Dose-Ranging Trial of Inhaled Cannabis for Acute Migraine Treatment

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

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.

Study Overview

• Status: Suspended
• Conditions: Migraine; Cannabis; THC
• Intervention / Treatment: Drug: THC ~2.5%; Drug: THC ~5%; Drug: THC ~10%; 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 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• 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

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 4.5 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

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 ~2.5%; Inhalation of cannabis flower containing THC ~2.5%	Drug: THC ~2.5%; Cannabis flower containing THC ~2.5%; Other Names: marijuana; THC; delta 9-tetrahydrocannabinol
Experimental: THC ~5%; Inhalation of cannabis flower containing THC ~5%	Drug: THC ~5%; Cannabis flower containing THC ~5%; Other Names: marijuana; THC; delta 9-tetrahydrocannabinol
Experimental: THC ~10%; Inhalation of cannabis flower containing THC ~10%	Drug: THC ~10%; Cannabis flower containing THC ~5%; Other Names: marijuana; THC; delta 9-tetrahydrocannabinol
Sham Comparator: Sham Cannabis; Inhalation of cannabis flower from which the THC and CBD have been extracted	Drug: Sham Cannabis; Cannabis 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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache pain freedom	Dichotomous outcome of reduction from moderate/severe to no pain	15 minutes, 30 minutes, 1 hour, 1.5 hours, 4 hours, 24 hours, 48 hours
Most bothersome symptom (MBS)	Dichotomous outcome of resolution of MBS (of photophobia, phonophobia, or nausea) selected at the beginning of the migraine prior to cannabis administration	15 minutes, 30 minutes, 1 hour, 1.5 hours, 4 hours, 24 hours, 48 hours
Headache pain relief	Dichotomous outcome of reduction from moderate/severe to mild/no pain	15 minutes, 30 minutes, 1 hour, 1.5 hours, 4 hours, 24 hours, 48 hours
Freedom from photophobia	Dichotomous outcome of resolution of photophobia	15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 24 hours, 48 hours
Freedom from phonophobia	Dichotomous outcome of resolution of phonophobia	15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 24 hours, 48 hours
Freedom from nausea	Dichotomous outcome of resolution of nausea	15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 24 hours, 48 hours
Freedom from vomiting	Dichotomous outcome of whether patient vomited during this migraine attack	At any time over 48 hours
Use of rescue medication	Dichotomous outcome of use of rescue medication	At any time over 48 hours
Sustained pain freedom	Dichotomous outcome of absence of headache pain at 2 hours after dose, with no use of rescue medication and no recurrence of headache pain	24 hours and 48 hours
Sustained most bothersome symptom freedom (MBS)	Dichotomous outcome of absence of MBS at 2 hours after dose, with no use of rescue medication and no recurrence of MBS	24 hours and 48 hours

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Nathaniel M Schuster, MD, Center for Pain Medicine, UC San Diego

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Migraine; Cannabis; THC
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Headache Disorders, Primary; Headache Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Migraine Disorders; Marijuana Abuse; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol; salicylhydroxamic acid; nabiximols; THC 5
• Other Study ID Numbers: 802999

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