Psilocybin-assisted CBT for Depression

Overseen By Shelby Grody

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Los Angeles

Must not be taking: Antidepressants, Serotonergic substances

Disqualifiers: Psychosis, Bipolar, Cardiovascular, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: 18

62 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objectives of this clinical investigation are to (1) determine the acceptability and feasibility of joining psilocybin-assisted therapy with cognitive-behavioral therapy (PA-CBT) for patients with depression, (2) optimize CBT to most effectively integrate the psilocybin experience with psychotherapy and (3) examine the clinical benefit of psilocybin as an adjunct to cognitive-behavioral therapy (CBT) for major depressive disorder. This study has two phases. Phase I will involve an open trial of PA-CBT where participants will receive two doses of psilocybin (10mg and then 25mg, separated by one month) plus 12 sessions of cognitive behavioral therapy. Phase II will be a randomized, two-arm, fixed dose trial that will test the feasibility, acceptability, and participant and therapist adherence to PA-CBT. Both treatment arms will receive two doses of psilocybin (10mg and then 25mg, separated by one month). In Phase II, participants will be randomized (1:1) to either a 12-session PA-CBT or a 6-session standard psilocybin-assisted therapy (PAT) condition (3 hours of preparation plus 3 hours of supportive therapy integration following the psilocybin experiences).

Will I have to stop taking my current medications?

Yes, you will need to stop taking antidepressants or other medications that affect serotonin, like St. John's Wort, to participate in this trial.

What data supports the effectiveness of the drug psilocybin for depression?

Research shows that psilocybin can quickly reduce symptoms of depression, with effects lasting long after just one or two doses. It has been well-tolerated in clinical trials, even helping some patients who didn't respond to other treatments. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin has been studied in healthy adults with escalating doses, showing a safety profile that supports its use under controlled conditions. However, caution is advised, especially for individuals with cardiovascular issues, as its safety in such conditions is not fully known. ^{4 6 7 8 9}

How is psilocybin-assisted CBT for depression different from other treatments?

Psilocybin-assisted CBT for depression is unique because it combines the psychedelic effects of psilocybin, which can rapidly reduce depression symptoms, with cognitive behavioral therapy (CBT), a structured talk therapy. This combination aims to enhance the therapeutic process by potentially opening new perspectives and emotional insights during therapy sessions. ^{1 9 10 11 12}

Eligibility Criteria

This trial is for adults aged 21-60 with depression, who are experiencing a major depressive episode. They must be able to swallow capsules and have someone to drive them home after sessions. Women should use effective contraception. Exclusions include active suicidality, current antidepressant use, certain cardiovascular conditions, insulin-dependent diabetes, history of psychosis or bipolar in the family, prior adverse reaction to psychedelics, pregnancy or nursing.

Inclusion Criteria

Patient has been medically cleared for the study by a physician

For women of child-bearing potential - using one form of highly effective contraception and willingness to continue contraceptive use for duration of study

I have been diagnosed with major depression now or in the past.

Exclusion Criteria

I am currently undergoing cognitive behavioral therapy.

Adverse prior reaction to a psychedelic agent

I have a heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Open trial of PA-CBT with two doses of psilocybin (10mg and 25mg) and 12 sessions of cognitive behavioral therapy

4 months

12 therapy sessions

Phase II Treatment

Randomized trial with two arms: 12-session PA-CBT or 6-session standard psilocybin-assisted therapy, both with two doses of psilocybin

4 months

6-12 therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests combining psilocybin (a psychedelic drug) with cognitive-behavioral therapy (CBT) for treating major depressive disorder. Participants will receive two oral doses of psilocybin during twelve CBT sessions over four months and then be followed up for three additional months.

Participant Groups

Group I: Psilocybin + CBT Experimental Treatment 2 Interventions

Participants will receive 12 sessions of cognitive-behavioral therapy (CBT) along with two psilocybin-drug sessions -- the first following the third CBT session (10mg of psilocybin, taken orally) and the second following the sixth CBT session (25mg of psilocybin, taken orally).

Group II: Psilocybin + Minimal supportive therapy Active Control 2 Interventions

Participants will receive 6 sessions of supportive, non-directive therapy along with two psilocybin-drug sessions -- the first following the third therapy session (10mg of psilocybin, taken orally) and the second following the fourth therapy session (25mg of psilocybin, taken orally).

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

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 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]

In a placebo-controlled study involving individuals with moderate to severe major depressive disorder, psilocybin (0.3 mg/kg) showed larger antidepressant effect sizes compared to placebo, with 66.7% of participants responding and 46.7% achieving remission after treatment.

The antidepressant effects of psilocybin persisted for an average of 2 months, indicating its potential as a long-lasting treatment option for depression, although the strength of the mystical experience during dosing did not correlate with these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. Sloshower, J., Skosnik, PD., Safi-Aghdam, H., et al.[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]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

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]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

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]

A systematic review and meta-analysis of seven studies involving 489 participants identified optimal dosages of psilocybin for reducing depression scores, with effective doses of 8.92 mg for secondary depression, 24.68 mg for primary depression, and 36.08 mg for both groups combined.

The study found significant dose-response relationships for both efficacy and side effects, indicating that while higher doses may be more effective, they also increase the risk of adverse effects like nausea and prolonged psychosis, highlighting the need for careful dosage management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies. Perez, N., Langlest, F., Mallet, L., et al.[2023]

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 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]

References

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

Assessing potential of psilocybin for depressive disorders. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. [2023]

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

The pharmacology of psilocybin. [2016]

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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

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

[Hallucinogenic mushrooms]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. [2021]

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

Intravenous mushroom poisoning. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies. [2023]

11. England pubmed.ncbi.nlm.nih.gov

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

12. Switzerland 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. [2020]