Combining hallucinogens with fatty acids

Abstract

The present application relates to a combination composition comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. The present application also relates to an intranasal pharmaceutical composition comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. For example, the one or more hallucinogens is 5-methoxy-N,N-dimethyltryptamine, or a pharma- ceutically acceptable salt thereof, and the one or more fatty acids is linoleic acid.

Description

[Technical field]

[0001] Related Applications This application claims the benefit of priority to co-pending U.S. Provisional Patent Application No. 63 / 202,081, filed May 26, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present application relates to combination treatments comprising hallucinogens. For example, the present application relates to compositions and kits comprising one or more hallucinogens and one or more fatty acids. The present application further relates to the use of these compositions in the fields of psychiatry, neurobiology, and pharmacotherapy, for example, for the treatment of psychiatric and neurological disorders. The present application also relates to intranasal pharmaceutical compositions comprising one or more hallucinogens and one or more fatty acids. For example, the one or more hallucinogens are 5-methoxy-N,N-dimethyltryptamine, or pharmaceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids are linoleic acid. [Background technology]

[0003] Mental health disorders or illnesses refer to a wide range of disorders, including, but not limited to, depression, anxiety and panic disorders, schizophrenia, eating disorders, substance abuse disorders, post-traumatic stress disorder, attention-deficit / hyperactivity disorder, addictive disorders, cognitive-aggressive disorders, and obsessive-compulsive disorders. Symptoms vary in severity, with some individuals experiencing debilitating illnesses that interfere with normal social functioning, while others suffer from intermittent recurrent episodes over the course of their lifespan. Although the presentation and diagnostic criteria between psychiatric disease states differ in part, there are notable common endophenotypes between disorders, and comorbidities often exist. Specifically, there are phenotypic endophenotypes associated with changes in mood, cognition, and behavior. Interestingly, many of these endophenotypes also extend to neurological conditions. For example, attention deficits have been reported in patients with attention deficit disorder, attention deficit hyperactivity disorder, cognitive aggression disorder, eating disorders, substance use disorders, schizophrenia, depression, obsessive-compulsive disorder, addictive disorders, traumatic brain injury, fragile X, Alzheimer's disease, mini-stroke, Parkinson's disease, and frontotemporal dementia.

[0004] Many mental health and neurological disorders are affected by changes, dysfunction, degeneration, and / or damage to the brain's serotonergic system and other neurotransmitter systems (dopamine, glutamate, etc.), which may partially explain the common endophenotypes and comorbidities between neuropsychiatric and neurological disorders. Many therapeutic agents that modulate serotonergic function, including serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, antidepressants, and monoamine oxidase inhibitors, are commercially available and have been developed primarily for depressive disorders, but many of these therapeutic agents are used across multiple medical indications, including, but not limited to, depression in Alzheimer's disease and other neurodegenerative diseases, chronic pain, existential distress, bipolar disorder, obsessive-compulsive disorder, anxiety disorders, and smoking cessation. However, commercially available drugs often show limited benefit compared to placebo, can take six weeks to act, and for some patients are associated with several side effects, including sleep disorders, drowsiness, fatigue, weakness, changes in blood pressure, memory problems, digestive disorders, weight gain, and sexual problems.

[0005] Hallucinogens are psychoactive drugs that often or usually cause hallucinations, perceptual abnormalities, and other substantial subjective changes in thinking, cognition, emotion, and / or consciousness. Hallucinogens are also often referred to as psychedelics, but some consider hallucinogens to be a class of hallucinogens along with dissociatives, stimulants, entactogens, empathogens, delirants, and other such psychoactive compounds. As used herein, all of these compounds are referred to interchangeably as hallucinogens or hallucinogens.

[0006] The field of hallucinogens / psychedelics neuroscience has recently experienced a renaissance after decades of limited research due to its legal status. Hallucinogens are one of the oldest classes of psychopharmacological agents known to humans and cannot be fully understood without reference to various fields of study including anthropology, ethnopharmacology, psychiatry, psychology, sociology, etc. Hallucinogens (serotonergic hallucinogens and serotonergic classes) are potent psychoactive substances that alter perception and mood and affect multiple cognitive processes.

[0007] Hallucinogens are generally considered physiologically safe and do not cause dependence or addiction. The origins of hallucinogens predate written history, and they were adopted by early cultures in many sociocultural and convention contexts. Following the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD, 4, Scheme 1) and the identification of serotonin in the brain, early research focused on the possibility that LSD and other hallucinogens may have a serotonergic basis for their actions. Today, hallucinogens are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A (5-HT2A) receptors, most importantly those expressed on the apical dendrites of neocortical pyramidal cells in layer V, but there is also consensus that they may bind with lower affinity to other receptors, such as other serotonergic receptors, sigma-1 receptors, and trace amino acid-associated receptors. To aid in elucidating the neurochemical correlates of serotonin 5-HT2A receptor activation in the brain, several useful rodent models have been developed over the years, and a variety of imaging techniques have been employed to identify key brain regions that are directly affected by hallucinogens.

[0008] Hallucinogens have both rapid onset effects and persistent effects after their acute effects, including changes in mood, cognition, brain morphology, and brain function. Long-lasting effects may result from their unique receptor affinity, which affects neurotransmission through neuromodulatory systems that help regulate brain activity, neuroplasticity, and promote cell survival, are neuroprotective, and regulate the brain neuroimmune system and similar systems in the periphery. The mechanisms that lead to these long-term neuromodulatory changes are related to epigenetic modifications, gene expression changes, and the regulation of pre- and post-synaptic receptor density, to name a few. These previously studied hallucinogens may provide the next generation of neurotherapeutics, where treatment-resistant psychiatric and neurological disorders, such as depression, post-traumatic stress disorder, dementia, and addiction, may become treatable with a reduced pharmacological risk profile.

[0009] Although there is a general perception that hallucinogens are dangerous, from a physiological safety standpoint, they are some of the safest known classes of central nervous system (CNS) drugs. Hallucinogens do not cause addiction, and no overdose deaths have occurred after ingestion of regular doses of classic hallucinogens such as LSD (4), psilocybin (5), or mescaline (1) (Scheme 1). Preliminary data indicate that hallucinogen administration in humans results in a unique profile of effects and potential adverse reactions that need to be appropriately addressed to maximize safety. The primary safety concerns are primarily psychological rather than physiological in nature. Physical effects vary but are relatively insignificant, even at doses that induce strong psychological effects.

[0010] Psilocybin (5) is often reported to cause a transient delayed headache that increases in incidence, duration, and severity in a dose-related manner when administered in a controlled setting [Johnson et al., Drug Alcohol Depend (2012) 123(1-3):132-140]. Repeated administration of hallucinogens has been found to result in the development of very rapid tolerance, known as tachyphylaxis, a phenomenon believed to be partially mediated by the 5-HT2A receptor. Indeed, several studies have shown that rapid tolerance to hallucinogens correlates with downregulation of the 5-HT2A receptor. For example, daily administration of LSD selectively reduced 5-HT2 receptor density in rat brain [Buckholtz et al., Eur. J. Pharmacol. 1990, 109:421-425. 1985; Buckholtz et al., Life Sci. 1985, 42:2439-2445].

[0011] [ka]

[0012] Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine (5, Scheme 1) is a tryptamine and one of the major psychoactive components of mushrooms of the psilocybe species. It was first isolated from the mushrooms of the genus Psilocybe by Hofmann in 1957 and subsequently synthesized by Hofmann in 1958 [Passie et al. Addict Biol., 2002, 7(4):357-364] and was used in psychiatric and psychological research and psychotherapy from the early to mid-1960s until its drug scheduling was controlled in the United States in 1970 and in Germany until 1980 [Passie 2005; Passie et al. Addict Biol., 2002, 7(4):357-364]. Perhaps because it has a shorter duration of action and is less well-known than LSD, research into the effects of psilocybin resumed in the mid-1990s, and it is now the preferred compound for use in studying the effects of serotonergic hallucinogens [Carter et al. J. Cogn. Neurosci., 2005 17(10): 1497-1508; Gouzoulis-Mayfrank et al. Neuropsychopharmacology 1999, 20(6): 565-581; Hasler et al, Psychopharmacology (Berl) 2004, 172(2): 145-156]. Like other members of this class, psilocybin can induce profound changes in perception, cognition, satiety, and emotion, including emotional lability.

[0013] In humans and other mammals, psilocybin is converted to the active metabolite psilocin, i.e. 4-hydroxy-N,N-dimethyltryptamine (6, Scheme 1). Psilocin may partially or entirely cause most of the subjective and physiological effects of psilocybin in humans and non-human animals. Recently, human psilocybin studies have confirmed the 5-HT2A activity of psilocybin and psilocin, providing some support for indirect effects on dopamine via 5-HT2A activity and possible activity at other serotonin receptors. In fact, the most consistent finding of the involvement of other receptors in hallucinogen behavior is the 5-HT1A receptor. This is especially true for tryptamine and LSD, which generally have significant affinity and functional potency at this receptor. 5-HT1A receptors are known to colocalize with 5-HT2A receptors on cortical pyramidal cells [Martin-Ruiz et al. J Neurosci. 2001, 21(24):9856-986], where the two receptor types have opposing functional effects [Araneda et al. Neuroscience 1991, 40(2):399-412].

[0014] Although the exact role of 5-HT2A receptors and other 5-HT2 receptor family members is not fully understood in the amygdala, it is clear that 5-HT2A receptors play an important role in emotional responses and are important targets to be considered in the action of 5-HT2A agonist hallucinogens. In fact, most of the known 5-HT2A agonists produce hallucinogenic effects in humans, and rodents generalize from one 5-HT2A agonist to another, such as between psilocybin and LSD [Aghajanian et al., Eur J Pharmacol., 1999, 367(2-3):197-206; Nichols at al., J Neurochem., 2004, 90(3):576-584]. Psilocybin has a stronger affinity for human 5-HT2A receptors than rat receptors, and a lower Ki for both 5-HT2A and 5-HT2C receptors than LSD. Furthermore, the results of a series of drug discrimination tests in rats found that 5-HT2A antagonists, but not 5-HT1A antagonists, prevented rats from recognizing psilocybin [Winter et al., Pharmacol Biochem Behav., 2007, 87(4):472-480].

[0015] There remains strong research and therapeutic potential for psilocybin, as recent studies have shown varying degrees of success in neurological disorders, alcoholism, depression in terminal cancer patients, obsessive-compulsive disorder, addiction, anxiety, post-traumatic stress disorder, and even cluster headaches. It may also be useful as a psychosis model for the development of new treatments for psychotic disorders [Dubovyk and Monahan-Vaughn, ACS Chem. Neurosci. (2018), 9(9):2241-2251].

[0016] Recent exciting developments in this field have occurred in clinical research, with several double-blind, placebo-controlled phase 2 trials of psilocybin-assisted psychotherapy in patients with treatment-resistant, major depressive disorder, and cancer-related psychosocial distress demonstrating unprecedented positive relief of anxiety and depression. Two recent small pilot studies of psilocybin-assisted psychotherapy have also shown positive benefits in the treatment of both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after hallucinogen administration, with results indicating that intravenously administered psilocybin and LSD result in reduced oscillatory activity in regions of the brain's default mode network [Nichols DE. Pharmacol Rev. (2016) 68(2):264-355].

[0017] Preliminary studies using positron emission tomography (PET) have shown that psilocybin ingestion (15 or 20 mg orally) increases the absolute metabolic rate of glucose in the frontal cortex and, to a lesser extent, in other cortical regions and subcortical structures of the striatum and limbic regions in healthy participants, suggesting that some of the important behavioral effects of psilocybin involve the frontal cortex [Gouzoulis-Mayfrank et al., Neuropsychopharmacology, 1999, 20(6):565-581; Vollenweider et al., Brain Res. Bull. 2001, 56(5):495-507]. Although 5-HT2A agonism is widely recognized as the primary action of classical hallucinogens, psilocybin has lower affinity for a wide range of other pre- and postsynaptic serotonin and dopamine receptors, as well as the serotonin reuptake transporter [Tyls et al., Eur. Neuropsychopharmacol. 2014, 24(3):342-356]. Psilocybin activates 5-HT1A receptors, which may contribute to its antidepressant / anxiety effects.

[0018] Depression and anxiety are two of the most common psychiatric disorders worldwide. Depression is a multifaceted condition characterized by episodes of mood disorders and other symptoms such as anhedonia, psychomotor complaints, self-blame, attention deficits, and suicidality, all of which can vary in severity. According to the World Health Organization, the discovery of mainstream antidepressants revolutionized the management of depression, but still up to 60% of patients are inappropriately treated. This is often due to delayed therapeutic effects of the drugs (generally 6 weeks after the start of treatment), side effects that lead to non-compliance, or inherent unresponsiveness to them. Similarly, anxiety disorders are a collection of etiologically complex disorders characterized by intense psychosocial distress and other symptoms depending on the subtype. Anxiety associated with life-threatening illnesses is the only anxiety subtype that has been studied in relation to hallucinogen-assisted therapy. This form of anxiety affects up to 40% of individuals diagnosed with life-threatening illnesses such as cancer. It manifests as anxiety about future danger or fate accompanied by physical symptoms of dysphoria or tension, and often coexists with depression. This is associated with poor quality of life, poor adherence to treatment, prolonged hospitalization, increased disability, and feelings of helplessness, which contribute to overall poor survival.Pharmacological and psychosocial interventions are commonly used to manage this type of anxiety, but their effectiveness is mixed and limited, as they often fail to provide satisfactory emotional relief.Recent interest in the use of hallucinogen-assisted therapy may be a promising alternative for patients with depression and anxiety that are not effectively managed by traditional methods.

[0019] In general, hallucinogen treatment models consist of administering an orally active drug to induce a mystical experience lasting 4-9 hours, depending on the hallucinogen [Halberstadt, Behav Brain Res., 2015, 277:99-120; Nichols, Pharmacol Rev., 2016, 68(2): 264-355]. This allows participants to overcome and integrate difficult emotions and situations, resulting in sustained antidepressant and anxiolytic effects. Classic hallucinogens such as psilocybin and LSD have been investigated as potential candidates. One study with classic hallucinogens for the treatment of depression and anxiety associated with a life-threatening illness found that in a supportive context, psilocybin and LSD consistently produced significant and sustained antidepressant and anxiolytic effects.

[0020] Further emerging clinical studies and evidence suggest that hallucinogen-assisted therapy may also show potential as an alternative treatment for volatile substance use disorders and mental health conditions, and thus may be an important tool in acute episodes where existing approaches have provided limited success. A recent systematic review of clinical trials published over the past 25 years summarizes some of the antidepressant, anxiolytic, and anti-addictive effects of classical hallucinogens. Among these, there are promising findings from a meta-analysis of randomized controlled trials of LSD therapy, and a recent pilot study of psilocybin-assisted therapy to treat alcohol use disorder [dos Santos et al., Ther Adv Psychopharmacol., 2016, 6(3):193-213]. Equally encouraging are findings from a recent pilot study of psilocybin-assisted therapy for tobacco use disorder, which demonstrated abstinence rates of 80% at 6-month follow-up and 67% at 12-month follow-up [Johnson et al., J Drug Alcohol Abuse, 2017 43(1):55-60; Johnson et al., 2014, Psychopharmacol. 2014, 28(11):983-992], rates significantly higher than any documented in the smoking cessation literature. Of note, mystical experiences evoked from psilocybin sessions were significantly correlated with positive treatment outcomes. These results are consistent with evidence of bullsion from recent clinical trials, supporting the efficacy of psilocybin-assisted treatment for treatment-resistant depression and end-of-life anxiety [Carhart-Harris et al. Neuropsychopharmacology, 2017 42(11):2105-2113].

[0021] Research on the potential benefits of hallucinogen-assisted treatment for opioid use disorder (OUD) is beginning to emerge, and accumulating evidence supports the need to advance this line of investigation. Available evidence from previous randomized clinical trials suggests a promising role for treating OUD; namely, higher abstinence rates were observed among participants receiving high-dose LSD- and ketamine-assisted treatment for heroin addiction compared to controls at long-term follow-up. Recently, a large US population study of 44,000 individuals found that hallucinogen use was associated with a 40% lower risk of opioid abuse and a 27% lower risk of opioid dependence in the following year, as defined by DSM-IV criteria [Pisano et al., J Psychopharmacol., 2017, 31(5):606-613]. Similarly, a protective moderating effect of hallucinogen use was found in the relationship between prescription opioid use and suicide risk in marginalized women [Argento et al., J. Psychopharmacol., 2018, 32(12):1385-1391].

[0022] Regular doses of hallucinogens also improve sleep disturbances, which are very common in depressed patients, with over 80% of depressed patients complaining of poor quality sleep. Sleep symptoms are often unresolved by first-line treatments and are associated with a higher risk of relapse and recurrence. Interestingly, sleep problems often appear before other depressive symptoms, and subjective sleep quality worsens before the onset of an episode in recurrent depression. Brain regions showing increased functional connectivity with sleep deprivation scores and higher depressive symptomatology scores included prefrontal and limbic regions, regions involved in emotion processing. Insomnia in healthy participants demonstrates that sleep is indeed involved in mood, emotional appraisal processes, and brain responses to emotional stimuli. For example, one study showed increased negative mood and mood-independent mislabeling of negative and neutral stimuli, while another study demonstrated an amplified reactivity of limbic brain regions in response to both negative and positive stimuli. Two other studies evaluating electroencephalography (EEG) brain activity during sleep have shown that hallucinogens such as LSD have a positive effect on sleep patterns. In addition, it has been shown that overnight partial sleep deprivation can alleviate symptoms of depression, suggested by resetting circadian rhythms via modification of clock gene expression. Furthermore, it has been suggested that a single dose of hallucinogens causes a resetting of the biological clock underlying the sleep / wake cycle, thereby improving cognitive and emotional processes in depressed individuals, but also improving well-being and enhancing mood in healthy individuals [Kuypers, Medical Hypotheses, 2019, 125:21-24].

[0023] A systematic meta-analysis of clinical trials from 1960 to 2018 investigating the therapeutic use of hallucinogen treatment in patients with serious or terminal illnesses and associated psychiatric illnesses found that hallucinogen therapy (mainly with LSD) can improve cancer-related depression, anxiety, and fear of death. Between 2011 and 2016, four randomized controlled clinical trials were published, mainly with psilocybin treatment, which demonstrated that hallucinogen-assisted treatment can result in rapid, robust, and sustained improvements in cancer-related psychological and existential distress [Ross, Int. Rev. Psychiatry, 2018, 30(4):317-330]. The use of hallucinogens in the field of oncology and palliative care is therefore of interest for several reasons. First, many patients facing cancer or other life-threatening illnesses experience significant existential distress related to the loss of meaning or purpose in life, which may be associated with feelings of helplessness, demoralization, apathy, a sense of perceived burden, and a desire for premature death. These features are also often at the heart of clinically significant anxiety and depression, which can substantially reduce the quality of life in this patient population. Relief of these forms of morbidity should be one of the central aims of palliative care. Thus, in recent years, several manualized psychotherapies for cancer-related existential distress have been developed, with an emphasis on dignity and meaning-making. However, currently there are no pharmacological interventions for existential distress itself, and available pharmacological treatments for depressive symptoms in patients with cancer have not demonstrated superiority over placebo. Additional effective treatments for these conditions remain needed [Rosenbaum et al., Curr. Oncol., 2019, 26(4): 225-226].

[0024] Recently, interest has been growing in a new administration paradigm for hallucinogens such as psilocybin and LSD, colloquially referred to as microdosing.Under this paradigm, approximately 10% or less of the total dose, which is the sub-perceptual dose of serotonergic hallucinogen, is taken on a more consistent basis, such as once a day, every other day, or every third day.Not only is this administration paradigm more consistent with the current standards in pharmacological care, but it may also be particularly beneficial for certain conditions, such as Alzheimer's disease and other neurodegenerative diseases, attention deficit disorder, attention deficit hyperactivity disorder, and for certain patient populations, such as the elderly, the young, and patients who fear or are opposed to hallucinogen-assisted therapy.In addition, this approach may be particularly well suited to managing cognitive deficits and preventing neurodegeneration. For example, subpopulations of low-attention and low-motivation rats demonstrate improved performance on five-choice serial reaction time and progressive ratio tasks, respectively, after a subthreshold dose of psilocybin to induce the classical wet dog shake behavioral response associated with hallucinogenic doses (Blumstock et al., WO 2020 / 157569A1; Higgins et al., 2021). Similarly, treatment of patients with hallucinogenic doses of 5-HT2A agonists is associated with increased BDNF and activation of the mTOR pathway, which are believed to promote neuroplasticity and are hypothesized to serve as molecular targets for the treatment of dementia and other neurodegenerative disorders (Ly et al. Cell Rep., 2018; 23(11):3170-3182).Moreover, several groups have demonstrated that non-hallucinogenic and non-psychotic low doses of 5-HT2A agonists also exhibit similar neuroprotective and increased neuroplastic effects (neuroplastogens) and reduced neuroinflammation, which may be beneficial in both neurodegenerative and neurodevelopmental diseases, as well as chronic disorders, and may be mediated by other receptors, including trace amino acid-associated receptors (Manfredi et al., WO 2020 / 181194, Flanagan et al., Int. Rev. Psychiatry, 2018, 13:1-13; Nichols et al., 2016, Psychedelics as medicines; an emerging new paradigm). This repeated low dose paradigm may extend the utility of these compounds to additional indications and may prove useful for health applications.

[0025] 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT; 3, Scheme 1) is a tryptamine natural product most commonly identified as the major psychoactive component of the parotid gland secretions of the Sonoran Desert toad, Incilius alvarius, and is present in low concentrations in a variety of plants, shrubs, and seeds [Uthaug, MV et al., Psychopharmacology 2019, 236:2653-2666; Weil et al., J. Ethnopharmacol. 1994, 41(1-2):1-8]. N,N-Dimethyltryptamine (DMT; 2, Scheme 1) is a tryptamine natural product most commonly identified as the primary psychoactive component of various natural plants and vines, including Acacia, Desmodium, Mimosa, Virola, Delosperma, and Phalaris. Human consumption of these substances for their psychoactive properties has been reported for hundreds of years [Agurell et al., Acta Chem. Scand. 1969, 23(3):903-916; Torres et al., Haworth Herbal Press: New York, 2014].

[0026] 5-MeO-DMT demonstrates submicromolar binding affinity at most serotonin receptor subtypes expressed in the CNS, with approximately 300-fold selectivity for human 5-HT1A (3±0.2 nM) versus 5-HT2A (907±170 nM) receptor subtypes [Halberstadt et al., Psychopharmacology, 2012, 221(4):709-718]. DMT has more than three-fold binding affinity for 5-HT1A (0.075 μM) versus 5-HT2A (0.237 μM). Data suggest that activation of 5-HT1A receptors may also play a significant role in contributing to the subjective and behavioral effects induced by hallucinogens, in synergy with 5-HT2A activation. In contrast to 5-MeO-DMT and DMT, psilocin (the active metabolite of psilocybin) is approximately five-fold more selective for the human 5-HT2A receptor (107 nM) versus 5-HT1A (567 nM) [Sherwood et al., ACS Omega, 2020, 5(49):32067-32075].

[0027] Consumption of 5-MeO-DMT has been reported to result in a general lack of colorful geometric visual hallucinations typically associated with other hallucinogens, including DMT. It has also been suggested that both 5-MeO-DMT and DMT may be useful in the treatment of clinical mental health conditions [Barsuglia et al. Front. Psychol. 2018, 9:2459; Davis et al., Am. J. Drug Alcohol Abuse, 2019, 45(2):161-169; Malcolm et al., Mental Health Clinician, 2017, 7(1):39-45; Uthaug, MV et al., Psychopharmacology 2019, 236:2653-2666]. These data suggest that 5-MeO-DMT and DMT produce mystical experiences of equal or greater intensity than those produced by psilocybin, but with a shorter duration of effect, lasting 10-60 minutes depending on the route of administration.

[0028] It has been reported that fatty acids can enhance the activity of certain antidepressant drugs at low, non-antidepressant doses [Laino, CH et al. European Journal of Pharmacology (2010), 648:117-126; Carlezon, WA Jr. et al. Biol. Psychiatry(2005), 57:343-350]. Some reports have shown that omega-3 fatty acids have antidepressant activity when administered chronically [Lakhwani, L. et al. Acta Poloniae Pharmaceutica-Drug Research (2007), 64:271-276]. Docosahexanaenoic acid (DHA) has been reported to provide a synergistic effect that enhances the absorption of carotenoids such as lutein (U.S. Patent Application Publication No. US2006 / 0270739). Furthermore, DHA has been implicated in enhancing brain and cognitive development and maintenance during aging and neuropsychiatric disorders in both humans and animals [Ciappolino, V. et al., Nutrients (2019), 11:769 doi 10.3990 / nu11040769; Lauritzen, L. et al. Nutrients (2016), 8:6 doi 10.3390 / nu8010006; Weiser, MJ et al., Nutrients (2016), 8:99 doi 10.3990 / nu8020099]. Summary of the Invention [Means for solving the problem]

[0029] In this application, the combination of fatty acids and hallucinogens is shown to provide synergistic effects in animal models for hallucinogenic activity.

[0030] Thus, in some embodiments, the present application includes pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0031] The application also includes kits comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are included in a single pharmaceutical composition or are included in separate pharmaceutical compositions.

[0032] In some embodiments, the application also includes a method of treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor, comprising administering to a subject in need thereof an effective amount of one or more hallucinogens, or pharma-ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma-ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0033] In some embodiments, the application also includes a method of improving the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, comprising administering to a subject in need thereof an effective amount of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in combination with an effective amount of one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0034] Other features and advantages of the present application will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while indicating embodiments of the present application, are given by way of illustration only, and the claims should not be limited by these embodiments, but should be accorded the broadest interpretation consistent with the description as a whole.

[0035] Embodiments of the present application will now be described in more detail with reference to the accompanying drawings. [Brief description of the drawings]

[0036] [Figure 1] FIG. 1 shows that linoleic acid (LA) alone has no significant effect on head twitching up to 10 mg / kg SC. [Diagram 2] FIG. 1 shows that the combination of linoleic acid (LA) with compounds I-4 or psilocybin produces more head twitches compared to I-4 or psilocybin alone. [Diagram 3] FIG. 1 shows that the increased number of head twitches produced by linoleic acid (LA) in combination with compound I-4 or psilocybin can be attributed to an increased duration of action. [Figure 4] FIG. 1 shows that pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.5 mg / kg IP) completely blocked the development of head twitches induced by either I-4 (6.2 mg / kg SC) or psilocybin (3 mg / kg SC). [Diagram 5] Figure 1 shows a comparison of the mean (±SD, n=3) plasma concentration versus time profiles of exemplary 5-MeO-DMT and its metabolite, bufotenine, between the standard and sponsor formulations following (A) intranasal (IN) and (B) subcutaneous (SC) administration of 5-MeO-DMT to groups of three male Sprague-Dawley rats. The standard formulation contained 5-MeO-DMT at the appropriate concentration prepared in 10% dimethylsulfoxide (DMSO) and 90% (v / v) saline, and the sponsor formulation additionally contained 3% linoleic acid. [Figure 6] FIG. 1 shows a comparison of the mean (±SD, n=3) CSF concentration versus time profiles of an exemplary 5-MeO-DMT and its metabolite, bufotenin, between the standard and sponsor formulations following (A) intranasal and (B) subcutaneous administration of 5-MeO-DMT to groups of three male Sprague-Dawley rats. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] I. Definition Unless otherwise indicated, the definitions and embodiments described in this section and other sections are intended to be applicable to all embodiments and aspects of the application described herein where they are suitable, as would be understood by one of ordinary skill in the art.

[0038] All features disclosed in this specification, including the claims, abstract, and drawings, and all steps of any disclosed method or process, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. Each feature disclosed in this specification, including the claims, abstract, and drawings, may be replaced by an alternative feature serving the same, equivalent, or similar purpose, unless otherwise stated.

[0039] As used herein, the terms "composition(s) of the application" or "composition(s) of the application" and the like refer to a composition, such as a pharmaceutical composition, that includes one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0040] As used herein, the terms "intranasal composition(s) of the application" or "intranasal composition(s) of the application" and the like refer to an intranasal composition, such as an intranasal pharmaceutical composition, that includes one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma-ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0041] The term "kit(s) of the application" or "kit(s) of the application" as used herein refers to a kit, such as a pharmaceutical kit, that includes one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, where the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are included in a single pharmaceutical composition or are included in separate pharmaceutical compositions.

[0042] The term "and / or" as used herein means that the listed items are present or used individually or in combination. In practice, the term means that "at least one" or "one or more" of the listed items are used or present. The term "and / or" with respect to pharma-ceutically acceptable salts and / or solvates thereof means that the compounds of the present application are present as individual salts and solvates as well as combinations of salts, for example, solvates of the compounds of the present application.

[0043] As used herein, the term "one or more" items includes a single item selected from a list, as well as mixtures of two or more items selected from a list.

[0044] As used in this application, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, an embodiment including "fatty acid" should be understood to present a particular embodiment having one fatty acid, or two or more additional fatty acids.

[0045] In embodiments that include an "additional" or "second" component, such as an additional fatty acid or a second fatty acid, the second component, as used herein, is chemically distinct from the other components or the first component. A "third" component is distinct from the other first and second components, and further recited or "additional" components are similarly distinct.

[0046] As used in this application and the claims, words such as "comprising" (and any form of including, such as "comprise" and "comprises"), "including" (and any form of including, such as "include" and "includes"), or "containing" (and any form of containing, such as "contain" and "contains") are inclusive or open ended and do not exclude additional, unrecited elements or process steps.

[0047] As used herein, the term "consisting of" and its derivatives are intended to be closed terms that specify the presence of stated features, elements, components, groups, integers, and / or steps, and also exclude the presence of other unrecited features, elements, components, groups, integers, and / or steps.

[0048] As used herein, the term "consisting essentially of" is intended to specify the presence of recited features, elements, components, groups, integers, and / or steps, as well as things that do not materially affect the basic and novel characteristics of those features, elements, components, groups, integers, and / or steps.

[0049] The term "suitable" as used herein means that the selection of a particular compound or condition will depend on the particular synthetic operation being performed, the identity of the molecule being transformed, and / or the particular use of the compound, but that the selection is well within the skill of one of ordinary skill in the art. All process / method steps described herein should be performed under conditions sufficient to provide the indicated product. One of ordinary skill in the art will understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reaction ratios, and whether the reaction should be performed under anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product, and that doing so is within the skill of one of ordinary skill in the art.

[0050] As used herein, the terms "about," "substantially," and "approximately" refer to a reasonable amount of deviation from the modified term such that the end result is not materially altered. These terms of degree should be interpreted as including a deviation of at least ±5% of the modified term, unless this deviation would negate the meaning of the word it modifies or the context would suggest otherwise to one of ordinary skill in the art.

[0051] This specification refers to several chemical terms and abbreviations used by those of ordinary skill in the art. Nonetheless, for clarity and consistency, definitions of selected terms are provided.

[0052] The term "solvate" as used herein means a compound or a salt or prodrug of a compound, wherein molecules of a suitable solvent are incorporated into the crystal lattice, said suitable solvent being physiologically acceptable at the dosage administered.

[0053] As used herein, the term "fatty acid" refers to a carboxylic acid having a long aliphatic chain, which is either saturated or unsaturated, straight chain or branched.

[0054] The term "hallucinogen" as used herein refers to a compound that is psychoactive and / or often or usually causes hallucinations, perceptual abnormalities, and / or other substantial subjective changes in thought, emotion, and / or consciousness. As used herein, hallucinogens include compounds classified as hallucinogens, dissociative agents, entactogens, stimulants, empathetic, psychotomimetic, and / or deliriant.

[0055] The term "hallucinogens" as used herein refers to a class of hallucinogenic compounds that exert their primary effects through serotonin receptors, generally regarded as 5-HT2A receptors, but may also exert effects through other serotonin receptors, such as 5-HT1A, dopamine receptors, N-methyl-D-aspartate receptors, kappa opioid receptors, sigma 1 receptors, or trace amino acid associated receptors, or any combination thereof.

[0056] As used herein, the term "alkyl" whether used alone or as part of another group, means a straight or branched chain saturated alkyl group. The number of possible carbon atoms in the referenced alkyl group is determined by the prefix "C n1~n2 ". So, for example, "C 1~6The term "alkyl" (or "C1-C6 alkyl") refers to an alkyl group having 1, 2, 3, 4, 5, or 6 carbon atoms, and includes, for example, any of the hexyl, alkyl, and pentyl alkyl isomers, as well as n-butyl, iso-butyl, sec-butyl, tert-butyl, n-propyl, iso-propyl, ethyl, and methyl. As another example, "C4 alkyl" refers to n-butyl, iso-butyl, sec-butyl, tert-butyl, n-isopropyl and isopropyl, ethyl, and methyl.

[0057] The term "alkenyl," whether used alone or as part of another group, refers to a straight or branched chain saturated alkylene group, i.e., a saturated carbon chain containing substituents at both ends. The number of possible carbon atoms in the referenced alkylene group is determined by the prefix "C n1~n2 For example, C 2~6 The term alkylene refers to alkylene groups having 2, 3, 4, 5 or 6 carbon atoms.

[0058] The term "alkynyl," as used herein, whether used alone or as part of another group, means a straight or branched chain unsaturated alkynyl group containing at least one triple bond. The number of possible carbon atoms in the referenced alkyl group is determined by the prefix "C". n1~n2 For example, C 2~6 The term alkynyl refers to alkynyl groups having 2, 3, 4, 5 or 6 carbon atoms.

[0059] The term "cycloalkyl," as used herein, whether used alone or as part of another group, means a saturated carbocyclic group containing from 3 to 20 carbon atoms and one or more rings. The number of possible carbon atoms in the referenced cycloalkyl group is indicated by the numerical prefix "C". n1~n2 For example, C 3~10The term cycloalkyl refers to a cycloalkyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.

[0060] As used herein, the term "aryl," whether used alone or as part of another group, refers to a carbocyclic group containing at least one aromatic ring and containing anywhere from 6 to 20 carbon atoms.

[0061] The term "available," such as "available hydrogen atom" or "available atom," refers to an atom known to one of ordinary skill in the art to be available for substitution with a substituent.

[0062] As used herein, the term "heterocycloalkyl," whether used alone or as part of another group, refers to a cyclic group containing at least one non-aromatic ring containing 3 to 20 atoms, where one or more atoms are hetero moieties selected from O, S, S(O), SO2, and N, and the remaining atoms are C. Heterocycloalkyl groups are either saturated or unsaturated (i.e., contain one or more double bonds). Heterocycloalkyl groups are denoted by the prefix C. n1~n2 Or, when it contains "n1-n2", the prefix indicates the number of carbon atoms of the corresponding carbocyclic group, where one or more, preferably 1 to 5, of the ring atoms are replaced with a hetero moiety such as selected from O, S, S(O), SO2, and N, and the remaining atoms are C. The heterocycloalkyl group is optionally benzo-fused.

[0063] As used herein, the term "heteroaryl," whether used alone or as part of another group, refers to a cyclic group containing at least one heteroaromatic ring containing 5 to 20 atoms, where one or more of the atoms are heteroatoms selected from O, S, and N, and the remaining atoms are C. Heteroaryl groups are denoted by the prefix C. n1~n2When the prefix "a" or "b" contains a cyclic group, the prefix indicates the number of carbon atoms in the corresponding carbocyclic group in which one or more, preferably one to five, of the ring atoms are replaced with a heteroatom as defined above. A heteroaryl group is optionally benzo-fused.

[0064] All cyclic groups, including aryl, heteroaryl, heterocycloalkyl, and cycloalkyl groups, contain one or more rings (i.e., are polycyclic). When a cyclic group contains more than one ring, the rings may be fused, bridged, spiro-fused, or joined by bonds.

[0065] As used herein, the term "benzofused" refers to a polycyclic group in which a benzene ring is fused to another ring.

[0066] A first ring is "fused" to a second ring means that the first ring and the second ring share two adjacent atoms between them.

[0067] A first ring is "bridged" with a second ring means that the first ring and the second ring share two non-adjacent atoms between them.

[0068] A first ring is "spirofused" to a second ring means that the first ring and the second ring share one atom between them.

[0069] The term "halogen" (or "halo"), whether used alone or as part of another group, refers to a halogen atom and includes fluoro, chloro, bromo, and iodo.

[0070] The term "haloalkyl" as used herein refers to an alkyl group as defined above in which one or more available hydrogen atoms have been replaced with a halogen. Thus, for example, "C 1~6"Haloalkyl" (or "C1-C6 haloalkyl") refers to a C1 to C6 straight or branched alkyl group, as defined above, having one or more halogen substituents.

[0071] As used herein, the term "haloalkenyl" refers to an alkenyl group as defined above in which one or more available hydrogen atoms have been replaced with a halogen. Thus, for example, "C 1~6 "(Haloalkenyl)" (or "C1-C6 haloalkenyl") refers to a C1-C6 straight or branched alkenyl group, as defined above, having one or more halogen substituents.

[0072] As used herein, the term "haloalkynyl" refers to an alkynyl group as defined above in which one or more available hydrogen atoms have been replaced with a halogen. Thus, for example, "C 1~6 "Haloalkynyl" (or "C1-C6 haloalkynyl") refers to a C1-C6 straight or branched alkynyl group as defined above having one or more halogen substituents.

[0073] As used herein, the term "alkoxy", alone or in combination, includes an alkyl group attached to an oxygen-linking atom.

[0074] The term "substituted," as used herein, unless otherwise indicated, means that the referenced group is substituted with one or more substituents independently selected from halogen, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, SOCH, SOCH, C-C alkyl, C-C haloalkyl, C-C alkenyl, C-C haloalkenyl, C-C alkynyl, C-C haloalkynyl, C-C cycloalkyl, and 3-6 membered heterocycles containing 1-2 ring members selected from O, S, S(O), SO, N, NH, and NCH.

[0075] As used herein, the term "alternate isotope" refers to an isotope of an element other than the most abundant isotope occurring in nature.

[0076] As used herein, the term "all available atoms optionally replaced with alternative isotopes" means that available atoms are optionally replaced with an isotope of that atom having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number primarily found in nature.

[0077] The term "compound" refers to a compound and, in certain embodiments, any hydrates and / or solvates thereof, so long as they are stable. A hydrate is a compound complexed with water, and a solvate is a compound complexed with a solvent, which may be an organic or inorganic solvent. A "stable" compound is one that can be prepared and isolated, and whose structure and properties remain unchanged or essentially unchanged for a period of time sufficient to permit the use of the compound for the purposes described herein (e.g., therapeutic administration to a subject).

[0078] The term "pharmaceutical acceptable" means compatible with the treatment of a subject.

[0079] The term "pharmaceutical acceptable carrier" means a non-toxic solvent, dispersant, excipient, adjuvant, or other material with which one or more active ingredients are combined to form a pharmaceutical composition, i.e., a dosage form that can be administered to a subject.

[0080] The term "pharmaceutically acceptable salt" means either an acid addition salt or a base addition salt that is suitable or compatible with the treatment of a subject.

[0081] The acid addition salt suitable or compatible for the treatment of a subject is any non-toxic organic or inorganic acid addition salt of any basic compound.

[0082] A base addition salt suitable or compatible for the treatment of a subject is any non-toxic organic or inorganic base addition salt of any acidic compound.

[0083] As used herein, terms such as "protecting group" or "PG" refer to a chemical moiety that protects or masks the reactive portion of a molecule while manipulating or reacting a different portion of the molecule, preventing side reactions at the reactive portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portion of the molecule. Selection of a suitable protecting group can be made by one of ordinary skill in the art. Many conventional protecting groups are described, for example, in "Protective Groups in Organic Chemistry" McOmie, JFW Ed., Plenum Press, 1973, in Greene, TW and Wuts, PGM, "Protective Groups in Organic Synthesis", John Wiley & Sons, 3 rd Edition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas).

[0084] As used herein, the term "subject" includes all members of the animal kingdom, including mammals, and preferably refers to humans. Thus, the methods of the present application are applicable to both human therapy and veterinary applications.

[0085] The terms "treated," "treating," or "treatment," as used herein and as well understood in the art, refer to an approach for obtaining beneficial or desired results, including clinical results.

[0086] As used herein, the term "effective amount" or "therapeutically effective amount" refers to an amount that is effective at the dosage and for the period of time necessary to achieve a desired result. For example, in the context of treating a disease, disorder, or condition that is treated by activating serotonin receptors, an effective amount is, for example, an amount that increases activation compared to activation in the absence of administration of one or more compounds.

[0087] "Palliating" a disease, disorder, or condition means that the severity and / or undesirable clinical signs of the disease, disorder, or condition are reduced and / or the time course of progression is slowed or prolonged compared to not treating the disorder.

[0088] As used herein, the term "administration" refers to administration of a therapeutically effective amount of one or more compositions of the present application to a cell, tissue, organ, or subject.

[0089] As used herein, the terms "prevention" or "prophylaxis" or synonyms thereof refer to a reduction in the risk or probability that a subject will suffer from a disease, disorder, or condition, or exhibit symptoms associated with a disease, disorder, or condition.

[0090] As used herein, a "disease, disorder, or condition" refers to a condition that affects a serotonin receptor, such as 5-HT 2A By way of activation of a serotonin receptor, the term refers in particular to a disease, disorder, or condition that is treated with a serotonin receptor agonist, such as one or more of the hallucinogens described herein.

[0091] As used herein, the term "disease, disorder, or condition treated by activation of serotonin receptors" means that the disease, disorder, or condition being treated is influenced by, regulated by, and / or has some biological basis, either directly or indirectly, that involves serotonergic activity, particularly increased serotonergic activity. These diseases respond favorably when serotonergic activity associated with the disease, disorder, or condition is stimulated by one or more hallucinogens.

[0092] As used herein, the term "activation" includes agonism, partial agonism, and positive allosteric modulation of serotonin receptors.

[0093] The terms "5-HT1A", "5-HT2A", and "5-HT2C" are used herein to refer to the 5-HT1A, 5-HT2A, and 5-HT2C receptor subtypes of the 5-HT1 and 5-HT2 serotonin receptors, respectively.

[0094] As used herein, the term "therapeutic agent" refers to any drug or active agent that has a pharmacological effect when administered to a subject.

[0095] As used herein, the term "intranasal composition" refers to a composition that is delivered to the nasal cavity and / or paranasal sinuses.

[0096] As used herein, the term “5-MeO-DMT” refers to a compound having the chemical name 5-methoxy-N,N-dimethyltryptamine and having the following chemical structure:

[0097] [ka]

[0098] The term "bioavailability" as used herein refers to the rate and extent to which an active compound reaches the systemic circulation as an intact drug.

[0099] The term "Cmax" as used herein refers to the maximum concentration (or peak concentration) of a compound in a reference material following a single administration of the compound.

[0100] The term "Tmax" as used herein refers to the time to reach the maximum concentration in a reference material following administration of a compound.

[0101] As used herein, the term "AUC" refers to the area under the curve that represents the change in concentration of a compound in a reference material over time. As used herein, the terms "increased" or "decreased" refer to any detectable increase / decrease in a parameter in the presence of a variable compared to otherwise similar / same conditions except in the absence of the variable.

[0102] II. Compositions and Kits of the Present Application The present application includes pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0103] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in an amount effective to treat or prevent a disease, disorder, or condition treated by activation of a serotonin receptor.

[0104] The application also includes pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, where the one or more fatty acids are present in an amount effective to improve the efficacy of the one or more hallucinogens in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor.

[0105] The application also includes kits comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are included in a single pharmaceutical composition or are included in separate pharmaceutical compositions.

[0106] The application also includes kits for treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor, comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are included in a single pharmaceutical composition or are included in separate pharmaceutical compositions, and wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in amounts to treat or prevent a disease, disorder, or condition treated by activation of a serotonin receptor.

[0107] The application also includes a kit for improving the effectiveness of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor, comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are included in a single pharmaceutical composition or are included in separate pharmaceutical compositions, and wherein the one or more fatty acids are present in an amount effective to improve the effectiveness of the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor.

[0108] In some embodiments, the kit further comprises instructions for administering the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, to a subject in need thereof.

[0109] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from any hallucinogen known to be used in medical therapy or treatment for any disease, disorder, or condition that is treated, for example, by activation of serotonin receptors. In some embodiments, the one or more hallucinogens are selected from one or more hallucinogens. In some embodiments, the one or more hallucinogens are selected from psilocybin, psilocin, dimethyltryptamine (DMT), 5-methoxy-dimethyltryptamine (5-MeO-DMT), mescaline, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ibogaine, ketamine, and salvinorin A, or pharma-ceutically acceptable salts thereof, prodrugs thereof, and / or solvates thereof. In some embodiments, the composition comprises one hallucinogen. In some embodiments, the one or more hallucinogens are phenethylamines, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. In some embodiments, the one or more hallucinogens are psilocybin, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0110] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the following: 9,10-didehydro-6-allyl-N,N-diethylergoline-8β-carboxamide; 9,10-didehydro-6,N,N-triethylergoline-8β-carboxamide; N,N-Dibutyltryptamine; N,N-Diethyltryptamine; N,N-Diisopropyltryptamine; 5-Methoxy-α-methyltryptamine; 2,α-Dimethyltryptamine; α,N-Dimethyltryptamine; N,N-Dipropyltryptamine; N-Ethyl-N-isopropyltryptamine; α-Ethyltryptamine; Harmaline (7-methoxy-1-methyl-β-carboline) (deaminase blocker); Harmine (7-methoxy-β-carboline) (deaminase blocker); 4-Hydroxy-diethyltryptamine and phosphate esters; 4-Hydroxy-diisopropyltryptamine; 4-hydroxy-methyl-tryptamine; 4-hydroxy-tryptamine; 5-hydroxy-tryptamine; 4-Hydroxy-dipropyltryptamine; 4-hydroxy-n-methyl-n-ethyl-tryptamine; 4-Hydroxy-N-methyl-N-isopropyl-tryptamine; 4-Hydroxy-N-methyl-N-ethyl-tryptamine; 4-Hydroxy-NN-tetramethylene-tryptamine; d-iso-LSD; l-LSD; l-iso-LSD; N,N-Diisopropyl-4,5-methylenedioxytryptamine; N,N-Diisopropyl-5,6-methylenedioxytryptamine; N,N-Dimethyl-4,5-methylenedioxytryptamine; N,N-Dimethyl-5,6-methylenedioxytryptamine; 2-Methyl-DMT; 5-MeO-diethyltryptamine; 5-MeO-diisopropyltryptamine; 4-MeO-N-isopropyl-N-methyl-tryptamine; 5-MeO-N-isopropyl-N-methyl-tryptamine; 5-MeO-NMT; 5-MeO-2,N,N-trimethyltryptamine; N-isopropyl-N-methyl-tryptamine; Alpha-methyltryptamine; Alpha-methyl-4-OH-tryptamine; N-methyl-tryptamine; 5-MeO-α,N-dimethyl-tryptamine; 4-Allyloxy-3,5-diemethoxyphenethylamine; 2,5-dimethoxy-4-methylthioamphetamine; 2,5-dimethoxy-4-ethylthioamphetamine; 2,5-Dimethoxy-4-(i)-propylthioamphetamine; 2,5-dimethoxy-4-phenylthioamphetamine; 2,5-Dimethoxy-4-(n)-propylthioamphetamine; 2,5-Dimethoxy-α-ethyl-4-methylphenethylamine; 3,4-Diethoxy-5-methoxy-phenethylamine; 4-(n)-Butoxy-3,5-dimethoxy-phenethylamine; 2,5-Dimethoxy-4,N-Dimethylamphetamine 4-Bromo-2,5-β-trimethoxyphenethylamine; 4-Methyl-2,5,β-trimethoxyphenethylamine; β-Methoxy-3,4-methylenedioxyphenethylamine; 3,4,5,β-Tetramethoxyphenethylamine; 3,5-Dimethoxy-4-bromoamphetamine; 2-Bromo-4,5-methylenedioxyamphetamine; 4-Bromo-2,5,dimethoxyphenethylamine; 4-benzyloxy-3,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-chlorophenethylamine; 2,5-Dimethoxy-4-methylphenethylamine; 2,5-Dimethoxy-4-ethylphenethylamine; 3,5-dimethoxy-4-ethoxyamphetamine; 2,5-Dimethoxy-4-fluorophenethylamine; 2,5-Dimethoxy-3,4-dimethylphenethylamine; 2,5-Dimethoxy-3,4-(trimethylene)phenethylamine; 2,5-Dimethoxy-3,4-(tetramethylene)phenethylamine; 3,6-Dimethoxy-4-(2-aminoethyl)benzonorborane; 1,4-Dimethoxynaphthyl-2-ethylamine; 2,5-Dimethoxyphenethylamine; 2,5-Dimethoxy-4-iodophenethylamine; 2,5-Dimethoxy-4-nitrophenethylamine; 2,5-Dimethoxy-4-(i)-propoxyphenethylamine; 2,5-Dimethoxy-4-(n)-propoxyphenethylamine; 4-Cyclopropyl-3,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-methylseleneophenethylamine; 2,5-Dimethoxy-4-methylthiophenethylamine; 2,5-Dimethoxy-4-ethylthiophenethylamine; 2,5-Dimethoxy-4-(i)-propylthiophenethylamine; 2,6-Dimethoxy-4-(i)-propylthiophenethylamine; 2,5-Dimethoxy-4-(n)-propylthiophenethylamine; 2,5-Dimethoxy-4-cyclopropylmethylthiophenethylamine; 2,5-Dimethoxy-4-(t)-butylthiophenethylamine; 2,5-Dimethoxy-4-(2-methoxyethylthio)phenethylamine; 2,5-Dimethoxy-4-cyclopropylthiophenethylamine; 2,5-Dimethoxy-4-(s)-butylthiophenethylamine; 2,5-Dimethoxy-4-(2fluorothio)phenethylamine; 3,5-Dimethoxy-4-trideuteromethoxyphenethylamine; 3,4,5-trimethoxy-β,β-dideuterophenethylamine; 3,5-Dimethoxy-4-methylphenethylamine; 2,4-Dimethoxyamphetamine; 2,5-dimethoxyamphetamine; 3,4-Dimethoxyamphetamine; 2,5-dimethoxy-3,4-methylenedioxyamphetamine; 2,5-Dimethoxy-4-bromoamphetamine; 2,5-dimethoxy-4-chloroamphetamine; 2,5-Dimethoxy-4-(2fluoroethyl)-amphetamine; 2,5-dimethoxy-4-iodoamphetamine; 2,5-dimethoxy-4-methylamphetamine; 2,6-dimethoxy-4-methylamphetamine; 2,5-dimethoxy-4-(n)-propylamphetamine; 3,5-Dimethoxy-4-ethoxyphenethylamine; 2,4,5-triethoxyamphetamine; 2,4-diethoxy-5-methoxyamphetamine; 2,5-diethoxy-4-methoxyamphetamine; 4,5-dimethoxy-2-ethoxyamphetamine; N-hydroxy-N-methyl-3,4-methylenedioxyamphetamine; 2,5-dimethoxy-3,4-(trimethylene)amphetamine; 3,6-Dimethoxy-4-(2-aminopropyl)benzonorborane; 2,5-dimethoxy-3,4-dimethylamphetamine; 2,5-Dimethoxy-4-ethylthio-N-hydroxyphenethylamine; 2,5-Dimethoxy-N-hydroxy-4-(n)-propylthiophenethylamine; 2,5-Dimethoxy-4-(s)-butylthio-N-hydroxyphenethylamine; 3,5-Dimethoxy-4-(i)-propoxyphenethylamine; 5-ethoxy-2-methoxy-4-methylamphetamine; 2-Amino-(3,4-methylenedioxyphenyl)butane; 3-Methoxy-4,5-methylenedioxyphenethylamine; 3,4,5-Trimethoxyphenethylamine; 3,5-Dimethoxy-4-Methoxyphenethylamine; 3,4-methylenedioxyamphetamine; 3,4-Methylenedioxy-N-ethylamphetamine; 3,4-methylenedioxy-n-methylamphetamine; 3,4-Methylenedioxy-N-hydroxyamphetamine; 3,4-methylenedioxy-5-ethoxyphenethylamine; 2,5-dimethoxy-4-ethoxyamphetamine; 3-Methoxy-4-ethoxyphenethylamine; 2-Methylamino-1-(3,4-methylenedioxyphenyl)butane; 3-Methoxy-4,5-methylenedioxyamphetamine; 2-Methoxy-4,5-methylenedioxyamphetamine; 2-Methoxy-3,4-methylenedioxyamphetamine; 4-Methoxy-2,3-methylenedioxyamphetamine; 3,5-Dimethoxy-4-(n)-propoxyphenethylamine; 4-ethoxy-5-methoxy-3-methylthiophenethylamine; 3,5-Dimethoxy-4-ethylthiophenethylamine; 3,4-Dimethoxy-5-methylthiophenethylamine; 3,5-Dimethoxy-5-methylthiophenethylamine; 3,4,5-trimethoxyamphetamine; 2,4,5-trimethoxyamphetamine; 2,3,5-trimethoxyamphetamine; 2,3,6-trimethoxyamphetamine; 2,4,6-trimethoxyamphetamine; 4,5-Dimethoxy-3-ethylthiophenethylamine; 4-Ethyl-2-methoxy-5-methylthioamphetamine; 5-Methoxy-4-methyl-2-methylthioamphetamine; 2-Methoxy-4-methyl-5-methylthioamphetamine; 2-Methoxy-4-methyl-5-methylsulfinylamphetamine; and 3,5-dimethoxy-4-(n)-propylthiophenethylamine, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof.

[0111] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from salvinorin A, ibotenic acid, muscimol, dextromethorphan, ketamine, esketamine, phencyclidine, dizocilpine (MK-801), scopolamine, hyoscyamine, aporphine, lysergic acid amide, cassine, cathinone, and voacangin, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the following: [Table 1] [Table 2] [Table 3] [Table 4]

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

[0112] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the compounds disclosed and claimed in Applicant's co-pending PCT Patent Application No. PCT / CA2021 / 050123, filed February 4, 2021, the entire contents of which are incorporated by reference. Thus, in some embodiments, the one or more hallucinogens are selected from compounds of formula (I), or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof: [ka] In the formula, R 1 is hydrogen, C1-C3 alkyl, C(O)R 12 , CO2OR 12 , C(O)N(R 12 )2, S(O)R 12 , and SO2R 12 Selected from; R 3 , R 4 , R 5 , and R 6 is independently selected from hydrogen and C1-C6 alkyl; R 7 and R 8 is independently selected from hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; R 7 and R8 are O, S, S(O), SO2, N, and NR, with nitrogen atoms between them. 13 forming a 3- to 7-membered heterocyclic ring, optionally containing 1-2 additional ring hetero moieties selected from Here, the C3-C7 cycloalkyl and 3-7 membered heterocycle are each independently selected from halogen, COR 13 , C(O)N(R 13 )2, SO2R 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, N, S(O), SO2, and NR 13 each optionally further substituted with a substituent selected from a 3-6 membered heterocycle containing 1-2 ring hetero moieties selected from R 9 , R 10 , and R 11 are independently hydrogen, halogen, CN, OR 13 , N(R 13 )2, S.R. 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, CO2R 13 , C(O)N(R 13 )2, SOR 13 , SO2R 13 , C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 13 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 13 , N(R 13 )2, and S.R. 13 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 13 , C(O)N(R 13)2, SO2R 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 13 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from Y is selected from halogen and XA; X is O, NR 13 , S, S(O), and SO2; A is selected from hydrogen, C1-C 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C7 cycloalkyl, C4-C6 cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, and P(O)(OR 12 )2 is selected; Each R 12 are independently hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, substituted hetero selected from aryl or unsubstituted heteroaryl, substituted C1-C6 alkylene C3-C7 cycloalkyl or unsubstituted C1-C6 alkylene C3-C7 cycloalkyl, substituted C1-C6 alkylene C3-C7 heterocycloalkyl or unsubstituted C1-C6 alkylene C3-C7 heterocycloalkyl, substituted C1-C6 alkylene aryl or unsubstituted C1-C6 alkylene aryl, and substituted C1-C6 alkylene heteroaryl or unsubstituted C1-C6 alkylene heteroaryl; Each R 13are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 14 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 14 , N(R 14 )2, and S.R. 14 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 14 , C(O)N(R 14 )2, SO2R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 14 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from R 14 is selected from hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted heterocycloalkyl or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; Here, R 3 , R 4 , R 5 , and R 6 At least one of R is deuterium or 3 , R 4 , R5 , and R 6 At least one of the groups contains deuterium, wherein all available hydrogen atoms are optionally replaced with halogen atoms, and / or all available atoms are optionally replaced with alternative isotopes thereof.

[0113] In some embodiments, the compound of formula I is the following compound: [Table 18]

[0114] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the compounds disclosed and claimed in Applicant's co-pending PCT Patent Application No. PCT / CA2021 / 050122, filed February 4, 2021, the entire contents of which are incorporated by reference. Thus, in some embodiments, the one or more hallucinogens are selected from compounds of formula (II), or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof: [ka] or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof; During the ceremony: R 1 is hydrogen, C1-C3 alkyl, C1-C6 alkyleneP(O)(OR 9 )2, C(O)R 9 , CO2R 9 , C(O)N(R 9 )2, S(O)R 9 , and SO2R 9 Selected from; R 2 , R 3 , and R 4 is independently selected from hydrogen and C1-C6 alkyl; R 5 is selected from hydrogen and C1-C6 alkyl; R6 , R 7 , and R 8 are independently hydrogen, halogen, CN, OR 9 , N(R 9 )2, S.R. 9 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, CO2R 9 , C(O)N(R 9 )2, S(O)R 9 , SO2R 9 , C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 9 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 9 , N(R 9 )2, and S.R. 9 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 9 , C(O)N(R 9 )2, SO2R 9 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 9 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from Y is selected from halogen and QA; Q is O, NR 10 , S, S(O), and SO2; Here, each R 9 and R 10are independently hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, substituted heteroaromatic alkyl or unsubstituted C3-C7 heteroaromatic alkyl, aryl or unsubstituted heteroaryl, substituted C1-C6 alkylene C3-C7 cycloalkyl or unsubstituted C1-C6 alkylene C3-C7 cycloalkyl, substituted C1-C6 alkylene C3-C7 heterocycloalkyl or unsubstituted C1-C6 alkylene C3-C7 heterocycloalkyl, substituted C1-C6 alkylene aryl or unsubstituted C1-C6 alkylene aryl, and substituted C1-C6 alkylene heteroaryl or unsubstituted C1-C6 alkylene heteroaryl; and A is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C4-C6 cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, P(O)(OR 11 )2, C1-C6 alkylene P(O)(OR 11 )2, C1-C6 alkylene C3-C7 cycloalkyl, C1-C6 alkylene C4-C6 cycloalkenyl, C1-C6 alkylene heterocycloalkyl, C1-C6 alkylene aryl, C1-C6 alkylene heteroaryl, C(O)Q', CO2Q', C(O)N(Q')2, S(O)Q', and SO2Q'; where Q' is hydrogen, C1-C 20 Alkyl, C1-C 20 Haloalkyl, C2-C 20 Alkenyl, C2-C 20 Haloalkenyl, C2-C 20 Alkynyl, C2-C 20 Haloalkynyl, C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and O, S, S(O), SO2, N, and NR 10and wherein the C1 to C6 heterocyclic ring is selected from the group consisting of 3 to 7 membered heterocyclic rings containing 1 to 2 ring hetero moieties selected from the group consisting of C1 to C 20 Alkyl, C2-C 20 Haloalkyl, C2-C6 alkenyl, C2-C 20 Haloalkenyl, C2-C 20 Alkynyl, C2-C 20 Haloalkynyl, C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and 3- to 7-membered heterocyclic groups are CN, OR 10 , N(R 10 )2, CO2R 10 , and S.R. 10 and / or on the same carbon atom with one or more substituents independently selected from C 1~6 By alkyl or C 2~6 disubstituted by alkylene to form a C3-C7 cycloalkyl ring, wherein each of said C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and 3- to 7-membered heterocycle is optionally further substituted with a substituent selected from C1-C3 alkyl and C1-C3 haloalkyl; and Each R 11 are independently hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted aryl, substituted heteroaryl, aryl or unsubstituted heteroaryl, substituted C1-C6 alkylene C3-C7 cycloalkyl or unsubstituted C1-C6 alkylene C3-C7 cycloalkyl, substituted C1-C6 alkylene C3-C7 heterocycloalkyl or unsubstituted C1-C6 alkylene C3-C7 heterocycloalkyl, substituted C1-C6 alkylene aryl or unsubstituted C1-C6 alkylene aryl, and substituted C1-C6 alkylene heteroaryl or unsubstituted C1-C6 alkylene heteroaryl; wherein all available hydrogen atoms are optionally replaced with halogen atoms, and / or all available atoms are optionally replaced with alternative isotopes thereof.

[0115] In some embodiments, the compound of formula II is: [Table 19] [Table 20] [Table 21] [Table 22] [Table 23] [Table 24] [Table 25] [Table 26] [Table 27] [Table 28]

[0116] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the compounds disclosed and claimed in Applicant's co-pending PCT Patent Application No. PCT / CA2021 / 050125, filed February 4, 2021, the entire contents of which are incorporated by reference. Thus, in some embodiments, the one or more hallucinogens are selected from a compound of formula (III), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof: [ka] In the formula, R 1 is hydrogen, C1-C3 alkyl, C1-C6 alkyleneP(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 , and SO2R 12 Selected from; R 2 ~R 6 is independently selected from hydrogen and C1-C6 alkyl; R 7 and R 8 is independently selected from hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; R 7 and R 8 are O, S, S(O), SO2, N, and NR, with nitrogen atoms between them. 13 forming a 3- to 7-membered heterocyclic ring, optionally containing 1-2 additional ring hetero moieties selected from Here, the C3-C7 cycloalkyl and 3-7 membered heterocycle are each independently selected from halogen, COR 13 , C(O)N(R 13 )2, SO2R 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, N, S(O), SO2, and NR 13 each optionally further substituted with a substituent selected from a 3-6 membered heterocycle containing 1-2 ring hetero moieties selected from R 9 , R 10 , and R 11 are independently hydrogen, halogen, CN, OR 13 , N(R 13 )2, S.R. 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, CO2R 13 , C(O)N(R 13 )2, SOR 13 , SO2R 13 , C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 13 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 13 , N(R 13 )2, and S.R. 13 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 13 , C(O)N(R 13 )2, SO2R 13, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 13 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from Y is selected from halogen and XA; X is O, NR 13 , S, S(O), and SO2; A is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C4-C6 cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, P(O)(OR 12 )2, C1-C6 alkylene P(O)(OR 12 )2, C1-C6 alkylene C3-C7 cycloalkyl, C1-C6 alkylene C4-C6 cycloalkenyl, C1-C6 alkylene heterocycloalkyl, C1-C3 alkylene aryl, C1-C6 alkylene heteroaryl, C(O)Q', CO2Q', C(O)N(Q')2, S(O)Q', and SO2Q'; Here, Q' is C1 to C 20 Alkyl, C1-C 20 Haloalkyl, C2-C 20 Alkenyl, C2-C 20 Haloalkenyl, C2-C 20 Alkynyl, C2-C 20 Haloalkynyl, C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and O, S, S(O), SO2, N, and NR 13 wherein the C1 to C6 are each independently selected from the group consisting of 3 to 7 membered heterocyclic rings containing 1 to 2 ring hetero moieties selected from the group consisting of C1 to C6 20 Alkyl, C2-C 20 Haloalkyl, C2-C 20 Alkenyl, C2-C 20 Haloalkenyl, C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and 3- to 7-membered heterocyclic groups are CN, OR 13 , N(R 13)2, CO2R 13 , S.R. 13 , C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and 3- to 7-membered heterocycle, and / or 1~6 Alkyl or C 2~6 disubstituted with alkylene to form a C3-C7 cycloalkyl ring, wherein each of said C3-C7 cycloalkyl, C4-C7 cycloalkenyl, and 3- to 7-membered heterocycle are each optionally further substituted with substituents selected from C1-C3 alkyl and C1-C3 haloalkyl; Each R 12 are independently hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, substituted hetero selected from aryl or unsubstituted heteroaryl, substituted C1-C6 alkylene C3-C7 cycloalkyl or unsubstituted C1-C6 alkylene C3-C7 cycloalkyl, substituted C1-C6 alkylene C3-C7 heterocycloalkyl or unsubstituted C1-C6 alkylene C3-C7 heterocycloalkyl, substituted C1-C6 alkylene aryl or unsubstituted C1-C6 alkylene aryl, and substituted C1-C6 alkylene heteroaryl or unsubstituted C1-C6 alkylene heteroaryl; Each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 14wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 14 , N(R 14 )2, and S.R. 14 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 14 , C(O)N(R 14 )2, SO2R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 14 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from R 14 is selected from hydrogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted heterocycloalkyl or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; wherein all available hydrogen atoms are optionally replaced with halogen atoms, and / or all available atoms are optionally replaced with alternative isotopes thereof; However, R 1 is C1~C6P(O)(OR 12 )2, and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R9 , R 10 , R 11 , R 12 , R 13 , and R 14 , Q', X, Y, and A are as defined above for formula (I); or Y is XA, where A is a C1-C6 alkylene P(O)(OR 12 )2, C1-C6 alkylene C3-C7 cycloalkyl, C1-C6 alkylene C4-C6 cycloalkenyl, C1-C6 alkylene heterocycloalkyl, C1-C3 alkylene aryl, C1-C6 alkylene heteroaryl, C(O)Q', CO2Q', C(O)N(Q')2, S(O)Q', and SO2Q'; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 , Q' and X are as defined above for formula (III).

[0117] In some embodiments, the compound of formula III is: [Table 29] [Table 30] [Table 31] [Table 32] [Table 33] [Table 34] [Table 35] [Table 36]

[0118] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the compounds disclosed and claimed in Applicant's co-pending U.S. Provisional Patent Application No. 63 / 122,181, filed December 7, 2021, the entire contents of which are incorporated by reference. Thus, in some embodiments, the one or more hallucinogens are selected from compounds of formula (IV), or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof: [ka] or a pharma- ceutically acceptable salt thereof, During the ceremony, R 1 is hydrogen, C1-C3 alkyl, -(CH2)P(O)(OR 8 );CO(R 9 ), COO(R 8 ), C(O)N(R 8 )2, SO(R 8 ), and SO2(R 8 ) selected from the group consisting of; R 2 , R 3 , R 4 , and R 5 is independently selected from the group consisting of hydrogen, deuterium, and lower alkyl; R 6 , R7 , and R 8 are independently hydrogen, halogen, CN, OR 9 , N(R 9 )2, S.R. 9 , C1-C6 alkyl, C1-C6 haloalkyl, OR 9 C1-C6 alkyl substituted with SR 9 C1-C6 alkyl substituted with N(R 9 )2-substituted C1-C6 alkyl, C2-C6 haloalkyl, COOR 9 , C(O)N(R 9 )2, SO2R 9 , COOR 9 , C(O)N(R 9 )2, SO2R 9 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, N, and N(R 9 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic group are selected from the group consisting of CN, OR 9 , N(R 9 )2, and S.R. 9 wherein the C3-C7 cycloalkyl and 3-7 membered heterocycle are selected from the group consisting of C1-C3 alkyl and C1-C3 haloalkyl, halogen, CN, OR 9 , N(R 9 ) 2, COOR 9 , C(O)N(R 9 )2, S.R. 9 , SO2R 9 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, N, and N(R 8each of which is optionally further substituted with a member of the group consisting of 3-6 membered heterocycles containing 1-2 ring members selected from the group consisting of C1-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl; and Q is C, O, NR 10 , S, SO, and SO2; Here, R 9 and R 10 is independently selected from hydrogen, substituted alkyl or unsubstituted alkyl, substituted alkenyl or unsubstituted alkenyl, substituted alkynyl or unsubstituted alkynyl, substituted haloalkyl or unsubstituted haloalkyl, substituted cycloalkyl or unsubstituted cycloalkyl, substituted heterocycloalkyl or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; and A is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heterocycloalkynylaryl, heteroaryl, C0-C1P(O)(OR 9 )2, CO(Q'), COO(Q'), C(O)N(Q')2, SO(Q'), SO2(Q'), where Q' is hydrogen, C1-C 20 Alkyl, C1-C 20 Haloalkyl, C2-C 20 Alkenyl, C2-C 20 Haloalkenyl, C2-C 20 Alkynyl, C2-C 20 Haloalkynyl, C3-C7 cycloalkyl, and O, S, N, and N(R 10 ) 3-7 membered heterocycles containing 1-2 ring members selected from the group consisting of C1-C 20 Alkyl, C2-C 20 Haloalkyl, C2-C6 alkenyl, C2-C 20 Haloalkenyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic groups are CN, OR 10 , N(R 10 )2, and S.R. 10wherein said C3-C7 cycloalkyl and 3-7 membered heterocycle are each optionally further substituted with a member of the group consisting of C1-C3 alkyl and C1-C3 haloalkyl; R 8 and R 9 are independently defined above; and n=1, 2.

[0119] In some embodiments, the compound of formula IV is: [Table 37] [Table 38] [Table 39] [Table 40] [Table 41] [Table 42] [Table 43]

[0120] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from the compounds disclosed and claimed in Applicant's co-pending U.S. Provisional Patent Application No. 63 / 155,634, filed March 2, 2021, the entire contents of which are incorporated by reference. Thus, in some embodiments, the one or more hallucinogens are selected from compounds of formula (V), or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is hydrogen, deuterium, C1-C3 alkyl, CH2P(O)(OR 6 )2;C(O)R 6 , CO2R 6 , C(O)N(R 6 )2, S(O)R 6 , and SO2R 6 Selected from; Q is independently [ka] and [ka] Selected from; R 2 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , and R 17 is independently selected from hydrogen, deuterium, halogen, and C1-C6 alkyl; R 3 , R 4 , and R5 are independently hydrogen, deuterium halogen, CN, OR 18 , N(R 18 )2, S.R. 18 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, CO2R 18 , C(O)N(R 18 )2, S(O)R 18 , SO2R 18 , C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 18 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 18 , N(R 18 )2, and S.R. 18 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 18 , C(O)N(R 18 )2, SO2R 18 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 18 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from A is hydrogen, deuterium, halogen, OR 19 , N.R. 19 , S.R. 19 , S(O)R 19 , and S(O2)R 19 Selected from; Each R 18are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and O, S, S(O), SO2, N, and NR 20 wherein the C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C7 cycloalkyl, and 3-7 membered heterocyclic groups are selected from CN, OR 20 , N(R 20 )2, and S.R. 20 and wherein the C3-C7 cycloalkyl and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, COR 20 , C(O)N(R 20 )2, SO2R 20 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, and O, S, S(O), SO2, N, and NR 20 each optionally further substituted with a substituent selected from a 3- to 6-membered heterocycle containing 1-2 ring hetero moieties selected from R 19 and R 20 are independently selected from hydrogen, deuterium, halogen, substituted C1-C6 alkyl or unsubstituted C1-C6 alkyl, substituted C2-C6 alkenyl or unsubstituted C2-C6 alkenyl, substituted C2-C6 alkynyl or unsubstituted C2-C6 alkynyl, substituted C1-C6 haloalkyl or unsubstituted C1-C6 haloalkyl, substituted C3-C7 cycloalkyl or unsubstituted C3-C7 cycloalkyl, substituted C3-C7 heterocycloalkyl or unsubstituted C3-C7 heterocycloalkyl, substituted aryl or unsubstituted aryl, and substituted heteroaryl or unsubstituted heteroaryl; wherein all available hydrogen atoms are optionally replaced with halogen atoms, and / or all available atoms are optionally replaced with alternative isotopes thereof.

[0121] In some embodiments, the compound of formula V is: [Table 44] [Table 45] [Table 46] [Table 47] [Table 48] [Table 49] [Table 50]

[0122] In some embodiments, the one or more hallucinogens are selected from the compounds disclosed and claimed in Applicant's co-pending U.S. Provisional Patent Application No. 63 / 260,470, filed August 20, 2021, the entire contents of which are incorporated by reference. Accordingly, in some embodiments, the one or more hallucinogens are selected from a compound of formula (VI), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony: R 1 H, D, C 1~6 Alkyl, C1-6P(O)(OR 6 )(OR 7 ), C(O)R 6 , CO2R 6 , C(O)N(R 6 )(R 7’ ), S(O)R 6 , and SO2R 6 Selected from; Q is selected from Q1 and Q2: [ka] [ka] is a single or double bond, where [ka] is a double bond of Q1, R 9 and R 15 does not exist, [ka] is a double bond of Q2, R 17 and R 25 does not exist; R 2 , R 3 , R 4 , R 5 , R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 , R 22 , R 23 , R 24 , and R 25H, D, halo, and C 1~6 independently selected from alkyl; Each R 6 H, D, C 1~20 Alkyl, C 2~20 Alkenyl, C 2~20 Alkynyl, Aryl, C 3~10 Cycloalkyl, O, S, S(O), SO2, N, and NR 26 and 3-10 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 26 wherein the C is independently selected from 5-10 membered heteroaryl containing 1-4 hetero moieties independently selected from 1~20 Alkyl, C 2~20 Alkenyl, C 2~20 Alkynyl, C 3~10 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each independently selected from halo, CN, OR 27 , N(R 27 )(R 28 ), and S.R. 27 and wherein the C is optionally substituted with one or more substituents independently selected from 3~7 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are COR 29 , C(O)N(R 29 )(R 30 ), S(O)R 29 , SO2R 29 , C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, O, S, S(O), SO2, N, and NR 31 and 3-6 membered heterocycloalkyl containing 1-2 ring hetero moieties independently selected from O, S, S(O), SO2, N, and NR 31 each optionally further substituted with substituents selected from 5-6 membered heteroaryl containing 1-2 ring hetero moieties independently selected from Each R 7 H and C 1~6independently selected from alkyl; R 12 and R 20 are independently H, D, and C 1~6 Alkyl, C(O)C 1~20 Alkyl, C(O)C 2~20 Alkenyl, and C(O)C 2~20 alkynyl; A is H, D, halo, C 1~6 Alkyl, CN, OR 32 , N(R 32 )(R 33 ), S.R. 32 , S(O)R 32 , SO2R 32 , C(O)R 32 , CO2R 32 , C(O)N(R 32 )(R 33 ), C(NR 34 )R 32 , C(NR 34 )NR 32 R 33 , C(NR 34 ) OR 32 , Aryl, C 3~10 Cycloalkyl, O, S, S(O), SO2, N, and NR 32 and 3-10 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 32 wherein the C is selected from 5-10 membered heteroaryl containing 1-4 hetero moieties independently selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~7 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each independently selected from halo, CN, OR 35 , C(O)2R 35 , N(R 35 )(R 36 ), and S.R. 35 wherein the C 3~10 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are COR37 , C(O)N(R 37 )(R 38 ), S(O)R 37 , SO2R 38 , C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, O, S, S(O), SO2, N, and NR 39 and 3-6 membered heterocycloalkyl containing 1-2 ring hetero moieties independently selected from O, S, S(O), SO2, N, and NR 39 each optionally further substituted with substituents selected from 5-6 membered heteroaryl containing 1-2 ring hetero moieties independently selected from Each R 32 , H, C 1~20 Alkyl, C 2~20 Alkenyl, C 2~20 Alkynyl, C 3~10 Cycloalkyl, O, S, S(O), SO2, N, and NR 40 and 3-10 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 40 wherein the C is independently selected from 5-10 membered heteroaryl containing 1-4 hetero moieties independently selected from 1~20 Alkyl, C 2~20 Alkenyl, C 2~20 Alkynyl, C 3~ C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each selected from the group consisting of CN, OR 41 , CO2R 41 , N(R 41 )(R 42 ), and S.R. 41 wherein the C 3~10 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are COR 43 , C(O)N(R 43 )(R 44 ), S(O)R43 , SO2R 43 , C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, O, S, S(O), SO2, N, and NR 45 and 3-6 membered heterocycloalkyl containing 1-2 ring hetero moieties independently selected from O, S, S(O), SO2, N, and NR 45 each optionally further substituted with substituents selected from 5-6 membered heteroaryl containing 1-2 ring hetero moieties independently selected from R 35 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , and R 45 are independently H and C 1~6 alkyl; and all available hydrogen atoms are optionally replaced with halogen atoms and / or all available atoms are optionally replaced with alternative isotopes thereof; However, R 1 is H, A is H, OH, or OC 1~4 Not alkyl.

[0123] In some embodiments, the compound of formula VI is: [Table 51] [Table 52] [Table 53]

Table 54

Table 55

Table 56

Table 57

Table 58

Table 59

Table 60

Table 61

Table 62

Table 63

Table 64

Table 65

[0124] In some embodiments, the one or more hallucinogens are selected from the compounds disclosed and claimed in Applicant's co-pending U.S. Provisional Patent Application No. 63 / 326,406, filed April 1, 2022, the entire contents of which are incorporated by reference. Accordingly, in some embodiments, the one or more hallucinogens are selected from a compound of formula (VII), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof: [ka] or a pharma- ceutically acceptable salt and / or solvate thereof, During the ceremony: R 1 is C(O)R 7 , CO2R 7 , and C(O)N(R 7 )(R 7’ ) are selected from; S(O)R 7 and SO2R 7 ; Q is selected from Q1, Q2, Q3, Q4, and Q5; [ka] [ka] is a single bond or a double bond, provided that in Q1 [ka] If is a double bond, R 9 and R 15 does not exist, and [ka] If is a double bond, R 17 and R 25 does not exist; R 2 , R 5 , and R 6 are independently H, halo, CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 alkoxy; R 3 and R 4 One is H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 alkoxy; R 3 and R 4 The other is A, H, halo, C. 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 1~6 alkoxy; A is OR 54 , OP(O)(OR 54 )(OR 55 ), N(R 54 )(R 55 ), S.R. 54 , S(O)R 54 , SO2R 54 , C(O)R 54 , CO2R 54 , C(O)N(R 54 )(R 55 ), C(NR 56 )R 54 , C(NR 56 )NR 54 R 55 , C(NR 56 ) OR 54 , Aryl, C 3~10 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-10 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54wherein the C is selected from 5-10 membered heteroaryl containing 1-4 hetero moieties independently selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~7 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each independently selected from halo, CN, OR 57 , CO2R 57 , N(R 57 )(R 58 ), and S.R. 57 and wherein the C is optionally substituted with one or more substituents independently selected from 3~10 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are COR 59 , C(O)N(R 59 )(R 60 ), S(O)R 59 , SO2R 59 , C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, O, S, S(O), SO2, N, and NR 60 and 3-6 membered heterocycloalkyl containing 1-2 ring hetero moieties independently selected from O, S, S(O), SO2, N, and NR 60 each optionally further substituted with substituents selected from 5-6 membered heteroaryl containing 1-2 ring hetero moieties independently selected from R 7 is C 7~30 Alkyl, C 7~30 Alkenyl, and C 7~30 alkynyl, wherein C 7~30 Alkyl, C 7~30 Alkenyl, and C 7~30 Alkynyl is a radical that is selected from halo, OR 61 , N(R 61 )(R 62 ), and S.R. 61 and / or O, C(O), CO, and NR 63and optionally interrupted by 1 to 6 heterologous moieties independently selected from: R 7’ H and C 1~6 alkyl; R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 32 , R 33 , R 34 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , R 52 , and R 53 H, halo, and C 1~6 independently selected from alkyl; R 54 , H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, aryl, O, S, S(O), SO2, N, and NR 64 and 3-10 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 64wherein the C is selected from 5-10 membered heteroaryl containing 1-4 hetero moieties independently selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~ C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are each selected from the group consisting of CN, OR 65 , CO2R 65 , N(R 65 )(R 66 ), and S.R. 65 and wherein the C is optionally substituted with one or more substituents independently selected from 3~10 Cycloalkyl, aryl, 3- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl are COR 67 , C(O)N(R 67 )(R 68 ), S(O)R 67 , SO2R 67 , C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, phenyl, O, S, S(O), SO2, N, and NR 69 and 3-6 membered heterocycloalkyl containing 1-2 ring hetero moieties independently selected from O, S, S(O), SO2, N, and NR 69 each optionally further substituted with substituents selected from 5-6 membered heteroaryl containing 1-2 ring hetero moieties independently selected from R 12 , R 20 , R 35 , and R 45 are independently H, C 1~6 Alkyl, and C(O)C 1~6 alkyl; R 30 and R 31 are independently H, C 1~6 Alkyl, and C(O)C 1~6 alkyl, or R 30 and R 31are O, S, S(O), SO2, N, and NR along with the N atom to which they are attached. 70 forming a 3-8 membered heterocycle, optionally containing 1 or 2 additional hetero moieties independently selected from R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , R 63 , R 64 , R 65 , R 66 , R 67 , R 68 , R 69 , and R 70 are independently H and C 1~6 alkyl; and wherein all available hydrogen atoms are optionally independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0125] In some embodiments, the compound of formula VII is: [Table 67] [Table 68] [Table 69] [Table 70] [Table 71] [Table 72] [Table 73] [Table 74] [Table 75] [Table 76] [Table 77] [Table 78] [Table 79] [Table 80]

[0126] In some embodiments, the one or more hallucinogens are selected from the compounds disclosed and claimed in Applicant's co-pending U.S. Provisional Patent Application No. 63 / 332,450, filed April 19, 2022, the entire contents of which are incorporated by reference. Accordingly, in some embodiments, the one or more hallucinogens are selected from a compound of formula (VIII), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony: R 1 is H,C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , and SO2R 7 Selected from; Q is selected from Q1, Q2, Q3, Q4, and Q5; [ka] [ka] is a single bond or a double bond, provided that in Q1 [ka] If is a double bond, R 9 and R 15 does not exist, and [ka] If is a double bond, R 17 and R 25 does not exist; R 2 , R 2’ , R 2” , R 3 , and R 6 are independently H, halo, and C 1~6 Alkyl, and C 1~6 alkoxy; R 4 and R 5 One or both of are independently H, halo, C 1~6 Alkyl, and C 1~6 alkoxy; or R 4 and R5 are bonded together to form O-(CH2) 1~2 Forming O, or R 4 and R 5 One is A, OA, and C. 1~4 alkylene A; R 4 and R 5 the other is H; A is phenyl, C 3~6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 wherein the phenyl, C 3~10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are also included, including halo, C 1~4 Alkyl and OC 1~4 optionally substituted with one or more substituents independently selected from alkyl; R 7 H and C 1~6 alkyl, wherein said C 1~6 Alkyl, halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or O, C(O), CO, and NR 57 and optionally interrupted by 1 to 3 heterologous moieties independently selected from: R 7’ H and C 1~6 alkyl; R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 32 , R 33 , R 34 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , R 52 , and R 53 H, halo, and C 1~6 independently selected from alkyl; R 12 , R 20 , R 35 , and R 45 are independently H, C 1~6 Alkyl, and C(O)C 1~6 alkyl; R 30 and R 31 are independently H, C 1~6 Alkyl, and C(O)C 1~6 alkyl, or R 30 and R 31 are O, S, S(O), SO2, N, and NR along with the N atom to which they are attached. 58 forming a 3- to 6-membered heterocycle, optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C 1~6 alkyl; and Any available hydrogen atom is optionally independently replaced with a fluorine atom or a chlorine atom, and any available atom is optionally replaced with its alternative isotope; However, if Q is Q3, then R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and: R 1 , R 2 , R 2’ , R2 ” , R 3 , R 4 , R 5 , and R 6 are all H, R 1 , R 2 , R 2’ , R 2” , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2” , R 3 , R 4 , R 5 , and R 6 are all H and R 5 is OCH3, Thus, the compounds of formula I are either the (R)-enantiomer or the (S)-enantiomer of the carbon to which Q is attached.

[0127] In some embodiments, the compound of formula VIII is: [Table 81] [Table 82]

Table 83

Table 84

Table 85

Table 86

Table 87

Table 88

Table 89

Table 90

Table 91

Table 92

Table 93

Table 94

[0128] In some embodiments, the one or more fatty acids are selected from any acid derived from fat by hydrolysis and having from 4 to 30 carbon atoms, from 6 to 28 carbon atoms, or from 6 to 24 carbon atoms, in some embodiments, the fatty acid is selected from myristic acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.

[0129] In some embodiments, the pharma- ceutically acceptable salt is an acid addition salt or a base addition salt.The selection of suitable salt can be performed by those skilled in the art.Suitable salts include, for example, acid addition salts that can be formed by mixing a solution of a compound with a solution of a pharma- ceutically acceptable acid such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, or benzoic acid. Additionally, acids generally considered to be suitable for the formation of pharma- ceutically useful salts from basic pharmaceutical compounds are described, for example, in P. Stahl et al, Camille G. (eds.) and Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich:Wiley VCH; S. Berge et al, Journal of Pharmaceutical Sciences 1977 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, DC on their website).

[0130] The acid addition salt suitable for or compatible with the treatment of a subject is any non-toxic organic or inorganic acid addition salt of any basic compound. Basic compounds that form acid addition salts include, for example, compounds that contain an amine group. Exemplary inorganic acids that form suitable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, as well as acid metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Exemplary organic acids that form suitable salts include monocarboxylic acids, dicarboxylic acids, and tricarboxylic acids. Examples of such organic acids are, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, mandelic acid, salicylic acid, 2-phenoxybenzoic acid, p-toluenesulfonic acid, and other sulfonic acids, such as methanesulfonic acid, ethanesulfonic acid, and 2-hydroxyethanesulfonic acid. In some embodiments, exemplary acid addition salts also include acetate, ascorbate, benzoate, benzenesulfonate, hydrogen sulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate ("mesylate"), naphthalenesulfonate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, and toluenesulfonate (also known as tosylate). In some embodiments, mono- or di-acid salts are formed, and such salts exist in either hydrated, solvated, or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents, and generally exhibit higher melting points compared to their free base forms. The criteria for selecting an appropriate salt are known to those skilled in the art. For example, in isolating the compounds of the present application for laboratory use or for subsequent conversion to pharma-ceutically acceptable acid addition salts, other pharma-ceutically unacceptable salts, such as, but not limited to, oxalates, may be used.

[0131] The base addition salt suitable for or compatible with the treatment of a subject is any non-toxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form base addition salts include, for example, compounds that contain a carboxylic acid group. Exemplary inorganic bases that form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide, and ammonia. Exemplary organic bases that form suitable salts include aliphatic, alicyclic, or aromatic organic amines, such as isopropylamine, methylamine, trimethylamine, picoline, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of suitable salts may be useful, for example, to prevent ester functional groups from being hydrolyzed when present elsewhere in the compound. The criteria for selecting suitable salts are known to those skilled in the art. In some embodiments, exemplary basic salts also include ammonium salts, alkali metal salts (such as sodium salts, lithium salts, and potassium salts), alkaline earth metal salts (such as calcium salts and magnesium salts), salts with organic bases (e.g., organic amines) (such as dicyclohexylamine, A-butylamine, choline), and salts with amino acids (such as arginine, lysine, etc.). Basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl sulfate, diethyl sulfate, and dibutyl sulfate), long chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides, and iodides), and aralkyl halides (e.g., benzyl bromide and phenethyl bromide).Compounds bearing an acidic moiety can be mixed with suitable pharma- ceutically acceptable salts to obtain salts formed with appropriate organic ligands, such as, for example, alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), and quaternary ammonium salts.

[0132] In some embodiments, when an acid (-COOH) or alcohol group is present, a pharma- ceutically acceptable ester can be employed to modify the solubility or hydrolysis properties of the compound. In some embodiments, the ester is an alkyl ester. In some embodiments, the alkyl ester is selected from an isopropyl ester, a methyl ester, an ethyl ester, a propyl ester, and mixtures thereof.

[0133] The formation of pharma- ceutically acceptable salts can be accomplished using standard techniques, for example, treating the neutral compound with an acid or base in a suitable solvent and isolating the formed salt by filtration, extraction, or any other suitable method.

[0134] Examples of suitable solvents are ethanol, water, etc. When water is the solvent, the molecule is referred to as a "hydrate." The formation of solvates varies depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in a suitable solvent and isolating the solvate by cooling the solvent or using an anti-solvent. The solvate is usually dried or azeotroped under ambient conditions. Selection of suitable conditions for forming a particular solvate can be performed by one of ordinary skill in the art.

[0135] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the compositions and kits of the present application are formulated as separate pharmaceutical compositions for separate administration to or use in a subject. In this embodiment, the separate pharmaceutical compositions are formulated according to a desired mode of administration, which may be the same or different, for each of the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, independently of one another.

[0136] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the compositions and kits of the present application are formulated in a single pharmaceutical composition for administration to or use in a subject.

[0137] The one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, may be administered to a subject or used in various forms depending on the route of administration selected, as will be understood by those skilled in the art. For example, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, may be administered orally, inhaled, parenterally, buccal, sublingually, insufflated, epidurally, nasally, rectally, vaginally, by patch, pump, minipump, topically, or transdermally, and may be formulated accordingly in pharmaceutical compositions. Conventional procedures and ingredients for the selection and preparation of suitable compositions are described, for example, in Remington's Pharmaceutical Sciences (2000 - 20th edition) and The United States Pharmacopeia: The National Formulary (USP 24 NF19), published in 1999.

[0138] Parenteral administration includes systemic delivery routes other than the gastrointestinal (GI) tract, and includes, for example, intravenous, intraarterial, intraperitoneal, subcutaneous, intramuscular, transepithelial, nasal, pulmonary (e.g., by use of an aerosol), intrathecal, rectal, and topical (including use of a patch or other transdermal delivery device) modes of administration. Parenteral administration can be by continuous infusion over a selected period of time.

[0139] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are administered orally, for example, with an inert diluent or an assimilable edible carrier, or are enclosed in a hard or soft shell gelatin capsule, or are compressed into a tablet, or are directly incorporated into dietary foods. In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are incorporated with non-medicinal ingredients and used in the form of ingestible tablets, buccal tablets, troches, capsules, caplets, pellets, granules, lozenges, chewing gum, powders, syrups, elixirs, wafers, aqueous solutions, and suspensions. For tablets, carriers used include lactose, corn starch, sodium citrate, and salts of phosphoric acid. Pharmaceutically acceptable non-medicinal ingredients include binders (e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose); fillers (e.g., lactose, microcrystalline cellulose, or calcium phosphate); lubricants (e.g., talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate), or solvents (e.g., water). In embodiments, the tablets are coated by methods well known in the art. For tablets, capsules, caplets, pellets, or granules for oral administration, pH-sensitive enteric coatings such as Eudragits™, which are designed to control the release of the active ingredient, are optionally used. Oral dosage forms also include modified release formulations, such as immediate release formulations and sustained release formulations.Examples of modified release formulations include, for example, sustained release (SR), extended release (ER, XR, or XL), time-release or timed-release, controlled release (CR), or continuous release (CR or Contin), employed in the form of, for example, coated tablets, osmotic delivery devices, coated capsules, microencapsulated microparticles, agglomerated particles, such as molecular sieve type particles, or fine hollow permeable fiber bundles or chopped hollow permeable fibers agglomerated or held in fibrous packets. For oral administration in capsule form, useful carriers, solvents, or diluents include, but are not limited to, lactose, ethanol, and dried cornstarch.

[0140] In some embodiments, liquid preparations for oral administration are suitable for example in the form of a solution, syrup, or suspension, or as a dry product for constitution with water or other suitable vehicle before use. If necessary, certain sweeteners and / or flavorings and / or colorants are added. Such liquid preparations for oral administration are prepared by conventional means using pharma- ceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, or methylcellulose); emulsifying agents (e.g., lecithin or acacia); non-aqueous solvents; and preservatives (e.g., methyl or propyl p-hydroxybenzoate or sorbic acid). Useful diluents include lactose and high molecular weight polyethylene glycols.

[0141] It is also possible to lyophilize one or more hallucinogens, or salts, prodrugs and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs and / or solvates thereof, in the same or separate compositions, and use the resulting lyophilizates, for example, for the preparation of an injectable product.

[0142] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are administered or used parenterally. For example, solutions are prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. In some embodiments, dispersions are prepared in glycerol, liquid polyethylene glycols, DMSO, and mixtures thereof, with or without alcohol. Under normal conditions of storage and use, these preparations contain preservatives to prevent the growth of microorganisms. Those skilled in the art will know how to prepare suitable formulations. For parenteral administration, sterile solutions of the compounds of the present application are usually prepared, and the pH of the solutions is suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled to make the preparation isotonic. For ocular administration, ointments or droppable liquids are delivered by ocular delivery systems known in the art, such as applicators or eyedroppers. In some embodiments, such compositions contain a mucomimetic (such as hyaluronic acid, chondroitin sulfate, hydroxypropyl methylcellulose, or polyvinyl alcohol), a preservative (such as sorbic acid, EDTA, or benzyl chromium chloride), and a diluent or carrier in the usual amounts. For pulmonary administration, the diluent or carrier is selected to be appropriate to allow the formation of an aerosol.

[0143] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are formulated for parenteral administration by injection, including using conventional catheterization techniques or infusion. For example, the formulation for injection is provided in unit dosage form, for example in ampoules, or in multi-dose containers, with added preservatives. In some embodiments, the composition is in the form of a sterile suspension, solution, or emulsion, etc., and contains formulating agents, such as suspending, stabilizing, and / or dispersing agents. In all cases, the form must be sterile and fluid to the extent that easy injectability exists. Alternatively, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are preferably in sterile powder form for reconstitution with a suitable solvent, for example pyrogen-free water, before use.

[0144] In some embodiments, compositions for nasal administration are conveniently formulated as aerosols, sprays, drops, gels, and powders. For intranasal administration or administration by inhalation, the compositions of the present application are conveniently delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is squeezed or pumped by the patient, or as a presentation from an aerosol spray from a pressurized container or nebulizer. Aerosol formulations usually contain a solution or fine suspension of an active substance in a physiologically acceptable aqueous or non-aqueous solvent, and are usually provided in single or multi-dose amounts in sterile form in a sealed container, for example in the form of a cartridge or refill for use with an atomizing device. Alternatively, the sealed container is an integrated dispensing device, such as a single-dose nasal inhaler or aerosol dispenser, equipped with a metering valve intended for disposal after use. When the dosage form includes an aerosol dispenser, it will contain a propellant that is, for example, a compressed gas, such as compressed air, or an organic propellant, such as a fluorochlorohydrocarbon. Suitable propellants include, but are not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, heptafluoroalkane, carbon dioxide, or another suitable gas. In the case of a pressurized aerosol, the dosage unit is determined by suitably providing a valve to deliver a metered amount. In some embodiments, the pressurized container or nebulizer contains a solution or suspension of the active compound. Capsules and cartridges (e.g., made from gelatin) for use in an inhaler or insufflator are formulated to contain, for example, a powder mix of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and a suitable powder base, such as lactose or starch. The aerosol dosage form can also be in the form of a pump-atomiser.

[0145] Compositions suitable for buccal or sublingual administration include tablets, lozenges, and pastilles, in which the compounds of the present application are formulated with a carrier such as sugar, acacia, tragacanth, or gelatin and glycerin. Compositions for rectal administration are conveniently in the form of suppositories containing a conventional suppository base.

[0146] Suppository forms are useful for vaginal, urethral and rectal administration.Such suppositories are generally constructed from a mixture of materials that are solid at room temperature but melt at body temperature.The materials commonly used to make such a solvent include, but are not limited to, glycerin gelatin, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol.For example, for further discussion of suppository dosage forms, see Remington's Pharmaceutical Sciences, 16th Ed., Mack Publishing, Easton, PA, 1980, pp. 1530-1533.

[0147] The one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, will generally be administered in the form of a pharmaceutical composition in which the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or pharma-ceutically acceptable salts, prodrugs, and / or solvates thereof, are in association with a pharma- ceutically acceptable carrier. Depending on the mode of administration, the pharmaceutical composition comprises from about 0.05% to about 99% by weight or from about 0.10% to about 70% by weight of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and from about 1% to about 99.95% by weight or from about 30% to about 99.90% by weight of a pharma- ceutical acceptable carrier, all weight percentages being based on the total composition.

[0148] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are present in the composition in an effective amount, e.g., an amount effective to treat or prevent a disease, disorder, or condition that is treated by activation of a serotonin receptor. In some embodiments, the effective amount is determined as described in the Methods and Uses section below.

[0149] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in a composition that includes an additional therapeutic agent. Thus, the present application also includes pharmaceutical compositions that include one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and an additional therapeutic agent thereof, and optionally one or more pharma- ceutically acceptable non-medicinal ingredients. In some embodiments, the additional therapeutic agent is another known agent useful for treating a disease, disorder, or condition due to activation of serotonin receptors. In some embodiments, the additional therapeutic agent is a psychoactive agent.

[0150] III. Methods and Uses of the Present Application The present application includes a method of treating or preventing a disease, disorder, or condition treated by activation of serotonin receptors comprising administering to a subject in need thereof an effective amount of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0151] The present application also includes the use of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, for treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor, as well as the use of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the preparation of a medicament for treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor. The present application also includes one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, for use in treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor.

[0152] In some embodiments, the present application also includes methods of improving the effectiveness of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, comprising administering to a subject in need thereof an effective amount of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in combination with an effective amount of one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0153] The present application also includes the use of one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, to improve the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, as well as the use of one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the preparation of a medicament to improve the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. The present application also includes one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, for use to improve the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0154] In some embodiments, the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, is improved in the treatment or prevention of a disease, disorder, or condition treated by activation of a serotonin receptor.

[0155] In some embodiments, the serotonin receptor that is activated is 5-HT2A. In some embodiments, the disease, disorder, or condition that is treated by activation of a serotonin receptor is a psychiatric disorder.

[0156] In some embodiments, the psychiatric disorder is an anxiety disorder (such as, for example, generalized anxiety disorder, panic disorder, social anxiety disorder, or specific phobia); depression (such as, for example, feelings of helplessness, loss of pleasure, fatigue, or suicidal ideation); mood disorder (such as, for example, depression, bipolar disorder, cancer-related depression, anxiety disorder, or cyclothymic disorder); psychotic disorder (such as, for example, hallucinations, delusions, schizophrenia, etc.); impulse control disorder or addictive disorder (such as, for example, pyromancy (fire starting), kleptomania (stealing), or gambling addiction); alcohol addiction; drug addiction (such as opioid addiction); personality disorder (such as, for example, antisocial personality disorder, obsessive-compulsive personality disorder, or delusional personality disorder); obsessive-compulsive disorder (OCD) (such as, for example, thoughts or fears that cause one to perform certain activities or daily activities); post-traumatic stress disorder (PTSD); stress response syndrome (formerly known as adjustment disorder); dissociative disorder (formerly known as multiple personality disorder), or "split personality disorder" (SPD). These include: depersonalization disorder ("disordered personality") or depersonalization disorder; factitious disorder; sexual or gender disorder (e.g. sexual dysfunction, gender identity disorder, or paraphilia); somatic symptom disorder (formerly called psychosomatic or somatoform disorder); and combinations of these.

[0157] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors includes cognitive impairment; ischemia, including stroke; neurodegeneration; volatile substance use disorder; sleep disorder; pain, such as social pain, acute pain, cancer pain, chronic pain, breakthrough pain, bone pain, soft tissue pain, neuralgia, referred pain, phantom limb pain, neuropathic pain, cluster headache, or migraine; obesity or eating disorders; epilepsy or seizure disorders; neuronal cell death; excitotoxic cell death; or combinations thereof.

[0158] In some embodiments, the psychiatric disorder is hallucinations or delusions, or a combination thereof.

[0159] In some embodiments, the hallucination is a visual hallucination, an auditory hallucination, an olfactory hallucination, a gustatory hallucination, a tactile hallucination, a proprioceptive hallucination, a vestibular hallucination, a nociceptive hallucination, a thermosensory hallucination, or a chronosensory hallucination, or a combination thereof.

[0160] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is psychosis or a psychotic condition.

[0161] In some embodiments, administering a therapeutically effective amount of a composition of the present application to a subject in need thereof does not result in a worsening of psychosis or psychotic symptoms, including but not limited to, hallucinations and / or delusions. In some embodiments, administering a therapeutically effective amount of a composition of the present application to a subject in need thereof results in an improvement of psychosis or psychotic symptoms, including but not limited to, hallucinations and / or delusions. In some embodiments, administering a therapeutically effective amount of a compound of the present application to a subject in need thereof results in an improvement of psychosis or psychotic symptoms.

[0162] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition. In some embodiments, the CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition is Alzheimer's disease, presenile dementia, senile dementia, vascular dementia, dementia with Lewy bodies, cognitive impairment, Parkinson's disease, Parkinson's disease-related disorders (e.g., Parkinsonism, corticobasal degeneration, or supranuclear palsy), epilepsy, CNS trauma, CNS infection, CNS inflammation, stroke, multiple sclerosis, Huntington's disease, mitochondrial disorders, fragile X syndrome, Angelman syndrome, hereditary ataxias, neurological disorders ... Otologic movement disorders, oculomotor disorders, retinal neurodegenerative diseases, amyotrophic lateral sclerosis, tardive dyskinesia, hyperactivity disorder, attention deficit hyperactivity disorder, attention deficit disorder, restless legs syndrome, Tourette's syndrome, schizophrenia, autism spectrum disorder, tuberous sclerosis, Rett's syndrome, cerebral palsy, disorders of the reward system including eating disorders such as anorexia nervosa ("AN") or bulimia nervosa ("BN"), binge eating disorder ("BED"), trichotillomania, self-injurious dermatosis, nail biting, etc; migraine of any etiology, fibromyalgia, or peripheral neuropathy, or a combination thereof.

[0163] In some embodiments, the subject is a mammal. In other embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. In some embodiments, the subject is a canine. In some embodiments, the subject is a feline. Thus, the compositions, kits, methods, and uses of the present application are directed to both human and veterinary diseases, disorders, and conditions.

[0164] In some embodiments, the compositions of the present application are useful for treating behavioral problems in a feline or canine subject.

[0165] Thus, in some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a behavioral problem in a feline or canine subject.

[0166] In some embodiments, the behavioral problem is selected from, but is not limited to, anxiety, fear, stress, sleep disturbance, cognitive impairment, aggression, excessive noise making, scratching, biting, and combinations thereof.

[0167] In some embodiments, the non-human subject is a canine. In some embodiments, the non-human subject is a feline.

[0168] In the context of treating a disease, disorder, or condition that is treated by activation of a serotonin receptor, an effective amount of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, is, for example, an amount that treats the disease, disorder, or condition compared to the disease, disorder, or condition to which the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof and one or more fatty acids, or salts, prodrugs, and / or solvates thereof are not administered. Furthermore, with respect to improving the efficacy of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, for the treatment of a disease, disorder, or condition treated by activation of a serotonin receptor, an effective amount of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, is, for example, an amount that improves the efficacy of the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, compared to not administering the one or more fatty acids, or salts, prodrugs, and / or solvates thereof.

[0169] An effective amount may vary depending on factors such as the disease state, age, sex, and / or weight of the subject. The amount of a given compound or composition that corresponds to such an amount will vary depending on a variety of factors, such as the given compound or composition, pharmaceutical formulation, route of administration, type of condition, type of disease, or type of disorder, and the identity of the subject being treated, but can nevertheless be routinely determined by one of ordinary skill in the art.

[0170] The terms "treated," "treating," or "treatment," as used herein and as well understood in the art, refer to an approach to obtain beneficial or desired results, including clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, whether detectable or undetectable, reduction in the extent of the disease, stabilization of the disease state (i.e., not worsening), prevention of the spread of the disease, delay or slowing of the progression of the disease, improvement or mitigation of the disease state, reduction in recurrence of the disease, and remission (whether partial or total). "Treating" and "treatment" can also mean prolonging survival compared to expected survival in the absence of treatment. "Treating" and "treatment," as used herein, also include prophylactic treatment. For example, a subject with early stage depression can be treated to prevent progression, or a subject in remission can be treated with the compositions of the present application to prevent recurrence.

[0171] The method of treatment comprises administering to the subject one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or salts, prodrugs, and / or solvates thereof, optionally consisting of a single administration or comprising a series of administrations. The length of the treatment period depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the dosage of the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, the activity of the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, or a combination thereof.

[0172] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used according to known treatment protocols for the one or more hallucinogens in the treatment of a disease, disorder, or condition treated by activation of a serotonin receptor.

[0173] In some embodiments, the dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof will vary depending on many factors, such as their pharmacodynamic properties, the mode of administration, the age of the subject, the health of the subject, and the weight of the subject, the nature and severity of the symptoms, the frequency of treatment, and the type of concurrent treatment, if any, and the clearance rate in the subject being treated. One of skill in the art will be able to determine the appropriate dosage based on the above factors.

[0174] In some embodiments, the dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, is equal to or less than the dosage of such agents when used alone or without the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, such dosages being known to or readily determined by one of skill in the art.

[0175] In some embodiments, the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used once a year, twice a year, three times a year, or four times a year. In some embodiments, the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used at least once a week. In some embodiments, the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used about once per two weeks, three weeks, or month. In some embodiments, the compound is administered about once per week to about once per day. In another embodiment, the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used once, twice, three times, four times, five times, or six times per day. The length of the treatment period depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the concentration or activity of the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, or combinations thereof. It will also be understood that the effective dosage of the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof used for treatment or prevention may increase or decrease over the course of a particular treatment regimen. Changes in dosage may occur and be evident by standard diagnostic assays known in the art. In some cases, chronic administration or use is required. For example, one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered to a subject or used in an amount and for a period of time sufficient to treat the subject.

[0176] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered in a dose that is hallucinogenic or psychotomimetic and is taken in combination with psychotherapy or therapy. In some embodiments, such psychotherapy or therapy is administered once, twice, three times, or four times a year. In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are administered to the subject once a day, once every two days, once every three days, once a week, once every two weeks, once a month, once every two months, or once every three months, and the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used in a dose that is not hallucinogenic or psychotomimetic.

[0177] The dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, varies depending on many factors, such as the pharmacodynamic properties of the compound, the mode of administration, the age of the recipient, the health of the recipient, and the weight of the recipient, the nature and severity of the symptoms, the frequency of treatment, and the type of concurrent treatment, if any, and the clearance rate of the compound in the subject being treated. Appropriate dosages can be easily determined based on the above factors. In some embodiments, one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are initially administered at a suitable dosage, which is adjusted as necessary depending on the clinical response. Dosages are generally selected to achieve or maintain serum levels of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, of about 0.01 μg / cc to about 1000 μg / cc, or about 0.1 μg / cc to about 100 μg / cc. As a representative example, oral dosages of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, range from about 10 μg / day to about 1000 mg / day, preferably about 10 μg / day to about 500 mg / day, and more preferably about 10 μg / day to about 200 mg / day in adults. For parenteral administration, a typical dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, is about 0.0001 mg / kg to about 10 mg / kg, about 0.0001 mg / kg to about 1 mg / kg, about 0.01 mg / kg to about 0.1 mg / kg, or about 0.0001 mg / kg to about 0.01 mg / kg is administered.For oral administration, a typical dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, is about 0.001 μg / kg to about 10 mg / kg, about 0.1 μg / kg to about 10 mg / kg, about 0.01 μg / kg to about 1 mg / kg, or about 0.1 μg / kg to about 1 mg / kg. For administration in suppository form, a typical dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, is about 0.1 mg / kg to about 10 mg / kg, or about 0.1 mg / kg to about 1 mg / kg.

[0178] In some embodiments, the weight ratio of the amount or dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, to the amount or dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, either contained in a single composition or administered in separate compositions, is from about 0.1:1 to about 5:1.

[0179] In some embodiments of the present application, the compositions are formulated for oral administration, and the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are suitably in amounts of 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1.0 mg, 5.0 mg, 10.0 mg, 20.0 mg, 25.0 mg, 30.0 mg, 40.0 mg, 50.0 mg, 60.0 mg, 70.0 mg, 80.0 mg, 90.0 mg, 100.0 mg, 120.0 mg, 140.0 mg, 160.0 mg, 180.0 mg, 190.0 mg, 210.0 mg, 220.0 mg, 230.0 mg, 240.0 mg, 250.0 mg, 260.0 mg, 270.0 mg, 280.0 mg, 300.0 mg, 350.0 mg, 360.0 mg, 370.0 mg, 380.0 mg, 390.0 mg, 400.0 mg, 410.0 mg, 420.0 mg, 430.0 mg, 440.0 mg, 450.0 mg, 460.0 mg, 470.0 mg, 480.0 mg, 490.0 mg, 500.0 mg, 500.0 mg, 500.0 mg, 500.0 mg, 600.0 mg, 700.0 mg, 750.0 mg, 800.0 mg, 850.0 mg, 900.0 mg, 950.0 and in the form of a tablet containing 0.0 mg, 50.0 mg, 60.0 mg, 70.0 mg, 75.0 mg, 80.0 mg, 90.0 mg, 100.0 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg of active ingredient. In some embodiments of the present application, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are administered or used in a daily dose, a weekly dose, or a monthly dose, or the total daily dose is divided into two doses, three doses, or four doses per day.

[0180] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in an effective amount, including administration of a dose or dosage regimen that lacks clinically meaningful hallucinogenic / psychotometic effects. In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in an effective amount, including administration of a dose or dosage regimen that provides a clinical effect similar to that exhibited by a human plasma psilocin Cmax of about 1 ng / mL to about 5 ng / mL or less and / or 40% or less human 5-HT2A human CNS receptor occupancy, or a clinical effect exhibited by a human plasma psilocin Cmax of 1 ng / mL or less and / or 30% or less human 5-HT2A human CNS receptor occupancy. In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in an effective amount, including administration of a dose or dosage regimen that provides a clinical effect similar to that indicated by a human plasma psilocin Tmax of greater than 60 minutes, greater than 120 minutes, or greater than 180 minutes.

[0181] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in an effective amount, which includes administration of a dose or dosage regimen that exhibits a clinical effect similar to that indicated by a human plasma psilocin Cmax of 1 ng / mL or more and / or a human 5-HT2A human CNS receptor occupancy of 40% or more, or a clinical effect indicated by a human plasma psilocin Cmax of about 1 ng / mL to about 50 ng / mL, or about 20 ng / mL to about 50 ng / mL, or about 40 ng / mL to about 50 ng / mL.

[0182] IV. INTRANASAL COMPOSITIONS OF THE PRESENT APPLICATION AND METHODS AND USES THEREOF (i) The intranasal composition of the present application The present application also includes intranasal pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0183] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in an amount effective to treat or prevent a disease, disorder, or condition treated by activation of a serotonin receptor.

[0184] The application also includes intranasal pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, wherein the one or more fatty acids are present in an amount effective to improve the efficacy of the one or more hallucinogens in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor.

[0185] The present application also includes kits comprising one or more intranasal pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and instructions for administering the one or more intranasal pharmaceutical compositions to a subject in need thereof.

[0186] The application also includes kits for treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor, comprising one or more intranasal pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and instructions for administering the one or more intranasal pharmaceutical compositions to a subject in need thereof, wherein the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in amounts to treat or prevent a disease, disorder, or condition treated by activation of a serotonin receptor.

[0187] The application also includes a kit for improving the effectiveness of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor, the kit comprising one or more intranasal pharmaceutical compositions comprising one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and instructions for administering the intranasal pharmaceutical compositions to a subject in need thereof, wherein the one or more fatty acids are present in an amount effective to improve the effectiveness of the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in treating or preventing a disease, disorder, or condition treated by activation of a serotonin receptor.

[0188] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are selected from any hallucinogen known to be used in medical therapy or treatment, for example, for any disease, disorder, or condition treated by activation of serotonin receptors. In some embodiments, the one or more hallucinogens are selected from one or more of the hallucinogens as described above in "Compositions and Kits of the Present Application."

[0189] In some embodiments, the one or more hallucinogens are in the form of a free base or a pharma- ceutically acceptable salt.

[0190] In some embodiments, the one or more hallucinogens are 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof. In some embodiments, the one or more hallucinogens are methoxy-N,N-dimethyltryptamine (5-MeO-DMT), or a pharma- ceutically acceptable salt thereof. In some embodiments, the one or more hallucinogens are methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (free base).

[0191] In some embodiments, the one or more fatty acids are derived from fat by hydrolysis and are selected from any acid having from 4 to 30 carbon atoms, from 6 to 28 carbon atoms, or from 6 to 24 carbon atoms. In some embodiments, the fatty acid is selected from myristic acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.

[0192] In some embodiments, the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. In some embodiments, the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are linoleic acid (free acid). One skilled in the art will understand that the one or more fatty acids are present in the composition in acid form or as an acid salt, depending on the pH of the composition.

[0193] Thus, in some embodiments, the one or more hallucinogens is methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharma- ceutically acceptable salt thereof, and the one or more fatty acids, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is linoleic acid.

[0194] Thus, the present application also includes an intranasal pharmaceutical composition comprising a hallucinogen or a pharma- ceutically acceptable salt thereof, and a fatty acid. The present application also includes an intranasal pharmaceutical composition comprising 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharma- ceutically acceptable salt thereof, and a fatty acid. The present application also includes an intranasal pharmaceutical composition comprising 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharma- ceutically acceptable salt thereof, and linoleic acid.

[0195] In some embodiments, compositions for nasal administration are conveniently formulated as aerosols, sprays, drops, gels, and powders. For intranasal administration or administration by inhalation, the compositions of the present application are conveniently delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is squeezed or pumped by the patient, or as an aerosol spray presentation from a pressurized container or nebulizer. Aerosol formulations usually contain a solution or fine suspension of an active substance in a physiologically acceptable aqueous or non-aqueous solvent, and are usually provided in single or multiple dose amounts in a sterile form in a sealed container, for example in the form of a cartridge or refill for use with an atomizing device. Alternatively, the sealed container is an integrated dispensing device, such as a single-dose nasal inhaler or aerosol dispenser, equipped with a metering valve intended for disposal after use. When the dosage form includes an aerosol dispenser, the dosage form contains a propellant, which is, for example, a compressed gas, such as compressed air, or an organic propellant, such as a fluorochlorohydrocarbon. Suitable propellants include, but are not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, heptafluoroalkanes, carbon dioxide, or another suitable gas. In the case of a pressurized aerosol, the dosage unit is determined by suitably providing a valve to deliver a metered amount. In some embodiments, the pressurized container or nebulizer contains a solution or suspension of the active compound. Capsules and cartridges (e.g., made from gelatin) for use in an inhaler or insufflator are formulated to contain, for example, a powder mix of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and a suitable powder base, such as lactose or starch. The aerosol dosage form can also be in the form of a pump-atomiser.

[0196] The aerosol dosage forms can also take the form of a pump-atomiser.

[0197] Thus, in some embodiments, the intranasal pharmaceutical composition is formulated as a solution, aerosol, spray, drops, gel, or powder.

[0198] In some embodiments, the powder is a free flowing or inhalable powder.

[0199] In some embodiments, the inhalable powder is formulated for administration via a medication dispenser selected from a reservoir dry powder inhaler, a unit dose dry powder inhaler, a pre-metered multi-dose dry powder inhaler, a nasal inhaler, or a pressurized metered dose inhaler.

[0200] In some embodiments, the intranasal pharmaceutical composition is delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is squeezed or pumped by the patient, or as an aerosol spray presentation from a pressurized container or nebulizer.

[0201] In some embodiments, the intranasal pharmaceutical composition is formulated as an aerosol for use in a pump sprayer.

[0202] In some embodiments, the intranasal pharmaceutical composition is a powder. In some embodiments, the intranasal pharmaceutical composition is a dry powder. In some embodiments, the dry powder is formulated to be reconstituted with a suitable solvent prior to use or administration. In some embodiments, the suitable solvent is sterile pyrogen-free water.

[0203] In some embodiments, the powder is formulated for use or administration in an inhaler or insufflator. Thus, in some embodiments, the dry powder is formulated for use or administration in capsules and cartridges for use in an inhaler or insufflator.

[0204] In some embodiments, the powder comprises one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, in amounts or dosages of about 0.1:1 to about 5:1, about 0.5:1 to about 1:1.5, about 0.75:1.25 to about 1:1.25, or about 1:1.2 by weight ratio. In some embodiments, the dry powder comprises one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, in amounts or dosages of about 0.5:1 to about 1:1.5, about 0.75:1.25 to about 1:1.25, or about 1:1.2 by weight ratio.

[0205] In some embodiments, the dry powder further comprises a suitable powder base, hi some embodiments, suitable powder bases include lactose or starch.

[0206] In some embodiments, the intranasal pharmaceutical composition further comprises water. Thus, in some embodiments, the intranasal pharmaceutical composition further comprises water and is an aqueous intranasal pharmaceutical composition.

[0207] In some embodiments, the intranasal pharmaceutical composition is a solution, a suspension, or an emulsion, hi some embodiments, the intranasal pharmaceutical composition is a solution.

[0208] In some embodiments, the aqueous intranasal pharmaceutical composition is formulated for administration to the nose in the form of droplets. In some embodiments, the aqueous intranasal pharmaceutical composition is formulated for administration as a nasal spray. In some embodiments, the nasal spray is delivered in the form of a solution or suspension from a pump spray container that is squeezed or pumped by the patient, or as an aerosol spray presentation from a pressurized container or nebulizer. In some embodiments, the aqueous intranasal pharmaceutical composition is formulated as an aerosol for use with a pump sprayer.

[0209] In some embodiments, water is present in an amount of about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 33% to about 75%, about 55% to about 70%, or about 55% to about 65% by weight of the composition. In some embodiments, water is present in an amount of about 50%, about 60%, about 65%, or about 70% by weight of the composition. In some embodiments, water is present in an amount of about 55% to about 65% by weight of the composition. In some embodiments, water is about 60% by weight of the composition.

[0210] In some embodiments, the one or more hallucinogens is 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, and the 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount by weight of the composition of about 1% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 2% to about 5%, about 2% to about 4%, about 2% to about 3%, or about 3% to about 4%. In some embodiments, 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount of about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, or about 6% by weight of the composition. In some embodiments, 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount of about 3% to about 4% by weight of the composition. In some embodiments, 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in about 3.5% by weight of the composition.

[0211] In some embodiments, the pharma- ceutically acceptable salt of 5-MeO-DMT is selected from acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, solubilize, maleate, methanesulfonate ("mesylate"), naphthalenesulfonate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate (also known as tosylate), and tartrate.

[0212] In some embodiments, the 5-MeO-DMT pharmaceutically acceptable salt is selected from hydrochloride, sulfate, fumarate, succinate, maleate, solubilizer, oxalate, benzoate, tartrate, mesylate, and acetate. In some embodiments, the 5-MeO-DMT pharmaceutically acceptable salt is selected from benzoate and succinate. In some embodiments, the 5-MeO-DMT pharmaceutically acceptable salt is succinate.

[0213] In some embodiments, the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, is linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, and the linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount of about 1% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 3% to about 6%, about 3% to about 5%, about 2% to about 5%, or about 2% to about 4% by weight of the composition. In some embodiments, the linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount of about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, or about 6% by weight of the composition. In some embodiments, the linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, is present in an amount of about 2% to about 4% by weight of the composition. In some embodiments, the linoleic acid is about 3% by weight of the composition.

[0214] In some embodiments, the aqueous intranasal pharmaceutical composition comprises one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, in an amount or dosage of about 0.1:1 to about 5:1, about 0.5:1 to about 1:1.5, about 0.75:1.25 to about 1:1.25, or about 1:1.2 by weight ratio. In some embodiments, the aqueous intranasal composition formulation comprises one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, in an amount or dosage of about 0.5:1 to about 1:1.5, about 0.75:1.25 to about 1:1.25, or about 1:1.2 by weight ratio.

[0215] In some embodiments, the pH of the aqueous intranasal medicament is about 4 to about 8, about 4 to about 7, about 4.5 to about 6, or about 4.5 to about 5.5. In some embodiments, the pH of the aqueous intranasal medicament is about 4, about 4.5, about 5, about 5.5, or about 6. In some embodiments, the pH of the aqueous intranasal medicament is about 4.5 to about 5.5, or about 5.

[0216] In some embodiments, the intranasal pharmaceutical composition is stable. In some embodiments, the physical properties and pH of the intranasal pharmaceutical composition remain substantially unchanged after 90 days at about 45° C. In some embodiments, the appearance (i.e., liquid), color, and / or pH of the remaining intranasal pharmaceutical composition remains substantially unchanged after 90 days at about 45° C.

[0217] In some embodiments, the intranasal pharmaceutical composition further comprises one or more non-medicinal ingredients. In some embodiments, the one or more non-medicinal ingredients are selected from pH adjusting agents, buffering agents, surfactants, humectants, co-solvents, emulsifiers, preservatives, gelling agents, isotonicity agents, antioxidants, stabilizers, and sweeteners. In some embodiments, the one or more non-medicinal ingredients are selected from buffering agents, surfactants, co-solvents, humectants, and sweeteners.

[0218] In some embodiments, the intranasal pharmaceutical composition further comprises from about 10% to about 35%, or from about 10% to about 30%, or from about 10% to about 25%, or from about 15% to about 25% by weight of the composition of one or more surfactants. In some embodiments, the intranasal pharmaceutical composition further comprises from about 15% to about 25% by weight of the composition of one or more surfactants. In some embodiments, the intranasal pharmaceutical composition further comprises from about 10%, about 15%, about 20%, about 25%, or about 30% by weight of the composition of one or more surfactants. In some embodiments, the intranasal pharmaceutical composition further comprises from about 20%, about 25%, or about 30% by weight of the composition of one or more surfactants.

[0219] In some embodiments, the one or more surfactants are one or more non-ionic surfactants. In some embodiments, the one or more non-ionic surfactants are selected from, but are not limited to, tyloxapol, polyoxyethylene sorbitan fatty acid esters (polysorbates), polyoxyethylene products of hydrogenated vegetable oils, polyethoxylated castor oil, polyethoxylated hydrogenated castor oil, polyoxyethylene castor oil derivatives, and poloxamers, and mixtures thereof.

[0220] In some embodiments, the polyoxyethylene sorbitan fatty ester is selected from, but is not limited to, polyethylene sorbitan monooleate (Polysorbate 80), polyoxyethylene (20) sorbitan monolaurate (Polysorbate 20), polyoxyethylene (20) sorbitan tristearate (Polysorbate 65), polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan monopalmitate, and polyoxyethylene (20) sorbitan monostearate, and mixtures thereof. In some embodiments, the polyoxyethylene sorbitan fatty ester is polyoxyethylene (20) sorbitan monolaurate (Polysorbate 20, Tween® 20). Thus, in some embodiments, the surfactant is polyoxyethylene (20) sorbitan monolaurate (Polysorbate 20, Tween® 20) and mixtures thereof.

[0221] In some embodiments, the intranasal pharmaceutical composition further comprises one or more co-solvents at about 1% to about 10%, about 2% to about 8%, about 2% to about 7%, about 3% to about 7%, about 3% to about 6%, or about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more co-solvents at about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more co-solvents at about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more co-solvents at about 5% by weight of the composition.

[0222] In some embodiments, the one or more co-solvents are selected from hydroxylated solvents such as alcohols, including isopropyl alcohol; glycols (such as propylene glycol, polyethylene glycol, polypropylene glycol, glycol ethers, and glycerol); polyoxyethylene alcohols; medium chain glycerides and diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol), and mixtures thereof. In some embodiments, the co-solvent is diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol, Transcutanol®).

[0223] In some embodiments, the intranasal pharmaceutical composition further comprises one or more buffering agents at about 0.1% to about 5%, about 0.5% to about 5%, about 0.5% to about 4%, about 0.5% to about 3%, about 1% to about 3%, or about 2% to about 3% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more buffering agents at about 1% to about 3% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more buffering agents at about 0.1%, about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, or about 5% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more buffering agents at about 3% by weight of the composition.

[0224] In some embodiments, the one or more buffering agents are selected from sodium phosphate, sodium citrate, and citric acid, and mixtures thereof. In some embodiments, the one or more buffering agents are selected from sodium citrate, and citric acid, and mixtures thereof.

[0225] In some embodiments, the intranasal pharmaceutical composition further comprises one or more humectants at about 1% to about 10%, about 2% to about 8%, about 2% to about 7%, about 3% to about 7%, about 3% to about 6%, or about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more humectants at about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more humectants at about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more humectants at about 5% by weight of the composition.

[0226] In some embodiments, the one or more humectants are selected from glycerin, sorbitol, mannitol, and xylitol, and mixtures thereof, hi some embodiments, the one or more humectants is xylitol.

[0227] In some embodiments, the intranasal pharmaceutical composition further comprises one or more preservatives. In some embodiments, the one or more preservatives are selected from, but are not limited to, phenylethyl alcohol, benzalkonium chloride, benzoic acid, benzoates such as sodium benzoate, and phenylethyl alcohol. In some embodiments, the intranasal pharmaceutical composition does not comprise a preservative.

[0228] In some embodiments, the intranasal pharmaceutical composition further comprises one or more sweeteners. In some embodiments, the one or more sweeteners are sugar alcohols, including glycerol, sorbitol, xylitol, mannitol, galactitol, maltitol, hydrogenated isomaltulose (isomalt), lactitol, erythritol, glucitol, ribitol; sugars (such as monosaccharides, disaccharides, and polysaccharides), such as sucrose, dextrose, maltose, dextrin, maltodextrin, xylose, ribose, glucose, including liquid glucose, mannose, galactose, fulveol; sugar sweeteners, including sucrose (levulose), lactose, invert sugar, fructooligosaccharide syrup, trehalose, tagatose, fucose, gulose, raffinose, ribulose, raffinose, stachyose, xylulose, adonose, amylase, arabinose, deoxyribose, corn syrup solids (e.g., high fructose corn syrup), or combinations thereof; artificial sweeteners, for example, soluble saccharin salts, i.e., sodium saccharin or calcium saccharin. salts such as potassium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazin-4-one-2,2-dioxide (acesulfame-K), the free acid form of saccharin, L-aspartic acid derived sweeteners such as L-aspartyl-L-phenylalanine methyl ester (aspartame), L-alpha aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamide hydrate (alitame), N-[N-(3,3-dimethylbutyl)-L-aspartyl]-L-phenylalanine and the like; L-aspartyl-L-(1-cyclohexene)-alanine or a combination thereof; sucralose; maltol; stevia; ammonium glycerol glycyrrhizinate (MagnaSweet®); or a combination thereof.In some embodiments, the one or more sweetening agents are selected from sugar alcohols, stevia, and ammonium glycerol glycyrrhizinate.

[0229] Thus, in some embodiments, the present application includes an intranasal pharmaceutical composition comprising about 3% to about 6% 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, and 2% to about 4% linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, and about 55% to about 65% water by weight of the composition.

[0230] In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more non-medicinal ingredients selected from a buffering agent, a surfactant, a co-solvent, and a wetting agent. In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more surfactants at about 15% to about 25% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more co-solvents at about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more buffering agents at about 1% to about 3% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more wetting agents at about 4% to about 6% by weight of the composition.

[0231] In some embodiments, the intranasal pharmaceutical composition further comprises one or more surfactants at about 15% to about 25% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more surfactants at about 15% to about 25% by weight of the composition, and one or more co-solvents at about 4% to about 6% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more surfactants at about 15% to about 25% by weight of the composition, one or more co-solvents at about 4% to about 6% by weight of the composition, and one or more buffering agents at about 1% to about 3% by weight of the composition. In some embodiments, the intranasal pharmaceutical composition further comprises one or more surfactants at about 15% to about 25% by weight of the composition, one or more co-solvents at about 4% to about 6% by weight of the composition, one or more buffering agents at about 1% to about 3% by weight of the composition, and one or more humectants at about 4% to about 6% by weight of the composition.

[0232] Thus, in some embodiments, the present application includes an intranasal pharmaceutical composition comprising about 3% to about 6% 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharma- ceutically acceptable salt thereof, by weight of the composition, as well as 2% to about 4% linoleic acid, about 55% to about 65% water, about 15% to about 25% surfactant(s), about 4% to about 6% co-solvent(s), about 1% to about 3% buffering agent(s), and about 4% to about 6% humectant(s).

[0233] In an exemplary embodiment, the surfactant is polyoxyethylene(20) sorbitan monolaurate (polysorbate 20), the co-solvent is diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol), the one or more buffering agents are selected from sodium citrate and citric acid, and / or the one or more humectants are xylitol. In some embodiments, the intranasal pharmaceutical composition further comprises one or more sweeteners selected from sugar alcohols, stevia, and ammonium glycyrrhizinate, and mixtures thereof.

[0234] Thus, in some embodiments, the present application includes an intranasal pharmaceutical composition comprising about 3% to about 6% 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharma- ceutically acceptable salt thereof, by weight of the composition, as well as 2% to about 4% linoleic acid, about 55% to about 65% water, about 15% to about 25% polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), about 4% to about 6% (2-(2-ethoxyethoxy)ethanol, about 1% to about 3% sodium citrate and citric acid, and about 4% to about 6% xylitol. In some embodiments, the intranasal pharmaceutical composition optionally further comprises one or more sweeteners.

[0235] One of ordinary skill in the art will appreciate that a single non-medicinal ingredient can serve more than one function, and it will be further understood that multiple non-medicinal ingredients that serve the same function may be used.

[0236] In some embodiments, the one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, increase the absorption rate of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the plasma and cerebrospinal fluid (CSF) of a subject, as compared to an otherwise identical intranasal pharmaceutical composition in the absence of the one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof. In some embodiments, the one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, increase the absorption rate of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the cerebrospinal fluid (CSF) of a subject, as compared to an otherwise identical intranasal pharmaceutical composition in the absence of the one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0237] Thus, in some embodiments, the intranasal pharmaceutical composition provides increased mucosal delivery of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, as compared to an identical intranasal pharmaceutical composition except for the absence of one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0238] In some embodiments, the intranasal pharmaceutical composition provides a Cmax of 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, in plasma that is about 3-fold to about 6-fold, or about 5-fold greater than the Cmax of an otherwise identical intranasal pharmaceutical composition in the absence of linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof.

[0239] In some embodiments, the intranasal pharmaceutical composition provides a Cmax of 5-MeO-DMT, or a pharma- cerebrospinal fluid (CSF) that is about 5-fold to about 20-fold, about 10-fold to about 17-fold, or about 10-fold greater than the Cmax of an otherwise identical intranasal pharmaceutical composition in the absence of linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof.

[0240] In some embodiments, the intranasal pharmaceutical composition achieves a Cmax in the CSF at about 3 minutes to about 25 minutes, about 5 minutes to about 20 minutes, or about 5 minutes to about 15 minutes after administration of the intranasal pharmaceutical composition.

[0241] In some embodiments, the intranasal pharmaceutical composition provides increased bioavailability of 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, in plasma and CSF when administered intranasally, compared to an otherwise identical intranasal pharmaceutical composition lacking the presence of linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof. In some embodiments, increased bioavailability of 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, in cerebrospinal fluid (CSF) refers to increased bioavailability of 5-MeO-DMT, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof, in the brain.

[0242] In some embodiments, the intranasal pharmaceutical composition increases plasma bioavailability by about 4-fold to about 8-fold, about 5-fold to about 7-fold, or about 7-fold as compared to an identical intranasal pharmaceutical composition except for the absence of linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof.

[0243] As used herein, the term "increased absorption rate" as used herein with respect to one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, refers to any detectable increase in the absorption rate of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an intranasal pharmaceutical composition of the present application compared to the absorption rate and bioavailability of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an identical intranasal pharmaceutical composition except that one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are absent. "Absorption rate" is estimated by comparison of the time (tmax) to reach maximum concentration (Cmax).

[0244] As used herein, the term "increased mucosal delivery" as used herein with respect to one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, means any detectable increase in mucosal delivery of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an intranasal pharmaceutical composition of the present application compared to mucosal delivery of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an identical intranasal pharmaceutical composition except for the absence of one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0245] As used herein, the term "increased bioavailability" as used herein with respect to one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, means any detectable increase in the bioavailability of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an intranasal pharmaceutical composition of the present application compared to the bioavailability of one or more hallucinogens, such as 5-MeO-DMT, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, using an identical intranasal pharmaceutical composition except for the absence of one or more fatty acids, such as linoleic acid, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0246] In some embodiments, the pharma- ceutically acceptable salt is an acid addition salt or a base addition salt.The selection of suitable salt can be performed by those skilled in the art.Suitable salts include, for example, acid addition salts that can be formed by mixing a solution of a compound with a solution of a pharma- ceutically acceptable acid such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, or benzoic acid. Additionally, acids generally considered to be suitable for the formation of pharma- ceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et al, Camille G. (eds.) and Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley VCH; S. Berge et al, Journal of Pharmaceutical Sciences 1977 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (on the website of the Food & Drug Administration, Washington, DC).

[0247] The acid addition salt suitable for or compatible with the treatment of a subject is any non-toxic organic or inorganic acid addition salt of any basic compound.Basic compounds that form acid addition salts include, for example, compounds that contain amine groups.Exemplary inorganic acids that form suitable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, as well as acid metal salts (such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate).Exemplary organic acids that form suitable salts include monocarboxylic acids, dicarboxylic acids, and tricarboxylic acids. Examples of such organic acids are, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, mandelic acid, salicylic acid, 2-phenoxybenzoic acid, p-toluenesulfonic acid, and other sulfonic acids, such as methanesulfonic acid, ethanesulfonic acid, and 2-hydroxyethanesulfonic acid. In some embodiments, exemplary acid addition salts also include acetate, ascorbate, benzoate, benzenesulfonate, hydrogen sulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate ("mesylate"), naphthalenesulfonate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, and toluenesulfonate (also known as tosylate). In some embodiments, mono- or di-acid salts are formed, and such salts exist in either hydrated, solvated, or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents, and generally exhibit higher melting points compared to their free base forms. The criteria for selecting an appropriate salt are known to those skilled in the art. For example, in isolating the compounds of the present application for laboratory use or for subsequent conversion to a pharma-ceutically acceptable acid addition salt, other pharma-ceutically unacceptable salts may be used, such as, but not limited to, oxalates.

[0248] In some embodiments, the pharma- ceutically acceptable salt of 5-MeO-DMT is a succinate salt.

[0249] The base addition salt suitable for or compatible with the treatment of a subject is any non-toxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form base addition salts include, for example, compounds that contain a carboxylic acid group. Exemplary inorganic bases that form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide, as well as ammonia. Exemplary organic bases that form suitable salts include aliphatic, alicyclic, or aromatic organic amines, such as isopropylamine, methylamine, trimethylamine, picoline, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of suitable salts may be useful, for example, to prevent hydrolysis when ester functional groups are present elsewhere in the compound. The criteria for selecting suitable salts are known to those skilled in the art. In some embodiments, exemplary basic salts also include ammonium salts, alkali metal salts (such as sodium salts, lithium salts, and potassium salts), alkaline earth metal salts (such as calcium salts and magnesium salts), salts with organic bases (e.g., organic amines) (such as dicyclohexylamine, A-butylamine, choline), and salts with amino acids (such as arginine, lysine, etc.). Basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl sulfate, diethyl sulfate, and dibutyl sulfate), long chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides, and iodides), aralkyl halides (e.g., benzyl bromide and phenethyl bromide).Compounds bearing an acidic moiety can be mixed with suitable pharma- ceutically acceptable salts to obtain salts formed with appropriate organic ligands, such as, for example, alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), and quaternary ammonium salts.

[0250] In some embodiments, when an acid (-COOH) or alcohol group is present, a pharma- ceutically acceptable ester can be employed to modify the solubility or hydrolysis properties of the compound. In some embodiments, the ester is an alkyl ester. In some embodiments, the alkyl ester is selected from an isopropyl ester, a methyl ester, an ethyl ester, a propyl ester, and mixtures thereof.

[0251] The formation of pharma- ceutically acceptable salts can be accomplished using standard techniques, for example, treating the neutral compound with an acid or base in a suitable solvent and isolating the formed salt by filtration, extraction, or any other suitable method.

[0252] Examples of suitable solvates include ethanol, water, etc. When water is the solvent, the molecule is referred to as a "hydrate." The formation of solvates varies depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in a suitable solvent and isolating the solvate by cooling the solvent or using an anti-solvent. The solvate is usually dried or azeotroped under ambient conditions. Selection of suitable conditions for forming a particular solvate can be performed by one skilled in the art.

[0253] In some embodiments, the one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the intranasal compositions and kits of the present application are formulated in a single intranasal pharmaceutical composition for administration to or use in a subject.

[0254] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are present in the composition in an effective amount, e.g., an amount effective to treat or prevent a disease, disorder, or condition that is treated by activation of a serotonin receptor. In some embodiments, the effective amount is determined as described in the Methods and Uses of Intranasal Compositions section of this application below.

[0255] In some embodiments, one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, are used or administered in an intranasal composition that includes an additional therapeutic agent. Thus, the present application also includes an intranasal pharmaceutical composition that includes one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and an additional therapeutic agent thereof, and optionally one or more pharma- ceutically acceptable non-medicinal ingredients. In some embodiments, the additional therapeutic agent is another known agent useful for treating a disease, disorder, or condition due to activation of serotonin receptors. In some embodiments, the additional therapeutic agent is a psychoactive agent.

[0256] (ii) Methods and Uses of the Intranasal Compositions of the Present Application The present application includes a method of treating or preventing a disease, disorder, or condition treated by activation of serotonin receptors, comprising administering to a subject in need thereof an effective amount of one or more intranasal formulations of the present application.

[0257] The present application also includes the use of one or more intranasal formulations of the present application for treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor, as well as the use of one or more intranasal formulations of the present application in the preparation of a medicament for treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor.The present application also includes one or more intranasal formulations of the present application for use in treating or preventing a disease, disorder, or condition that is treated by activation of a serotonin receptor.

[0258] In some embodiments, the present application also includes a method of improving the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, comprising administering to a subject in need thereof an effective amount of one or more intranasal formulations of the present application.

[0259] The present application also includes the use of one or more intranasal formulations of the present application for improving the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, as well as the use of one or more intranasal formulations of the present application in the preparation of a medicament for improving the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.The present application also includes one or more intranasal formulations of the present application for use in improving the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

[0260] In some embodiments, the efficacy of one or more hallucinogens, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, is improved in the treatment or prevention of a disease, disorder, or condition treated by activation of a serotonin receptor.

[0261] In some embodiments, the serotonin receptor that is activated is 5-HT2A. In some embodiments, the disease, disorder, or condition that is treated by activation of the serotonin receptor is as described above under the methods and uses in the application section above.

[0262] In the context of treating a disease, disorder, or condition that is treated by activation of a serotonin receptor, an effective amount of one or more intranasal formulations of the present application is, for example, an amount that treats the disease, disorder, or condition as compared to the disease, disorder, or condition in which an intranasal formulation of the present application is not administered. Further, in terms of improving the efficacy of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, for the treatment of a disease, disorder, or condition that is treated by activation of a serotonin receptor, an effective amount of one or more intranasal formulations of the present application is, for example, an amount that improves the efficacy of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, as compared to the absence of administration of one or more intranasal formulations of the present application.

[0263] An effective amount may vary depending on factors such as the disease state, age, sex, and / or weight of the subject. The amount of a given compound or composition that corresponds to such an amount will vary depending on a variety of factors, such as the given compound or composition, pharmaceutical formulation, route of administration, type of condition, type of disease, or type of disorder, identity of the subject being treated, etc., but can nevertheless be routinely determined by one of ordinary skill in the art.

[0264] The terms "treated," "treating," or "treatment," as used herein and as well understood in the art, refer to an approach to obtain beneficial or desired results, including clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, whether detectable or undetectable, reduction in the extent of disease, stabilization (i.e., not worsening) of the disease state, prevention of disease spread, delay or slowing of disease progression, improvement or mitigation of disease state, reduction in recurrence of disease, and remission (whether partial or total). "Treating" and "treatment" can also mean prolonging survival compared to expected survival in the absence of treatment. "Treating" and "treatment," as used herein, also include prophylactic treatment. For example, a subject with early stage depression can be treated to prevent progression, or a subject in remission can be treated with the compositions of the present application to prevent recurrence.

[0265] The method of treatment includes administering to the subject one or more, optionally consisting of a single administration or including a series of administrations. The length of treatment depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the dosage of one or more intranasal compositions of the present application, the activity of one or more intranasal compositions of the present application, or a combination thereof.

[0266] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used according to known treatment protocols for the one or more hallucinogens in the treatment of a disease, disorder, or condition treated by activation of a serotonin receptor.

[0267] In some embodiments, the dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, and / or one or more hallucinogens, or salts, prodrugs, and / or solvates thereof will vary depending on many factors, such as their pharmacodynamic properties, the mode of administration, the age of the subject, the health of the subject, and the weight of the subject, the nature and severity of the symptoms, the frequency of treatment, and the type of concurrent treatment, if any, and the clearance rate in the subject being treated. One of skill in the art will be able to determine the appropriate dosage based on the above factors.

[0268] In some embodiments, the dosage of one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, is equal to or less than the dosage of such agents when used alone or without the one or more fatty acids, or salts, prodrugs, and / or solvates thereof, such dosages being known to or readily determined by one of skill in the art.

[0269] In some embodiments, one or more intranasal compositions of the present application are administered or used once a year, twice a year, three times a year, or four times a year. In some embodiments, one or more intranasal compositions of the present application are administered or used at least once a week. In some embodiments, one or more intranasal compositions of the present application are administered or used about once every two weeks, about once every three weeks, or about once a month. In some embodiments, one or more intranasal compositions of the present application are administered about once a week to about once a day. In another embodiment, one or more intranasal compositions of the present application are administered or used once a day, twice a day, three times a day, four times a day, five times a day, or six times a day. The length of the treatment period depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the concentration and / or activity of the one or more intranasal compositions of the present application, or a combination thereof. It will also be understood that the effective dosage of one or more intranasal compositions of the present application used for treatment or prevention may increase or decrease over the course of a particular treatment regimen. Changes in dosage may occur and be evident by standard diagnostic assays known in the art. In some cases, chronic administration or use is required. For example, one or more intranasal compositions of the present application are administered to a subject or used in an amount and for a period of time sufficient to treat the subject.

[0270] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, in the intranasal compositions of the present application are administered in a dose that is hallucinogenic or psychotomimetic and is taken in combination with psychotherapy or therapy. In some embodiments, such psychotherapy or therapy is administered once, twice, three times, or four times a year. In some embodiments, the intranasal compositions of the present application are administered to a subject once a day, once every two days, once every three days, once a week, once every two weeks, once a month, once every two months, or once every three months, and the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, are administered or used in a dose that is not hallucinogenic or psychotomimetic in the intranasal compositions of the present application.

[0271] In some embodiments, the weight ratio of the amount or dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, to one or more hallucinogens, or salts, prodrugs, and / or solvates thereof is about 0.1:1 to about 5:1. In some embodiments, the weight ratio of the amount or dosage of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, to one or more hallucinogens, or salts, prodrugs, and / or solvates thereof is about 0.1:1 to about 5:1, about 0.5:1 to about 1:1.5, about 0.75:1.25 to about 1:1.25, or about 1:1.2. In some embodiments, the weight ratio of the amounts or dosages of one or more fatty acids, or salts, prodrugs, and / or solvates thereof, to one or more hallucinogens, or salts, prodrugs, and / or solvates thereof is from about 0.5:1 to about 1:1.5, from about 0.75:1.25 to about 1:1.25, or about 1:1.2.

[0272] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, in the intranasal compositions of the present application are used or administered in an effective amount, which includes administering a dose or dosage regimen that is devoid of clinically meaningful hallucinogenic / psychotometic effects. In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, in the intranasal compositions of the present application are used or administered in an effective amount, which includes administration of a dose or dosage regimen that provides a clinical effect similar to a clinical effect indicated by a human plasma psilocin Cmax of about 1 ng / mL to about 5 ng / mL or less and / or a human 5-HT2A human CNS receptor occupancy of 40% or less, or a clinical effect indicated by a human plasma psilocin Cmax of 1 ng / mL or less and / or a human 5-HT2A human CNS receptor occupancy of 30% or less. In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, in the intranasal compositions of the present application are used or administered in an effective amount, including administration of a dose or dosage regimen that provides a clinical effect similar to that demonstrated by a human plasma psilocin Tmax of greater than 60 minutes, greater than 120 minutes, or greater than 180 minutes.

[0273] In some embodiments, the one or more hallucinogens, or salts, prodrugs, and / or solvates thereof, and / or one or more fatty acids, or salts, prodrugs, and / or solvates thereof, in the intranasal compositions of the present application are used or administered in an effective amount, which includes administering a dose or dosage regimen that exhibits a clinical effect similar to that indicated by a human plasma psilocin Cmax of 1 ng / mL or more and / or a human 5-HT2A human CNS receptor occupancy of 40% or more, or a clinical effect indicated by a human plasma psilocin Cmax of about 1 ng / mL to about 50 ng / mL, or about 20 ng / mL to about 50 ng / mL, or about 40 ng / mL to about 50 ng / mL.

[0274] The following non-limiting examples are illustrative of the present application. EXAMPLES

[0275] Example 1: Mouse head twitch experiment method Male C57BL / 6J mice (weight range 20-30 g) were administered the appropriate dose(s) of test compound or combination of test compounds, and after pretreatment, the animals were placed in individual observation chambers. The animals were visually assessed for head twitches that occurred continuously over a 1-hour period. A head twitch is defined as a rapid muscle reflex of the head that is not elicited by external tactile stimulation (Corne SJ, Pickering RW (1967) Psychopharmacologia 11(1): 65-78). Each head twitch was counted individually by a trained observer, and data were expressed as the mean + SEM of 4-10 mice per group. In addition to the total number of head twitches recorded over the 1-hour observation period, head twitches were also scored according to each specific 10-minute time bin within the 1-hour observation period (i.e., 0-10 minutes, 10-20 minutes, 20-30 minutes, etc.).

[0276] Two types of experiments were performed. One investigated the effect of linoleic acid in combination with a test compound (psilocybin or I-4). In these experiments, both the test compound or a saline control were injected subcutaneously (SC) 1 min before testing. In the second set of experiments, the effect of the selective 5-HT2A receptor antagonist M100907 (Kehne JH, et al. (1996) J Pharmacol Exp Ther. 277(2): 968-981) on test compound-induced head twitches was investigated. In these experiments, M100907 (0.5 mg / kg, IP) was injected 30 min before a single dose of the test compound (i.e., psilocybin or I-4). The dose of the test compound was selected as one that produced a reliable head twitch response based on previous dose-response studies. One minute after SC administration of the test compound, the mice were placed in the observation chamber for measurement of the head twitch response.

[0277] result Effect of Linoleic Acid in Combination with Test Compounds Administration of linoleic acid alone (0.1-10 mg / kg SC) did not induce head twitches to a significant extent compared to vehicle pretreated mice (e.g., vehicle: 0.8 ± 0.5; linoleic acid 10 mg / kg: 1.0 ± 0.7, Figure 1). However, combination of linoleic acid with an equimolar dose of test compound (I-4 or psilocybin) resulted in a greater head twitch response compared to an equivalent dose of test substance alone (Figure 2). e.g., I-4 administered at 0.3 mg / kg SC + vehicle = 3.3 ± 0.8; I-4 administered at 0.3 mg / kg SC + linoleic acid administered at 0.39 mg / kg SC = 7.8 ± 0.6. This increase appeared to be the result of an increase in the duration of the head twitch response (Figure 3).

[0278] Effect of M100907 in combination with test compounds Pretreatment with M100907 (0.5 mg / kg IP) completely inhibited the development of head twitches induced by either I-4 (6.2 mg / kg SC) or psilocybin (3 mg / kg SC) (FIG. 4).

[0279] Example 2: Intranasal and Subcutaneous 5-MeO-DMT (16) Formulations General Methods and Materials Preparation of 5-MeO-DMT intranasal formulation The following ingredients were used in this process: [Table 99]

[0280] In a stainless steel vessel, component number 2, component number 3, and component number 4 were added and stirred until the mixture was homogenous (Phase B). In the main tank, component number 10, component number 5, component number 6, component number 7, component number 8, and component number 9 were added with stirring and continued to stir until the mixture was homogenous (Phase C). Phase B was then added to Phase C in the main tank. The mixture was stirred until it was homogenous. In the next step, component number 1 (Phase A) was added and stirred until the mixture was homogenous (Phase A+Phase B+Phase C). The resulting mixture was a light to dark yellow liquid with a pH of 5.00±0.50 (25° C.).

[0281] Stability of 5-MeO-DMT intranasal formulations The stability of the products prepared according to the above protocol was evaluated for appearance, color, odor, pH, and viscosity, where applicable, in glass jars over a period of 90 days at 45° C. The results are shown in Table 1 below. [Table 100] As can be seen from the data presented in Table 1, the product exhibits stability with respect to appearance, odor, color, and pH after 90 days at 45°C.

[0282] Preparation of 5-MeO-DMT subcutaneous formulation The following ingredients were used in this process: [Table 101]

[0283] The product was prepared using the protocol described above for the intranasal formulation. The resulting mixture was a yellow colored liquid with a pH of 5.00±0.50 (25° C.).

[0284] Stability of subcutaneous 5-MeO-DMT formulations The stability of the products prepared according to the above protocol was evaluated for appearance, color, odor, pH, and viscosity, where applicable, in glass jars over a period of 90 days at 45° C. The results are shown in Table 2 below. [Table 102]

[0285] As can be seen from the data presented in Table 2, the product exhibits stability with respect to appearance, odor, color, and pH after 90 days at 45°C.

[0286] method Justification and welfare of animals Procedures were designed to avoid or minimize discomfort, distress, and pain to animals in accordance with the principles of the Ontario Laboratory Animal Act and the Canadian Council on Animal Care (CCAC) guidelines. The CCAC Guide for the Care and Use of Laboratory Animals and associated policies were followed.

[0287] The method followed Institutional Animal Care and Use Committee (IACUC) standard operating procedures and was reviewed and approved by the IACUC prior to initiation.

[0288] animal Twelve male Sprague-Dawley rats (250-325 g) from Charles River Laboratories were used. Animals were acclimated to their new environment for a minimum of 5 days prior to surgery. Food and water were available ad libitum throughout the study.

[0289] Health monitoring Animals were closely monitored until recovery from anesthesia and at least twice daily during recovery from surgery. Only healthy animals were used for dosing. Animals were closely observed for 1 hour after dosing and at each sample collection time point for the remainder of the study. Any adverse reactions to administration of test material were recorded and tabulated.

[0290] Catheter Placement All animals were implanted with a catheter in the carotid artery (CAC) for continuous blood sampling and blood sample volume replacement, and a catheter in the cisterna magna (CMC) for continuous cerebrospinal fluid (CSF) collection. All catheters were implanted at least 1 day prior to dosing according to standard operating procedures.

[0291] Test substances The test substance, 5-MeO-DMT (16) (MW 遊離塩基(fb) = 218.30 g / mol, M.F. fb =C 13 H 18 NO;MW 塩 = 336.39 g / mol, M.F. 塩 =C 17 H 24 N2O5, batch number VPI-62-021, correction factor = 1.54) was stored at room temperature with a desiccant and protected from light until use.

[0292] Test substance formulation Test substances were freshly prepared at appropriate concentrations in a standard formulation of 10% dimethyl sulfoxide (DMSO) and 90% (v / v) saline (Groups 1 and 2), while the sponsor's formulation contained 3% linoleic acid (Groups 3 and 4).

[0293] Treatment Group Four treatment groups were used, with 3 animals in each group. The experimental parameters are summarized in Table 3 below. [Table 103]

[0294] body weight Animals were weighed prior to surgery and on the day of test article administration for dose volume calculations.

[0295] Test substance administration After at least one day of recovery from surgery, animals were administered the appropriate test article formulation either intranasally (in) under light isoflurane anesthesia via a pipette into each nape or subcutaneously (sc) into the nape of the neck or flank according to Tables 4(A) and 4(B) below. [Table 104]

[0296] Blood collection Approximately 0.25 mL of blood was collected from the carotid artery (CAC) at each time point via a 1 mL syringe and immediately transferred to a 0.8 mL K2EDTA tube and placed on wet ice. After each sample collection, an equivalent aliquot of heparinized saline was slowly injected into the CAC to replace the sample volume. Blood samples were centrifuged at 3200×g for 5 minutes at 4° C. within 5 minutes of collection to obtain plasma. Plasma was transferred to 1.5 mL flip-top cryogenic storage vials, and one cryogenic storage vial of plasma was sampled for each collection time point and stored at approximately −80° C. until analysis.

[0297] Cerebrospinal fluid (CSF) collection CSF (approximately 15 μL) was collected from the cisternal catheter into labeled microcentrifuge tubes at the same time as plasma sampling according to standard operating procedures. Samples were stored frozen at approximately -80°C until shipped on dry ice to the biochemistry facility for analysis.

[0298] Biochemical analysis methods and sample analysis Qualification of Biochemical Analytical Methods for Test Compounds in Rat Plasma and CSF An LC-MS / MS method for the quantification of 5-MeO-DMT and its active metabolite bufotenine (MW=204.27 g / mol, MF=C12H16N2O) in rat plasma was used as follows. A quantitative method for 5-MeO-DMT and bufotenine in rat CSF was developed and quantified. Method qualification and sample analysis were performed using an AB Sciex API 4000 or 6500 Q-TRAP mass spectrometry (MS / MS) system equipped with a binary pump, a solvent degasser, a thermostatted column compartment, and a liquid chromatography (LC) system equipped with a multiplate autosampler.

[0299] Method development included the following: 1. Development of a sample purification method using artificial CSF spiked with test substances.

[0300] Validation of the method(s) included the following: 2. Determination of the calibration dynamic range (e.g., 0.25-2000 ng / mL) using at least six non-zero point calibration standards in singlets, including blank samples (without internal standard (IS)) and zero standards (with IS); 3. Triplicate injections of system suitability sample (neat solution containing analyte and IS) to round out the batch.

[0301] The requirements for acceptance of the method(s) were: 1. At least 75% of the non-zero calibration standards must be included in the calibration curve and all back-calculated concentrations must deviate within ±20% from the nominal concentration (except for the lower limit of quantification (LLOQ) where a deviation of ±25% is permitted); 2. The correlation coefficient (r) of the calibration curve is calculated by quadratic regression analysis (1 / x 2 Weighting) must be 0.99 or greater. 3. System suitability: The variation in area ratio between pre-run and post-run injections of samples is within ±25%.

[0302] Sample analysis Samples in each matrix were analyzed as one or more separate batches using a qualified LC-MS / MS method. Sample batches consisted of triplicate system suitability standards (containing analyte and IS), blank samples (without IS), zero samples (with IS), and ascending calibration standards with at least six non-zero standards, blank matrix (plasma) followed by the assay samples and dosing solutions diluted into the triplicate system suitability samples. Calibration standards were bracketed analytical batches of more than 40 samples. Analytical batches were considered acceptable if the acceptance criteria stated in the method requalification above were met. Samples determined to be above the highest level of quantitation (AQL) were accepted up to 25% above the highest calibration standard. Samples with concentrations more than 25% above the highest calibration standard were diluted and reanalyzed along with the corresponding diluted quality control (QC) samples. Dilution standards were acceptable if they were accurate within 30% of the target concentration.

[0303] Data analysis Plasma and CSF concentrations of 5-MeO-DMT and bufotenin were analyzed by noncompartmental methods using Phoenix® WinNonlin 8.3 (Certara, Mountainview, Calif.). The area under the plasma concentration versus time curve (AUC) for each animal was calculated by the linear upper / lower trapezoidal rule. AUC was calculated as the mean time from time of administration to (1) the time of last measurable concentration (t last ) area under the curve C last (AUC 0-tlast ), and (2) the area under the curve extrapolated to infinity (AUC 0-inf ) stands for AUC. 0-inf If possible, AUC0-tlast and C last / λ z where λ z represents the terminal (or elimination) rate constant. λ z was estimated by regression analysis of a minimum of three time points from the terminal (log-linear) portion of the concentration versus time curve. 1 / 2 ) to ln(2) / λ z The mean residence time (MRT) was calculated as AUMC / AUC, where AUMC represents the area under the first moment curve.max Time to reach t max was determined from the nominal value.

[0304] result This study assessed the pharmacokinetics (PK) of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT (16)) in plasma and cerebrospinal fluid (CSF) following intranasal (in) and subcutaneous (sc) administration of 3 mg / kg 5-MeO-DMT in standard (10% DMSO in saline) or sponsor-supplied (3% linoleic acid) formulations to groups of three male Sprague-Dawley rats. Plasma and CSF were sampled continuously at eight time points over an 8-h period from surgically placed carotid and cisternal catheters, respectively.

[0305] The liquid chromatography-tandem mass spectrometry (LC-MS / MS) method was requalified for quantification of 5-MeO-DMT and the active metabolite, bufotenin, in rat plasma and cross-qualified for quantification in CSF, as described above. Calibration dynamic ranges were 0.1-2500 ng / mL for 5-MeO-DMT and 0.05-1000 ng / mL for bufotenin in plasma and CSF. Both method qualification and sample analysis batches passed the acceptance criteria. PK parameters for each analyte were estimated from the plasma and CSF concentration versus time curves for each animal using Phoenix® WinNonlin 8.3 (Certara, Mountainview, CA). As the intranasal dose was constant (0.9 mg per animal = 0.04 mL x 22.5 mg / mL), the mg / kg dose for each intranasally administered animal was calculated by dividing 0.9 mg by the body weight of each rat. Bioavailability (F) is the dose-normalized AUC for 5-MeO-DMT following a 1 mg / kg intravenous dose. 0-inf 5-MeO-DMT plasma and CSF exposure (C max To determine whether a statistically significant difference in mean mean and AUC (AUC and AUC) existed between the two formulations, a two-tailed T-test (assuming equal variances) was performed using GraphPad Prism® 9.3 software. A p-value of less than 0.05 was considered significant.

[0306] The mean plasma concentration versus time profiles are shown in Figure 5. Comparisons of the plasma and CSF concentration versus time profiles between the reference and sponsor formulations are shown in Figures 6(A)-6(B) and 7(A-7(B), respectively. Comparisons of the plasma and CSF concentration profiles between the routes of administration of each formulation are shown in Figure 8. In some cases, the AUC cannot be extrapolated to infinity and therefore the time from 0 to the last measurable concentration (t last ) were compared, so overall plasma exposure (AUC 0-∞ ) was not possible. Comparison of plasma and CSF PK parameters (fold change) between the reference and sponsor formulations is summarized in Table 5 below. [Table 105]

[0307] Mean maximum plasma concentrations (C max = 234 ng / mL) was achieved at the first sampling time point (0.0833 hours) and after administration of the reference formulation (C max = 43.2 ng / mL) was 5.4 times higher (P = 0.0538). in Overall plasma exposure, as measured by the reference formulation (F in = 8.93%) compared with the sponsor's formulation (F in = 59.0%) was 6.6-fold higher (P = 0.0617). 1 / 2 ) was 0.566 hours after administration of the reference formulation; however, because plasma concentrations declined below the lower level of quantification 6 hours after administration and then increased to measurable levels 8 hours after administration (Figure 5), this estimate is closer to the true t 1 / 2 Similar plasma profiles were observed in 1 / 2 This was observed for the sponsor's products for which estimation was not possible (Figures 5 and 6).

[0308] 5-MeO-DMT appears rapidly in the CSF and max The CSF C was achieved 0.0833–0.25 hours after intranasal administration (Figure 6). max and AUC 0-tlast is the standard preparation (C max = 10.9 ng / mL; AUC = 11.2 h × ng / mL) compared with the sponsor's formulation (C max = 186 ng / mL, P = 0.2361; AUC = 113 h × ng / mL, P = 0.0008), respectively (Figure 6). 1 / 2 Although the CSF / plasma AUC for 5-MeO-DMT could not be reliably estimated, CSF concentrations were higher than plasma concentrations by 1 hour after dosing and it appeared to be cleared from the CSF at a slower rate compared to plasma (Figure 6). 0-tlast The ratios were 2.89 and 0.953 after administration of the sponsor and reference products, respectively. In one animal (R09, CSF / plasma AUC 0-tlast The variability of this ratio for the sponsor's formulation was high because the other two animals had similar CSF exposures, but their plasma exposures were lower compared to the other animals. The CSF / plasma AUC 0-tlast The ratio was 1.24.

[0309] Very low levels of the 5-MeO-DMT metabolite bufotenin were observed in plasma after intranasal administration of both formulations (Figure 5). max The levels were compared with the standard formulation (C max = 0.390ng / mL) compared with the sponsor's formulation (C max = 0.649 ng / mL) (Table 6, FIG. 5(A)). CSF bufotenin levels were below the lower limit of quantification (BLQ) after administration of the sponsor's formulation. [Table 106]

[0310] In contrast to intranasal administration, mean plasma C after subcutaneous administration of 5-MeO-DMTmax was 4-fold lower for the sponsor's formulation (50.2 ng / mL) compared with the reference formulation (207 ng / mL, P = 0.0022) (Tables 4 and 5). max Levels were achieved 0.33 and 0.58 hours after administration for the reference and sponsor formulations, respectively (Table 4). Apparent plasma t 1 / 2 was approximately 4-fold longer when compared to the reference formulation (0.366 hours, n=2), likely due to the presence of linoleic acid in the sponsor's formulation causing a sustained release "depot" effect. However, total plasma exposure (AUC 0-inf ) and bioavailability (F sc ) were comparable between the two formulations: 151 h × ng / mL and 139% for the reference formulation and 149 h × ng / mL (P = 0.8804) and 141% for the sponsor's formulation (Table 4).

[0311] Maximum CSF concentration after subcutaneous administration (C max ) 5-MeO-DMT administration was achieved 0.25-0.5 hours after administration for the reference formulation and 0.083-2 hours after administration for the sponsor's formulation. max and AUC 0-tlast is the standard preparation (C max = 48.2 ng / mL; AUC = 58.6 hours × ng / mL) and the sponsor's formulation (C max = 39.1 ng / mL, P = 0.7329; AUC = 42.4 h × ng / mL, P = 0.2173), and therefore the overall CSF exposure of 5-MeO-DMT relative to the total plasma exposure was also similar following administration of the reference formulation (CSF / plasma AUC ratio = 0.403) and the sponsor's formulation (0.318). Similar to what was observed following intranasal administration, CSF concentrations of 5-MeO-DMT declined at a slower rate compared to plasma (Figure 5), but the t in CSF 1 / 2 could not be reliably estimated.

[0312] C of bufotenin achieved in plasma after subcutaneous 5-MeO-DMT administrationmax is the standard preparation (C max =0.378ng / mL) and the sponsor's formulation (C max = 0.197 ng / mL). After administration of both formulations, the bufotenin concentration in the CSF was BLQ.

[0313] Comparison of intranasal and subcutaneous administration routes of each formulation showed that plasma and CSF exposure of 5-MeO-DMT was significantly greater for the standard formulation than for the intranasal route (AUC 0-tlast = 147 h × ng / mL and 58.6 h × ng / mL, respectively) compared with the control group (AUC 0-tlast = 11.5 h × ng / mL and 11.2 h × ng / mL) (Figures 5 and 6). In contrast, the sponsor's formulation resulted in lower plasma exposure (AUC 0-tlast = 62.1 h × ng / mL and 144 h × ng / mL, respectively, and CSF exposure was high (AUC 0-tlast = 113 h × ng / mL and 42.4 h × ng / mL) (Figures 5 and 6).

[0314] In summary, intranasal administration of the sponsor's formulation of 5-MeO-DMT resulted in plasma (6.6-fold higher bioavailability (P=0.0617)) and CSF (10-fold higher AUC 0-tlast Although the intranasal and subcutaneous administration of the sponsor's formulation of 5-MeO-DMT resulted in a higher exposure of 5-MeO-DMT in the plasma (P=0.0008), only the higher CSF exposure reached statistically significant levels. In contrast, subcutaneous administration of the sponsor's formulation of 5-MeO-DMT resulted in a 4-fold lower plasma Cmax (P=0.0022) but a longer half-life, likely due to the presence of linoleic acid in the sponsor's formulation causing a sustained release "depot" effect. However, the bioavailability of the two formulations was similar, and as a result, CSF exposure was also comparable between the two formulations. After both intranasal and subcutaneous administration, 5-MeO-DMT appeared to be cleared from the CSF at a slower rate compared to plasma.

[0315] All publications, patents, and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. In the event that any term in this application is found to have a different definition in a document incorporated herein by reference, the definition provided herein shall serve as the definition of that term.

Claims

1. one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof; The one or more compounds are selected from one or more of the following compounds: Pharmaceutical compositions. II-1: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-2: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-3: ((R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-ol; II-4: (S)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-5: (R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-6: (S)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-7: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-8: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-9: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate; II-10: (R)-(((3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-11: (R)-(((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-12: (R)-((4-hydroxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-13: (R)-((4-hydroxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-14: (R)-((4-hydroxy-3-(pyrrolidin-2-ylmethyl)-1H-indol-1-yl)methyl)-phosphonic acid; II-15: (R)-((3-((1-methylpyrrolidin-2-yl)methyl)-4-(phosphonooxy)-1H-indol-1-yl)methyl)phosphonic acid; II-16: (1-((3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-17: (1-((3-(((R)-pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-18: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl glycinate; II-19: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl D-alaninato; II-20: (R,Z)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-21: (R,E)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-22: (R)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobutanoic acid; II-23: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-24: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl acetate; II-25: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-26: (R)-((4-acetoxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-27: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-28: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-29: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-30: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-31: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-32: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-33: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)-cyclohexyl)acetate; II-34: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)cyclohexyl)-acetate; II-35: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl[1,4′-bipiperidine]-1′-carboxylate; II-36: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yldimethylcarbamate; II-37: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-38: (R)-4-chloro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-39: (R)-4-methoxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-40: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-41: (R)-4-fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole; II-42: (S)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-43: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-44: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-ol; II-45: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-46: (R)-4-(benzyloxy)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole; II-47: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-48: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-49: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-50: (R)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-51: (S)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-52: (S)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-53: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-54: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate.

2. 2. The pharmaceutical composition of claim 1, wherein the one or more fatty acids are selected from myristic acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.

3. 1. A kit comprising one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma-ceutically acceptable salts, prodrugs, and / or solvates thereof, said one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and said one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are contained in a single pharmaceutical composition or are contained in separate pharmaceutical compositions; The one or more compounds are selected from one or more of the following compounds: kit. II-1: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-2: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-3: ((R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-ol; II-4: (S)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-5: (R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-6: (S)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-7: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-8: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-9: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate; II-10: (R)-(((3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-11: (R)-(((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-12: (R)-((4-hydroxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-13: (R)-((4-hydroxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-14: (R)-((4-hydroxy-3-(pyrrolidin-2-ylmethyl)-1H-indol-1-yl)methyl)-phosphonic acid; II-15: (R)-((3-((1-methylpyrrolidin-2-yl)methyl)-4-(phosphonooxy)-1H-indol-1-yl)methyl)phosphonic acid; II-16: (1-((3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-17: (1-((3-(((R)-pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-18: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl glycinate; II-19: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl D-alaninato; II-20: (R,Z)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-21: (R,E)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-22: (R)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobutanoic acid; II-23: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-24: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl acetate; II-25: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-26: (R)-((4-acetoxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-27: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-28: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-29: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-30: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-31: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-32: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-33: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)-cyclohexyl)acetate; II-34: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)cyclohexyl)-acetate; II-35: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl[1,4′-bipiperidine]-1′-carboxylate; II-36: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yldimethylcarbamate; II-37: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-38: (R)-4-chloro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-39: (R)-4-methoxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-40: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-41: (R)-4-fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole; II-42: (S)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-43: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-44: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-ol; II-45: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-46: (R)-4-(benzyloxy)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole; II-47: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-48: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-49: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-50: (R)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-51: (S)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-52: (S)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-53: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-54: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate.

4. The one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in amounts to treat or prevent a disease, disorder, or condition; the disease, disorder, or condition is a mental health disease, disorder, or condition; The kit of claim 3.

5. The one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, are present in an amount effective to improve the efficacy of the one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in treating or preventing the disease, disorder, or condition. The kit according to claim 4.

6. 6. The kit of claim 5, wherein the one or more fatty acids are selected from myristic acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.

7. Use of an effective amount of one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in combination with an effective amount of one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the manufacture of a medicament for improving the efficacy of one or more compounds, comprising: The one or more compounds are selected from one or more of the following compounds: The above uses. II-1: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-2: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-3: ((R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-ol; II-4: (S)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-5: (R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-6: (S)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-7: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-8: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-9: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate; II-10: (R)-(((3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-11: (R)-(((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-12: (R)-((4-hydroxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-13: (R)-((4-hydroxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-14: (R)-((4-hydroxy-3-(pyrrolidin-2-ylmethyl)-1H-indol-1-yl)methyl)-phosphonic acid; II-15: (R)-((3-((1-methylpyrrolidin-2-yl)methyl)-4-(phosphonooxy)-1H-indol-1-yl)methyl)phosphonic acid; II-16: (1-((3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-17: (1-((3-(((R)-pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-18: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl glycinate; II-19: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl D-alaninato; II-20: (R,Z)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-21: (R,E)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-22: (R)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobutanoic acid; II-23: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-24: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl acetate; II-25: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-26: (R)-((4-acetoxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-27: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-28: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-29: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-30: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-31: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-32: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-33: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)-cyclohexyl)acetate; II-34: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)cyclohexyl)-acetate; II-35: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl[1,4′-bipiperidine]-1′-carboxylate; II-36: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yldimethylcarbamate; II-37: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-38: (R)-4-chloro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-39: (R)-4-methoxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-40: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-41: (R)-4-fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole; II-42: (S)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-43: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-44: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-ol; II-45: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-46: (R)-4-(benzyloxy)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole; II-47: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-48: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-49: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-50: (R)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-51: (S)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-52: (S)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-53: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-54: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate.

8. Use of effective amounts of one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, and one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in the manufacture of a medicament for treating or preventing a disease, disorder, or condition, comprising: The one or more compounds are selected from one or more of the following compounds: The above uses. II-1: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-2: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-3: ((R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-ol; II-4: (S)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-5: (R)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-6: (S)-3-(pyrrolidin-2-ylmethyl)-1H-indol-4-yl dihydrogen phosphate; II-7: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-8: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl dihydrogen phosphate; II-9: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate; II-10: (R)-(((3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-11: (R)-(((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)methyl)phosphonic acid; II-12: (R)-((4-hydroxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-13: (R)-((4-hydroxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-14: (R)-((4-hydroxy-3-(pyrrolidin-2-ylmethyl)-1H-indol-1-yl)methyl)-phosphonic acid; II-15: (R)-((3-((1-methylpyrrolidin-2-yl)methyl)-4-(phosphonooxy)-1H-indol-1-yl)methyl)phosphonic acid; II-16: (1-((3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-17: (1-((3-(((R)-pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)ethyl)phosphonic acid; II-18: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl glycinate; II-19: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl D-alaninato; II-20: (R,Z)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-21: (R,E)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobut-2-enoic acid; II-22: (R)-4-((3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl)oxy)-4-oxobutanoic acid; II-23: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-24: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl acetate; II-25: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl acetate; II-26: (R)-((4-acetoxy-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)methyl)phosphonic acid; II-27: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-28: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-29: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-30: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate-11,11-d2; II-31: 3-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-32: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(S)-3-(aminomethyl)-5-methylhexanoate; II-33: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)-cyclohexyl)acetate; II-34: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl 2-(1-(aminomethyl)cyclohexyl)-acetate; II-35: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-yl[1,4′-bipiperidine]-1′-carboxylate; II-36: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yldimethylcarbamate; II-37: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-38: (R)-4-chloro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-39: (R)-4-methoxy-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-40: (R)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-41: (R)-4-fluoro-3-(pyrrolidin-2-ylmethyl-d2)-1H-indole; II-42: (S)-4-fluoro-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-43: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indole; II-44: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-ol; II-45: (R)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-46: (R)-4-(benzyloxy)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole; II-47: (R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-48: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-49: 3-(((R)-1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl(9Z,12Z)-octadeca-9,12-dienoate; II-50: (R)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-51: (S)-3-(pyrrolidin-2-ylmethyl-d2)-1H-indol-4-ol; II-52: (S)-4-(benzyloxy)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indole; II-53: (S)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl)-1H-indol-4-ol; II-54: (R)-3-((1-(methyl-d3)pyrrolidin-2-yl)methyl-d2)-1H-indol-4-yl dihydrogen phosphate.

9. 9. The use of claim 8, wherein the one or more fatty acids are selected from myristic acid, caproic acid, caprylic acid, capric acid, lauric acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.

10. The use of claim 8 or claim 9, wherein the disease, disorder, or condition comprises cognitive impairment; ischemia including stroke; neurodegeneration; refractory substance use disorder; sleep disorder; pain such as social pain, acute pain, cancer pain, chronic pain, breakthrough pain, bone pain, soft tissue pain, neuralgia, referred pain, phantom limb pain, neuropathic pain, cluster headache, or migraine; obesity or eating disorders; epilepsy or seizure disorders; neuronal cell death; excitotoxic cell death; or combinations thereof.

11. The use described in claim 8 or claim 9, wherein the disease, disorder or condition is a CNS disease, disorder or condition, and / or a neurological disease, disorder or condition.

12. An intranasal pharmaceutical composition comprising the pharmaceutical composition described in claim 1 or claim 2.

13. 13. The intranasal pharmaceutical composition of claim 12, wherein the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, is linoleic acid, or a pharma- ceutically acceptable salt, prodrug, and / or solvate thereof.

14. 13. The intranasal pharmaceutical composition of claim 12, further comprising water and being an aqueous intranasal pharmaceutical composition.

15. 10% to 35% by weight of said intranasal pharmaceutical composition of said one or more surfactants; 1% to 10% by weight of said intranasal pharmaceutical composition of one or more co-solvents; 1% to 3% by weight of said intranasal pharmaceutical composition of one or more buffering agents; and 1% to 10% by weight of the intranasal pharmaceutical composition of one or more humectants 13. The intranasal pharmaceutical composition of claim 12, further comprising:

16. the one or more surfactants are selected from tyloxapol, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene products of hydrogenated vegetable oils, polyethoxylated castor oil, polyethoxylated hydrogenated castor oil, polyoxyethylene castor oil derivatives, poloxamers, and mixtures thereof; the polyoxyethylene sorbitan fatty acid ester is selected from polyethylene sorbitan monooleate (polysorbate 80), polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan tristearate (polysorbate 65), polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, and mixtures thereof; the one or more co-solvents are selected from isopropyl alcohol, propylene glycol, polyethylene glycol, polypropylene glycol, glycol ethers, glycerol, polyoxyethylene alcohols; medium chain glycerides, diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol), and mixtures thereof; 16. The intranasal pharmaceutical composition of claim 15.

17. 17. The intranasal pharmaceutical composition of claim 16, wherein the co-solvent is (2-(2-ethoxyethoxy)ethanol).

18. The intranasal pharmaceutical composition of claim 12, wherein the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, increase the absorption rate of the one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, into the plasma and cerebrospinal fluid (CSF) of a subject, compared to an otherwise identical intranasal pharmaceutical composition in the absence of the one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

19. 13. The intranasal pharmaceutical composition of claim 12, which provides a Cmax of said one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in plasma that is 3- to 6-fold greater than the Cmax of an otherwise identical intranasal pharmaceutical composition in the absence of said one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

20. 13. The intranasal pharmaceutical composition of claim 12, which results in a Cmax of said one or more compounds, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof, in cerebrospinal fluid that is 5-fold to 20-fold greater than the Cmax of an otherwise identical intranasal pharmaceutical composition in the absence of said one or more fatty acids, or pharma- ceutically acceptable salts, prodrugs, and / or solvates thereof.

Images