Psilocybin Microdosing for Depression

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Rotem Petranker

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if very small doses of psilocybin can safely and effectively improve mood in people with major depression who don't respond to or don't want standard treatments. Psilocybin may help by affecting brain chemicals related to mood. Psilocybin has shown promise as a treatment for major depressive disorder and was designated as a breakthrough therapy by the FDA in 2019.

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

Yes, you may need to stop taking certain medications. Participants cannot take psychotropic medications, antidepressants, or medications affecting serotonin neurons. If you were on antidepressants, a washout period of five half-lives plus seven days is required. You must also refrain from starting new medications and using certain metabolic inducers or inhibitors. Consult the research team for specific guidance.

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

The available research shows that psilocybin can be effective in reducing symptoms of depression. Several clinical trials have demonstrated that psilocybin-assisted therapy can have rapid and lasting effects on depression symptoms, even with just one or two doses. These studies suggest that psilocybin may work faster than traditional treatments. Additionally, psilocybin has been shown to be well tolerated with limited side effects, and some patients with treatment-resistant depression have experienced significant improvements. However, more research is needed to fully understand its benefits and how it compares to other treatments. ^{1 2 3 4 5}

What safety data exists for psilocybin microdosing for depression?

The safety data for psilocybin, particularly in the context of microdosing for depression, is still emerging. Historical use and recent studies suggest that psilocybin, found in 'magic mushrooms,' has been used for its psychoactive effects. Pharmacokinetic studies have been conducted with escalating doses in healthy adults to understand its safety profile. Preliminary research indicates potential therapeutic benefits for depression and other disorders, but adverse reactions can occur, such as hallucinations and physical symptoms like ataxia and hyperkinesis. Supportive care is effective in managing severe cases. Overall, while promising, more research is needed to fully understand the safety and efficacy of psilocybin microdosing for depression. ^{6 7 8 9 10}

Is the drug Psilocybin a promising treatment for depression?

Yes, Psilocybin is considered a promising treatment for depression. Research shows it can reduce symptoms of depression and is seen as a novel and breakthrough therapy for major depressive disorder. ^{2 5 11 12 13}

Research Team

Eligibility Criteria

Adults aged 18-65 with Major Depressive Disorder can join this trial. They must speak and read English well, have a high school education, not use psychoactive drugs or alcohol before sessions, and women must test negative for pregnancy and use birth control. Excluded are those with certain medical conditions like uncontrolled blood pressure, seizures, cancer history; those on specific medications; smokers; substance abuse disorders within the last 5 years; unstable health conditions.

Inclusion Criteria

You have given informed consent.

I have been diagnosed with persistent depressive disorder, dysthymic subtype.

If of childbearing potential, must have a negative pregnancy test at study entry and must agree to use adequate birth control through 10 days after the last Experimental Session (refer to section 9.4.2 for contraceptive guidelines).

Exclusion Criteria

I have had a stroke, mini-stroke, brain aneurysm, or a blood vessel malformation.

I will not start any new medications during the trial.

The subject has blood pressure exceeding screening criteria

Treatment Details

Interventions

• Psilocybin (Psychedelic)

Trial Overview The trial is testing if small doses of psilocybin (2mg) can safely improve mood in people with depression without causing hallucinations. Participants will receive either psilocybin or a placebo first to compare effects.

Participant Groups

Group I: Open Label Experimental Treatment 2 Interventions

In this condition participants will receive psilocybin once weekly for 4 weeks, and will be told that they are receiving psilocybin.

Group II: Blinded Psilocybin Experimental Treatment 1 Intervention

In this condition participants will receive psilocybin once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin.

Group III: Blinded Placebo Placebo Group 1 Intervention

In this condition participants will receive an inert placebo once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin.

Who Is Running the Clinical Trial?

Rotem Petranker

Lead Sponsor

Trials

1

Recruited

50+

Nikean Foundation

Collaborator

Trials

2

Recruited

70+

Findings from Research

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., 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, 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]

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-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]

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 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 compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

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]

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]

Mycelial cultures of Psilocybe cubensis can effectively convert synthetic N,N-diethyl-tryptamine into 4-hydroxy-N,N-diethyltryptamine, demonstrating a unique ability for hydroxylation at the 4-position, with yields of up to 3.3%.

This study marks the first instance of fungi being used for directed biosynthesis of tryptamine compounds, highlighting the potential for using fungal cultures in the production of psychoactive substances like psilocybin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe. Gartz, J.[2019]

References

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

Psilocybin in Palliative Care: An Update. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

[Hallucinogenic mushrooms]. [2018]

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

The pharmacology of psilocybin. [2016]

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

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

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

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

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

Intravenous mushroom poisoning. [2019]

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe. [2019]