Accurate Education – Marijuana (Cannabis): Terpenes – Myrcene

Entourage Effect – Synergy with Cannabinoids & Other Terpenes

Myrcene may also have a role in assisting cannabinoids to be transported across the blood-brain barrier, thereby increasing levels in the brain and enhancing psychoactive effects. It has been proposed that potential benefits of β-myrcene for peripheral and central analgesia may be related to boosting endocannabinoid levels in synergy with  other terpenes.

However, a recent study evaluated terpenoids found in cannabis either alone or when combined with 19- tetrahydrocannabinol (THC) and cannabidiol. The study concluded that none of the tested terpenes present in the cannabis plant (β-myrcene, pinene, caryophyllene and limonene) have a direct interaction with CB1 or CB2 receptors or by modifying the signalling of THC.

There are possibilities of entourage effects through the impact of terpenoids on other pathways of endocannabinoid system or through non-cannabinoid receptor mechanisms. However, there is limited research evaluating these theories.

Mechanisms of Action of Myrcene

The mechanism(s) behind myrcene’s proposed analgesic effects are not well understood. Several members of the Transient Receptor Potential  (TRP) super-family of non-selective cation channels have been identified both as pain receptors for and as targets for cannabinoids and terpenes. A 2019 study proposed mechanism is action on the TRPV1 channel. Other plant compounds (e.g., capsaicin (from peppers), allicin (from garlic), menthol) and possibly the terpene caryophyllene are known to act on TRPV1 to reduce nerve pain.

Both antagonism (blocking) and agonism (stimulation) of the TRPV1 are important pharmacological approaches for pain management. For example, TRPV1 antagonism has benefit in acute pain whereas chronic pain management requires longer-term actions such as receptor and nerve desensitization using TRPV1 agonists such as capsaicin. Topical 8% capsaicin treatment is standard for treating shingles pain but capsaicin is painful when applied initially until the nerves become desensitized and the pain resolves.

However, a 2020 study found no evidence that the terpenoids tested (a-pinene, b-pinene, b-caryophyllene, linalool, limonene, myrcene or a-humulene) activate TRPA1 and TRPV1 channels or modulate their activation by THC and other cannabis-related agonists, including endocannabinoids.

One mechanism of action of Myrcene thought to be via alpha 2-adrenoreceptors based on antagonism of the Myrcene effect by yohimbine and naloxone (See above, Analgesia). There is a connection between adrenoreceptors and TRPV1, where the adrenoreceptor activation inhibits TRPV1. Also, regarding the naloxone inhibition indicating opioid receptor involvement, functional interactions between opioid and TRPV1 receptors are known.

In 2020, another study concluded that terpenes commonly found in cannabis do not activate TRPA1 and TRPV1 channels nor do they modulate their activation by THC  or endogenous cannabinoids. Although they found no evidence for terpenoid–cannabinoid interactions at CB1, CB2, TRPV1, or TRPA1 receptors, terpene modulation of THC effects at TRPV2, TRPV3, GPR18, GPR55 were not excluded. The authors suggest that pharmacokinetic synergy may play a role where the terpenes modulate the absorption, distribution, metabolism, and/or excretion of the cannabinoids.

In a 2022 study on rats, myrcene was found to have anti-inflammatory and analgesic effects in inflammatory joint disease possibly by activating articular cannabinoid receptors. While chronic myrcene treatment had no effect on joint pathology, long-term administration of myrcene did reduce inflammatory parameters with its activity on immune cells. In this study co-administration of myrcene with CBD failed to produce any synergistic response, arguing against an entourage effect between these two compounds. These findings may explain why arthritis patients may prefer Cannabis strains rich in myrcene to help manage their pain and inflammation.