In 1998, a group of researchers proposed a hypothesis known as the Entourage Effect, in which a multitude of the compounds found in cannabis can synergistically work together based on the fact that these effects were also seen in the synergism properties associated with our own endocannabinoids. However, after 26 years, this hypothesis has never been supported clinically, meaning that while we have a lot of proposals and a lot of research suggesting interactions, we've never actually applied it to a patient population in a real-life setting. In this episode of Cannabis Nurse Truths, we examine this hypothesis known as the Entourage Effect, because while there is a lot of research suggesting this phenomenon is occurring, meaning that something is happening - we just don't know what it is - critics state that there is not enough evidence to support this in science. Their claim is that it is really just a marketing tool to help promote cannabis products. So which is it - an actual phenomenon that explains why cannabis compounds work together to heal the body, or is it just a gimmick to sell more weed? Bottom line; cannabis contains over 500 compounds that all have beneficial physiological effects, so does it really matter which is true? EPISODE RESOURCES Al-Khazaleh, A.K., Zhou, X., Bhuyan, D.J., Münch, G.W., Al-Dalabeeh, E.A., Jaye, K., & Chang, D. (2024). The neurotherapeutic arsenal in Cannabis sativa: Insights into anti-neuroinflammatory and neuroprotective activity and potential entourage effects. Molecules, 29(2), Article 2. https://doi.org/10.3390/molecules29020410 Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M.-H., Vogel, Z., Bisogno, T., De Petrocellis, L., Di Marzo, V., & Mechoulam, R. (1998). An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology, 353(1), 23–31. https://doi.org/10.1016/S0014-2999(98)00392-6 Blasco-Benito, S., Seijo-Vila, M., Caro-Villalobos, M., Tundidor, I., Andradas, C., García-Taboada, E., Wade, J., Smith, S., Guzmán, M., Pérez-Gómez, E., Gordon, M., & Sánchez, C. (2018). Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer. Biochemical Pharmacology, 157, 285–293. https://doi.org/10.1016/j.bcp.2018.06.025 Boggs, D.L., Nguyen, J.D., Morgenson, D., Taffe, M.A., & Ranganathan, M. (2018). Clinical and preclinical evidence for functional interactions of cannabidiol and Δ9-tetrahydrocannabinol. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 43(1), 142–154. https://doi.org/10.1038/npp.2017.209 Christensen, C., Rose, M., Cornett, C., & Allesø, M. (2023). Decoding the postulated entourage effect of medicinal cannabis: What it is and what it isn’t. Biomedicines, 11(8), 2323. https://doi.org/10.3390/biomedicines11082323 Cogan, P.S. (2020). The “entourage effect” or “hodge-podge hashish”: The questionable rebranding, marketing, and expectations of cannabis polypharmacy. Expert Review of Clinical Pharmacology, 13(8), 835–845. https://doi.org/10.1080/17512433.2020.1721281 Cunha, J.M., Carlini, E.A., Pereira, A.E., Ramos, O.L., Pimentel, C., Gagliardi, R., Sanvito, W.L., Lander, N., & Mechoulam, R. (1980). Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology, 21(3), 175–185. https://doi.org/10.1159/000137430 Fowler, C.J. (2003). Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents non-psychoactive cannabinoids, ‘entourage’ compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid psychotropic effects. Brain Research Reviews, 18. https://pubmed.ncbi.nlm.nih.gov/12505646/ Gallily, R., Yekhtin, Z., & Hanuš, L.O. (2015). Overcoming the bell‐shaped dose‐response of cannabidiol by using cannabis extract enriched in cannabidiol. Pharmacology & Pharmacy, 6(02), 75–85. https://doi.org/10.4236/pp.2015.62010 Namdar, D., Anis, O., Poulin, P., & Koltai, H. (2020). Chronological review and rational and future prospects of cannabis-based drug development. Molecules, 25(20), Article 20. https://doi.org/10.3390/molecules25204821 Pamplona, F.A., da Silva, L.R., & Coan, A.C. (2018). Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: Observational data meta-analysis. Frontiers in Neurology, 9, 759. https://doi.org/10.3389/fneur.2018.00759 Russo, E.B. (2011). Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects: Phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x Russo, E.B. (2016). Beyond cannabis: Plants and the endocannabinoid system. Trends in Pharmacological Sciences, 37(7), 594–605. https://doi.org/...
