University of Arizona researchers have found new evidence that the entourage effect — whereby the pain-relieving effects of the cannabis plant as a whole are greater than any of its individual parts — could be a reality.

The findings suggest terpenes — molecules found in cannabis that provide flavour and aroma — could be a promising new target for pain therapies, requiring lower doses and producing fewer side effects.

The study, published in the journal Scientific Reports, found that terpenes by themselves mimic the effects of cannabinoids, which can create a reduction in pain. However, these effects were amplified when paired with cannabinoids, without an increase in negative side effects.

The two most commonly known cannabinoids in cannabis sativa are CBD and THC.

Lead researcher Dr John Streicher said: “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.”

Dr John Streicher

Using both in vitro cell experiments and in vivo mouse models, the study focused on the terpenes alpha-humulene, geraniol, linalool and beta-pinene and evaluated each terpene alone and in combination with a synthetic cannabinoid, WIN55,212-2.

WIN55,212-2 is an agonist that stimulates the body’s natural cannabinoid receptors found within the endocannabinoid system.

Just like THC, all four terpenes studied activated CB1R in lab tests, which is the most abundant cannabinoid receptor throughout the human body.

Behavioural studies in the mouse models found that pain responses in the animals were reduced when terpenes were combined with WIN55,212-2, compared to the terpenes and the synthetic cannabinoid being administered alone.

Dr Streicher said of the findings: “It was unexpected, in a way. It was our initial hypothesis, but we didn’t necessarily expect terpenes, these simple compounds that are found in multiple plants, to produce cannabinoid-like effects.”

Dr Streicher’s ongoing research is focused on the use of terpenes in combination with opioids and for specific types of cancer-related pain. His long-term goal is to create a dose-reduction strategy that uses terpenes in combination with cannabinoids or opioids to achieve lower doses of drugs administered and fewer side effects with the same levels of pain relief.