Drug Design, Development and Therapy (Aug 2020)
Cannabis Extract CT-921 Has a High Efficacy–Adverse Effect Profile in a Neuropathic Pain Model
Abstract
Elham Rouhollahi, Bernard A MacLeod, Alasdair M Barr, Ernest Puil Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, CanadaCorrespondence: Ernest Puil Tel +1 604 822 5080Fax +1 604 822 6012Email [email protected]: Legalization of cannabis encourages the development of specific cultivars to treat disease such as neuropathic pain. Because of the large number of cultivars, it is necessary to prioritize extracts before proceeding to clinical trials.Purpose: To compare extracts of two unique cannabis cultivars (CT-921, CT-928) for treatment of neuropathic pain induced by constriction of sciatic nerve in mice and to illustrate the use of this animal model to set priority for future trials.Methods: Pain severity was measured by threshold force causing paw withdrawal. Dose–response relationships and time course were determined for intravenously injected extracts of cultivars and vehicle. The doses for allodynia relief were correlated with decreased respiratory rate, temperature and behavioral changes.Results: Effective analgesic dose for 50 and 95% (ED50An and ED95An) was 15, and 29 mg/kg for CT-921 and 0.9 and 4.7 for CT-928. At ED50An, for both extracts, the duration was 120 min. At ED95An, administration of CT-928 significantly decreased respiratory rate while CT-921 did not. CT-928 decreased temperature more than CT-921. CT-928 produced frantic hyperactivity not seen with CT-921. At equivalent analgesic doses, THC was much less in CT-921 than in CT-928 suggesting interactions with components other than THC influenced the analgesia. At equivalent analgesic doses, efficacy-to-adverse effect profile for CT-928 was worse than for CT-921.Conclusion: Both extracts relieved neuropathic pain; however, CT-921 had a better efficacy-to-adverse effect profile, a rational basis for prioritizing cultivars for future clinical evaluation.Keywords: cannabinoid analgesia, neuropathic pain, medical marijuana
