Researchers from the University of Arizona Health Sciences have dug up damning evidence that supports the “entourage effect” theory and its connection with pain relief. Their findings were published in a Scientific Reports paper, titled, “Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity.”

According to the Centers for Disease Control and Prevention (CDC), chronic pain affects some 50 million U.S. adults. Although conventional types of medication like opioids may offer satisfactory relief, over-the-counter OTC) meds can be addictive and, in some cases, may cause fatal overdose. 

This is where cannabis comes in handy, since the plant has never been connected with a fatal overdose. What’s more, as a plant that produces an amalgamation of compounds, including cannabinoids, terpenoids and flavonoids, it’s therapeutic benefits are widespread.

The recently-published study from University of Arizona researchers hypothesize that chronic pain patients can benefit from consuming the cannabis plant’s aromatic compounds, A.K.A. “terpenes”, which would require lower doses and produce less side effects.

According to the team, terpene consumption may stimulate the therapeutic efficacy of cannabinoids via the “entourage effect” — a chemical reaction that modulates the potency of commonly-occurring cannabinoids like CBD (cannabidiol) and THC (tetrahydrocannabinol).

Terpenes for pain relief: Cannabis compounds offer promising new target for pain therapies

Responsible for giving cannabis strains their distinctive scent, terpenes are fragrant compounds that act as the basic component in all essential oils. Aside from cannabis, terpenes are also found in other plants and fruits. Some of the most common cannabis terpenes include myrcene, linalool, limonene, eucalyptol and caryophyllene. 

Four different cannabis terpenes were focused on for this study: alpha-humulene, geraniol, linalool and beta-pinene. Each terpene was evaluated on its own and in conjunction with the use of synthetic cannabinoid WIN55,212-2, which arouses the body’s natural cannabinoid receptors.

University of Arizona Health Science researchers determined that, when used on their own, terpenes can actually replicate the effects of cannabinoids. Pain sensation reduction was a noticeable side effect of terpenoid administration. What’s more, when consumed with cannabinoids, patients experienced better overall symptomatic relief; devoid of any negative side effects.

“A lot of people are taking cannabis and cannabinoids for pain,” said the study’s lead researcher John Streicher, PhD. His research team included former postdoctoral fellow Attila Kerestztes, PhD, former graduate student and first author Justin LaVigne, PhD, and former undergraduate researcher Ryan Hecksel.

“We’re interested in the concept of the entourage effect, with the idea being that maybe we can boost the modest pain-relieving efficacy of THC and not boost the psychoactive side effects, so you could have a better therapeutic,” continued Dr. Streicher, who is also a member of the UArizona Health Sciences Comprehensive Pain and Addiction Center and serves as the associate professor of pharmacology at the College of Medicine.

Dr. Streicher noted that the team’s findings are somewhat unexpected, since the cannabinoid-like effects of terpenes were not anticipated in the team’s initial hypothesis.

Terpenes for pain relief: Cannabis’ aromatic compounds activate CB1R receptor

When cannabinoids like THC make their way into the human body, the compounds bind to either CB1R or CB2R – two of the primary cannabinoid receptors found in the body’s Endocannabinoid System (ECS). Once bound to receptors, cannabinoids work by activating neurons that influence various physiological processes, including mood, appetite, memory, and overall health and well-being.

Controlled laboratory experiments showed that all four of the tested cannabis compounds were capable of activating CB1R in the same way that THC does. After conducting behavioral studies in rodent models, the team of researchers found that individual administration of all four terpenes successfully reduced pain sensitivity. 

Moreover, the terpenes helped to lower body temperature, minimize pain sensation, pause the psychoactive side effects of cannabinoids and relieve poor mobility (catalepsy).

When combined with WIN55,212-2, researchers noticed that terpenes were more effective at relieving pain sensation; as opposed to using WIN55,212-2 or the specific terpene on its own. This, the researchers say, demonstrates how pain can be controlled by means of a cannabinoid-terpene reaction.

Dr. Streicher’s long-term vision is to help improve quality of life for people with cancer-related pain by establishing a dose-reduction strategy involving the use of cannabinoids or opioids and cannabis terpenes. Ideally, his strategy will help chronic pain patients to depend on lower drug doses for symptomatic relief.