Psilocybin for Depression

Overseen By Lauren Turow

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

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

Disqualifiers: Psychotic disorders, Bipolar, SUDs, others

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: 2

Duration: 1 day

40 Participants Needed

Trial Summary

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

The trial protocol does not specify if you must stop all current medications, but some medications are not allowed. You need to stop using drugs or supplements that interfere with the study, like certain antidepressants and serotonergic supplements, for 5 half-lives before the baseline visit. SSRIs and SNRIs may be allowed at the PI's discretion. Benzodiazepines and non-benzodiazepine sleeping meds can continue if stable for 6 weeks before screening. Psychostimulants must be stopped for 5 half-lives before the baseline visit.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but certain drugs like antipsychotics, trazodone, and others must be stopped for a period before the trial. Some medications, like SSRIs, may be allowed at the discretion of the investigator.

What data supports the idea that Psilocybin for Depression is an effective drug?

The available research shows that psilocybin can effectively reduce symptoms of depression. Several clinical trials have demonstrated its potential, with some studies indicating that even a single dose can lead to significant improvements. Additionally, psilocybin has been found to be well tolerated with limited side effects, and it has shown promise even in patients who have not responded to other treatments. This suggests that psilocybin could be a valuable option for treating depression. ^{1 2 3 4 5}

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

Several clinical trials have shown that psilocybin can reduce symptoms of depression, with some patients experiencing significant, long-term improvements even after just one or a few sessions. ^{1 2 3 4 5}

What safety data exists for psilocybin treatment for depression?

Psilocybin has been studied for its pharmacology, pharmacodynamics, and clinical effects. It affects the central nervous system rapidly, producing effects like ataxia and hallucinations. Safety data from a study on healthy adults showed that escalating oral doses of psilocybin were administered to assess pharmacokinetics and safety. Another study suggested that psilocybin-containing mushrooms did not aggravate certain heart conditions and protected against cell injury in controlled conditions. However, caution is advised with higher concentrations. Overall, psilocybin has shown promise in clinical trials for depression, but its safety in specific conditions like cardiovascular disease is not fully known. ^{2 5 6 7 8}

Is psilocybin safe for human use?

Psilocybin has been studied for its safety in humans, showing that it can be used safely under controlled conditions, although higher doses may pose risks. In healthy adults, escalating doses of psilocybin were generally well-tolerated, and extracts from magic mushrooms did not worsen certain heart conditions in lab studies. ^{2 5 6 7 8}

Is psilocybin a promising drug for treating depression?

Yes, psilocybin is a promising drug for treating depression. Research shows it can reduce symptoms of depression and acts quickly compared to traditional treatments. It is considered a novel and breakthrough therapy for major depression. ^{1 2 4 9 10}

How is psilocybin different from other depression drugs?

Psilocybin is unique because it acts quickly and is used in a few doses, unlike traditional antidepressants that require long-term use. It works by affecting serotonin receptors in the brain, which can lead to rapid improvements in depression symptoms. ^{1 2 4 9 10}

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.

Research Team

Andrew M Novick, MD PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for individuals who have major depressive disorder that hasn't improved with standard treatments. Participants should be experiencing anhedonia, which is the inability to feel pleasure.

Inclusion Criteria

Right-handed

Currently under the care of a psychiatric practitioner who practices within the Department of Psychiatry at the University of Colorado Anschutz Medical Campus. Participants engaged in additional psychosocial treatments beyond seeing a psychiatric practitioner will be evaluated on a case-by-case basis

I can avoid caffeine and nicotine for 2 hours before my MRI scan visits.

Exclusion Criteria

I don't have any physical or mental conditions that would make me unsuitable for the study, including claustrophobia, lack of internet access, weight over 300 pounds, unsafe metal in my body for MRI, or conditions making MRI unsafe. I am not allergic to clonidine, diazepam, or olanzapine and don't have myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, sleep apnea syndrome, acute narrow-angle glaucoma or a history of valvular heart disease.

I haven't taken certain psychiatric drugs or supplements recently and don't have allergies to the study drugs.

I have a significant brain condition or mental health issue confirmed by medical review.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Psilocybin 1mg or 25mg capsule orally, administered with psychological support, on dosing day

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in depression and anhedonia scores post-dosing

8 weeks

Multiple assessments at 1, 4, and 8 weeks post-dosing

Treatment Details

Interventions

• Psilocybin

Trial Overview The study is testing the effects of psilocybin on depression symptoms. Two different doses of psilocybin (1mg and 25mg) are being compared to see how they affect anhedonia in participants.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

Participants receive Psilocybin 25mg capsule orally, administered with psychological support, on dosing day.

Group II: Active Placebo Placebo Group 1 Intervention

Participants receive Psilocybin 1mg capsule (identical to the Psilocybin 25mg capsule) orally, administered with psychological support, on dosing day.

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 Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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 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]

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-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 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, 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, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

8. 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]

9. 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]

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

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]