Anti-migraine effect of ∆9-tetrahydrocannabinol in the female rat

Abstract

Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat. Microinjection of the TRPA1 agonist allyl isothiocyanate (AITC) onto the dura mater produced migraine-like pain for 3h as measured by depression of home cage wheel running. Concurrent systemic administration of 0.32 but not 0.1mg/kg of THC prevented AITC-induced depression of wheel running. However, 0.32mg/kg was ineffective when administered 90min after AITC. Administration of a higher dose of THC (1.0mg/kg) depressed wheel running whether rats were injected with AITC or not. Administration of a CB, but not a CB, receptor antagonist attenuated the anti-migraine effect of THC. These data suggest that: 1) THC reduces migraine-like pain when administered at the right dose (0.32mg/kg) and time (immediately after AITC); 2) THC's anti-migraine effect is mediated by CB receptors; and 3) Wheel running is an effective method to assess migraine treatments because only treatments producing antinociception without disruptive side effects will restore normal activity. These findings support anecdotal evidence for the use of cannabinoids as a treatment for migraine in humans and implicate the CB receptor as a therapeutic target for migraine.

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

“…We divided our sample into non-responders (i.e., <50%; n = 56, 39%) and responders (i.e., ≥50%; responders n = 89, 61%) based on their reduction of monthly frequency of migraine attacks from pre-MC to the current post-MC period. No significant difference was found in monthly migraine attack frequency prior to MC treatment initiation (15 (7.8-30) and 14 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), respectively) (0.06 95% CI (−0.27 to 0.41); p = 0.71), strengthening the division methodology, as both subgroups started from a similar standpoint. Moreover, there were no significant differences between the subgroups in any of the current migraine features, including the age of migraine diagnosis, average duration of migraine attacks, activity-induced aggravation of migraine, unilateral migraine, bilateral migraine, presence of aura prior to migraine, nausea during migraine, or phono-or photophobia during migraine (Table 2).…”

“…Furthermore, reduced levels of AEA degrading enzymes were found in platelets of patients with chronic migraine [ 12 ]. In animal models of migraine, administration of AEA diminished hyperalgesic behavior [ 13 ], and the plant-derived (-)-Δ 9 - trans -tetrahydrocannabinol (THC) showed anti-migraine effects in rats [ 14 ]. Whilst the available evidence suggests involvement of the endocannabinoid system and a potential for MC treatment to be therapeutic in migraine, more research is required to demonstrate the efficacy parameters of MC treatment for migraine.…”

Emerging Role of (Endo)Cannabinoids in Migraine

“…As the TRPV1 channels can also bind eCB AEA ( Chakrabarti et al, 2015 ), this may result in unwanted pro-nociceptive action of cannabinoids, causing neuroinflammation in meninges. This complexity may explain why increased doses of cannabinoids diminished their analgesic effect ( Kandasamy et al, 2018 ). It further creates an incentive for development of new synthetic CBs with minimal activity on TRPV1 receptors, or specific MAGL inhibitors, which, apart from triggering the accumulation of anti-nociceptive 2-AG, can decrease the level of the pro-nociceptive arachidonic acid (AA) and reduce pain ( Aaltonen et al, 2016 ).…”

“…In a study of the cannabis use for self-medication in Germany, Austria and Switzerland, 10.2% of patients reported using it for migraine headache symptoms ( Kandasamy et al, 2018 ). Another group found that the self-treatment outcome was highly variable, with low doses tending to alleviate migraine while higher doses even triggering headaches ( Lu and Anderson, 2017 ).…”

“…One of the main problems arising from the long-term usage of cannabis is the physical reliance on the pCBs, mainly THC. Moreover, there is evidence that patients can develop tolerance for pCBs ( Kandasamy et al, 2018 ). Carelessly establishing a reliance on any form of medication may carry more ill effects on the patient’s mentality, and may even lead to weakening or loss of pain relief.…”