Peanut butter and jelly, Kraft and dinner, maple and syrup - some things just work better together. When it comes to cannabis, there is a popular school of thought that interactions between some of the 480+ chemical compounds, such as cannabinoids CBD and THC, terpenes and other flavonoids, produce a synergistic ‘entourage effect’ that magnifies the therapeutic aspects of cannabis. Basically, the whole is greater than the sum of its parts. While indica, sativa, or hybrid categories and THC/CBD levels have historically been used to identify expected effects, increasingly the ‘entourage effect’ of cannabinoids and terpenoids is being looked as a way of understanding and predicting individual experiences.  

Popularized by Ethan Russo in 2011, the term entourage effect was coined by professors Raphael Mechoulam and Shimon Ben-Shabat back in 1998 when they noted that full-spectrum (whole plant) botanical drugs were often more effective than isolated versions of the active compounds. Research is still ongoing but various theories centre around the notion that the whole plant is more effective than just THC or CBD on its own, due to the effects that terpenes and other cannabinoids have on each other.  

What’s the science behind the entourage effect?  

Mechoulam and Ben-Shabat posited that “botanical drugs were often more efficacious than their isolated components” and that “the endocannabinoid system demonstrated an ‘entourage effect’ in which a variety of inactive metabolites and closely related molecules markedly increased the activity of the primary endogenous cannabinoids.” It might sound confusing but all it essentially means is that non-cannabinoids (for example, terpenes) affected the interaction of THC and CBD with the body’s Endocannabinoid System.

Russo adds to the case for the entourage effect with a list of examples: A whole-plant extract proves to be more effective in treating pain than just a THC extract or a placebo; pure CBD products produce a biphasic dose-response curve (e.g smaller doses reduce pain responses), but full-spectrum extracts have a linear dose-response (e.g it works at any dose); and breast cancer cell treatment was more effective in full-spectrum extract than pure THC-- thought to be because of the presence of the cannabinoid cannabigerol (CBG) and  tetrahydrocannabinolic acid (THCA).

Working together: CBD and THC

Here’s a quick recap of how the two most well-known cannabinoids interact with your body through the Endocannabinoid System (ECS). The ECS regulates everyday bodily functions (sleep, pain, metabolism etc) and cannabinoids act as chemical messengers that bind to cell CB1 and CB2 receptors to start and stop processes in the body. CB1 receptors are mainly found in the brain and central nervous system and are thought to regulate stress, anxiety, appetite, and nausea. CB2 receptors are more associated with anti-inflammatory and healing properties in other major organs.

THC mainly interacts with CB1 receptors and CBD has been shown to affect this interaction and mitigate some of the ‘negative/anxious effects of THC when the two are consumed together in certain ratios.

Terpenes and the entourage effect

You may have experienced the entourage effects of terpenes and cannabinoids without realizing it. Maybe you’ve tried the old trick of chewing some pepper to lessen an anxious high. Anecdotally, this seems to work. Why? It’s thanks to terpenes-- aromatic compounds found in plants that each have their own properties and uses. Carolyphyllene is the spicy terpene that gives pepper its kick. It’s also found in some cultivars of cannabis and it’s thought that it’s unique molecular structure allows it to bind to CB2 receptors and help to lessen the anxiety that can occur in overconsumption of THC. This is still being studied and more recent findings suggest that terpenes might not interact with the ECS as much as first thought.

The entourage effect could also explain why we generally categorize cannabis into indica and sativa, even though there has been so much hybridization of the species. Indicas tend to be high in the sedating terpene myrcene and sativas lean towards being high in stimulating limonene. These effects are often attributed to plant type, rather than entourage effect of cannabinoids such as THC and CBD interacting with terpenes.

What’s next for the entourage effect?

Data mapping the reported effects from consumers is one of the ways that anecdotal evidence can be utilized for scientific study. Increased research into the entourage effect will shine more light on the interactions between cannabinoids and terpenes in the body. More recent research from the University of Sydney has disputed earlier findings of the entourage effect of terpenes and THC  in relation to the ECS. However, the authors of the Australian study suggest that there could be different, and as yet unknown, pathways for these interactions to take place. The report ends on a positive note that sets the scene for more investigation into the entourage effect: "The quest for entourage does not end here; in many ways, it has only just begun.”