Psilocybin-Assisted Therapy for Depression

Overseen By Brittania Ricketts

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: MAOIs, Antipsychotics, Tramadol, others

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test how well psilocybin-assisted therapy works in treating people with depression. The main questions this study aims to answer are: * Does psilocybin with assisted therapy help improve symptoms for people with depression? * How long do the effects of this treatment last? Participants will: * Take part in a couple of screening and preparation visits. * Be given psilocybin in one or two treatment sessions. * Attend a series of follow-up sessions over the following year. * Complete forms and surveys to test how their symptoms have changed and what they thought of their experience. Researchers will also compare whether one treatment or two treatments help improve symptoms more for participants.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, like Monoamine oxidase inhibitors (MAOIs), antipsychotics, and tramadol, at least 4 weeks before psilocybin administration. Other medications may be allowed at the investigator's discretion.

What data supports the effectiveness of this drug for depression?

Several clinical trials have shown that psilocybin can reduce symptoms of depression, even in patients who have not responded to other treatments. It is generally well tolerated with limited side effects, and some patients experience long-term improvements after just one or a few sessions. ^{1 2 3 4 5}

Is psilocybin-assisted therapy generally safe for humans?

Psilocybin has been studied for its safety in humans, showing that while it can cause challenging experiences, the risk of physical harm or long-term psychological distress is low when used in controlled settings with proper support. In a study with healthy adults, escalating doses of psilocybin were well-tolerated, and most participants reported benefits despite some difficult experiences. ^{2 6 7 8 9}

How is psilocybin different from other drugs for depression?

Psilocybin is unique because it is a psychedelic drug that can rapidly reduce depression symptoms with just one or two doses, unlike traditional antidepressants that often require daily use and take weeks to show effects. It is typically given with psychological support, and its effects can last for several weeks after a single dose. ^{1 2 4 8 10}

Research Team

Robert K McClure, MD

Principal Investigator

Director of Interventional Psychiatry

Eligibility Criteria

This trial is for individuals with depression that hasn't improved with standard treatments. Participants will undergo screening visits, receive psilocybin in one or two sessions, and attend follow-ups over a year to monitor changes in their symptoms.

Inclusion Criteria

Provision of signed and dated informed consent form

Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-V) diagnosis of major depressive disorder

Use of effective contraception throughout the study by those with child-bearing potential

Exclusion Criteria

Borderline personality disorder, defined by DSM-V criteria, that in the judgement of the Investigator is likely to complicate the assessment of clinical response to study treatments or limits the patient's ability to comply with study procedures

I am currently taking tramadol.

I have not used esketamine, ketamine, psilocybin, or LSD in the last 6 months or more than 10 times ever.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive one or two doses of a 25mg capsule of psilocybin

2 weeks

1-2 visits (in-person)

Follow-up

Participants attend follow-up sessions and complete forms and surveys to assess changes in symptoms over the following year

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests the effectiveness of psilocybin-assisted therapy on improving depressive symptoms and how long these benefits last. It compares the outcomes between receiving one versus two treatment sessions.

Participant Groups

Group I: Single Psilocybin Treatment Experimental Treatment 1 Intervention

Participants will be administered one dose of a 25mg capsule of psilocybin. This will be administered one time.

Group II: Two Psilocybin Treatments Active Control 1 Intervention

Participants will be administered one dose of a 25mg capsule of psilocybin. Two weeks later, the participant will be administered one more dose of a 25mg capsule of psilocybin.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Foundation of Hope, North Carolina

Collaborator

Trials

18

Recruited

670+

Findings from Research

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, 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]

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]

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 shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[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]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

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]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

Psilocybin, a psychedelic drug, shows promising safety and efficacy in treating major depression and treatment-resistant depression (TRD), with initial phase 2 trials indicating positive outcomes when combined with psychological support.

The first international randomized controlled trial in 2022 found that a 25 mg dose of psilocybin was effective compared to an active placebo, and phase 3 trials are set to begin in 2023, suggesting a growing interest in psilocybin as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of psilocybin therapy for treatment-resistant depression: an update. Borissova, A., Rucker, JJ.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

10. England pubmed.ncbi.nlm.nih.gov

The development of psilocybin therapy for treatment-resistant depression: an update. [2023]