Methods and compositions comprising a 5ht receptor agonist for the treatment of psychological, cognitive, behavorial, and/or mood disorders

Abstract

Provided herein are methods and compositions for the treatment of psychological, cognitive, behavioral, and/or mood disorders, the composition comprising a 5HT agonist (e.g. psilocybin). In certain embodiments, such compositions are administered in amounts or levels high enough to provide a therapeutic effect, but insufficient to provide an adverse effect.

What is claimed is: 
     
         1 . A method of managing a neurological condition or one or more symptoms thereof in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising:
 a) a therapeutically effective amount of one or more 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof; and   b) a pharmaceutically acceptable excipient   wherein the therapeutically effective amount of the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is provided to the subject in need thereof in an amount insufficient to provide an adverse side effect, such as hallucinogenic experience.   
     
     
         2 . A method of treating the symptoms of a neurological condition in a subject suffering from or susceptible to the neurological condition, comprising administering to the subject a pharmaceutical composition comprising:
 a) a therapeutically effective amount of one or more 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof; and   b) a pharmaceutically acceptable excipient;   wherein the therapeutically effective amount of the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is provided to the subject in need thereof in an amount insufficient to provide an adverse side effect, such as hallucinogenic experience.   
     
     
         3 . The method of any one of the preceding claims, wherein the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is present in an amount of from about 0.1 mg to about 50 mg (e.g. about 0.1 mg to about 10 mg, about 0.2 mg to about 5 mg, about 10 mg to about 50 mg, or the like). 
     
     
         4 . The method of any one of the preceding claims, wherein the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is present in an amount of from about 0.1 mg to about 2 mg. 
     
     
         5 . The method of any one of the preceding claims, wherein the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is present in an amount of from about 1 mg to about 15 mg. 
     
     
         6 . The method of any one of the preceding claims, wherein the pharmaceutical composition is a low-dose pharmaceutical composition. 
     
     
         7 . The method of any one of the preceding claims, wherein the pharmaceutical composition comprises a controlled release component. 
     
     
         8 . The method of any one of the preceding claims, wherein the pharmaceutical composition comprises a controlled release component and an immediate release component. 
     
     
         9 . The method of any one of the preceding claims, wherein the therapeutically effective amount of 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is provided to a subject in need thereof in an amount and/or formulation insufficient to provide a maximum plasma concentration (C max ) of (e.g. active form of the) 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof of 6 ng/mL or more. 
     
     
         10 . The method of any one of the preceding claims, wherein the therapeutically effective amount of 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is provided to a subject in need thereof in an amount and/or formulation to provide a maximum plasma concentration (C max ) of (e.g. active form of the) 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof of about 0.1 ng/mL or more and less than 6 ng/mL (e.g. at least 0.5 ng/mL and less than 6 ng/mL, about 1 ng/mL to about 5.5 ng/mL, about 2 ng/mL to about 5 ng/mL, or the like). 
     
     
         11 . The method of any one of the preceding claims, wherein the therapeutically effective amount of 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof is provided to a subject in need thereof in an amount and/or formulation to provide a plasma concentration of (e.g. active form of the) 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof of at least 0.1 ng/mL (e.g. at least 0.2 ng/mL, at least 0.3 ng/mL, at least 0.5 ng/mL, or the like) after at least 6 hours (e.g. at least 12 hours, at least 24 hours, at least 36 hours, at least 48 hours, at least 72 hours, at least 96 hours, at least 120 hours, at least 144 hours, or the like). 
     
     
         12 . The method of any one of the preceding claims, wherein the 5HT receptor agonist is a 5HT2 receptor agonist. 
     
     
         13 . The method of any one of the preceding claims, wherein the 5HT receptor agonist is psilocybin or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof. 
     
     
         14 . The method of any one of  claims 1 - 12 , wherein the 5HT receptor agonist is psilocin or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof. 
     
     
         15 . The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises one or more agents selected from the group consisting of surfactants, preservatives, flavoring agents, sweetening agents, and antifoaming agents. 
     
     
         16 . The method of any one of the preceding claims, wherein the pharmaceutical composition is an oral formulation, a buccal formulation, a nasal formulation, or an inhalation formulation. 
     
     
         17 . The method of any one of the preceding claims, wherein the pharmaceutical composition is in a form selected from a spray, aerosol, mist, nebulae, ointment, cream, gel, paste, salve, solution, suspension, tincture, patch, and atomized vapor. 
     
     
         18 . The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises an effective amount of a second agent. 
     
     
         19 . The method of  claim 18 , wherein the second agent is a vasodilator or vasoconstrictor. 
     
     
         20 . The method of  claim 19 , wherein the vasoconstrictor is epinephrine, phenylephrine, methoxamine, norepinephrine, zolmitriptan, tetrahydrozaline, naphazoline, or combinations thereof. 
     
     
         21 . The method of  claim 18 , wherein the second agent is a stimulant, an antihistamine, an antiemetic, an antidepressant, an anti-inflammatory, a growth factor, a lithium compound, resveratrol, phosphatidylcholine, curcumin, magnesium, melatonin, pregnenolone, ginseng, lysergic acid diethylamide, or combinations thereof. 
     
     
         22 . The method of  claim 18 , wherein the second agent is a 5HT receptor antagonist. 
     
     
         23 . The method of  claim 18 , wherein the second agent is an anti-psychotic agent. 
     
     
         24 . The method of  claim 23 , wherein the anti-psychotic agent is olanzapine, clozapine, risperidone, paliperidone, aripiprazole, quetiapine, iloperidone, ziprasidone, asenapine, lurasidone, sertindole, amisulpride, clotiapine, mosapramine, perospirone, sulpiride, zotepine, haloperidol, benperidol, loxapine, molindone, pimozide, thioridazine, mesoridazine, thiothixene, chlorprothixene, fluphenazine, trifluoperazine, chlorpromazine, perphenazine, prochlorperazine, droperidol, and zuclopenthixol. 
     
     
         25 . The method of  claim 18 , wherein the second agent is administered simultaneously, sequentially, or alternately with the pharmaceutical composition. 
     
     
         26 . The method of  claim 25 , wherein the second agent is administered simultaneously, sequentially, or alternately with the pharmaceutical composition. 
     
     
         27 . The method of  claim 25 , wherein the pharmaceutical composition is administered first and the second agent is administered at least once before the pharmaceutical composition is administered a subsequent time. 
     
     
         28 . The method of  claim 25 , wherein the pharmaceutical composition is administered first and the second agent is administered more than once before the pharmaceutical composition is administered a subsequent time. 
     
     
         29 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to a subject in need thereof no more frequently than once a day (e.g. no more frequently than once every other day, no more frequently than once every third day, no more frequently than twice a week, no more frequently than once a week, no more frequently than once every two weeks, or the like). 
     
     
         30 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to a subject in need thereof once a day, every alternate day, three times a week, twice a week, once a week, every other week, two weeks per month, three weeks per month, once a month, twice a month or three times per month. 
     
     
         31 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered about once a day. 
     
     
         32 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered about every alternate day. 
     
     
         33 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered about once a week. 
     
     
         34 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered about once every two weeks or more. 
     
     
         35 . The method of any one of the preceding claims, wherein the pharmaceutical composition is administered for at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 2 years, or 3 years. 
     
     
         36 . The method of any one of the preceding claims, wherein the neurological condition is a neurological disorder. 
     
     
         37 . The method of any one of the preceding claims, wherein the neurological condition is a neurocognitive disorder. 
     
     
         38 . The method of any one of the preceding claims, wherein the symptoms of the neurological condition are physical, behavioral, emotional, mental or a combination thereof. 
     
     
         39 . The method of any one of the preceding claims, wherein the neurological condition is an addictive disorder. 
     
     
         40 . The method of  claim 39 , wherein the addictive disorder is alcohol abuse, substance abuse, smoking, or obesity. 
     
     
         41 . The method of any one of  claims 1 - 38 , wherein the neurological condition is an eating disorder or an auditory disorder. 
     
     
         42 . The method of any one of  claims 1 - 38 , wherein the neurological condition is pain (e.g. chronic pain). 
     
     
         43 . The method of any one of  claims 1 - 38 , wherein the neurological condition is depression, bipolar disorder, anxiety, social anxiety, post-traumatic stress disorder (PTSD), panic disorder, phobia, schizophrenia, psychopathy, or antisocial personality disorder. 
     
     
         44 . The method of any one of  claims 1 - 38 , wherein the neurological condition is an impulsive disorder. 
     
     
         45 . The method of  claim 44 , wherein the impulsive disorder is attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), Tourette's syndrome or autism. 
     
     
         46 . The method of any one of  claims 1 - 38 , wherein the neurological condition is a compulsive disorder. 
     
     
         47 . The method of  claim 46 , wherein the compulsive disorder is obsessive compulsive disorder (OCD), gambling, or aberrant sexual behavior. 
     
     
         48 . The method of any one of  claims 1 - 38 , wherein the neurological condition is a personality disorder. 
     
     
         49 . The method of  claim 48 , wherein the personality disorder is conduct disorder, antisocial personality, or aggressive behavior.