Efficacy of Inhaled Cannabis for Acute Migraine Treatment

Sponsor

University of California, San Diego (Other)

Overall Status

Recruiting

CT.gov ID

NCT04360044

Collaborator

Migraine Research Foundation (Other)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine Cannabis THC CBD	Drug: THC ~5% Drug: CBD ~12% Drug: THC ~5% and CBD ~12% Drug: Sham Cannabis	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized, Double-blind, Placebo-controlled, Crossover TrialRandomized, Double-blind, Placebo-controlled, Crossover Trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Each participant will have an identification number and randomization of drug sequence allocation will be performed a priori using a random number generator by the study pharmacist. The 4 treatments will be identically encapsulated by the study pharmacist using Storz & Bickel filling set. The study pharmacist will place the capsules in identical sealed plastic bags labeled "Migraine 1" through "Migraine 4."

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 20, 2020

Anticipated Primary Completion Date :

Nov 20, 2023

Anticipated Study Completion Date :

Nov 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: THC ~5% 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% 4 puffs of vaporized flower containing THC ~5% Other Names: THC delta 9-tetrahydrocannabinol marijuana
Experimental: THC ~5%/CBD ~12% 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% 4 puffs of vaporized flower containing THC ~5% and CBD ~12% Other Names: THC CBD delta 9-tetrahydrocannabinol cannabidiol marijuana hemp
Experimental: CBD ~12% 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% 4 puffs of vaporized flower containing CBD ~12% Other Names: CBD cannabidiol hemp
Sham Comparator: Sham Cannabis 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 4 puffs of vaporized flower from which the THC and CBD have been extracted Other Names: Placebo Sham

Outcome Measures

Primary Outcome Measures

Headache Pain Relief at 2 Hours Post-Treatment [2 Hours Post-Treatment]
Dichotomous endpoint of pain reduction defined as reduction from moderate/severe pain to mild/no pain

Secondary Outcome Measures

Headache pain freedom [2 hours]
Dichotomous endpoint of reduction from moderate/severe pain to no pain
Most bothersome symptom freedom [2 hours]
Dichotomous endpoint of resolution of most bothersome symptom (of photophobia, phonophobia, and nausea) selected at the beginning of the migraine prior to cannabis administration

Other Outcome Measures

Headache pain relief [1 hour, 24 hours, 48 hours]
Dichotomous endpoint of reduction from moderate/severe pain to mild/no pain
Headache pain freedom [1 hour, 24 hours, 48 hours]
Dichotomous endpoint of reduction from moderate/severe pain to no pain
Most bothersome symptom freedom [1 hour, 24 hours, 48 hours]
Dichotomous endpoint of resolution of most bothersome symptom (of photophobia, phonophobia, and nausea) selected at the beginning of the migraine prior to cannabis administration
Freedom from photophobia [1 hour, 2 hours, 24 hours, 48 hours]
Dichotomous endpoint of resolution of photophobia
Freedom from phonophobia [1 hour, 2 hours, 24 hours, 48 hours]
Dichotomous endpoint of resolution of phonophobia
Freedom from nausea [1 hour, 2 hours, 24 hours, 48 hours]
Dichotomous endpoint of resolution of nausea
Freedom from vomiting [At any time over 48 hours]
Dichotomous endpoint of whether patient vomited during this migraine attack
Use of rescue medication [At any time over 48 hours]
Dichotomous endpoint of use of rescue medication
Sustained pain freedom [24 hours and 48 hours]
Dichotomous endpoint of absence of headache pain at 2 hours after dose, with no use of rescue medication and no relapse of headache pain
Sustained most bothersome symptom freedom [24 hours and 48 hours]
Dichotomous endpoint of absence of most bothersome symptom at 2 hours afer dose, with no use of rescue medication and no relapse of most bothersome symptom

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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