Top

Published in:

Open Access 01-12-2024 | Study Protocol

Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial

Authors: Laetitia Vanderijst, Felix Hever, Anne Buot, Charles Dauré, Janaïna Benoit, Catherine Hanak, Johannes Veeser, Margot Morgiève, Salvatore Campanella, Charles Kornreich, Luc Mallet, Christophe Leys, Xavier Noël

Published in: BMC Psychiatry | Issue 1/2024

Abstract

Background

A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction.

Methods

In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21–64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters.

Discussion

The discussion outlines issues that might arise from our design.

Trial registration

EudraCT 2022-002369-14 and NCT06160232.

Available only for authorised users

Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016. https://doi.org/10.1016/S2215-0366(16)00104-8.CrossRefPubMedPubMedCentral

World Health Organization. Global status report on alcohol and health 2018. Geneva: World Health Organization. 2018. https://iris.who.int/handle/10665/274603. Accessed 15 Oct 2023.

Simioni N, Cottencin O, Guardia D, Rolland B. Early relapse in alcohol dependence may result from late withdrawal symptoms. Med Hypotheses. 2012. https://doi.org/10.1016/j.mehy.2012.09.021.CrossRefPubMed

Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for Alcohol Dependence: the COMBINE Study: a Randomized Controlled Trial. JAMA. 2006. https://doi.org/10.1001/jama.295.17.2003.CrossRefPubMed

Nutt D. Illegal drugs laws: Clearing a 50-Year-old obstacle to Research. PLoS Biol. 2015. https://doi.org/10.1371/journal.pbio.1002047.CrossRefPubMedPubMedCentral

Carhart-Harris RL, Goodwin GM. The therapeutic potential of psychedelic drugs: past, Present, and Future. Neuropsychopharmacology. 2017. https://doi.org/10.1038/npp.2017.84.CrossRefPubMedPubMedCentral

Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, et al. Structure of a Hallucinogen-activated Gq-Coupled 5-HT2A serotonin receptor. Cell. 2020. https://doi.org/10.1016/j.cell.2020.08.024.CrossRefPubMedPubMedCentral

Nichols DE. Psychedelics Pharmacol Rev. 2016. https://doi.org/10.1124/pr.115.011478.CrossRefPubMed

Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008. https://doi.org/10.1177/0269881108093587.CrossRefPubMedPubMedCentral

10.

Tylš F, Páleníček T, Horáček J. Psilocybin–summary of knowledge and new perspectives. Eur Neuropsychopharmacol. 2014. https://doi.org/10.1016/j.euroneuro.2013.12.006.CrossRefPubMed

11.

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. https://doi.org/10.1016/j.neuropharm.2018.05.012.CrossRefPubMedPubMedCentral

12.

van Amsterdam J, Opperhuizen A, van den Koeter M. Ranking the Harm of Alcohol, Tobacco and Illicit Drugs for the individual and the Population. Eur Addict Res. 2010. https://doi.org/10.1159/000317249.CrossRefPubMed

13.

Roscoe J, Lozy O. Can psilocybin be safely administered under medical supervision? A systematic review of adverse event reporting in clinical trials. Drug Sci Policy Law. 2022. https://doi.org/10.1177/2050324522108522.CrossRef

14.

Krebs TS, Johansen PØ. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol. 2012. https://doi.org/10.1177/0269881112439253.CrossRefPubMed

15.

Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, et al. Percentage of Heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with Alcohol Use Disorder: a Randomized Clinical Trial. JAMA Psychiatry. 2022. https://doi.org/10.1001/jamapsychiatry.2022.2096.CrossRefPubMedPubMedCentral

16.

Haikazian S, Chen-Li DCJ, Johnson DE, Fancy F, Levinta A, Husain MI, et al. Psilocybin-assisted therapy for depression: a systematic review and meta-analysis. Psychiatry Res. 2023. https://doi.org/10.1016/j.psychres.2023.115531.CrossRefPubMed

17.

Holze F, Gasser P, Müller F, Dolder PC, Liechti ME. Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness: a Randomized, Double-Blind, placebo-controlled phase II study. Biol Psychiatry. 2023. https://doi.org/10.1016/j.biopsych.2022.08.025.CrossRefPubMed

18.

Burns L, Teesson M. Alcohol use disorders comorbid with anxiety, depression and drug use disorders: findings from the Australian National Survey of Mental Health and well being. Drug Alcohol Depend. 2002. https://doi.org/10.1016/s0376-8716(02)00220-x.CrossRefPubMed

19.

Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the national epidemiologic survey on Alcohol and related conditions. Arch Gen Psychiatry. 2004. https://doi.org/10.1001/archpsyc.61.8.807.CrossRefPubMed

20.

Carhart-Harris RL, Wagner AC, Agrawal M, Kettner H, Rosenbaum JF, Gazzaley A, et al. Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine? J Psychopharmacol. 2022. https://doi.org/10.1177/02698811211008567.CrossRefPubMedPubMedCentral

21.

Purgato M, Barbui C, Stroup S, Adams C. Pragmatic design in randomized controlled trials. Psychol Med. 2015. https://doi.org/10.1017/S0033291714001275.CrossRefPubMed

22.

D’Hondt F, Rolland B, Maurage P. Social cognition in severe alcohol use disorder. In: Frings D, Albery IP, editors. The handbook of Alcohol Use. Cambridge: Academic Press; 2021. pp. 175–99.CrossRef

23.

Christensen E, Brydevall M, Albertella L, Samarawickrama SK, Yücel M, Lee RSC. Neurocognitive predictors of addiction-related outcomes: a systematic review of longitudinal studies. Neurosci Biobehav Rev. 2023. https://doi.org/10.1016/j.neubiorev.2023.105295.CrossRefPubMed

24.

Duka T, Townshend JM, Collier K, Stephens DN. Impairment in cognitive functions after multiple detoxifications in alcoholic inpatients. Alcohol Clin Exp Res. 2003. https://doi.org/10.1097/01.ALC.0000090142.11260.D7.CrossRefPubMed

25.

Sliedrecht W, de Waart R, Witkiewitz K, Roozen HG. Alcohol use disorder relapse factors: a systematic review. Psychiatry Res. 2019. https://doi.org/10.1016/j.psychres.2019.05.038.CrossRefPubMed

26.

Maisto SA, Hallgren KA, Roos C, Swan J, Witkiewitz K. Patterns of transitions between Relapse to and Remission from Heavy drinking over the First Year after Outpatient Alcohol Treatment and their relation to long-term outcomes. J Consult Clin Psychol. 2020. https://doi.org/10.1037/ccp0000615.CrossRefPubMedPubMedCentral

27.

Holst C, Tolstrup JS, Sørensen HJ, Becker U. Alcohol dependence and risk of somatic diseases and mortality: a cohort study in 19 002 men and women attending alcohol treatment. Addiction. 2017. https://doi.org/10.1111/add.13799.CrossRefPubMed

28.

Bogenschutz MP, Pommy JM. Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses: Hallucinogens for addictions. Drug Test Anal. 2012. https://doi.org/10.1002/dta.1376.CrossRefPubMed

29.

Rieser NM, Herdener M, Preller KH. Psychedelic-assisted therapy for Substance Use disorders and potential mechanisms of action. Curr Top Behav Neurosci. 2022. https://doi.org/10.1007/7854_2021_284.CrossRefPubMed

30.

Zafar R, Siegel M, Harding R, Barba T, Agnorelli C, Suseelan S, et al. Psychedelic therapy in the treatment of addiction: the past, present and future. Front Psychiatry. 2023. https://doi.org/10.3389/fpsyt.2023.1183740.CrossRefPubMedPubMedCentral

31.

Urban MM, Stingl MR, Meinhardt MW. Mini-review: the neurobiology of treating substance use disorders with classical psychedelics. Front Neurosci. 2023. https://doi.org/10.3389/fnins.2023.1156319.CrossRefPubMedPubMedCentral

32.

van Elk M, Fried EI. History repeating: guidelines to address common problems in psychedelic science. Ther Adv Psychopharmacol. 2023. https://doi.org/10.1177/20451253231198466.CrossRefPubMedPubMedCentral

33.

Aday JS, Heifets BD, Pratscher SD, Bradley E, Rosen R, Woolley JD. Great expectations: recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology. 2022. https://doi.org/10.1007/s00213-022-06123-7.CrossRefPubMedPubMedCentral

34.

Muthukumaraswamy SD, Forsyth A, Lumley T. Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Rev Clin Pharmacol. 2021. https://doi.org/10.1080/17512433.2021.1933434.CrossRefPubMed

35.

von Rotz R, Schindowski EM, Jungwirth J, Schuldt A, Rieser NM, Zahoranszky K, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. eClinicalMedicine. 2023. https://doi.org/10.1016/j.eclinm.2022.101809.CrossRef

36.

Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016. https://doi.org/10.1177/0269881116675512.CrossRefPubMedPubMedCentral

37.

Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, et al. Pilot study of Psilocybin Treatment for Anxiety in patients with Advanced-Stage Cancer. Arch Gen Psychiatry. 2011. https://doi.org/10.1001/archgenpsychiatry.2010.116.CrossRefPubMed

38.

Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, et al. Single-dose psilocybin for a treatment-resistant episode of Major Depression. N Engl J Med. 2022. https://doi.org/10.1056/NEJMoa2206443.CrossRefPubMed

39.

Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021. https://doi.org/10.1056/NEJMoa2032994.CrossRefPubMed

40.

van Elk M, Yaden DB. Pharmacological, neural, and psychological mechanisms underlying psychedelics: a critical review. Neurosci Biobehav Rev. 2022. https://doi.org/10.1016/j.neubiorev.2022.104793.CrossRefPubMed

41.

Uher R, Zwicker A. Etiology in psychiatry: embracing the reality of poly-gene‐environmental causation of mental illness. World Psychiatry. 2017. https://doi.org/10.1002/wps.20436.CrossRefPubMedPubMedCentral

42.

Hyman SE, Addiction. A Disease of Learning and Memory. Am J Psychiatry. 2005. https://doi.org/10.1176/appi.ajp.162.8.1414.CrossRefPubMed

43.

Calder AE, Hasler G. Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology. 2023. https://doi.org/10.1038/s41386-022-01389-z.CrossRefPubMed

44.

Olson DE, Psychoplastogens. A Promising Class of plasticity-promoting neurotherapeutics. J Exp Neurosci. 2018. https://doi.org/10.1177/1179069518800508.CrossRefPubMedPubMedCentral

45.

de Vos CMH, Mason NL, Kuypers KPC. Psychedelics and neuroplasticity: a systematic review unraveling the Biological underpinnings of Psychedelics. Front Psychiatry. 2021. https://doi.org/10.3389/fpsyt.2021.724606.CrossRefPubMedPubMedCentral

46.

Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002. https://doi.org/10.1176/appi.ajp.159.10.1642.CrossRefPubMedPubMedCentral

47.

Noël X, Brevers D, Bechara A. A Triadic Neurocognitive Approach to Addiction for Clinical interventions. Front Psychiatry. 2013. https://doi.org/10.3389/fpsyt.2013.00179.CrossRefPubMedPubMedCentral

48.

Meinhardt MW, Pfarr S, Fouquet G, Rohleder C, Meinhardt ML, Barroso-Flores J, et al. Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism. Sci Adv. 2021. https://doi.org/10.1126/sciadv.abh2399.CrossRefPubMedPubMedCentral

49.

Augier E, Dulman RS, Rauffenbart C, Augier G, Cross AJ, Heilig M. The mGluR2 positive allosteric modulator, AZD8529, and Cue-Induced Relapse to Alcohol seeking in rats. Neuropsychopharmacology. 2016. https://doi.org/10.1038/npp.2016.107.CrossRefPubMedPubMedCentral

50.

Caprioli D, Justinova Z, Venniro M, Shaham Y. Effect of Novel Allosteric modulators of Metabotropic Glutamate receptors on Drug Self-administration and relapse: a review of Preclinical studies and their clinical implications. Biol Psychiatry. 2018. https://doi.org/10.1016/j.biopsych.2017.08.018.CrossRefPubMed

51.

Holmes A, Spanagel R, Krystal JH. Glutamatergic targets for new alcohol medications. Psychopharmacology. 2013. https://doi.org/10.1007/s00213-013-3226-2.CrossRefPubMedPubMedCentral

52.

Kufahl PR, Martin-Fardon R, Weiss F. Enhanced sensitivity to attenuation of conditioned reinstatement by the mGluR2/3 agonist LY379268 and increased functional activity of mGluR2/3 in rats with a history of ethanol dependence. Neuropsychopharmacology. 2011. https://doi.org/10.1038/npp.2011.174.CrossRefPubMedPubMedCentral

53.

Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016. https://doi.org/10.1177/0269881116675513.CrossRefPubMedPubMedCentral

54.

Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa P, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015. https://doi.org/10.1177/0269881114565144.CrossRefPubMed

55.

Johnson MW, Hendricks PS, Barrett FS, Griffiths RR. Classic psychedelics: an integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol Ther. 2019. https://doi.org/10.1016/j.pharmthera.2018.11.010.CrossRefPubMed

56.

Wolff M, Evens R, Mertens LJ, Koslowski M, Betzler F, Gründer G, et al. Learning to let go: a cognitive-behavioral model of how psychedelic therapy promotes Acceptance. Front Psychiatry. 2020. https://doi.org/10.3389/fpsyt.2020.00005.CrossRefPubMedPubMedCentral

57.

Hasler G. Toward the helioscope hypothesis of psychedelic therapy. Eur Neuropsychopharmacol. 2022. https://doi.org/10.1016/j.euroneuro.2022.02.006.CrossRefPubMed

58.

Ii T, Sato H, Watanabe N, Kondo M, Masuda A, Hayes SC, et al. Psychological flexibility-based interventions versus first-line psychosocial interventions for substance use disorders: systematic review and meta-analyses of randomized controlled trials. J Context Behav Sci. 2019. https://doi.org/10.1016/j.jcbs.2019.07.003.CrossRef

59.

Davis AK, Barrett FS, Griffiths RR. Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. J Context Behav Sci. 2020. https://doi.org/10.1016/j.jcbs.2019.11.004.CrossRef

60.

Mangini P, Averill LA, Davis AK. Psychedelic treatment for co-occurring alcohol misuse and post-traumatic stress symptoms among United States Special Operations forces Veterans. J Psychedelic Stud. 2021. https://doi.org/10.1556/2054.2021.00176.CrossRef

61.

Watts R, Day C, Krzanowski J, Nutt D, Carhart-Harris R. Patients’ accounts of increased connectedness and Acceptance after psilocybin for treatment-resistant depression. J Humanist Psychol. 2017. https://doi.org/10.1177/0022167817709585.CrossRef

62.

Argento E, Capler R, Thomas G, Lucas P, Tupper KW. Exploring ayahuasca-assisted therapy for addiction: a qualitative analysis of preliminary findings among an indigenous community in Canada. Drug Alcohol Rev. 2019. https://doi.org/10.1111/dar.12985.CrossRefPubMed

63.

Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, et al. The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world. Psychopharmacology. 2022. https://doi.org/10.1007/s00213-022-06187-5.CrossRefPubMedPubMedCentral

64.

Carhart-Harris RL, Erritzoe D, Haijen E, Kaelen M, Watts R. Psychedelics and connectedness. Psychopharmacology. 2018. https://doi.org/10.1007/s00213-017-4701-y.CrossRefPubMedPubMedCentral

65.

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed., text rev.). 2022. https://doi.org/10.1176/appi.books.9780890425787.

66.

Clapp WC, Hamm JP, Kirk IJ, Teyler TJ. Translating long-term potentiation from animals to humans: a novel method for noninvasive assessment of cortical plasticity. Biol Psychiatry. 2012. https://doi.org/10.1016/j.biopsych.2011.08.021.CrossRefPubMedPubMedCentral

67.

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013. https://doi.org/10.7326/0003-4819-158-3-201302050-00583.CrossRefPubMedPubMedCentral

68.

Sobell LC, Sobell MB. Timeline follow-back: a technique for assessing self-reported alcohol consumption. Measuring alcohol consumption: Psychosocial and biochemical methods. Totowa, NJ, US: Humana Press; 1992. pp. 41–72.CrossRef

69.

Folstein MF, Folstein SE, McHugh PR. Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975. https://doi.org/10.1016/0022-3956(75)90026-6.CrossRefPubMed

70.

Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and commitment therapy: model, processes and outcomes. Behav Res Ther. 2006. https://doi.org/10.1016/j.brat.2005.06.006.CrossRefPubMed

71.

Holze F, Becker AM, Kolaczynska KE, Duthaler U, Liechti ME. Pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of oral psilocybin administration in healthy subjects. Neurosci Appl. 2022. https://doi.org/10.1016/j.nsa.2022.100410.CrossRef

72.

Garcia-Romeu A, Barrett FS, Carbonaro TM, Johnson MW, Griffiths RR. Optimal dosing for psilocybin pharmacotherapy: considering weight-adjusted and fixed dosing approaches. J Psychopharmacol. 2021. https://doi.org/10.1177/0269881121991822.CrossRefPubMedPubMedCentral

73.

Jefsen OH, Elfving B, Wegener G, Müller HK. Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. J Psychopharmacol. 2021. https://doi.org/10.1177/0269881120959614.CrossRefPubMed

74.

Nichols CD, Garcia EE, Sanders-Bush E. Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration. Mol Brain Res. 2003. https://doi.org/10.1016/s0169-328x(03)00029-9.CrossRefPubMed

75.

Nichols CD, Sanders-Bush E. Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase-1, C/EBP-β and ILAD-1, a novel gene with homology to arrestins. J Neurochem. 2004. https://doi.org/10.1111/j.1471-4159.2004.02515.x.CrossRefPubMed

76.

Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology. 2011. https://doi.org/10.1007/s00213-011-2358-5.CrossRefPubMedPubMedCentral

77.

Ko K, Knight G, Rucker JJ, Cleare AJ, Psychedelics. Mystical experience, and therapeutic efficacy: a systematic review. Front Psychiatry. 2022. https://doi.org/10.3389/fpsyt.2022.917199.CrossRefPubMedPubMedCentral

78.

Chwelos N, Blewett DB, Smith CM, Hoffer A. Use of d-lysergic acid diethylamide in the treatment of alcoholism. Q J Stud Alcohol. 1959;20:577–90.CrossRefPubMed

79.

Kyriakopoulos AA, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of lorazepam: a review. J Clin Psychiatry. 1978;39:16–23.PubMed

80.

Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989. https://doi.org/10.1111/j.1360-0443.1989.tb00737.x.CrossRefPubMed

81.

Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. JAMA. 1997. https://doi.org/10.1001/jama.278.2.144.CrossRefPubMed

82.

Cavarra M, Falzone A, Ramaekers JG, Kuypers KPC, Mento C. Psychedelic-assisted Psychotherapy—A systematic review of Associated Psychological interventions. Front Psychol. 2022. https://doi.org/10.3389/fpsyg.2022.887255.CrossRefPubMedPubMedCentral

83.

Osaji J, Ojimba C, Ahmed S. The Use of Acceptance and Commitment Therapy in Substance Use disorders: a review of literature. J Clin Med Res. 2020. https://doi.org/10.14740/jocmr4311.CrossRefPubMedPubMedCentral

84.

Byrne SP, Haber P, Baillie A, Costa DSJ, Fogliati V, Morley K. Systematic reviews of Mindfulness and Acceptance and Commitment Therapy for Alcohol Use Disorder: should we be using third Wave therapies? Alcohol Alcohol. 2019. https://doi.org/10.1093/alcalc/agy089.CrossRefPubMed

85.

Guss J, Krause R, Sloshower J. The Yale Manual for Psilocybin-Assisted Therapy of Depression (using Acceptance and Commitment Therapy as a Therapeutic Frame). Preprint at https://osf.io/preprints/psyarxiv/u6v9y/ (2020).

86.

Hayes SC, Strosahl KD, Wilson KG. Acceptance and Commitment Therapy. 2nd ed. New York: Guilford Press; 2011.

87.

Sloshower J, Guss J, Krause R, Wallace RM, Williams MT, Reed S, et al. Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame. J Context Behav Sci. 2020. https://doi.org/10.1016/j.jcbs.2019.11.002.CrossRef

88.

Carhart-Harris RL, Roseman L, Haijen E, Erritzoe D, Watts R, Branchi I, et al. Psychedelics and the essential importance of context. J Psychopharmacol. 2018. https://doi.org/10.1177/0269881118754710.CrossRefPubMedPubMedCentral

89.

Goodwin GM, Malievskaia E, Fonzo GA, Nemeroff CB. Must Psilocybin always assist psychotherapy? Am J Psychiatry. 2023. https://doi.org/10.1176/appi.ajp.20221043.CrossRefPubMed

90.

Pahnke WN. The psychedelic mystical experience in the human encounter with death. Harv Theol Rev. 1969;62(1):1–21.CrossRef

91.

Messell C, Summer L, Bonde LO, Beck BD, Stenbæk DS. Music programming for psilocybin-assisted therapy: guided imagery and music-informed perspectives. Front Psychol. 2022. https://doi.org/10.3389/fpsyg.2022.873455.CrossRefPubMedPubMedCentral

92.

Holze F, Ley L, Müller F, Becker AM, Straumann I, Vizeli P, et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2022. https://doi.org/10.1038/s41386-022-01297-2.CrossRefPubMedPubMedCentral

93.

Frymann T, Whitney S, Yaden DB, Lipson J. The psychedelic integration scales: tools for measuring psychedelic integration behaviors and experiences. Front Psychol. 2022. https://doi.org/10.3389/fpsyg.2022.863247.CrossRefPubMedPubMedCentral

94.

Gastfriend DR, Garbutt JC, Pettinati HM, Forman RF. Reduction in heavy drinking as a treatment outcome in alcohol dependence. J Subst Abuse Treat. 2007. https://doi.org/10.1016/j.jsat.2006.09.008.CrossRefPubMed

95.

Falk DE, O’Malley SS, Witkiewitz K, Anton RF, Litten RZ, Slater M, et al. Evaluation of drinking risk levels as outcomes in Alcohol Pharmacotherapy trials: a secondary analysis of 3 randomized clinical trials. JAMA Psychiatry. 2019. https://doi.org/10.1001/jamapsychiatry.2018.3079.CrossRefPubMedPubMedCentral

96.

European Medicines Agency. Guideline on the development of medicinal products for the treatment of alcohol dependence. 2010. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-medicinal-products-treatment-alcohol-dependence_en.pdf. Accessed 27 Sep 2023.

97.

Manning V, Garfield JBB, Reynolds J, Staiger PK, Piercy H, Bonomo Y, et al. Alcohol use in the year following approach bias modification during inpatient withdrawal: secondary outcomes from a double-blind, multi‐site randomized controlled trial. Addiction. 2022. https://doi.org/10.1111/add.15989.CrossRefPubMedPubMedCentral

98.

Carey KB. Reliability and validity of the time-line follow-back interview among psychiatric outpatients: a preliminary report. Psychol Addict Behav. 1997. https://doi.org/10.1037/0893-164X.11.1.26.CrossRef

99.

Sobell LC, Brown J, Leo GI, Sobell MB. The reliability of the Alcohol Timeline Followback when administered by telephone and by computer. Drug Alcohol Depend. 1996. https://doi.org/10.1016/0376-8716(96)01263-x.CrossRefPubMed

100.

Breeksema JJ, Kuin BW, van den Kamphuis J, Vermetten E, Schoevers RA. Adverse events in clinical treatments with serotonergic psychedelics and MDMA: a mixed-methods systematic review. J Psychopharmacol. 2022. https://doi.org/10.1177/02698811221116926.CrossRefPubMedPubMedCentral

101.

Walther L, De Bejczy A, Löf E, Hansson T, Andersson A, Guterstam J, et al. Phosphatidylethanol is Superior to Carbohydrate-Deficient transferrin and γ -Glutamyltransferase as an alcohol marker and is a Reliable Estimate of Alcohol Consumption Level. Alcohol Clin Exp Res. 2015;39(11):2200–8.CrossRefPubMed

102.

Smith NDL, Cottler LB. The epidemiology of post-traumatic stress disorder and Alcohol Use Disorder. Alcohol Res Curr Rev. 2018;39(2):113.

103.

Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–71.CrossRefPubMed

104.

Spielberger CD. Manual for the state-trait anxiety inventory (self-Evaluation questionnaire). Palo Alto, CA: Consulting Psychologists Press; 1983.

105.

Cloitre M, Shevlin M, Brewin CR, Bisson JI, Roberts NP, Maercker A, et al. The International Trauma Questionnaire: development of a self-report measure of ICD‐11 PTSD and complex PTSD. Acta Psychiatr Scand. 2018. https://doi.org/10.1111/acps.12956.CrossRefPubMed

106.

Neale J, Vitoratou S, Finch E, Lennon P, Mitcheson L, Panebianco D, et al. Development and validation of ‘SURE’: a patient reported Outcome measure (PROM) for recovery from drug and alcohol dependence. Drug Alcohol Depend. 2016. https://doi.org/10.1016/j.drugalcdep.2016.06.006.CrossRefPubMedPubMedCentral

107.

Campanella S, Schroder E, Kajosch H, Hanak C, Veeser J, Amiot M, et al. Neurophysiological markers of cue reactivity and inhibition subtend a three-month period of complete alcohol abstinence. Clin Neurophysiol. 2020. https://doi.org/10.1016/j.clinph.2019.10.020.CrossRefPubMed

108.

Pahnke WN. Psychedelic drugs and mystical experience. Int Psychiatry Clin. 1969;5(4):149–62.PubMed

109.

Wolff M, Mertens LJ, Walter M, Enge S, Evens R. The Acceptance/Avoidance-Promoting experiences Questionnaire (APEQ): a theory-based approach to psychedelic drugs’ effects on psychological flexibility. J Psychopharmacol. 2022. https://doi.org/10.1177/02698811211073758.CrossRefPubMedPubMedCentral

110.

Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, et al. Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 2011. https://doi.org/10.1016/j.beth.2011.03.007.CrossRefPubMed

111.

Mehling WE, Price C, Daubenmier JJ, Acree M, Bartmess E, Stewart A. The Multidimensional Assessment of Interoceptive Awareness (MAIA). PLoS ONE. 2012. https://doi.org/10.1371/journal.pone.0048230.CrossRefPubMedPubMedCentral

112.

Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol craving scale. Alcohol Clin Exp Res. 1999;23(8):1289–95.CrossRefPubMed

113.

DiClemente CC, Carbonari JP, Montgomery RPG, Hughes SO. The Alcohol abstinence self-efficacy scale. J Stud Alcohol. 1994. https://doi.org/10.15288/jsa.1994.55.141.CrossRefPubMed

114.

Younger J, Gandhi V, Hubbard E, Mackey S. Development of the Stanford Expectations of Treatment Scale (SETS): a tool for measuring patient outcome expectancy in clinical trials. Clin Trials Lond Engl. 2012. https://doi.org/10.1177/1740774512465064.CrossRef

115.

Corbière M, Bisson J, Lauzon S, Ricard N. Factorial validation of a French short-form of the Working Alliance Inventory. Int J Methods Psychiatr Res. 2006. https://doi.org/10.1002/mpr.27.CrossRefPubMedPubMedCentral

116.

Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbæk DS, Kristiansen S, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019. https://doi.org/10.1038/s41386-019-0324-9.CrossRefPubMedPubMedCentral

117.

Spriggs M, Douglass H, Park R, Read T, Danby J, Magalhaes F, et al. Study protocol for psilocybin as a treatment for Anorexia Nervosa: a pilot study. Front Psychiatry. 2021. https://doi.org/10.3389/fpsyt.2021.735523.CrossRefPubMedPubMedCentral

Title: Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial
Authors: Laetitia Vanderijst
Felix Hever
Anne Buot
Charles Dauré
Janaïna Benoit
Catherine Hanak
Johannes Veeser
Margot Morgiève
Salvatore Campanella
Charles Kornreich
Luc Mallet
Christophe Leys
Xavier Noël
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: BMC Psychiatry / Issue 1/2024
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-024-05502-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2024

Non-equivalence of sub-tasks of the Rey-Osterrieth Complex Figure Test with convolutional neural networks to discriminate mild cognitive impairment

Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer

Antipsychotic medication non-adherence and factors associated among patients with schizophrenia in eastern Ethiopia

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis

Associations of perceived stress with loneliness and depressive symptoms: the mediating role of sleep quality

Continuing the conversation: a cross-sectional study about the effects of work-related adverse events on the mental health of Dutch (resident) obstetrician-gynaecologists (ObGyns)