Science & Health
Do Terpenes Contribute To Medical Marijuana’s ‘Entourage Effect’? New Study Says It’s ‘Plausible,’ But Still ‘Unproven’
A review of research into the synergistic effects of the chemical components in medical marijuana—an idea commonly known as the entourage effect—says that terpenes, popularly credited with modulating the experience of cannabis, may indeed be “influencers in the therapeutic benefits of cannabinoids,” though for now that influence “remains unproven.”
The literature review, published this month on the academic website Preprints.org by university researchers in Portugal, notes that initial research into some terpenes is promising, but it encourages further clinical trials “to confirm these constituents’ individual and combined effects.”
Authors said two questions guided the review: “What are the Physiological Effects of Terpenes and Terpenoids found in Cannabis?” and “What are the proven Entourage Effects of Terpenes in Cannabis?”
The paper details a number of preliminary findings around the therapeutic benefits of individual cannabinoids on a range of ailments.
“Exploratory evidence,” it notes, citing earlier studies, “suggest various therapeutic benefits of terpenes, such as myrcene for relaxing; linalool as sleep aid, exhaustion relief and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection, borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain.”
Authors also touched on evidence of a lack of certain effects, for example pointing out that their analysis “shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity, however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa-prevalent monoterpenes and their triterpene friedelin.”
The study also notes that while myrcene “demonstrated anti-inflammatory proprieties topically,” it appeared the terpene offered no additional anti-inflammatory effect when combined with the cannabinoid CBD.
The study doesn’t settle on the ultimate role of terpenes in the so-called entourage effect, however.
“Up to date, no reliable scientific evidence of this synergy exists, at least at the cannabinoid (CB) receptor level,” the report says. “Nonetheless, it would be premature to deny the existence of either pharmacodynamic or pharmacokinetic interactions among active compounds present in Cannabis, as many biological activities have been attributed to its terpenes, including analgesic, anti-inflammatory, and anxiolytic properties.”
Authors wrote that the entourage effect appears “plausible, particularly when considering minor Phyto cannabinoids, monoterpenes, sesquiterpenes, and sesquiterpenoids.”
“However, the practical application of this effect is complicated by several factors,” they added, “including variability in the levels of minor secondary metabolites, across different cannabis preparations, the often-limited scope of analytical methods used, and the low bioavailability of many of these components of interest.”
The manuscript notes that those obstacles are common with many herbal medicines, as “without a clear understanding of the key active agents, it is very difficult to produce reliable products with a consistent level of these constituents.”
“In conclusion, while current research suggests a potential overlap in therapeutic benefits between cannabinoids and terpenes as influencers, the hypothesis that these effects are additive or synergistic remains unproven,” it says. “Further research is expected to understand which factors may enhance cannabinoid efficacy in an additive or synergistic manner.”
The latest research also comes as scientists come to better understand the roles and interactions between cannabinoids and other chemical components of marijuana, such as terpenes.
A separate study, for example, published earlier this year in the International Journal of Molecular Sciences, said that the “complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches,” potentially laying the groundwork for a new era of innovation in cannabis-based medicines.
“The plant Cannabis exhibits an effect called the ‘entourage effect’, in which the combined actions of terpenes and phytocannabinoids results in effects that exceed the sum of their separate contributions,” that study found. “This synergy emphasizes how important it is to consider the entire plant when utilizing cannabinoids medicinally as opposed to just concentrating on individual cannabinoids.”
A federally funded study published in May, meanwhile, found that terpenes could be “potential therapeutics for chronic neuropathic pain,” finding that an injected dose of the compounds produced a “roughly equal” reduction in pain markers when compared to a smaller dose of morphine. Terpenes also appeared to enhance the efficacy of morphine when given in combination.
Unlike with morphine, however, none of the studied terpenes produced a meaningful reward response, that research found, indicating that “terpenes could be effective analgesics with no rewarding or dysphoric side effects.”
Another study published earlier this year looked at the “collaborative interactions” between cannabinoids, terpenes, flavonoids and other molecules in the plant, concluding that a better understanding of the relationships of various chemical components “is crucial for unraveling cannabis’s complete therapeutic potential.”
Other recent research funded by the National Institute on Drug Abuse (NIDA) found that a citrusy-smelling terpene in marijuana, D-limonene, could help ease anxiety and paranoia associated with THC. Researchers similarly said the finding could help unlock the maximum therapeutic benefit of THC.
A separate study last year found that cannabis products with a more diverse array of natural cannabinoids produced stronger psychoactive experiences in adults, which also lasted longer than the high generated by pure THC.
And a 2018 study found that patients suffering from epilepsy experience better health outcomes—with fewer adverse side effects—when they use plant-based CBD extracts compared to “purified” CBD products.
Scientist last year also discovered “previously unidentified cannabis compounds” called flavorants that they believe are responsible for the unique aromas of different varieties of marijuana. Previously, many had thought terpenes alone were responsible for various smells produced by the plant.
Similar phenomena are also beginning to be recorded around psychedelic plants and fungi. In March, for example, researchers published findings showing that use of full-spectrum psychedelic mushroom extract had a more powerful effect than chemically synthesized psilocybin alone. They said the findings imply that mushrooms, like cannabis, demonstrate an entourage effect.