Psilocybin for Depression and Personality Disorders

Overseen By Laurie Avila, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Disqualifiers: Bipolar, Schizophrenia, Schizoaffective, others

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

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: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests psilocybin, a compound from certain mushrooms, on adults with major depressive disorder and borderline personality disorder. It aims to see if psilocybin can improve mood and reduce symptoms by affecting brain chemicals. Psilocybin has shown promise as a treatment for major depressive disorder and has been designated as a breakthrough therapy by the FDA.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this drug for depression and personality disorders?

Research shows that psilocybin can reduce symptoms of depression, with some patients experiencing long-term improvements after just one or a few sessions. It has been studied in clinical trials for various psychiatric disorders, showing promise in treating depression and substance use disorders. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin has been studied for its safety in humans, and research suggests that it can be used safely under controlled conditions. However, caution is advised with higher doses, and its safety in people with heart conditions is not fully known. ^{4 6 7 8 9}

How is psilocybin different from other drugs for depression?

Psilocybin is unique because it is a natural compound found in certain mushrooms and is being studied as a rapid-acting treatment for depression, potentially offering benefits with just one or two doses, unlike traditional antidepressants that require prolonged use and can have significant side effects. ^{1 3 10 11 12}

Research Team

Jon E Grant, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults aged 18-65 with both major depressive disorder and borderline personality disorder, as indicated by specific scores on the MADRS and ZAN-BPD scales. Participants must understand and sign a consent form. Those with bipolar I, schizophrenia, active substance use disorders (except cannabis), or unstable medical conditions cannot join.

Inclusion Criteria

I have been diagnosed with major depression.

Your ZAN-BPD score is higher than 9.

Ability to understand and sign the consent form

Exclusion Criteria

You currently have a drug addiction.

You have been diagnosed with bipolar I disorder, schizophrenia, or schizoaffective disorder in the past or currently.

Illegal substance use based on urine toxicology screening (except cannabis use)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single 25 mg oral dose of psilocybin

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Weekly assessments

Treatment Details

Interventions

• Psilocybin

Trial Overview The study aims to test the safety and effectiveness of psilocybin—a psychedelic compound—in treating individuals who have both major depressive disorder (MDD) and borderline personality disorder (BPD).

Participant Groups

Group I: Experimental: Psilocybin Experimental Treatment 1 Intervention

Single 25 mg capsule oral dose 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 Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

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 phase 2 trial with patients suffering from major depressive disorder, psilocybin therapy (PT) led to significant improvements in personality traits associated with mental health, such as decreased neuroticism and increased openness, after 6 weeks.

Both psilocybin and escitalopram treatments resulted in positive changes in personality, but no significant differences were found between the two treatments, suggesting that both may be effective in improving mental health through similar mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression. Weiss, B., Ginige, I., Shannon, L., et al.[2023]

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 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-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]

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]

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]

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, 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]

Psilocybin treatment in depressed patients leads to transient increases in brain connectivity and activation in key neural areas, which are associated with positive antidepressant responses, suggesting a 'brain reset' effect.

The review analyzed 5 studies involving neuroimaging techniques, indicating that psilocybin-assisted psychotherapy may be particularly effective in both refractory and non-refractory depression cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurobiological Correlates of Psilocybin Response in Depression. Qasim, S., Zaheer, Z., Jawad, MY., et al.[2023]

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. England pubmed.ncbi.nlm.nih.gov

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

The pharmacology of psilocybin. [2016]

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

Intravenous mushroom poisoning. [2019]

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

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

11. United States 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. [2023]

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

Neurobiological Correlates of Psilocybin Response in Depression. [2023]