Cannabis-Based Medicines and Pain: A Review of Potential Synergistic and Entourage Effects

Abstract

The recent legalization of medicinal cannabis in several jurisdictions has spurred the development of therapeutic formulations for chronic pain. Unlike pure delta-9-tetrahydrocannabinol (THC), full-spectrum products contain naturally occurring cannabinoids and have been reported to show improved efficacy or tolerability, attributed to synergy between cannabinoids and other components in the cannabis plant. Although ‘synergy’ indicates that two or more active compounds may produce an additive or combined effect greater than their individual analgesic effect, potentiation of the biological effect of a compound by related but inactive compounds, in combination, was termed the ‘entourage effect’. Here, we review current evidence for potential synergistic and entourage effects of cannabinoids in pain relief. However, definitive clinical trials and in vitro functional studies are still required.

Lay abstract

Cannabis-based medicines have been used for millennia, and recent studies have identified their main constituents for pain relief, delta-9-tetrahydrocannabinol and cannabidiol (CBD). However, cannabis contains hundreds of other potentially active compounds, and their combined effects may underlie the reported preference of some patients for cannabinoid extracts, rather than pure delta-9-tetrahydrocannabinol. Further, cannabis-based drugs may interact with endocannabinoids, which are produced within the body and are related to the compounds found in cannabis. We have reviewed the evidence for cannabinoids in combination, and with other drugs, for pain relief. Although there is some evidence for an advantage of combinations, basic research and clinical studies are still required.

Keywords::

• cannabinoids
• entourage effect
• neuropathic
• pain
• terpenoids

Author contributions

MH Sodergren and P Anand proposed the review, U Anand drafted the manuscript and all authors contributed to and approved the final manuscript.

Financial & competing interests disclosure

Funded by EMMAC Life Sciences Ltd. Barbara Pacchetti reports personal fees from EMMAC Life Sciences, outside the submitted work. M Sodergren reports consultancy for Emmac Life Sciences, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Funded by EMMAC Life Sciences Ltd. Barbara Pacchetti reports personal fees from EMMAC Life Sciences, outside the submitted work. M Sodergren reports consultancy for Emmac Life Sciences, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.