Psilocybin for Depression and Alcoholism
(PsiloMDDAUD Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Johns Hopkins University
Must not be taking: MAOIs, Antidepressants, others
Disqualifiers: Pregnancy, Cardiovascular conditions, Seizures, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing if psilocybin can help people with both depression and alcohol problems. The drug might improve mood and reduce drinking by changing brain activity. The study involves giving psilocybin to see if it helps. Psilocybin is a naturally occurring psychedelic that has shown promise in treating mood and substance use disorders.
Do I need to stop taking my current medications for the trial?
You can continue taking SSRIs, SNRIs, and bupropion if you've been stable on them for at least two months before the trial and will remain stable during the study. However, you must stop taking any other antidepressants or medications with a primary serotonergic effect before participating.
What evidence supports the effectiveness of the drug psilocybin for treating depression and alcoholism?
Research shows that psilocybin, found in 'magic mushrooms', has been studied in clinical trials for various psychiatric disorders, including depression and substance use disorders. Initial results are promising, with some patients experiencing significant, long-lasting improvements after just one or a few sessions, although more research is needed to fully understand its benefits.
12345Is psilocybin safe for human use?
Psilocybin has been studied in clinical trials and is generally considered safe when used in controlled settings, although it can cause temporary effects like hallucinations and changes in perception. Recent studies have shown promise for its use in treating depression and anxiety, with a good safety profile in healthy adults.
36789How is psilocybin different from other drugs for depression and alcoholism?
Psilocybin is unique because it is a psychedelic drug that can produce rapid and long-lasting effects after just one or a few doses, unlike traditional antidepressants or alcohol treatments that often require daily use. It works by affecting serotonin receptors in the brain, which can lead to changes in mood and perception, and has shown promise in treating depression and alcohol dependence, even in cases where other treatments have failed.
15101112Eligibility Criteria
Adults aged 21-65 with both Major Depressive Disorder and Alcohol Use Disorder, not currently on antidepressants or medications for alcohol dependency. Participants must have a history of depression therapy, limited use of hallucinogens, be medically stable, at low risk for suicide, agree to contraception if applicable, and refrain from certain substances before sessions.Inclusion Criteria
Have at least a high-school level of education or equivalent (e.g. GED)
I have been diagnosed with Major Depressive Disorder and am currently having a depressive episode.
Have given written informed consent
+31 more
Exclusion Criteria
Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
I am currently on medication for depression or alcohol use.
Current or history within one year of meeting DSM-5 criteria for a moderate or severe substance use disorder (excluding caffeine, nicotine, and alcohol)
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a single high (25 mg) oral dose of psilocybin or placebo, followed by a Motivational Interviewing intervention for alcohol use
1 day
1 visit (in-person)
Follow-up
Participants are monitored for changes in depressive symptoms and alcohol use, with assessments at 1 month and 3 months post-treatment
3 months
Multiple visits (in-person and virtual)
Open-label extension
All participants receive a second, unblinded intervention with a single high dose of psilocybin to test the secondary hypothesis
1 day
1 visit (in-person)
Long-term Follow-up
Participants are monitored for long-term effects with follow-up assessments at 6 and 12 months after the second psilocybin administration
12 months
Multiple visits (in-person and virtual)
Participant Groups
The trial is testing the effectiveness of psilocybin versus a placebo in reducing symptoms of depression and alcohol consumption in patients with co-occurring MDD and AUD. It aims to see if this hallucinogenic drug can help where standard treatments haven't been started or are no longer desired.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Psilocybin TreatmentExperimental Treatment1 Intervention
Participants will be administered 25mg of psilocybin in a clinical setting. Psilocybin is administered orally as a capsule and taken with water.
Group II: PlaceboPlacebo Group1 Intervention
Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins Center for Psychedelic and Consciousness ResearchBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins UniversityLead Sponsor
Usona InstituteCollaborator
References
[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]After a cessation of almost 40 years, there is renewed interest into therapeutic applicationsof the serotonergic psychedelic psilocybin for the treatment of patients with various psychiatric disorders. PubMed was searched for clinical trials into "psilocybin" between 2000 and 2020, complemented by handsearching. Articles were also screened for explanatory models and working mechanisms. Psilocybin has been studied in 9 clinical trials: for the treatment of substance use disorders, depression, end-of-life anxiety, demoralization, and obsessive-compulsive disorder. Results show that psilocybin is well tolerated, with only limited side-effects, while even patients with treatment-resistant disorders sometimes show marked, long-term improvements after one or a few sessions. Initial results are encouraging, but there are several limitations. More research is needed to determine which patient populations can benefit, what role setting and the placebo response play, and how these novel treatments can be optimized.
Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Psilocybin is the psychoactive component in Psilocybe mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.
The pharmacology of psilocybin. [2016]Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.
DARK Classics in Chemical Neuroscience: Psilocybin. [2019]Psilocybin is found in a family of mushrooms commonly known as "magic mushrooms" that have been used throughout history to induce hallucinations. In the late 1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic psychopharmacological and therapeutic clinical research. Psilocybin saw a rapid rise in popularity during the 1960s and was classed as a Schedule I drug in 1970. This led to a significant decrease in psilocybin research. Recently, however, preliminary studies with psilocybin have shown promise as potential for the treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction, and major depressive disorder, and the treatment of depression in terminally ill cancer patients. This review describes in detail the synthesis, metabolism, pharmacology, adverse drug reactions, and importance of psilocybin to neuroscience in the past and present.
Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. [2023]Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition.
[Hallucinogenic mushrooms]. [2018]The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults.
A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. [2023]The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.
Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = -4.589; 95% CI = -4.207 to -0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = -5.906; 95% CI = -7.852 to -3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = -6.032; 95% CI = -8.900 to -3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety.
Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. [2022]Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p
Return of the psychedelics: Psilocybin for treatment resistant depression. [2017]Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested.
Assessing potential of psilocybin for depressive disorders. [2023]There has been increasing interest in the role psilocybin may play in the treatment of depressive disorders. Several clinical trials have shown psilocybin to have efficacy in reducing symptoms of depression.