Microdose Psilocybin for Psychedelic Experiences

Recruiting in Palo Alto (17 mi)

Overseen by Sandeep Nayak, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive drugs, MAOIs

Disqualifiers: Pregnancy, Cardiovascular conditions, Epilepsy, others

Trial Summary

What is the purpose of this trial?

The goal of this laboratory study is to establish whether and which microdoses of psilocybin are safe to administer at home to healthy participants. Eligible participants will be given ascending doses of psilocybin trihydrate and a single, interspersed, randomized placebo on separate days in double-blind fashion. The participants will be asked to complete questionnaires and undergo safety assessments.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any psychoactive drugs and certain medications with serotonergic effects. You must also refrain from nonprescription medications, nutritional, or herbal supplements for one week before each drug session, unless approved by the study investigators.

What data supports the effectiveness of the drug microdose psilocybin?

Research suggests that psilocybin, even in small doses, may help improve symptoms in conditions like depression and anxiety, with some studies showing long-term benefits after just a few sessions. However, more research is needed to fully understand its effectiveness and safety. ^{1 2 3 4 5}

Is microdosing psilocybin generally safe for humans?

Psilocybin, when given in controlled settings to screened and supported participants, has a very low incidence of risky behavior or long-lasting psychological distress. However, some individuals have reported challenging experiences, and a small percentage have sought medical help or experienced enduring psychological symptoms. ^{6 7 8 9 10}

How is microdose psilocybin different from other drugs for psychedelic experiences?

Microdose psilocybin is unique because it involves taking very small doses of psilocybin, which is a compound found in certain mushrooms, to potentially improve mental health without causing full psychedelic effects. This approach is different from traditional treatments as it aims to enhance resilience to stress and reduce compulsive behaviors with minimal side effects, as suggested by studies in animals. ^{1 9 11 12 13}

Research Team

Sandeep Nayak, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for healthy, psychologically stable adults aged 21-60 who speak English and have at least a high school education. Participants must not use psychoactive substances or certain medications before sessions and agree to safety screenings including interviews, physical exams, ECGs, and lab tests.

Inclusion Criteria

I have completed high school or equivalent and am fluent in English.

Be healthy and psychologically stable as determined by screening for medical and psychiatric problems

I agree not to use any mind-altering substances, including alcohol and nicotine, 24 hours before each treatment, except for caffeine.

Exclusion Criteria

I am not pregnant, nursing, or if capable of becoming pregnant, I am using effective birth control.

My weight is more than 20% above or below the ideal range.

History of schizophrenia spectrum disorder

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person, with remote portions)

Treatment

Participants receive ascending doses of psilocybin trihydrate and a single, interspersed, randomized placebo in double-blind fashion

5 sessions

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Microdose Psilocybin (Psychedelic Therapy)

Trial Overview The study is testing the safety of self-administering microdoses of psilocybin trihydrate at home. Participants will receive increasing doses of the drug along with a placebo in a single-blind setup while completing questionnaires and undergoing safety assessments.

Participant Groups

Group I: 4.2 mg psilocybin trihydrate microdose Experimental Treatment 1 Intervention

Participants will receive a single microdose of 4.2 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Group II: 3.0 mg psilocybin trihydrate microdose Experimental Treatment 1 Intervention

Participants will receive a single microdose of 3.0 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Group III: 2.0 mg psilocybin trihydrate microdose Experimental Treatment 1 Intervention

Participants will receive a single microdose of 2.0 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Group IV: 1.2 mg psilocybin trihydrate microdose Experimental Treatment 1 Intervention

Participants will receive a single microdose of 1.2 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Group V: Placebo Placebo Group 1 Intervention

Participants will receive a single placebo oral capsule in the laboratory in double-blind fashion.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

Private Philanthropic Funds

Collaborator

Trials

4

Recruited

150+

Findings from Research

Microdosing psychedelics like LSD and psilocybin has shown subtle positive effects on cognitive processes and brain regions related to mood, but its therapeutic value for depression remains unclear based on a review of 14 studies.

Low doses of these psychedelics are generally well tolerated with minimal physiological effects, suggesting potential safety for repeated use, but more extensive clinical trials in depressed patients are needed to fully understand their efficacy and therapeutic role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic potential of microdosing psychedelics in depression. Kuypers, KPC.[2023]

Psychedelic substances like psilocybin, DMT, LSD, and MDMA are being researched for their potential therapeutic effects on psychiatric disorders, which are a leading cause of global disability.

The review highlights ongoing and recently completed clinical trials, indicating a renewed interest in the safety and efficacy of these compounds, especially in combination with psychotherapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders. Rhee, TG., Davoudian, PA., Sanacora, G., et al.[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 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]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

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]

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]

Psilocin, isolated from psychotropic mushrooms, showed varying levels of acute toxicity, with the highest toxicity observed at an LD50 of 293.07 mg/kg for pure psilocin, compared to 316.87 mg/kg for Pholiotina cyanopus and 324.37 mg/kg for Psilocybe semilanceata.

Both psilocin and mushroom extracts acted as agonists on the serotonergic system, with psilocin significantly reducing head-twitch responses in mice, indicating its potential effects on serotonin pathways, which are linked to hallucinogenic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice. Zhuk, O., Jasicka-Misiak, I., Poliwoda, A., et al.[2018]

In a study using rats, repeated low doses of psilocybin (microdosing) were well-tolerated and did not cause negative effects like anxiety or changes in movement, suggesting safety for this dosing regimen.

The microdosing regimen increased 5-HT7 receptor expression and synaptic density in a specific brain region, indicating a potential physiological mechanism for the reported mental health benefits of psilocybin microdosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Kiilerich, KF., Lorenz, J., Scharff, MB., et al.[2023]

In a study analyzing the tryptamine content of freshly cultivated Psilocybe cubensis mushrooms, it was found that the caps contained the highest concentration of psilocybin and psilocin, while the mycelium had a lower concentration and no tryptamines were detected in the basidiospores.

Storage conditions significantly affected the stability of tryptamines, with fresh mushrooms stored at -80°C showing the highest degradation, while dried biomass stored in the dark at room temperature maintained the tryptamine levels better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Gotvaldová, K., Hájková, K., Borovička, J., et al.[2021]

Psilocybin (PY) is rapidly converted to its active form, psilocin (PI), in the body, with peak plasma levels occurring approximately 105 minutes after oral administration and 1.9 minutes after intravenous injection, indicating a quick onset of action.

The study found that psilocin has an estimated absolute bioavailability of about 52.7% when taken orally, suggesting that a significant portion of the drug is effectively absorbed into the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Hasler, F., Bourquin, D., Brenneisen, R., et al.[2019]

References

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

The therapeutic potential of microdosing psychedelics in depression. [2023]

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

Psychedelic renaissance: Revitalized potential therapies for psychiatric 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

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. [2023]

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

[Hallucinogenic mushrooms]. [2018]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice. [2018]

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

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. [2019]