Psilocybin for Depression and Alcoholism

(PsiloMDDAUD Trial)

Overseen By Jaydin Hill

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: MAOIs, Antidepressants, others

Disqualifiers: Pregnancy, Cardiovascular conditions, Seizures, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if psilocybin, a hallucinogenic drug, can help individuals with both Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) by reducing depression symptoms and drinking habits. Participants will receive either psilocybin or a placebo in a controlled setting. Suitable candidates include those diagnosed with both conditions, currently experiencing a major depressive episode, and who have tried therapy but are not interested in standard medication treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, the main ingredient in some hallucinogenic mushrooms, is usually safe for people. In past studies, most participants experienced only mild and short-lived side effects, such as headaches, nausea, or a slight increase in heart rate. Serious side effects were rare.

Although researchers continue to study psilocybin, it has been used safely in controlled settings for other conditions. This suggests it might be safe for new uses, such as treating depression and alcoholism. However, since testing continues, more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about psilocybin for treating depression and alcoholism because it offers a unique approach compared to standard treatments. Unlike typical antidepressants or alcohol use disorder medications that often target neurotransmitters like serotonin over a prolonged period, psilocybin acts on serotonin receptors in the brain in a different way, potentially providing rapid and lasting effects after just one or a few doses. This psychedelic compound can induce profound changes in consciousness, which might help patients gain new perspectives on their mental health challenges. Additionally, psilocybin is administered in a controlled clinical setting, ensuring a safe environment that maximizes the therapeutic experience.

What evidence suggests that psilocybin might be an effective treatment for depression and alcoholism?

Research has shown that psilocybin, a hallucinogenic drug, can help treat depression. One study found that a single 25 mg dose significantly lowered depression scores over three weeks. This dose proved more effective than smaller amounts, indicating that 25 mg is particularly beneficial. In this trial, participants in the psilocybin treatment arm will receive a 25 mg dose. Another study found that the positive effects on depression could last up to a year. While researchers continue to study psilocybin's effects on alcohol use disorder (AUD), its ability to reduce depression symptoms offers promise for individuals with both depression and AUD. Participants in the placebo arm will receive a placebo capsule for comparison. ^{6 7 8 9 10}

Who Is on the Research Team?

Frederick S Barrett, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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

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)

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Psilocybin

Trial Overview 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.

How Is the Trial Designed?

Group I: Psilocybin Treatment Experimental Treatment 1 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: Placebo Placebo Group 1 Intervention

Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

Published Research Related to This Trial

In a proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[2022]

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.

The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

A single, moderate dose of psilocybin significantly reduced depressive symptoms in 52 participants with major depressive disorder, showing a decrease of 13.0 points on the MADRS scale compared to baseline, which was significantly greater than the placebo group.

54% of participants in the psilocybin group met the criteria for remission of depression 14 days after treatment, and no serious adverse events were reported, indicating a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. von Rotz, R., Schindowski, EM., Jungwirth, J., et al.[2023]

Psilocybin has been rigorously tested in a randomized trial for its safety and efficacy in treating treatment-resistant depression, confirming its positive effects seen in previous studies.

The paper discusses psilocybin's mechanism of action and highlights its relative safety and lack of addiction potential, suggesting it could be a promising option for larger trials aimed at establishing its risk-benefit ratio in depression treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Return of the psychedelics: Psilocybin for treatment resistant depression. Patra, S.[2017]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40047545/

Results From a Long-Term Observational Follow-Up Study ... Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg.

2. compasspathways.com compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD The New England Journal of Medicine publishes results from phase 2b trial of investigational COMP360 psilocybin treatment for treatment-resistant depression.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724020494

The role of the psychedelic experience in psilocybin ... To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression MADRS score change at week 3 was the primary outcome of the study though a large reduction in depressive symptoms was evident on the day following psilocybin ...

6. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

8. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

9. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

10. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...