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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a compound in certain mushrooms, can reduce the frequency and severity of migraine headaches. Researchers are investigating if taking psilocybin once or twice can make a difference and are examining its effects on brain inflammation. Individuals who experience two or more migraines each week and manage them without using triptans more than twice a week may be suitable for this study. Participants will receive either psilocybin or a placebo in different combinations to assess the treatment's effectiveness. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, the substance under study for migraines, has been tested in people for other health issues. These studies have found it generally safe, with most experiencing only mild to moderate side effects like headaches, nausea, or temporary mood and perception changes. These effects usually do not last long.

Psilocybin is also being researched for its potential to help with depression and anxiety, showing similar safety results. It is important to know that psilocybin is the active ingredient in "magic mushrooms," but in this study, doses are carefully controlled to reduce side effects.

This study is in its early stages, focusing on safety and dosage. Participation helps researchers understand how psilocybin might work for migraines. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard migraine treatments that typically involve pain relievers, triptans, or preventative medications, psilocybin offers a unique approach by targeting the brain's serotonin receptors. Researchers are excited about psilocybin for migraine relief because it has the potential to modify how the brain processes pain and could offer long-lasting effects after just one or two doses. This is a stark contrast to current therapies that often require continuous use and may not address the root cause of migraines. By exploring psilocybin, scientists hope to uncover a more effective and enduring solution for migraine sufferers.

What evidence suggests that this trial's treatments could be effective for migraines?

Research shows that psilocybin might help reduce migraine symptoms. Some studies suggest it can decrease the frequency and severity of headaches. Psilocybin likely works by affecting certain brain chemicals that control mood and pain. Early research also indicates it might reduce brain inflammation, which is linked to migraines. Although more studies are needed, these early results offer promise for those seeking new migraine treatments. Participants in this trial will receive either psilocybin or a placebo in different sequences to evaluate its effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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 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]

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]

Citations

1. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Psilocybine. Formula: C12H17N2O4P ... 4-Phosphoryloxy-N,N-dimethyltryptamine; Psilocibin; Psilocin phosphate ester; Psilotsibin; Teonanacatl; Psylocybin ...

2. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/psilocybine

Definition of psilocybine - NCI Drug Dictionary A tryptamine alkaloid, isolated from various genera of fungi including the genus Psilocybe, with hallucinogenic, anxiolytic, and psychoactive activities.

4. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

5. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4.

6. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.