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Current Psychopharmacology

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ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

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Review Article

Psilocybin in the Management of Substance Use Disorders: A Summary of Current Evidence

Author(s): Hussein El Bourji, Aziz Farhat, Zahi Hamdan, Ritvij Satodiya, Rashmi Shukla and Samer El Hayek*

Volume 12, 2024

Published on: 03 July, 2024

Article ID: e030724231519 Pages: 9

DOI: 10.2174/0122115560288779240628043307

Price: $65

Abstract

Background: Following clinical trials on psilocybin for the treatment of pain, anxiety, and depression in patients with cancer, scientific interest emerged in its use for substance use disorders.

Methods: In this review of the literature, we summarize available trials looking at the use of psilocybin in addiction.

Results: One double-blind, randomized clinical trial looked at the effect of psilocybin on heavy drinking in adults diagnosed with alcohol dependence. Several trials are currently ongoing to assess psilocybin’s efficacy in the management of different substance use disorders. Otherwise, the current evidence is insufficient to derive any conclusions on the possible efficacy of psilocybin in substance use disorders.

Conclusions: More well-powered, blinded, randomized controlled trials are needed to investigate the possible therapeutic effects of psilocybin in addiction while identifying the appropriate conditions that promote its safe use.

[1]
UNODC. World Drug Report 2021. 2021. Available From: https://www.unodc.org/unodc/data-and-analysis/wdr2021.html
[2]
PAHO. The burden of drug use disorders in the Region of the Americas, 2000-2019. Noncommunicable Diseases and Mental Health Data Portal 2021. 2021. Available From: https://www.paho.org/en/noncommunicable-diseases-and-mental-health/noncommunicable-diseases-and-mental-health-data-34#:~:text=The%20burden%20of%20health%20loss,613.8%20DALYs%20per%20100%2C000%20population
[3]
NIDA. COVID-19 & substance use. Research Topics 2022. 2022. Available From: https://nida.nih.gov/research-topics/comorbidity/covid-19-substance-use#:~:text=Researchers%20have%20 observed %20increases%20in,national%20emergency%20in%20March%202020
[4]
López G, Orchowski LM, Reddy MK, Nargiso J, Johnson JE. A review of research-supported group treatments for drug use disorders. Subst Abuse Treat Prev Policy 2021; 16(1): 51.
[http://dx.doi.org/10.1186/s13011-021-00371-0] [PMID: 34154619]
[5]
Douaihy AB, Kelly TM, Sullivan C. Medications for substance use disorders. Soc Work Public Health 2013; 28(3-4): 264-78.
[http://dx.doi.org/10.1080/19371918.2013.759031] [PMID: 23731419]
[6]
Maqbool M. Substance use disorder and availability of treatment options: An overview. J Res Health Sci 2019; 1: 4-10.
[7]
de Veen BTH, Schellekens AFA, Verheij MMM, Homberg JR. Psilocybin for treating substance use disorders? Expert Rev Neurother 2017; 17(2): 203-12.
[http://dx.doi.org/10.1080/14737175.2016.1220834] [PMID: 27684102]
[8]
Blackman S. Chilling out: The cultural politics of substance consumption, youth and drug policy. UK: McGraw-Hill Education 2004.
[9]
Gurschler I. The fourfold discovery of Mescaline (1896–1919). Monatshefte fuer Chem 2019; 150(2): 941-7.
[10]
Nutt D. Psychedelic drugs—a new era in psychiatry? Dialogues Clin Neurosci 2019; 21(2): 139-47.
[http://dx.doi.org/10.31887/DCNS.2019.21.2/dnutt] [PMID: 31636488]
[11]
Garcia-Romeu A, Kersgaard B, Addy PH. Clinical applications of hallucinogens: A review. Exp Clin Psychopharmacol 2016; 24(4): 229-68.
[http://dx.doi.org/10.1037/pha0000084] [PMID: 27454674]
[12]
Nichols DE. Psychedelics. Pharmacol Rev 2016; 68(2): 264-355.
[http://dx.doi.org/10.1124/pr.115.011478] [PMID: 26841800]
[13]
Grinspoon L, Bakalar JB. Psychedelic drugs reconsidered. New York: Basic Books 1979.
[14]
Busch AK, Johnson WC. L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Dis Nerv Syst 1950; 11(8): 241-3.
[PMID: 14793387]
[15]
Rucker JJH, Jelen LA, Flynn S, Frowde KD, Young AH. Psychedelics in the treatment of unipolar mood disorders: A systematic review. J Psychopharmacol 2016; 30(12): 1220-9.
[http://dx.doi.org/10.1177/0269881116679368] [PMID: 27856684]
[16]
Krebs TS, Johansen PØ. Lysergic acid diethylamide (LSD) for alcoholism: Meta-analysis of randomized controlled trials. J Psychopharmacol 2012; 26(7): 994-1002.
[http://dx.doi.org/10.1177/0269881112439253] [PMID: 22406913]
[17]
Hall W. Why was early therapeutic research on psychedelic drugs abandoned? Psychol Med 2022; 52(1): 26-31.
[http://dx.doi.org/10.1017/S0033291721004207] [PMID: 34670633]
[18]
Nutt DJ, King LA, Phillips LD. Drug harms in the UK: A multicriteria decision analysis. Lancet 2010; 376(9752): 1558-65.
[http://dx.doi.org/10.1016/S0140-6736(10)61462-6] [PMID: 21036393]
[19]
Honig E. In close vote, denver becomes 1st U.S. city to decriminalize psychedelic mushrooms. 2019. Available From: https://www.npr.org/sections/health-shots/2019/05/09/721660053/in-close-vote-denver-becomes-first-u-s-city-to-decriminalize-psychedelic-mushroo
[20]
Kennedy M. Oakland city council effectively decriminalizes psychedelic mushrooms. 2019. Available From: https://www.npr.org/2019/06/05/730061916/oakland-city-council-effectively-decriminalizespsychedelic-mushrooms
[21]
Kaur H. Santa Cruz decriminalizes magic mushrooms and other natural psychedelics, making it the third US city to take such a step. 2020. Available From: https://edition.cnn.com/2020/01/30/us/santa-cruz-mushrooms-psychedelics-trnd/index.html
[22]
Geiger HA, Wurst MG, Daniels RN. DARK classics in chemical neuroscience: Psilocybin. ACS Chem Neurosci 2018; 9(10): 2438-47.
[http://dx.doi.org/10.1021/acschemneuro.8b00186] [PMID: 29956917]
[23]
Kargbo RB. Psilocybin therapeutic research: The present and future paradigm. ACS Med Chem Lett 2020; 11(4): 399-402.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00048] [PMID: 32292538]
[24]
Halberstadt AL. Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav Brain Res 2015; 277: 99-120.
[http://dx.doi.org/10.1016/j.bbr.2014.07.016] [PMID: 25036425]
[25]
Mertens LJ, Preller KH. Classical psychedelics as therapeutics in psychiatry – current clinical evidence and potential therapeutic mechanisms in substance use and mood disorders. Pharmacopsychiatry 2021; 54(4): 176-90.
[http://dx.doi.org/10.1055/a-1341-1907] [PMID: 33472250]
[26]
Halberstadt AL, Geyer MA. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 2011; 61(3): 364-81.
[http://dx.doi.org/10.1016/j.neuropharm.2011.01.017] [PMID: 21256140]
[27]
Erkizia-Santamaría I, Alles-Pascual R, Horrillo I, Meana JJ, Ortega JE. Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response. Biomed Pharmacother 2022; 154: 113612.
[http://dx.doi.org/10.1016/j.biopha.2022.113612] [PMID: 36049313]
[28]
Mckenna DJ, Repke DB, Lo L, Peroutka SJ. Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology 1990; 29(3): 193-8.
[http://dx.doi.org/10.1016/0028-3908(90)90001-8] [PMID: 2139186]
[29]
Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res 2018; 46(D1): D1074-82.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[30]
Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: A double-blind, placebo-controlled dose?effect study. Psychopharmacology 2004; 172(2): 145-56.
[http://dx.doi.org/10.1007/s00213-003-1640-6] [PMID: 14615876]
[31]
Vollenweider FX, Vollenweider-Scherpenhuyzen MFI, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 1998; 9(17): 3897-902.
[http://dx.doi.org/10.1097/00001756-199812010-00024] [PMID: 9875725]
[32]
Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol Psychiatry 2012; 72(11): 898-906.
[http://dx.doi.org/10.1016/j.biopsych.2012.04.005] [PMID: 22578254]
[33]
Madsen MK, Fisher PM, Burmester D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology 2019; 44(7): 1328-34.
[http://dx.doi.org/10.1038/s41386-019-0324-9] [PMID: 30685771]
[34]
Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol 2002; 7(4): 357-64.
[http://dx.doi.org/10.1080/1355621021000005937] [PMID: 14578010]
[35]
Griffiths RR, Johnson MW, Richards WA, et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. J Psychopharmacol 2018; 32(1): 49-69.
[http://dx.doi.org/10.1177/0269881117731279] [PMID: 29020861]
[36]
Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology 2018; 142: 143-66.
[http://dx.doi.org/10.1016/j.neuropharm.2018.05.012] [PMID: 29753748]
[37]
Lim TH, Wasywich CA, Ruygrok PN. A fatal case of ‘magic mushroom’ ingestion in a heart transplant recipient. Intern Med J 2012; 42(11): 1268-9.
[http://dx.doi.org/10.1111/j.1445-5994.2012.02955.x] [PMID: 23157524]
[38]
Borowiak K. Psilocin multiple intake resulted and in cardiotoxic effects. Acta Toxicologica 2006; 14(1-2)
[39]
Lowe H, Toyang N, Steele B, et al. The therapeutic potential of psilocybin. Molecules 2021; 26(10): 2948.
[http://dx.doi.org/10.3390/molecules26102948] [PMID: 34063505]
[40]
ClinicalTrials.gov. A double-blind trial of psilocybin-assisted treatment of alcohol dependence. 2014. Available From: https://clinicaltrials.gov/ct2/show/NCT02061293
[41]
ClinicalTrials.gov. Clinical and mechanistic effects of psilocybin in alcohol addicted patients. 2019. Available From: https://clinical trials.gov/ct2/show/NCT04141501
[42]
ClinicalTrials.gov. Psilocybin-assisted therapy for treatment of alcohol use disorder. 2022. Available From: https://clinical trials.gov/ct2/show/NCT05416229
[43]
ClinicalTrials.gov. 5-HT2A agonist psilocybin in the treatment of tobacco use disorder. 2024. Available From: https://clinical trials.gov/ct2/show/NCT05452772
[44]
ClinicalTrials.gov. Psilocybin for opioid use disorder in patients on methadone maintenance with ongoing opioid use. 2022. Available From: https://clinicaltrials.gov/ct2/show/NCT05242029
[45]
ClinicalTrials.gov. Psilocybin-facilitated Treatment for Cocaine use. 2014. Available From: https://clinicaltrials.gov/ct2/show/NCT02037126
[46]
ClinicalTrials.gov. Psilocybin treatment of major depressive disorder with co-occurring alcohol use disorder (PsiloMDDAUD). 2020. Available From: https://clinicaltrials.gov/ct2/show/NCT04620759
[47]
ClinicalTrials.gov. Can a one-off administration of psilocybin reduce alcohol intake in patients with alcohol use disorder? A randomized, double-blinded, placebo-controlled clinical trial. 2020. Available From: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000829-55/DK
[48]
Meinhardt MW, Pfarr S, Fouquet G, et al. Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism. Sci Adv 2021; 7(47): eabh2399.
[http://dx.doi.org/10.1126/sciadv.abh2399] [PMID: 34788104]
[49]
Meinhardt MW, Güngör C, Skorodumov I, Mertens LJ, Spanagel R. Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse. Neuropsychopharmacology 2020; 45(8): 1316-22.
[http://dx.doi.org/10.1038/s41386-020-0694-z] [PMID: 32369828]
[50]
Bogenschutz MP, Ross S, Bhatt S, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder. JAMA Psychiatry 2022; 79(10): 953-62.
[http://dx.doi.org/10.1001/jamapsychiatry.2022.2096] [PMID: 36001306]
[51]
Bogenschutz MP, Podrebarac SK, Duane JH, et al. Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder. Front Pharmacol 2018; 9: 100.
[http://dx.doi.org/10.3389/fphar.2018.00100] [PMID: 29515439]
[52]
Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PCR, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. J Psychopharmacol 2015; 29(3): 289-99.
[http://dx.doi.org/10.1177/0269881114565144] [PMID: 25586396]
[53]
Pisano VD, Putnam NP, Kramer HM, Franciotti KJ, Halpern JH, Holden SC. The association of psychedelic use and opioid use disorders among illicit users in the United States. J Psychopharmacol 2017; 31(5): 606-13.
[http://dx.doi.org/10.1177/0269881117691453] [PMID: 28196428]
[54]
Jones G, Ricard JA, Lipson J, Nock MK. Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. Sci Rep 2022; 12(1): 4099-9.
[http://dx.doi.org/10.1038/s41598-022-08085-4] [PMID: 35393455]
[55]
Garcia-Romeu A, Davis AK, Erowid E, Erowid F, Griffiths RR, Johnson MW. Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Front Psychiatry 2020; 10: 955.
[http://dx.doi.org/10.3389/fpsyt.2019.00955] [PMID: 32038317]
[56]
Argento E, Socias ME, Hayashi K, et al. Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting. Int J Drug Policy 2022; 100: 103518.
[http://dx.doi.org/10.1016/j.drugpo.2021.103518] [PMID: 34758431]
[57]
Jones GM, Nock MK. Exploring protective associations between the use of classic psychedelics and cocaine use disorder: A population-based survey study. Sci Rep 2022; 12(1): 2574.
[http://dx.doi.org/10.1038/s41598-022-06580-2] [PMID: 35173246]
[58]
Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT 2A R agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014; 28(11): 983-92.
[http://dx.doi.org/10.1177/0269881114548296] [PMID: 25213996]
[59]
Garcia-Romeu A, Griffiths R, Johnson M. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev 2015; 7(3): 157-64.
[http://dx.doi.org/10.2174/1874473708666150107121331] [PMID: 25563443]
[60]
Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse 2017; 43(1): 55-60.
[http://dx.doi.org/10.3109/00952990.2016.1170135] [PMID: 27441452]
[61]
Noorani T, Garcia-Romeu A, Swift TC, Griffiths RR, Johnson MW. Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. J Psychopharmacol 2018; 32(7): 756-69.
[http://dx.doi.org/10.1177/0269881118780612] [PMID: 29938565]
[62]
Jones G, Lipson J, Nock MK. Associations between classic psychedelics and nicotine dependence in a nationally representative sample. Sci Rep 2022; 12(1): 10578.
[http://dx.doi.org/10.1038/s41598-022-14809-3] [PMID: 35732796]
[63]
Schlag AK, Aday J, Salam I, Neill JC, Nutt DJ. Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. J Psychopharmacol 2022; 36(3): 258-72.
[http://dx.doi.org/10.1177/02698811211069100] [PMID: 35107059]
[64]
Johnson MW, Griffiths RR. Potential therapeutic effects of psilocybin. Neurotherapeutics 2017; 14(3): 734-40.
[http://dx.doi.org/10.1007/s13311-017-0542-y] [PMID: 28585222]
[65]
Nutt D, Erritzoe D, Carhart-Harris R. Psychedelic psychiatry’s brave new world. Cell 2020; 181(1): 24-8.
[http://dx.doi.org/10.1016/j.cell.2020.03.020] [PMID: 32243793]
[66]
Goldberg SB, Pace BT, Nicholas CR, Raison CL, Hutson PR. The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Res 2020; 284: 112749.
[http://dx.doi.org/10.1016/j.psychres.2020.112749] [PMID: 31931272]
[67]
da Costa SC, Oesterle T, Rummans TA, Richelson E, Gold M. Psychedelic drugs for psychiatric disorders. J Neurol Sci 2022; 440: 120332.
[http://dx.doi.org/10.1016/j.jns.2022.120332] [PMID: 35841696]

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