Dose-Ranging Trial of Inhaled Cannabis for Acute Migraine Treatment

Study Overview
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Brief Summary
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This pilot crossover study will evaluate 3 different potencies of inhaled cannabis (2.5%, 5%, and 10%) and inhaled 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 system. Subjects will self-administer inhaled cannabis as early as possible in the course of a migraine, taking 4 puffs of 1) THC 2.5%, 2) THC 5%, 3) THC 10%, or 4) placebo. Patients will treat each of the 4 distinct migraine attacks with a different cannabis sample. Outcomes measured will include pain freedom, most bothersome symptom (MBS), and pain relief as well as presence or absence of photophobia, phonophobia, and nausea at 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 24 hours, and 48 hours.

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

Conditions
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Migraine, Cannabis, THC

Intervention / Treatment
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* Drug: THC  2.5%
* Drug: THC  5%
* Drug: THC  10%
* 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 4.5 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 to 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, Dose-ranging Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THC  2.5%<br>Inhalation of cannabis flower containing THC  2.5% | Drug: THC  2.5%<br>* Cannabis flower containing THC  2.5%<br>* Other names: marijuana;|
| Experimental: THC  5%<br>Inhalation of cannabis flower containing THC  5% | Drug: THC  5%<br>* Cannabis flower containing THC  5%<br>* Other names: marijuana;|
| Experimental: THC  10%<br>Inhalation of cannabis flower containing THC  10% | Drug: THC  10%<br>* Cannabis flower containing THC  5%<br>* Other names: marijuana;|
| Sham Comparator: Sham Cannabis<br>Inhalation of cannabis flower from which the THC and CBD have been extracted | Drug: Sham Cannabis<br>* Cannabis 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 Freedom at 2 Hour Post-Treatment | Dichotomous outcome of pain freedom defined as reduction from moderate/severe pain to no pain | 2 Hours Post-Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Most Bothersome Symptom (MBS) Freedom at 2 Hours Post-Treatment | Dichotomous outcome of resolution of most bothersome symptom (of photophobia, phonophobia, or nausea) selected at the beginning of the migraine prior to cannabis administration | 2 Hours Post-Treatment | 
| Headache Pain Relief at 2 Hours Post-Treatment | Dichotomous outcome of pain reduction defined as reduction from moderate/severe pain to mild/no pain | 2 Hours Post-Treatment | 

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