期刊
PAIN
卷 158, 期 12, 页码 2452-2460出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000001051
关键词
Cannabis; Neuropathic pain model; Phytocannabinoid; Synergy; Receptor
资金
- Lambert Initiative (University of Sydney)
- Australian Pain Society
- Australian Pain Relief Association Seqirus scholarship
Cannabis and its psychoactive constituent Delta 9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain, however, this is hampered by their side effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy, and sedation. Cannabidiol produced a lesser dose-dependent reduction in allodynia, but did not produce the cannabinoid side effects. When co-administered in a fixed ratio, THC and CBD produced a biphasic dose-dependent reduction in allodynia. At low doses, the THC: CBD combination displayed a 200-fold increase in anti-allodynic potency, but had lower efficacy compared with that predicted for an additive drug interaction. By contrast, high THC: CBD doses had lower potency, but greater anti-allodynic efficacy compared with that predicted for an additive interaction. Only the high dose THC: CBD anti-allodynia was associated with cannabinoid side effects and these were similar to those of THC alone. Unlike THC, the low dose THC: CBD anti-allodynia was not cannabinoid receptor mediated. These findings demonstrate that CBD synergistically enhances the pain-relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side effects. This suggests that low dose THC: CBD combination treatment has potential in the treatment of neuropathic pain.
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