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THC and gabapentin interactions in a mouse neuropathic pain model.

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.
AuthorsNicholas Atwal, Sherelle L Casey, Vanessa A Mitchell, Christopher W Vaughan
JournalNeuropharmacology (Neuropharmacology) Vol. 144 Pg. 115-121 (01 2019) ISSN: 1873-7064 [Electronic] England
PMID30312630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Ltd. All rights reserved.
Chemical References
  • Analgesics
  • Gabapentin
  • Dronabinol
Topics
  • Analgesics (adverse effects, pharmacology)
  • Animals
  • Cold Temperature
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dronabinol (adverse effects, pharmacology)
  • Drug Synergism
  • Gabapentin (adverse effects, pharmacology)
  • Hyperalgesia (drug therapy)
  • Male
  • Mice, Inbred C57BL
  • Motor Activity (drug effects)
  • Neuralgia (drug therapy)
  • Sciatic Nerve (injuries)
  • Time Factors
  • Touch

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