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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a compound in certain mushrooms, is safe and effective for treating major depressive disorder (MDD) and borderline personality disorder (BPD). The main aim is to determine if a single 25 mg capsule can reduce symptoms of depression and personality challenges. The study seeks adults diagnosed with MDD and BPD who experience significant daily impacts from these conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that psilocybin is likely to be safe for humans?

Research has shown that psilocybin has been tested in various studies for its safety in treating depression. In one study, a single 25 mg dose of psilocybin significantly lowered depression scores but also caused some side effects, such as headaches and nausea.

Another study on psilocybin for treatment-resistant depression found it to be generally safe for patients. Most side effects were mild and short-lived, including dizziness or tiredness, while serious side effects were rare.

Although the safety of psilocybin is still under investigation, current research suggests it is usually well-tolerated. Prospective participants should discuss any concerns with the clinical trial team before joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression and personality disorders?

Psilocybin is unique because it offers a new approach to treating depression and personality disorders by using a psychedelic compound derived from certain types of mushrooms. Unlike traditional antidepressants, which often take weeks to start working, psilocybin has the potential to produce rapid improvements in mood and mental health after just a single dose. Researchers are excited about psilocybin because it works by targeting serotonin receptors in the brain, which may help reset and improve brain connectivity, offering a potentially transformative experience for individuals with these mental health conditions.

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

Research has shown that psilocybin, administered as a single 25 mg oral capsule in this trial, can help reduce depression symptoms. One study found that this dose significantly lowered depression scores over three weeks compared to a very low dose. Another study demonstrated that this dose helped maintain antidepressant effects for up to a year. While most research focuses on depression, these findings suggest that psilocybin might also help treat major depressive disorder and possibly borderline personality disorder. ^{1 3 4 6 7}

Who Is on the Research Team?

Jon E Grant, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

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 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, 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]

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. 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 ...

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

COMP360 psilocybin treatment in TRD This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England Journal ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06308653

NCT06308653 | Psilocybin for Major Depressive Disorder ... The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

Efficacy, Safety, and Tolerability of COMP360 in ... This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study.

7. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression COMP360 showed a statistically significant reduction in TRD symptom severity compared to placebo, with a clinically meaningful MADRS score ...