Cannabis Extract CT-921 Has a High Efficacy–Adverse Effect Profile in a Neuropathic Pain Model

Abstract

Background

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% (ED_50An and ED_95An) was 15, and 29 mg/kg for CT-921 and 0.9 and 4.7 for CT-928. At ED_50An, for both extracts, the duration was 120 min. At ED_95An, 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

Acknowledgments

The authors thank Ying Dong for technical assistance and Dr Andrew Hegle for preparing the cultivar extracts and HPLC analysis and Dr Richard Wall for his comments on the analysis.

Disclosure

Dr Elham Rouhollahi had Postdoctoral Fellowship supported by the MITACS Accelerate Program (#IT10243), University of British Columbia, jointly with Cannevert Therapeutics Ltd.

Dr MacLeod reports being a colleague and friend of Dr E Puil who has recorded a conflict of interest. Dr Bernard A. MacLeod is a minor shareholder in Veritas Pharma Inc which is research-based cannabis company.

Dr Barr reports grants and personal fees from Cannevert Therapeutics, grants from Global Cannabis Applications Corp, Emerald Health Therapeutics, and Entourage Biosciences, and personal fees from Medipure Pharmaceuticals and Vitality Biopharma, outside the submitted work; and has been a scientific advisor to Emerald Health Therapeutics, Cannevert Therapeutics, Global Cannabis Applications Corp, Medipure Pharmaceuticals, Vitality Biopharma and Oakum Cannabis Corp. Dr Puil reports personal fees from Cannevert Therapeutics Ltd, during the conduct of the study; has been a consultant with Cannevert Therapeutics Ltd, and is a minor shareholder in Veritas Pharma Inc., a research-based cannabis company. The authors report no other potential conflicts of interest for this work.