THC and gabapentin interactions in a mouse neuropathic pain model

Neuropharmacology. 2019 Jan;144:115-121. doi: 10.1016/j.neuropharm.2018.10.006. Epub 2018 Oct 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / pharmacology*
  • Animals
  • Cold Temperature
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dronabinol / adverse effects
  • Dronabinol / pharmacology*
  • Drug Synergism
  • Gabapentin / adverse effects
  • Gabapentin / pharmacology*
  • Hyperalgesia / drug therapy*
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuralgia / drug therapy*
  • Sciatic Nerve / injuries
  • Time Factors
  • Touch

Substances

  • Analgesics
  • Gabapentin
  • Dronabinol