Efficacy of Inhaled Cannabis for Acute Migraine Treatment

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine; Cannabis; CBD; THC
• Intervention / Treatment: Drug: THC ~5%; Drug: THC ~5% and CBD ~12%; Drug: CBD ~12%; Drug: Sham Cannabis

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 Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Center for Pain Medicine, UC San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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: marijuana; THC; delta 9-tetrahydrocannabinol
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: cannabidiol; CBD; marijuana; THC; delta 9-tetrahydrocannabinol; 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: cannabidiol; CBD; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache pain relief	Dichotomous endpoint of reduction from moderate/severe pain to mild/no pain	1 hour, 24 hours, 48 hours
Headache pain freedom	Dichotomous endpoint of reduction from moderate/severe pain to no pain	1 hour, 24 hours, 48 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	1 hour, 24 hours, 48 hours
Freedom from photophobia	Dichotomous endpoint of resolution of photophobia	1 hour, 2 hours, 24 hours, 48 hours
Freedom from phonophobia	Dichotomous endpoint of resolution of phonophobia	1 hour, 2 hours, 24 hours, 48 hours
Freedom from nausea	Dichotomous endpoint of resolution of nausea	1 hour, 2 hours, 24 hours, 48 hours
Freedom from vomiting	Dichotomous endpoint of whether patient vomited during this migraine attack	At any time over 48 hours
Use of rescue medication	Dichotomous endpoint of use of rescue medication	At any time over 48 hours
Sustained pain freedom	Dichotomous endpoint of absence of headache pain at 2 hours after dose, with no use of rescue medication and no relapse of headache pain	24 hours and 48 hours
Sustained most bothersome symptom freedom	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	24 hours and 48 hours

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Migraine Research Foundation
• Investigators: Principal Investigator: Nathaniel M Schuster, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Migraine; CBD; Cannabis; THC
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Substance-Related Disorders; Headache Disorders, Primary; Headache Disorders; Marijuana Abuse; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Cannabidiol
• Other Study ID Numbers: 2018 MRF Impact Award

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.
• IPD Sharing Time Frame: Beginning 1 year and ending 5 years after article publication
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No