Microdose Psilocybin for Psychedelic Experiences

Overseen By Matthew Nielsen Dick

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive drugs, MAOIs

Disqualifiers: Pregnancy, Cardiovascular conditions, Epilepsy, others

Compensation: Varies

Number of Visits: 6

Duration: 5 sessions

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of small doses of psilocybin, a compound found in some mushrooms, to determine if healthy individuals can safely take them at home. Participants will receive doses ranging from 1.2 mg to 4.2 mg, along with a placebo on different days, to compare effects. Suitable candidates should be healthy, stable, and willing to avoid other drugs and certain medications before each session. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this novel treatment.

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.

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

Research has shown that taking a small dose of psilocybin is generally safe when administered once under medical supervision. Studies have found that side effects are usually mild and resolve soon after dosing. Common side effects include increased blood pressure, anxiety, and occasional sleep disturbances. Some individuals may also experience low mood, reduced energy, or an upset stomach.

Psilocybin carries a low risk of causing serious harm in humans. While mild side effects may occur, the likelihood of more serious issues is quite low. It remains important to exercise caution and follow healthcare professionals' advice when considering participation in such a study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for mental health conditions, which often involve antidepressants or therapy, microdoses of psilocybin offer a novel approach through their unique mechanism of action. Psilocybin is a psychedelic compound that targets serotonin receptors in the brain, potentially enhancing mood and cognitive flexibility in a way that traditional medications do not. Researchers are excited about these treatments because they promise rapid effects with potentially fewer side effects due to the low dosages used. Additionally, the diverse dosage levels being explored in this study (ranging from 1.2 mg to 4.2 mg) could help fine-tune the balance between efficacy and safety, offering personalized treatment options.

What evidence suggests that microdose psilocybin could be effective for psychedelic experiences?

This trial will compare different microdoses of psilocybin with a placebo. Research has shown that taking very small amounts of psilocybin, the main ingredient in magic mushrooms, might improve mood and concentration. In one study, about 27% of participants felt happier, and about 15% found it easier to focus. Another study found that microdosing could help reduce feelings of stress and anxiety for most participants. While some people might feel uncomfortable or anxious, many find the benefits outweigh these issues. There's still much to learn, but these early results are encouraging for those interested in the potential of psilocybin microdoses. ^{2 4 6 7 8}

Who Is on the Research Team?

Sandeep Nayak, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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

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

I agree not to take any over-the-counter drugs or supplements without approval a week before each drug session.

Licensed to drive (for driving simulator test)

Exclusion Criteria

History of schizophrenia spectrum disorder

Current history of meeting DSM-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Microdose Psilocybin

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.

How Is the Trial Designed?

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+

Private Philanthropic Funds

Collaborator

Trials

4

Recruited

150+

Private Philanthropic Funds

Collaborator

Published Research Related to This Trial

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 (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]

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]

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]

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]

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]

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]

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]

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]

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]

The HOPE trial, involving 12 cancer patients, showed that psilocybin-assisted group therapy is safe, with no serious adverse events reported, and resulted in significant reductions in depression symptoms over six months.

Participants experienced substantial decreases in depression scores, with six out of twelve achieving remission at two weeks, indicating that this group therapy model could be an effective treatment for depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Lewis, BR., Garland, EL., Byrne, K., et al.[2023]

Citations

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Microdosing with psilocybin mushrooms: a double-blind ... Furthermore, there is anecdotal evidence supporting that microdosing psychedelics can increase creativity and problem-solving abilities, as well ...

2. nccih.nih.gov nccih.nih.gov/health/psilocybin-for-mental-health-and-addiction-what-you-need-to-know

Psilocybin for Mental Health and Addiction: What You Need ... Adverse effects from psilocybin can include increased blood pressure and heart rate, headache, nausea, dizziness, fatigue, poor sleep, anxiety, paranoia, ...

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Review Microdosing Psychedelics: Current Evidence From ... The findings suggest that low doses of LSD are safe and produce acute behavioral and neural effects in healthy adults.

4. psychiatrist.com psychiatrist.com/pcc/modern-psychedelic-microdosing-research-mental-health-systematic-review/

Modern Psychedelic Microdosing Research on Mental Health Using a mixed-methods approach, outcomes included improved mood (26.6%) and focus (14.8%), alongside discomfort (18.0%) and anxiety (6.7%).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07063862

Study Details | NCT07063862 | Psilocybin Microdose for ... We recently completed a small study of psilocybin microdosing. Our results showed psilocybin microdose improved psychological distress in most participants ...

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Side effects of microdosing lysergic acid diethylamide and ... Side effects of microdosing include increases in blood pressure and anxiety. Most adverse effects are mild and transient, resolving post-intoxication.

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1654/psilocybin

Psilocybin - Uses, Side Effects, and More When taken by mouth: Psilocybin is possibly safe when used as a single dose under medical supervision. Single doses of psilocybin have been used in controlled ...

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Mushroom 'microdosing' trend has led to increased poison ... Therefore, psilocybin-containing mushrooms are generally considered to have a low potential for acute toxicity in humans, to the point where it ...