Psilocybin-Assisted Therapy for Depression

Recruiting in Palo Alto (17 mi)

Overseen by Robert K McClure, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of North Carolina, Chapel Hill

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

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

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.

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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.

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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.

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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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UNC Chapel Hill Medical Center Chapel Hill, NC

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill Lead Sponsor

Foundation of Hope, North Carolina Collaborator

References

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

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.

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

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.

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

[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.

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] 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.

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

Psilocybin in Palliative Care: An Update. [2023] This review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care.

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

[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.

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

Intravenous mushroom poisoning. [2019] Mushrooms of the genus Psilocybe frequently are ingested by recreational drug users for their hallucinogenic effects. We present the case of a 30-year-old man who allegedly received an intravenous injection of an extract of Psilocybe mushrooms. His clinical course was characterized in part by vomiting, severe myalgias, hyperpyrexia, hypoxemia, and mild methemoglobinemia, and it was similar to two previously reported cases. The patient improved rapidly with supportive care.

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

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.

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] Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst "bad trip") after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.

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

The development of psilocybin therapy for treatment-resistant depression: an update. [2023] Psilocybin is a classic psychedelic drug that has attracted increasing research interest over the past 10 years as a possible treatment for mood, anxiety and related conditions. Initial phase 2 clinical trials of psilocybin given alongside psychological support for major depression and treatment-resistant depression (TRD) demonstrated encouraging signs of basic safety, further confirmed by a large study in groups of healthy volunteers. The first international multi-centre randomised controlled trial was published in 2022, with signs of efficacy for the 25 mg dose condition in people with TRD when compared with an active placebo. Phase 3 trials in TRD are scheduled to start in 2023. Early evidence suggests that single doses of psilocybin given with psychological support induce rapid improvement in depressive symptoms that endure for some weeks. We therefore provide a timely update to psychiatrists on what psilocybin therapy is, what it is not, and the current state of the evidence-base.