Vaporized Cannabis May Have a Role in Acute Migraine Treatment

Adults with migraine who used vaporized cannabis in a combined THC-CBD form showed significant improvement in pain and freedom from migraine symptoms after 2 hours compared to those who used a placebo, based on new data from more than 200 migraine attacks.

Although data from previous studies have suggested a role for cannabinoids in migraine treatment, randomized clinical trials to show the efficacy of cannabinoids for acute migraine have been lacking, said Nathaniel Schuster, MD, associate professor of anesthesiology, University of California, San Diego, in a presentation at the annual scientific meeting of the American Headache Society.

“Many people with migraine are self-treating with cannabinoids, but there hadn’t previously been a placebo-controlled study evaluating the efficacy of this common practice,” Dr. Schuster told MedCentral.

In the new study, adults with migraine were randomized to self-treatment of up to four separate migraine attacks, one each with four different methods:

• vaporized 6% Δ9-tetrahydrocannabinol (THC-dominant)

• 11% cannabidiol (CBD-dominant)

• a combination of 6% THC plus 11% CBD (THC-CBD)

• and placebo cannabis flower

The dosage was four puffs within the first 4 hours of a migraine attack, and the period between each treated attack was 1 week or more. The primary endpoint was pain relief, and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, assessed at 2 hours after vaporization use. After the 2-hour assessment, participants could use rescue medication if needed, but no additional cannabis.

The study population included 92 adults with migraine who were enrolled at a single center between November 2020 and February 2023; complete follow-up data were available for 73 participants and a total of 247 treated migraine attacks. The median age of the patients was 41 years, 83% were female, and 77% were white. Approximately one-third of the participants reported never having used cannabis.

Overall, the THC-CBD combination showed the greatest superiority over placebo, with 67.2% of patients reporting pain relief at 2 hours, compared to 46.6% with the placebo (odds ratio 2.85, P=0.016).

The secondary outcome of pain freedom also was significantly higher with the THC-CBD combination after 2 hours compared to placebo (34.5% vs. 15.5%, OR 3.30, P = 0.017) as was MBS freedom (60.3% vs. 34.5%, OR 3.32, P=0.005). Both pain freedom and MBS freedom were sustained at 24 hours and 48 hours compared to placebo.

Compared to placebo, the CBD-dominant option was not superior for pain relief, pain freedom, or MBS freedom at 2 hours, and the THC-dominant option was superior to placebo for pain relief only (68.9% vs. 46.6%, OR 3.14, P=0.008).

The THC-CBD combination was superior to placebo for relieving both photophobia and phonophobia associated with migraine attacks, but not nausea. No serious adverse events were reported during the study.

Low-Dose THC May Offer Enough Migraine Relief

“This was the first study of its kind, so we really didn’t know what to expect,” Dr. Schuster said. “The evidence from retrospective studies and survey studies prior to this study suggested that cannabinoids might provide pain relief, but not pain freedom, but this study suggests that over 30% of patients may receive pain freedom at 2 hours from vaporized cannabis containing THC-CBD.”

Clinicians can educate patients who may be self-treating their migraines with cannabinoids about the potential benefit achieved from relatively low doses; patients need not feel they are “high” to benefit, explained Dr. Schuster. However, cost may be a barrier for some individuals, as cannabis is not covered by insurance, he added.

Cannabis-Based Pain Management on the Rise

Previous research shows that approximately one-third of medical cannabis users report cannabis use for management of headaches and/or migraines, said Jason W. Busse, DC, PhD, a professor of anesthesia at McMaster University, Ontario, Canada.

“Recent systematic reviews of observational studies have suggested that cannabis is effective for reducing migraines,” he told MedCentral, but data from randomized trials are lacking, he said. “To my knowledge, this is the first randomized controlled trial that has explored the effectiveness of cannabis for migraine headaches,” said Dr. Busse, who was not involved in the study.

The current study showed evidence for large non-specific effects, and patients also experienced symptom relief with the placebo cannabis, he said. “This is consistent with other cannabis trials and highlights the importance of well-controlled, blinded, randomized trials to establish effectiveness.”

For individuals with migraine who do not find sufficient relief with conventional approaches such as over-the-counter pain relievers, prescription medications, mind-body therapies, and psychotherapy, the current study supports vaporized cannabis as a potential option, Dr. Busse said.

“The finding that CBD was not more effective than placebo is consistent with some prior trials of chronic pain; however, other studies have found CBD may have anti-inflammatory properties and may be helpful for reducing symptoms of neuropathic pain that could suggest a role for CBD in some forms of pain,” Dr. Busse added.

Inhaled Cannabis and Pulmonary Risk

“Some people living with chronic pain are disinclined to use inhaled forms of cannabis due to concerns about pulmonary harms,” Dr. Busse told MedCentral. “However, inhaled cannabis has a much faster onset of action compared to ingested forms (minutes vs. 1 to 2 hours), which is important in the management of acute migraine attacks,” he explained. “As with other management options for chronic pain, patients should be provided with the evidence for both benefits and harms of vaporized cannabis and supported to make a decision that reflects their values and preferences.”

Other considerations include the legal availability of therapeutic cannabis, cost, stigma, and challenges of finding a healthcare provider to authorize cannabis for medical use.

Although the current study findings are promising, replication in a larger group is needed, Dr. Busse told MedCentral. “The effects of inhaled cannabis peak within 30 minutes and tend to last no more than 6 hours; future trials might explore the effectiveness of allowing patients the option to re-administer cannabis,” he said. Since chronic migraines require ongoing management, evidence on long-term benefits and harms of cannabis use is an important area of research, he added.

Disclosures: The study was funded by the Migraine Research Foundation.

Dr. Schuster reported serving as a consultant for Schedule 1 Therapeutics and as a member of the advisory board for Vectura Fertin.

Dr. Busse reported serving as associate director for the Michael G. DeGroote Centre for Medicinal Cannabis Research and receiving government grants to study the effects of cannabis on chronic pain.