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.
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Authors | Nicholas Atwal, Sherelle L Casey, Vanessa A Mitchell, Christopher W Vaughan |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 144
Pg. 115-121
(01 2019)
ISSN: 1873-7064 [Electronic] England |
PMID | 30312630
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 Elsevier Ltd. All rights reserved. |
Chemical References |
- Analgesics
- Gabapentin
- Dronabinol
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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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