Efficacy of Inhaled Cannabis for Acute Migraine Treatment

Study Overview
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Brief Summary
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This crossover study will evaluate 3 different treatments of vaporized cannabis (THC, THC/CBD mix, and CBD) and vaporized placebo cannabis for the acute treatment of migraine.

Detailed Description
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In this double-blind, randomized, crossover trial, subjects will treat 4 separate migraine attacks with 4 different treatments. Inhaled cannabis will be administered using a portable vaporization system (Mighty Medic; Storz & Bickel) based on a validated Storz & Bickel system and using a standardized inhalation approach. Subjects will self-administer inhaled cannabis as early as possible in the course of a migraine (see Procedure), taking 4 puffs of 1) THC, 2) THC/CBD mix, 3) CBD, or 4) placebo. Patients will treat each of the 4 distinct migraine attacks with a different cannabis sample. Outcomes measured will include pain freedom and pain relief as well as presence or absence of photophobia, phonophobia, and nausea at 1 hour, 2 hours (primary outcome), 24 hours, and 48 hours.

Official Title
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Efficacy of Inhaled Cannabis Versus Placebo for the Acute Treatment of Migraine: a Randomized, Double-blind, Placebo-controlled, Crossover Trial

Conditions
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Migraine, Cannabis, THC, CBD

Intervention / Treatment
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* Drug: THC  5%
* Drug: CBD  12%
* Drug: THC  5% and CBD  12%
* Drug: Sham Cannabis


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 21 and ≤ 65 Able to communicate in English Migraine, with or without aura, in its episodic or chronic manifestations, as per the International Headache Society (IHS) classification International Classification of Headache Disorders (ICHD-3) criteria (section 1.1, 1.2, 1.3).(48) Ability to provide informed consent and complete website questionnaires in English Agrees not to use cannabis outside of the study during participation in the study Agrees not to use opioids or barbiturates during participation in the study Agrees not to drive a motor vehicle within 4 hours following last use of inhaled cannabis during participation in the study Exclusion Criteria: Positive urine drug test for THC, barbiturates, opioids, oxycodone, or methadone prior to enrollment Pregnancy Breastfeeding Prisoner Known cognitive impairment Institutionalized Current moderate-severe or severe depression Current or past history of bipolar depression, schizophrenia, or psychosis Current or past history of cannabis, alcohol, opioid, or amphetamine abuse or other substance use disorder at the discretion of the research team Active pulmonary disease class IV heart failure, cirrhosis, or other severe medical illnesses at the discretion of the research team. Allergy or past adverse effects or negative past experiences from cannabis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, Double-blind, Placebo-controlled, Crossover Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THC  5%<br>4 puffs of cannabis flower containing THC  5% administered by vaporizer using Foltin Uniform Puff Procedure for treatment of a moderate-severe migraine attack. The flower is from the United States National Institute on Drug Abuse (NIDA). | Drug: THC  5%<br>* 4 puffs of vaporized flower containing THC  5%<br>* Other names: marijuana;|
| Experimental: THC  5%/CBD  12%<br>4 puffs of cannabis flower containing THC  5% and CBD  12% administered by vaporizer using Foltin Uniform Puff Procedure for treatment of a moderate-severe migraine attack. The flower is from the United States National Institute on Drug Abuse (NIDA). | Drug: THC  5% and CBD  12%<br>* 4 puffs of vaporized flower containing THC  5% and CBD  12%<br>* Other names: hemp;|
| Experimental: CBD  12%<br>4 puffs of cannabis flower containing CBD  12% administered by vaporizer using Foltin Uniform Puff Procedure for treatment of a moderate-severe migraine attack. The flower is from the United States National Institute on Drug Abuse (NIDA). | Drug: CBD  12%<br>* 4 puffs of vaporized flower containing CBD  12%<br>* Other names: hemp;|
| Sham Comparator: Sham Cannabis<br>4 puffs of cannabis flower from which the THC and CBD have been extracted administered by vaporizer using Foltin Uniform Puff Procedure for treatment of a moderate-severe migraine attack. The flower is from the United States National Institute on Drug Abuse (NIDA). | Drug: Sham Cannabis<br>* 4 puffs of vaporized flower from which the THC and CBD have been extracted<br>* Other names: Sham;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Pain Relief at 2 Hours Post-Treatment | Dichotomous endpoint of pain reduction defined as reduction from moderate/severe pain to mild/no pain | 2 Hours Post-Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache pain freedom | Dichotomous endpoint of reduction from moderate/severe pain to no pain | 2 hours | 
| Most bothersome symptom freedom | Dichotomous endpoint of resolution of most bothersome symptom (of photophobia, phonophobia, and nausea) selected at the beginning of the migraine prior to cannabis administration | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Cannabis, THC, CBD