Effect of Cannabinoid Receptor Activation on Spreading Depression

Objective(s) The objective of this study was to evaluate the effect of cannabinoid on cortical spreading depression (CSD) in rat brain. Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine. CSD is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. Materials and Methods The effects of Delta۹-tetrahydrocannabinol (THC), as well as, cannabinoid CB۱ and CB۲ receptor agonists on CSD in rat neocortical slices were investigated. Furthermore, the effect of cannabinoid CB۱ agonist was tested on field excitatory postsynaptic potentials (fEPSP) and long-term potentiation (LTP). Results HC (۱-۲۰ microM) dose dependently suppressed CSD amplitude, duration, and propagation velocity. Cannabinoid CB۱ agonist, WIN ۵۵,۲۱۲-۲ mesylate (۱-۱۰ microM), also significantly suppressed all characteristic features of CSD. However, cannabinoid CB۲ agonist, JWH-۱۳۳ (۱-۲۰ microM), did not affect CSD. FEPSP and induction of LTP were suppressed by application of WIN۵۵۲۱۲-۲. Conclusion Suppression of CSD by activation of CB۱ receptors points to the potential therapeutic effects of cannabinoids in migraine with aura. More research is needed before we know whether cannabinoids may be helpful in treating migraine pain.

Keywords:

Endocannabinoid , Headache , Marijuana , Migraine , Pharmacotherapy , Synaptic transmission