The Entourage Effect: How THC Works Well with Others

It’s widely understood that the compound known as THC is responsible for the “high” associated with ingesting marijuana. What’s less well-known is that CBD, the other principle active ingredient in marijuana, may moderate the psychoactive effects of THC.

Entourage Effect, Explained

It’s part of the so-called “entourage effect” that accounts for why different strains of cannabis have different properties and using products made from cannabis plants may be more effective than simply taking isolated THC or CBD.

More than 480 different compounds have been identified in the cannabis plant, including cannabinoids, like THC and CBD, and terpenes, which give marijuana its distinctive odors and flavors, whether reminiscent of pine, citrus, or damp earth. Few of these compounds have been extensively studied by scientists, due to strict U.S. federal laws against cannabis, but some researchers hypothesize that terpenes and other lesser-known molecules may have specific therapeutic effects when ingested together.  

Why the whole plant may be better

Israeli chemist Raphael Mechoulam coined the term entourage effect in the 1990s after discovering that synthetic THC, prescribed to some patients for nausea and pain, led to undesirable psychoactive side effects. Those hallucinatory sensations were substantially reduced when THC was combined with CBD, as it is in botanical cannabis.

Since then researchers have postulated that other seemingly inert compounds within cannabis may have have noticeable effects when combined. For example, Dr. Ethan Russo, medical director of cannabis research company Phytecs, suggests that one terpene in marijuana may help minimize the short-term memory loss that can be associated with getting high.

The entourage effect is one reason Russo and some other cannabis researchers say medical-grade THC and CBD – isolated and sold by pharmaceutical companies in pill form – may not be as effective as whole-plant formulations ingested by smoking, vaping or edibles.

“THC alone is a lousy drug,” Russo told Scientific American magazine. “It is a very poor therapeutic index.”

Creating a designer experience

The concept of polypharmacology, the treatment of multiple conditions with an array of naturally derived substances, is foreign to most Western drug makers but an ancient and widely accepted concept in Eastern medicine. Chinese herbalists, for example, generally prescribe combinations of herbs designed to work in concert to support specific physiological functions.

Some scientists are skeptical about the entourage effect, and serious research is still in its infancy. But cannabis growers have been leaping ahead, breeding countless plant varieties to create a designer experience, whether to improve appetite, diminish pain, or help with relaxation and sleep.

Terpenes, THC and CBD

Pharmaceutical companies have taken note of the entourage effect and have created drugs that include both THC and CBD. Sativex, one of the most prominent examples, has been approved in Britain and other countries for the treatment of multiple sclerosis spasms and is being tested for other indications. Over-the-counter formulations also are available now with various ratios of THC, CBD and different terpenes. Little studied or understood, terpenes are beginning to draw increasing interest and may help improve the efficacy of cannabinoids by helping them penetrate the blood-brain barrier, according to Dr. Perry Solomon, chief medical officer of HelloMD, which sells CBD-based products and cannabis-related medical services.

Scientists and cannabis advocates agree that more research is needed, but the anecdotal evidence points to the many compounds in the complex cannabis plant working together to have different effects.

“I believe in this because I’ve known for 40 years the differences between different cannabis strains,” said Russo of Phytecs. “They smell different. They taste different. They have different effects.”

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