Psilocybin for Migraine

Overseen By Mackenzie Creighton, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Vasoconstrictives, Antiemetics, Antidepressants, Steroids

Disqualifiers: Psychotic disorders, Unstable medical condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants using vasoconstrictive medications, certain antiemetics, antidepressants, steroids, and some migraine treatments within specific time frames before the test days.

What evidence supports the effectiveness of the drug psilocybin for treating migraines?

An exploratory study found that a single dose of psilocybin significantly reduced the number of migraine days over a two-week period compared to a placebo, suggesting a lasting therapeutic effect without serious side effects. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin has been studied for its safety in humans, showing that it can cause rapid effects on the central nervous system, such as hallucinations and increased movement. In clinical studies, it has been tested in healthy adults with escalating doses to understand its safety profile, and it is being explored as a treatment for conditions like depression with careful monitoring of doses. ^{2 5 6 7 8}

How is psilocybin different from other migraine drugs?

Psilocybin is unique because it may provide long-lasting relief from migraines after just a single dose, unlike many other treatments that require regular use. It works by affecting serotonin receptors in the brain, and its therapeutic effects are separate from its psychedelic effects, which is a novel finding in migraine treatment. ^{2 4 7 8 9}

What is the purpose of this trial?

This trial is testing if psilocybin, a substance from certain mushrooms, can help people with migraines who don't get relief from usual treatments. The study will look at how psilocybin affects brain inflammation, which might be causing the migraines. Psilocybin is a well-known substance with a long history of use by indigenous cultures and has shown potential in treating cluster headaches and chronic pain disorders.

Eligibility Criteria

This trial is for individuals who have been diagnosed with migraine headaches according to ICHD-3 criteria and experience about two or more migraines weekly. Participants should not be using triptans more than twice a week. People with psychotic disorders, severe medical conditions, pregnant or breastfeeding women, those intolerant to psilocybin/LSD, recent drug abusers, heavy alcohol users, and those on certain medications are excluded.

Inclusion Criteria

You have been diagnosed with migraine headaches according to specific criteria.

You have frequent migraines, about two or more every week.

You use triptans for treating attacks no more than twice a week.

Exclusion Criteria

You have a severe mental illness like schizophrenia or bipolar disorder.

A close family member has a serious mental health condition like schizophrenia or bipolar disorder.

You have tested positive for drugs in a urine test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive single and repeated dosing of psilocybin or placebo up to two doses, approximately 7 days apart

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in migraine-related symptoms and neuroinflammatory markers

2 months

Follow-up assessments using a headache diary

Treatment Details

Interventions

• Placebo
• Psilocybin

Trial Overview The study is testing the effect of single and repeated doses of Psilocybin compared to a placebo in reducing the burden of migraine headaches. It will also measure neuroinflammatory markers to explore how Psilocybin might affect migraines.

Participant Groups

Group I: Psilocybin/Psilocybin Experimental Treatment 1 Intervention

Subjects will receive a dose of psilocybin, followed by a dose of psilocybin approximately 7 days later.

Group II: Psilocybin/Placebo Experimental Treatment 2 Interventions

Subjects will receive a dose of psilocybin, followed by a dose of placebo approximately 7 days later.

Group III: Placebo/Psilocybin Experimental Treatment 2 Interventions

Subjects will receive a dose of placebo, followed by a dose of psilocybin approximately 7 days later.

Group IV: Placebo/Placebo Experimental Treatment 1 Intervention

Subjects will receive a dose of placebo, followed by a dose of placebo approximately 7 days later.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

The Wallace Foundation

Collaborator

Wallace Research Foundation

Collaborator

Trials

4

Recruited

90+

Findings from Research

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]

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 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 meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[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, 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]

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 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. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

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

Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. [2023]

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

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

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

The pharmacology of psilocybin. [2016]

7. 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]

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

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