What side effects are associated with this type of intervention?

Common treatments for migraines that modulate serotonin receptors and reduce neuroinflammation include triptans and CGRP antagonists. Triptans, such as zolmitriptan and frovatriptan, can cause side effects like dizziness, fatigue, dry mouth, and, in some cases, more serious cardiovascular issues. CGRP antagonists, which target the calcitonin gene-related peptide involved in migraine pathophysiology, may cause side effects such as constipation, injection site reactions, and, less commonly, hypersensitivity reactions. Both classes of drugs are generally well-tolerated but should be used under medical supervision to manage potential adverse effects.

What prior FDA approvals exist?

Several FDA-approved treatments for migraine focus on the modulation of serotonin receptors, similar to the mechanism being studied for psilocybin. Triptans, such as sumatriptan, zolmitriptan, and frovatriptan, are 5-HT1 receptor agonists that have been widely used for acute migraine relief. These drugs work by stimulating serotonin receptors, leading to vasoconstriction and reduced neuroinflammation. Additionally, newer treatments like lasmiditan, a 5-HT1F receptor agonist, and gepants, such as ubrogepant and rimegepant, which are CGRP receptor antagonists, also target neuroinflammatory pathways. These treatments highlight the importance of serotonin modulation and neuroinflammation reduction in managing migraine.

What other types of research exist?

Promising novel alternatives to psilocybin for migraine treatment in 2024 include: 1) Triptans (e.g., almotriptan, eletriptan, rizatriptan, sumatriptan) which are serotonin receptor agonists. 2) Magnesium supplementation, which has shown efficacy in migraine prevention. 3) Feverfew (Tanacetum parthenium), an herbal remedy with anti-inflammatory properties. 4) Acupuncture, which has been associated with a moderate reduction in migraine episodes.

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Psilocybin for Migraine

Phase 1

Waitlist Available

Research Sponsored by Yale University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from two weeks before the first session to two months after second session using a headache diary

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not explicitly listed here, common side effects from Psilocybin may include nausea, sensory alteration (like seeing bright colors), mood changes (feeling extremely happy or sad), anxiety or panic reactions especially if one has had negative experiences with similar substances before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from two weeks before the first session to two months after second session using a headache diary

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from two weeks before the first session to two months after second session using a headache diary

This trial's timeline: 3 weeks for screening, Varies for treatment, and from two weeks before the first session to two months after second session using a headache diary for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Average intensity of nausea/vomiting

Change in duration of migraine attacks

Change in functional disability

+4 more

Secondary study objectives

Change in blood pressure- Diastolic

Change in blood pressure- Systolic

Change in heart rate

+8 more

Side effects data

From 2021 Phase 2 trial • 95 Patients • NCT02061293

Nausea

Pain

Viral upper resp. tract infection

Back pain

Bronchitis

Diarrhea

Influenza

Headache

Sinus headache

Depressed mood

Depression

Insomnia

Suicidal Ideation

Lower resp. tract congestion

Oropharyngeal pain

Alcohol withdrawal syndrome

Migraine

Thrombocytosis

Constipation

Vomiting

Oedema

Peripheral swelling

Pyrexia

Dermatitis contact

Bronchitis bacterial

Eye infection

Fungal infection

Traumatic lung injury

Hyponatremia

Arthralgia

Musculoskeletal pain

Pain in extremity

Malignant melanoma

Dizziness

Hypoesthesia

Sedation

Anger

Anxiety

Restlessness

Cough

Rhinorrhea

Sinus congestion

Sexual abuse

Endodontic procedure

Mallory-Weiss Syndrom

Anemia

Influenza like Illness

Gingivitis

Arthoscopic surgery

100%

80%

60%

40%

20%

Study treatment Arm

Diphenhydramine

Psilocybin

Trial Design

4Treatment groups

Experimental Treatment

Group I: Psilocybin/PsilocybinExperimental Treatment1 Intervention

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

Group II: Psilocybin/PlaceboExperimental Treatment2 Interventions

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

Group III: Placebo/PsilocybinExperimental Treatment2 Interventions

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

Group IV: Placebo/PlaceboExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Psilocybin

Not yet FDA approved

Placebo

1995

Completed Phase 3

~2670

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for migraine work through various mechanisms. NSAIDs like ibuprofen reduce inflammation and pain by inhibiting cyclooxygenase enzymes. Triptans, such as sumatriptan, target serotonin (5-HT1) receptors to constrict blood vessels and reduce neurogenic inflammation. Preventive treatments include beta blockers (e.g., propranolol) that modulate vascular tone, antidepressants (e.g., amitriptyline) that affect serotonin and norepinephrine levels, and anticonvulsants (e.g., topiramate) that stabilize neuronal activity. Psilocybin, being studied for its potential in migraine treatment, reduces neuroinflammation and modulates serotonin receptors, which could offer new avenues for managing migraine by addressing both inflammation and serotonin pathways. Understanding these mechanisms is crucial for tailoring effective treatments and improving patient outcomes.

Migraine: current therapeutic targets and future avenues.Beyond monotherapy: rational polytherapy in migraine.