dynamic light scattering, laser diffraction, nanoparticle tracking analysis, or equivalent optical methods.

[0248] In some embodiments, the emulsions comprise droplets having a D50 between about 30 nm and about 2,000 nm. In particular embodiments, the D50 is between about 50 nm and 1,000 nm; in more specific embodiments, between about 100 nm and 600 nm; and in preferred embodiments, between about 150 nm and 400 nm. The D10 and D90 values may fall within the ranges of 10-800 nm and 80-2,500 nm, respectively, such that the size span (D90- D10) / D50 is less than 2.5, preferably less than 1.8, and most preferably less than 1.3.

[0249] In certain embodiments, the droplet size distribution is further characterized by a poly dispersity index (PDI) between about 0.05 and 0.40, more preferably between about 0.10 and 0.30, and most preferably less than about 0.25, as determined by dynamic light scattering. Emulsions exhibiting PDI <0.25 are considered monodisperse and provide improved optical clarity, shelf stability, and bioavailability.

[0250] In some embodiments, the droplets possess a zeta potential (electrokinetic potential at the shear plane) between about -10 mV and -80 mV, more preferably between about -20 mV and -60 mV, and most preferably between about -30 mV and -50 mV. Such surface charge levels promote electrostatic repulsion sufficient to inhibit coalescence and Ostwald ripening during storage and thermal cycling.

[0251] In certain embodiments, the emulsions demonstrate thermal stability, defined by a limited change in droplet diameter following accelerated storage. For example, when stored at 40 °C for at least 3, 7, 10, 14, 30, 60, or 90 days, the increase in median droplet diameter (AD50) is less than 10%, 15%, 20%, or 25%, respectively, relative to the initial value. In preferred embodiments, the AD50 after 30 days at 40 °C does not exceed 10%, and the emulsionremains visually homogeneous with no evidence of creaming, flocculation, or phase separation.

[0252] In additional embodiments, the emulsions maintain optical clarity (transmittance >80% at 600 nm for D50 <150 nm) and constant zeta potential (change <5 mV) over the same storage interval. In certain embodiments, freeze-thaw stability is demonstrated by maintaining D50 growth <15% after three freeze-thaw cycles between -20 °C and 25 °C.

[0253] Accordingly, in some embodiments the invention provides emulsions characterized by (i) droplet size 30-2,000 nm, (ii) PDI <0.4, (iii) zeta potential -10 mV to -80 mV, and (iv) droplet growth <20% after 30 days at 40 °C, collectively defining a functionally stable nano- or submicron emulsion suitable for cannabinoid delivery.

[0254] In certain embodiments, the emulsions described herein are characterized by distinct pharmacokinetic (PK) properties that arise from controlled droplet size, emulsifier composition, and carrier oil ratio. The pharmacokinetic performance may be evaluated using standard noncompartmental analysis of plasma concentration-time exemplary data following oral administration of the emulsion.

[0255] Key PK metrics include the maximum plasma concentration (Cmax), the time to reach maximum concentration (Tmax), and the area under the plasma concentration-time curve (AUCo-t), which collectively describe the rate and extent of cannabinoid absorption.

[0256] In some embodiments, the emulsions described herein yield Cmax(THC) values between about 0.5 and 10 ng / mL, more typically between about 2.0 and 6.0 ng / mL, depending on dose and lipid composition. The corresponding Tmax(THC) may range from 15 minutes to 4 hours, with shorter Tmax values typically observed for MCT-rich emulsions (<60 min) and longer Tmax values for LCT-rich emulsions (>90-180 min).

[0257] In certain embodiments, systemic exposure as measured by AUCo-t(THC) increases proportionally with the LCT fraction up to an optimal window (e.g., 40-80% LCT), after which exposure plateaus or decreases due to delayed lipolysis or gastric retention. Typical AUCo-t(THC) values may range from 6-15 ng h / mL for a 10 mg oral dose, representing bioavailability improvements of at least 20%, 50%, 100%, or up to 200% relative to nonemulsified or MCT-only comparators.

[0258] In some embodiments, formulations are characterized by a reduced metabolite-to-parent ratio, expressed as AUCo-t(THC) / AUCo-t(l l-OH-THC), which may increase from approximately 1.2 under MCT conditions to >2.5, >3.0, or >4.0 when formulated with LCT or specific emulsifier combinations. This shift reflects reduced hepatic first-pass metabolism and enhanced lymphatic uptake.

[0259] In certain embodiments, inter-subject variability in systemic exposure is significantly reduced. The coefficient of variation (CV%) for AUC or Cmax may decrease by at least 10%, 20%, or 30% relative to conventional emulsions or tinctures, providing improved dosing predictability.

[0260] In some embodiments, enhanced bioavailability is observed across multiple cannabinoids, including A9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV), each demonstrating increased Cmax and AUC with controlled emulsifier and lipid ratios.

[0261] In certain embodiments, the relative bioavailability (Frei) of a cannabinoid administered as the described emulsion is at least 1.2x, 1.5x, 2. Ox, or 3. Ox that of a non-emulsified oil, tincture, or capsule under otherwise identical dosing conditions.

[0262] In further embodiments, the emulsions produce consistent pharmacokinetic profiles overtime, such that after storage at 40 °C for 30 days, the AUCo-t and Cmax values remain within ±15% of their initial values, indicating PK stability concurrent with physical stability.

[0263] Accordingly, in some embodiments, the invention provides emulsions and compositions characterized by (i) Cmax(THC) 0.5-10 ng / mL, (ii) Tmax(THC) 15-240 min, (iii) AUCo- t(THC) 6-15 ng h / mL for a 10 mg oral dose, (iv) AUCo-t(THC) / AUCo-t(l 1-OH-THC) >2.5, and (v) inter-subject CV% <30%, collectively defining a reproducible, high-bioavailability, low-variability cannabinoid delivery platform.

[0264] In certain embodiments, the emulsions and compositions described herein may comprise one or more cannabinoids in any ratio or combination, optionally together with terpenoids, flavonoids, and other phytochemicals derived from the Cannabis genus or other botanical sources. The multi-component nature of such formulations enables modulation of both pharmacokinetic and pharmacodynamic properties through synergistic or complementary mechanisms.

[0265] It was discovered that cannabinoid performance depends on three linked mechanisms: how quickly mixed micelles form, whether absorption proceeds through lymphatic or portal routes, and how emulsifier identity influences tissue distribution. By tuning droplet size, emulsifier type, and MCT / LCT ratios, these mechanisms can be directed to produce predictable PK and PD outcomes — an integrated framework not recognized in prior art

[0266] Suitable cannabinoids include, without limitation: A9-tetrahydrocannabinol (A9-THC), A8- tetrahydrocannabinol (A8-THC), Alo-tetrahydrocannabinol, tetrahydrocannabinolic acid A and B (THCA-A, THCA-B), cannabidiol (CBD), cannabidiolic acid (CBDa), cannabigerol (CBG), cannabigerolic acid (CBGa), cannabinol (CBN), cannabinolic acid (CBNa),cannabichromene (CBC), cannabichromenic acid (CBCa), cannabicyclol (CBL), cannabitriol (CBT), cannabielsoin (CBE), cannabinodiol (CBND), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVa), cannabidivarin (CBDV), cannabidivarinic acid (CBDVa), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVa), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVa), and cannabivarin (CBV), as well as hydrogenated, hydroxylated, or oxidized derivatives thereof, including hexahydrocannabinol (HHC), hydrogenated cannabidiol (H4-CBD), hydrogenated cannabigerol (H4-CBG), 11-hydroxy-THC (11-OH-THC), 8-hydroxy-THC, and 11-oxo- CBN.

[0267] Additional homologous and varin-class cannabinoids include tetrahydrocannabiphorol (THCP), cannabidiphorol (CBDP), tetrahydrocannabihexol (THCH), cannabidiphorol acid (CBDPa), tetrahydrocannabutol (THCB), cannabidibutol (CBD-B), and rare or minor cannabinoids including cannabiripsol (CBR), cannabifuran (CBF), cannabimovone (CBM), and cannabicyclovarin (CBLV). The invention further encompasses pharmaceutically acceptable salts, esters, ethers, isomers, prodrugs, and synthetic or semi-synthetic analogs of any of the foregoing cannabinoids.

[0268] In some embodiments, the emulsions further comprise one or more terpenoids or terpenes, either isolated or as part of a broad- or full-spectrum extract. Suitable terpenoids include, without limitation: myrcene, limonene, P-caryophyllene, a-humulene, pinene (a-pinene, P- pinene), linalool, terpinolene, ocimene, eucalyptol, nerolidol, bisabolol, valencene, guaiol, camphene, borneol, sabinene, fenchol, phytol, geraniol, isopulegol, phellandrene, and menthol. In some embodiments, oxygenated sesquiterpenes such as caryophyllene oxide, humulene oxide, or farnesol are included to enhance bioavailability or act as P450 enzyme modulators.

[0269] In certain embodiments, the emulsions comprise combinations of cannabinoids and terpenoids in defined or tunable ratios to achieve targeted pharmacodynamic effects. Non-limiting examples include THGCBD ratios from about 100: 1 to 1: 100, including intermediate ratios such as 20: 1, 10: 1, 5: 1, 1 : 1, 1:5, 1 :10, and 1 :20. Other examples include CBD:CBG ratios from 20: 1, 2: 1 to 1 :20. Further examples include CBDa: CBGa ratios from 10: 1 to 1 : 10. Som examples include THC:CBG ratios from about 50: 1 to 1 :50. Other examples include CBD:CBN ratios from about 10: 1 to 1 : 10. THGTHCV ratios from about 20: 1 to 1 :20. Further includes Som examples include CBD:CBG:CBN ternary blends wherein each cannabinoid constitutes between 5-90% of total cannabinoid content. Further examples includeTHC:CBD:terpenoid mixtures in which terpenoids constitute 0.01-10% of the total formulation.

[0270] In some embodiments, the specific cannabinoid and terpenoid ratios are selected to produce targeted physiological or experiential outcomes. For example THC-dominant formulations (THC:CBD >10: 1) yield euphoric, analgesic, and appetite-stimulating effects. In some examples CBD-dominant formulations (THC:CBD <1 : 10) yield anxiolytic, antiinflammatory, and anti-seizure benefits. In further examples CBG-rich formulations enhance alertness and focus. In other examples CBN- or THC-CBN formulations promote sedation and sleep. In further examples THCV- and CBDV-rich formulations provide metabolic and appetite control.

[0271] Terpenoid-enhanced formulations modify the pharmacodynamic profile: for instance, myrcene and linalool enhance sedation; limonene and pinene enhance mood and cognitive clarity; P-caryophyllene engages CB2 receptor-mediated anti-inflammatory pathways.

[0272] In certain embodiments, total cannabinoid load per unit dose ranges from 1 mg to 4000 mg as described herein, while terpenoids are present at 0.001-500 mg per unit dose or 0.001-10% (w / w) of the total formulation. Cannabinoid-to-terpenoid ratios may vary from 1000: 1 to 1 : 1000, depending on intended use, target physiology, or patient preference.

[0273] Accordingly, in some embodiments, the invention provides multi-cannabinoid and cannabinoid-terpenoid emulsions in which: (i) the combination comprises any one or more cannabinoids selected from at least 100 known cannabinoids; (ii) one or more terpenoids are present at 0.001-10% by weight; and (iii) the cannabinoid:terpenoid ratio is adjustable to modulate onset, intensity, or duration of pharmacodynamic effect.

[0274] In further embodiments, the emulsions are formulated to preserve the synergistic “entourage effect” of multiple cannabinoids and terpenoids while providing controlled droplet size, reproducible dose, and predictable bioavailability across potency ranges from 1 mg to 4000 mg total cannabinoids.

[0275] In certain embodiments, the emulsions described herein may be incorporated into any ingestible or orally administered format suitable for delivering cannabinoids or other lipophilic actives. The invention is not limited to any particular product matrix or consumption method but encompasses all ingestible forms and dosage systems in which a cannabinoid- containing emulsion can be integrated, dispensed, or reconstituted.

[0276] In some embodiments, the emulsions are incorporated into beverages and liquid consumables including but not limited to carbonated drinks, flavored waters, teas, coffees, juices, energy drinks, sports beverages, and functional tonics. The emulsions may also be incorporated intosemi-solid or solid food matrices such as gummies, fruit chews, chocolates, lozenges, nutrition bars, baked goods, sauces, dressings, condiments, or ready-to-eat meals. In certain embodiments, the emulsions may be dried or encapsulated to yield powders, capsules, softgels, tablets, or oral strips that reconstitute into nanoemulsions upon ingestion or hydration.

[0277] In certain embodiments, the emulsions and compositions described herein are not limited to a specific cannabinoid potency or dose, but may be formulated across an exceptionally broad range of cannabinoid concentrations to accommodate different use cases, patient populations, and administration formats.

[0278] The total cannabinoid content per unit dose, per serving, or per actuation may range from 0.001 mg to 10,000 mg, depending on the intended application, delivery format, and therapeutic objective.

[0279] In some embodiments, the total cannabinoid concentration per unit dose (e.g. , per capsule, per gummy, per beverage serving, or per pump actuation) is at least about 0.001 mg, 0.01 mg, 0.05 mg, 0.1 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 600 mg, 750 mg, 800 mg, 900 mg, 1000 mg, 1250 mg, 1500 mg, 1750 mg, 2000 mg, 2500 mg, 3000 mg, 3500 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, or up to about 10,000 mg of total cannabinoids per unit dose.

[0280] The same ranges may apply to single or combined cannabinoids, whether expressed as milligrams per unit, milligrams per serving, milligrams per kilogram body weight, or percentage of total formulation weight.

[0281] In certain embodiments, the emulsions are configured for microdosing or functional supplementation, wherein the total cannabinoid load per unit is between about 0.001 mg and 5 mg, preferably 0.01-2.5 mg, suitable for continuous wellness, nootropic, or stressmitigation applications.

[0282] In further embodiments, the emulsions are configured for general therapeutic or recreational use, wherein total cannabinoids per unit dose are between about 5 mg and 200 mg, preferably 10-100 mg. These formulations may be used in beverage enhancers, gummies, capsules, or edible products.

[0283] In certain embodiments, for specialized therapeutic protocols, veterinary treatments, or research, the total cannabinoid load per unit dose may be between 2000 mg and 10,000 mg, or an equivalent weight-based dose between 0.1 mg / kg and 200 mg / kg body weight in mammals, including humans, canines, and other animals.

[0284] In some embodiments, the stated total cannabinoid load includes one or more cannabinoids in any ratio, including but not limited to A9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabigerovarin (CBGV), cannabichromevarin (CBCV), and their acidic precursors (THCA, CBD A, CBGA, CBCA, etc.), as well as rare cannabinoids (THCP, CBDP, THCH, THCB, CBNV, CBND, CBM, CBF, CBT).

[0285] The total cannabinoid-to-oil ratio may vary from 0.001 : 1 to 1 : 1 (w / w), and the total cannabinoid-to-formulation ratio may vary from 0.001% to 50% (w / w), depending on desired potency and droplet stability.

[0286] In some embodiments, the following potency ranges can be associated with distinct pharmacodynamic categories. 0.001-1 mg cab be associated with microdose, subtle anxiolytic, and cognitive modulation. 1-25 mg can be associated with wellness, mild anxiolytic, or nootropic use. 25-200 mg can be associated as a standard psychoactive or therapeutic range for most consumers. 200-1000 mg can be associated with a strong analgesic range. 1000-4000 mg can be associated with highly potent clinical uses. >4000 mg can be associated with veterinary or investigational use.

[0287] Accordingly, in some embodiments, the invention is defined functionally such that the total cannabinoid content per unit dose is between 0.001 mg and 10,000 mg. In some embodiments the formulation remains physically stable (droplet size increase <20% at 40 °C for 30 days) across all potency ranges. In some embodiments the pharmacokinetic characteristics (Cmax, AUCo-sh, Tmax) remain consistent within ±15% variance across batches of different potency levels.

[0288] In further embodiments, the emulsions described herein maintain bioavailability enhancement (Frei >1.5) and inter-subject CV% <30% independent of absolute cannabinoid load, demonstrating that the disclosed emulsifier and lipid ratios provide scalable performance from microdose to megadose formulations.

[0289] In certain embodiments, the emulsions and compositions described herein may be coadministered, co-formulated, or co-dosed with one or more additional bioactive agents to enhance therapeutic efficacy, modulate pharmacokinetics, or broaden the spectrum of physiological effects. Such combinations may act through additive, synergistic, or complementary mechanisms.

[0290] In some embodiments, cannabinoid emulsions are co-administered with other lipidic or amphiphilic compounds that facilitate lymphatic transport, micellar solubilization, or intestinal permeability. Non-limiting examples include phospholipids (e.g., lecithin,phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine), fatty acids and esters (e.g., oleic acid, linoleic acid, alpha-linolenic acid, omega-3 DHA and EP A, medium- and long-chain mono- and diglycerides), bile salts or analogues (e.g., sodium taurocholate, glycocholate), and bioavailability enhancers (e.g., piperine, quercetin, curcumin, resveratrol, or gingerol derivatives).

[0291] These agents may enhance intestinal uptake, slow metabolism, or improve cellular penetration, producing increases in AUCo-sh or Cmax of at least 20%, 50%, or 100% compared to cannabinoid-only emulsions.

[0292] In some embodiments, emulsions are co-administered with natural adaptogens or nutraceuticals that synergize with cannabinoids in stress modulation, neuroprotection, or inflammation control. Examples include but are not limited to Ashwagandha, Rhodiola rosea, Panax ginseng, Cordyceps militaris, Lion’s Mane (Hericium erinaceus). Reishi (Ganoderma luciduni), Curcumin, resveratrol, coenzyme Q10, alpha-lipoic acid, vitamin D, vitamin E, magnesium, and zinc. These co-actives enhance mitochondrial function, antioxidant capacity, or hypothalamic-pituitary-adrenal axis balance. In certain embodiments, formulations containing cannabinoids and ashwagandha produce greater cortisol reduction (>20%) compared to either agent alone.

[0293] In certain embodiments, emulsions may be co-administered with compounds that modulate metabolism or other effects, including but not limited to Omega-3 fatty acids, gammalinolenic acid (GLA), or conjugated linoleic acid (CLA) for lipid metabolism. In some examples Probiotics or prebiotics (inulin, galacto-oligosaccharides) for gut-endocannabinoid axis modulation.

[0294] Such combinations may yield synergistic changes in various biomarkers, exceeding additive predictions.

[0295] In certain embodiments, synergistic activity is evidenced by at least one of: >25% greater efficacy of the combination versus additive expectation in validated assays (e.g., anxiety score improvement), >20% reduction in required cannabinoid dose to achieve the same pharmacodynamic effect when co-administered with the secondary agent, pharmacokinetic enhancement, defined as >1.5x increase in AUC or Cmax compared to cannabinoid-only controls, or variability suppression, with inter-subject CV% reduced by >20% for combination formulations.

[0296] Accordingly, in some embodiments the invention provides compositions and methods wherein a cannabinoid-containing nanoemulsion is co-administered or co-formulated withone or more secondary actives including but not limited to lipids, nutraceuticals, vitamins, minerals, amino acids, antioxidants, adaptogens, or metabolic regulators.

[0297] The combined administration yields an effect that is additive, supra-additive, or synergistic relative to either component alone, measured by at least one pharmacokinetic or pharmacodynamic endpoint.

[0298] The composition retains droplet size within 50-500 nm and stability (AD50 <20% at 40 °C for 30 days) in the presence of co-actives.

[0299] The various methods and techniques described above provide a number of ways to carry out the application. Of course, it is to be understood that not necessarily all objectives or advantages described are achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as taught or suggested herein. A variety of alternatives are mentioned herein. It is to be understood that some embodiments specifically include one, another, or several features, while others specifically exclude one, another, or several features, while still others mitigate a particular feature by including one, another, or several other features.

[0300] Furthermore, the skilled artisan will recognize the applicability of various features from different embodiments. Similarly, the various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be employed in various combinations by one of ordinary skill in this art to perform methods in accordance with the principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in diverse embodiments.

[0301] Although the application has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the embodiments of the application extend beyond the specifically disclosed embodiments to other alternative embodiments and / or uses and modifications and equivalents thereof.

[0302] In some embodiments, any numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, used to describe and claim certain embodiments of the disclosure are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and any included claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reportedsignificant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the application are approximations, the numerical values set forth in the specific examples are usually reported as precisely as practicable.

[0303] In some embodiments, the terms “a” and “an” and “the” and similar references used in the context of describing a particular embodiment of the application (especially in the context of certain claims) are construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (for example, “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the application and does not pose a limitation on the scope of the application otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the application.

[0304] Variations on preferred embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that skilled artisans can employ such variations as appropriate, and the application can be practiced otherwise than specifically described herein. Accordingly, many embodiments of this application include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the application unless otherwise indicated herein or otherwise clearly contradicted by context.

[0305] All patents, patent applications, publications of patent applications, and other material, such as articles, books, specifications, publications, documents, things, and / or the like, referenced herein are hereby incorporated herein by this reference in their entirety for all purposes, excepting any prosecution file history associated with same, any of same that is inconsistent with or in conflict with the present document, or any of same that may have a limiting effect as to the broadest scope of the claims now or later associated with the present document. By way of example, should there be any inconsistency or conflict between the description, definition, and / or the use of a term associated with any of the incorporated material and thatassociated with the present document, the description, definition, and / or the use of the term in the present document shall prevail.

[0306] In closing, it is to be understood that the embodiments of the application disclosed herein are illustrative of the principles of the embodiments of the application. Other modifications that can be employed can be within the scope of the application. Thus, by way of example, but not of limitation, alternative configurations of the embodiments of the application can be utilized in accordance with the teachings herein. Accordingly, embodiments of the present application are not limited to that precisely as shown and described.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A cannabinoid emulsion composition comprising A9-tetrahydrocannabinol (THC) in a triglyceride oil dispersed in an aqueous phase with an emulsifier, wherein the composition is characterized by:(a) an MCT:THC ratio of 1.5: 1 to 8: 1 defining a functional absorption window in which API exceeds NAF120;(b) optionally, an LCT fraction of 20-75%, which increases lymphatic uptake and suppresses first-pass metabolism;(c) a THC: 11-OH-THC AUC ratio of at least 2.0 under matched THC dose and droplet size; and(d) a pharmacodynamic profile determined by triglyceride composition, wherein LCT- containing emulsions produce a more cerebral psychoactive effect and MCT-dominant emulsions produce a more body-focused effect.

2. The composition of claim 1, wherein the triglyceride oil consists essentially of MCT and is substantially free of LCT.

3. The composition of claim 2, wherein MCT: THC between 1.5: 1 and 8: 1 yields API > NAF120, and ratios below 1.5: 1 or above 8: 1 exhibit API < NAF 120.

4. The composition of claim 2, wherein the MCT comprises caprylic acid (C8:0), capric acid (Cl 0:0), caproic acid (C6:0), lauric acid (C12:0), or any combination thereof.

5. The composition of claim 2, wherein droplet size (D50) is maintained between 230 nm and 290 nm across all MCT:THC ratios tested.

6. The composition of claim 1, wherein systemic THC exposure (AUCo-t) is increased by at least 20%, 30%, or 50% relative to an MCT-only formulation with the same THC dose and droplet size.

7. The composition of claim 1, wherein 11-OH-THC AUC is reduced by at least 50%, 60%, or 70% relative to an MCT-only comparator.

8. The composition of claim 1, wherein the THC: 11-OH-THC AUC ratio is at least 2.0, 2.5, 3.0, or greater.

9. The composition of claim 1, wherein the Tmax of THC is between about 55 minutes and about 120 minutes.

10. The composition of claim 1, wherein the LCT comprises palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18: l), linoleic acid (C18:2), a-linolenic acid (C18:3), arachidonicacid (C20:4), docosapentaenoic acid (C22:5), docosahexaenoic acid (C22:6), or any combination thereof.

11. The composition of claim 1, wherein LCT-containing emulsions produce increased ratings of alertness, sociability, creativity, or cognitive clarity relative to MCT-dominant emulsions.

12. The composition of claim 1, wherein MCT-dominant emulsions produce increased ratings of relaxation, physical heaviness, drowsiness, or body-focused sensations relative to LCT-containing emulsions.

13. The composition of claim 1, wherein pharmacodynamic differences occur despite at least 80% similarity in Tmax and at least 80% similarity in Cmax between two emulsions differing only in LCT content.

14. The composition of claim 1, wherein the absorption behavior exhibits a non-linear or inverted-U dependence on MCT:THC ratio, with decreased absorption efficiency at ratios above 8: 1.

15. The composition of claim 1, wherein increasing LCT beyond about 75% results in reduced THC AUC or delayed lipolysis.

16. The composition of claim 1, wherein particle size (D50) is maintained between 150 nm and 400 nm such that PK and PD differences are attributable to fat composition rather than particle size.

17. The composition of claim 1, wherein two emulsions compared for PK and PD assessment differ in LCT content but have D50 values within ±15 nm of each other.

18. The composition of claim 1, wherein the fatty-acid composition modulates mixed- micelle formation rate under simulated intestinal lipolysis, resulting in time-dependent differences in micellar THC fraction.

19. The composition of claim 1, wherein LCT digestion yields long-chain fatty acids that promote chylomicron assembly and lymphatic transport, whereas MCT digestion yields medium-chain fatty acids that promote portal uptake.

20. The composition of claim 1, wherein the THC dose is at least 10 mg such that PK and PD differences attributable to triglyceride composition are reliably detectable in human subjects.

21. A composition comprising at least one active cannabinoid, at least one fat, and at least one emulsifier, in a combination selected to have a pharmacokinetic (PK) or pharmacodynamic (PD) property that is at least 1. lx different from a comparable composition lacking either the fat or the emulsifier.

22. The composition of claim 21, wherein the emulsifier comprises gum acacia or a Quillaja saponin.

23. The composition of claim 21, wherein the fat is selected from at least one mediumchain triglyceride (MCT), at least one long-chain triglyceride (LCT), or any fatty acid of selected chain length and degree of saturation.

24. The composition of claim 21, wherein the PK property is selected from onset, peak intensity, duration of action, or any combination thereof.

25. The composition of claim 21, wherein the PD property is selected from THC psychoactive effect, degree of impairment, and therapeutic effect.

26. The composition of claim 24, wherein the PK property is onset, and the onset is at least 1.5 times faster than the comparable composition.

27. The composition of claim 24, wherein the PK property is peak intensity and the peak intensity is at least 1.5x higher than the comparable composition.

28. The composition of claim 24, wherein the PK property is duration of action, and the duration of action is either at least (a) 1.5 x longer, or (b) half as long, as the comparable composition.

29. The composition of claim 25, wherein the PD is THC psychoactive effect and the psychoactive effect is at least (a) 1 ,2x greater or (b) 1 / 3 less than the comparable composition.

30. The composition of claim 25, wherein the PD is degree of impairment and the degree of impairment is at least (a) 1.2x greater or (b) 1 / 3 less than the comparable composition.

31. The composition of claim 25, wherein the PD is therapeutic effect and the therapeutic effect is at least 1.2x greater than the comparable composition.

32. The composition of claim 21, wherein the at least one active cannabinoid comprises any of A9-tetrahydrocannabinol (A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol, A6a,10a-tetrahydrocannabinol, A7-tetrahydrocannabinol, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabicyclol (CBL), cannabitriol (CBT), cannabielsoin (CBE), cannabinodiol (CBND), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabigerovarin (CBGV), cannabichromevarin (CBCV), and cannabielsoin varin (CBEV). Acidic precursors such as A9-tetrahydrocannabinolic acid A (THCA-A), A9-tetrahydrocannabinolic acid B (THCA-B), A8-tetrahydrocannabinolic acid, Alo-tetrahydrocannabinolic acid, cannabidiolic acid (CBDa), cannabigerolic acid (CBGa), cannabichromenic acid (CBCa), cannabinolic acid (CBNa), cannabicyclolic acid (CBLa), cannabitriolic acid (CBTa), cannabielsoic acid (CBEa), cannabinodiolic acid (CBNDa), tetrahydrocannabivarinic acid (THCVa),cannabidivarinic acid (CBDVa), cannabigerovarinic acid (CBGVa), cannabichromevarinic acid (CBCVa). Hexahydrocannabinol (HHC), hydrogenated cannabidiol (H4-CBD), hydrogenated cannabigerol (H4-CBG), hydrogenated cannabinol (H4-CBN), hexahydrocannabivarin (HHC-V), hydrogenated cannabidiol varin (H4-CBDV), hydrogenated cannabigerovarin (H4-CBGV),11-hydroxy-THC (11-OH-THC), 8-hydroxy- THC, 11-hydroxy-CBD, 7-hydroxy-CBD, 11-hydroxy-CBG, 8-hydroxy-CBN, 11-oxo-CBN, 9-hydroxy-HHC, 10-hydroxy-HHC, dihydroxy-THC isomers, cannabinol-quinone, cannabinodiol (CBND), cannabichromanon (CBCN), cannabifuran (CBF), cannabicoumaronone, cannabiripsol, A9-THCV, A8-THCV, CBDV, CBGV, CBCV, CBLV, CBNDV, CBTv, CBEv, CBV, tetrahydrocannabiorcol (THCC), tetrahydrocannabutol (THCB), tetrahydrocannabihexol (THCH), THCP (tetrahydrocannabiphorol), CBDP (cannabidiphorol), CBGP (cannabigerophorol), CBCP (cannabichromephorol), CBNP, THCB (tetrahydrocannabutol), CBD-B, CBGB, CBCB, THCH (tetrahydrocannabihexol), CBDH, CBGH, CBCH, cannabiorcol (CBO), cannabiripsol (CBR), cannabicitran (CBT), cannabifuran (CBF), cannabimovone (CBM), cannabiripsin, cannabioxepane, cannabiglendol, dronabinol, nabilone, HU-210, HU-211, CP-55,940, WIN-55,212-2, JWH series cannabinoids, and pharmaceutically acceptable salts, esters, ethers, and prodrugs thereof.

33. The composition of claim 21, further comprising one or more terpene or terpenoid.

34. The composition of claim 33, wherein the terpene or terpenoid comprises at least one of myrcene, P-caryophyllene, a-humulene, limonene, a-pinene, P-pinene, linalool, terpinolene, geraniol, nerol, borneol, isopulegol, eucalyptol (1,8-cineole), camphene, sabinene, ocimene, valencene, farnesene, bisabolol, guaiol, cedrol, phytol, terpineol, perillyl alcohol, carvone, pulegone, citronellol, menthol, thymol, carvacrol, P-elemene, and P- selinene.

35. The composition of claim 21, in a single-serving oral dose comprising from about 0.5 mg to about 300 mg of cannabinoid per serving.

36. The composition of claim 35, comprising from about 5 mg to about 100 mg of cannabinoid per serving.

37. The composition of claim 21, in a dose from about 0.02 mg to about 5.0 mg per kg of a user’s total body weight.

38. The composition of claim 21, in the form of a beverage, a confection or chew, a capsule or softgel, or a tincture.

39. The composition of clam 21, wherein the composition comprises a nanoemulsion coformulated with one or more secondary actives selected from a lipids, a nutraceutical, a vitamin, a mineral, an amino acid, an antioxidant, a drug, an adaptogen, or a metabolic regulator.

40. The composition of claim 39, wherein the co-formulation yields an effect that is additive, supra-additive, or synergistic relative to either component alone, measured by at least one pharmacokinetic or pharmacodynamic endpoint.

41. The composition of claim 39, wherein the co-formulation retains droplet size within 50-500 nm and stability, defined as AD50 <20% at 40 °C for 30 days, in the presence of coactives.

42. A method of making any of the compositions of claims 21-41, comprising the steps of: determining a desired effect, wherein the effect comprises a desired PK or PD endpoint; selecting ingredients comprising at least one active cannabinoid, at least one fat, and at least one emulsifier suited to the desired effect; and processing the ingredients from the selecting step under conditions suitable to yield a stable emulsion capable of achieving the desired effect.

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