Efficacy of Inhaled Cannabis for Acute Migraine Treatment

• ClinicalTrials.gov Identifier: NCT04360044
• Recruitment Status: Completed
• First Posted: April 24, 2020
• Last Update Posted: February 28, 2023
• Sponsor: University of California, San Diego
• Collaborator: Migraine Research Foundation
• Information provided by (Responsible Party): Nathaniel Schuster, University of California, San Diego

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 (Clinical Trial)
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, 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: November 20, 2020
• Actual Primary Completion Date: February 23, 2023
• Actual Study Completion Date: February 23, 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 :

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

Secondary Outcome Measures :

1. Headache pain freedom [ Time Frame: 2 hours ]
   Dichotomous endpoint of reduction from moderate/severe pain to no pain
2. Most bothersome symptom freedom [ Time Frame: 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:

1. Headache pain relief [ Time Frame: 1 hour, 24 hours, 48 hours ]
   Dichotomous endpoint of reduction from moderate/severe pain to mild/no pain
2. Headache pain freedom [ Time Frame: 1 hour, 24 hours, 48 hours ]
   Dichotomous endpoint of reduction from moderate/severe pain to no pain
3. Most bothersome symptom freedom [ Time Frame: 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
4. Freedom from photophobia [ Time Frame: 1 hour, 2 hours, 24 hours, 48 hours ]
   Dichotomous endpoint of resolution of photophobia
5. Freedom from phonophobia [ Time Frame: 1 hour, 2 hours, 24 hours, 48 hours ]
   Dichotomous endpoint of resolution of phonophobia
6. Freedom from nausea [ Time Frame: 1 hour, 2 hours, 24 hours, 48 hours ]
   Dichotomous endpoint of resolution of nausea
7. Freedom from vomiting [ Time Frame: At any time over 48 hours ]
   Dichotomous endpoint of whether patient vomited during this migraine attack
8. Use of rescue medication [ Time Frame: At any time over 48 hours ]
   Dichotomous endpoint of use of rescue medication
9. Sustained pain freedom [ Time Frame: 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
10. Sustained most bothersome symptom freedom [ Time Frame: 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

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

Criteria

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

Contacts and Locations

Locations

United States, California

Center for Pain Medicine, UC San Diego

La Jolla, California, United States, 92037

Sponsors and Collaborators

University of California, San Diego

Migraine Research Foundation

Investigators

• Principal Investigator: Nathaniel M Schuster, MD; University of California, San Diego

More Information

• Responsible Party: Nathaniel Schuster, Assistant Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT04360044
• Other Study ID Numbers: 2018 MRF Impact Award
• First Posted: April 24, 2020
• Last Update Posted: February 28, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Beginning 1 year and ending 5 years after article publication
• Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nathaniel Schuster, University of California, San Diego:

Migraine; Cannabis; THC; CBD

Additional relevant MeSH terms:

Migraine Disorders; Marijuana Abuse; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Dronabinol; Cannabidiol; Anticonvulsants; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists