Phytocannabinoids, primarily cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), have garnered scientific interest for migraine management due to their effects on the endocannabinoid system, which regulates pain, inflammation, and neuronal activity. Historically, cannabis-based preparations were used for headache relief in various cultures, but modern scientific evidence remains limited and mixed. Several observational studies and surveys suggest that some migraine sufferers experience reduced frequency and intensity of attacks with cannabis use. For instance, a 2016 retrospective study published in Pharmacotherapy found migraine frequency dropped from 10.4 to 4.6 headaches per month among patients using medical marijuana. However, these studies often have methodological limitations, such as small sample sizes, lack of placebo controls, and reliance on self-reported outcomes.

Randomized controlled trials are scarce. A 2021 systematic review (Frontiers in Neurology) concluded that while some patients benefit, the evidence for phytocannabinoid efficacy and safety in migraine is insufficient for clinical recommendations. Potential mechanisms include modulation of serotonin receptors, inhibition of pain pathways, and anti-inflammatory effects, but these are mainly supported by animal and preclinical studies. Side effects, legal status, and individual variability in response further complicate recommendations. In summary, while there is increasing scientific interest and some preliminary support, robust clinical validation for phytocannabinoids in migraine treatment is lacking, justifying a modest evidence rating.