1. Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

Brain Sci. 2020, 10(6), 360



Migraine is currently not indicated for a MC treatment license in Israel. Nevertheless, in some cases it falls under the approved chronic neuropathic non‐cancer pain indication, making it possible to study migraine more extensively. In this study, we demonstrated that patients responding to MC treatment also reported less disability and lower conventional anti‐migraine medications intake.  Additionally, we highlighted the importance of recognizing and analyzing the doses of the pronounced MC constituents consumed by patients, which in turn allowed us to better understand MC treatment associations with reduction in migraine attacks frequency. We also identified specific cultivars that contain the favorable ratio of compounds that were associated with migraine frequency reduction. These results might shed light on the beneficial effects of MC on migraine and motivate future studies to utilize a cannabis cultivar with the specific phytocannabinoids mentioned here. This additional work could validate our results and possibly support making migraine an approved indication for MC license in Israel.


2. Emerging Role of (Endo)Cannabinoids in Migraine

Front. Pharmacol., 24 April 2018




In summary, cannabinoids – due to their anticonvulsive, analgesic, antiemetic, and anti-inflammatory effects – present a promising class of compounds for both acute and prophylactic treatment of migraine pain. In view of the rapidly unfolding changes in the legal status of cannabis, research on (endo)cannabinoids has become pertinent once again. Formal approval of a cannabinoid-based drug for other pathologies opens a possibility for repurposing these agents also to treat migraine. The abundance of CB1 receptors in the brain makes them an attractive target for treatment of migraine via blocking not only peripheral but also the central nociceptive traffic and reducing the pathologically enhanced cortical excitability predisposing to CSD. CB2 receptors in immune cells can be targeted to reduce the inflammatory component associated with severe forms of migraine. Exogenous compounds lacking the unwanted peripheral pro-nociceptive component or eCBs generated via inhibited degradation pathways and combined with other supportive agents are most desirable for this aim. Moreover, primary stratification of patients to identify and predict the effectiveness of cannabinoid treatment can greatly improve the efficiency of this approach.

3. Endocannabinoids in Chronic Migraine: CSF Findings Suggest a System Failure

Neuropsychopharmacology, 32 (6), 1384-90 Jun 2007




Reduced levels of AEA (anandamide) in the CSF of Chronic Migraine (CM) and PCM+PAOH (probable CM and probable analgesic-overuse headache) patients may reflect an impairment of the endocannabinoid system in these patients, which may contribute to chronic head pain and seem to be related to increased CGRP (Calcitonin gene-related peptide) and NO (nitric oxide) production. These findings support the potential role of the cannabinoid (CB)1 receptor as a possible therapeutic target in CM.

4. Endocannabinoid System and Migraine Pain: An Update

Front Neurosci. 2018; 12: 172




The human data and preclinical studies reviewed here confirm the importance of FAAH (fatty acid amide hydrolase)-regulated AEA (anandamide) signaling in the processing of nociceptive signals outside the CNS (Greco et al., 2010a; Piomelli and Sasso, 2014) and specifically point to peripheral FAAH inhibition as a possible therapeutic opportunity for migraine pain. Future experiments should be aimed at unlocking the precise cellular mechanisms and neural circuits through which peripheral FAAH blockade exerts its analgesic effects in migraine pain, further exploring the ground for potential clinical trials.

5. Short- and Long-Term Effects of Cannabis on Headache and Migraine

The Journal of Pain, Vol 00, No 00 (), 2019: pp 1−9




The present study indicates that inhaled cannabis reduces headache and migraine severity ratings by approximately 50%. Repeated use of cannabis is associated with tolerance to its effects, making tolerance a risk factor for the use of cannabis to treat headache and migraine. However, cannabis does not lead to the medication overuse headache that is associated with other conventional treatments, meaning that use of cannabis does not make headaches or migraines worse over time. Future double-blind, placebo controlled clinical trials are warranted and will help to rule out placebo effects and provide a more controlled examination of dose, type of cannabis, THC, CBD, and THC x CBD interactions.