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Neuropharmacology. 2018 Oct 9;144:115-121. doi: 10.1016/j.neuropharm.2018.10.006. [Epub ahead of print]

THC and gabapentin interactions in a mouse neuropathic pain model.

Author information

1
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, Royal North Shore Hospital, The University of Sydney, NSW, Australia.
2
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, Royal North Shore Hospital, The University of Sydney, NSW, Australia. Electronic address: chris.vaughan@sydney.edu.au.

Abstract

Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-line neuropathic pain medication gabapentin. This was done using the chronic constriction injury (CCI) model of neuropathic pain in C57BL6 mice. At 8 days post-CCI nerve injury, acute systemic administration of gabapentin produced a dose-dependent decrease in CCI-induced mechanical and cold allodynia, and increased motor incoordination. Coadministration of THC and gabapentin in a fixed-ratio dose-dependently reduced mechanical and cold allodynia, and produced all the side-effects observed for THC, including motor incoordination, catalepsy and sedation. Isobolographic analysis indicated that the ED50 for the THC:gabapentin induced reduction in allodynia was 1.7 times less than that predicted for an additive interaction. The therapeutic window of combination THC:gabapentin was greater than that for THC alone. These findings indicate that gabapentin synergistically enhances the anti-allodynic actions of THC and improves its therapeutic window. Thus, THC may represent a potential adjuvant for neuropathic pain medications such as gabapentin.

KEYWORDS:

Cannabinoid; Gabapentin; Isobolograph; Neuropathic pain; Synergy; Tetrahydrocannabinol

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