Ep. 48 - The Entourage Effect is Still a Theory

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-der