Introduction

Chronic pain affects millions of people, and while cannabis is increasingly used for symptom relief, most studies have focused on cannabinoids like THC and CBD. Far less is known about terpenes, aromatic compounds in cannabis that may also influence pain. One of the most abundant terpenes, myrcene, has shown potential analgesic properties in animal studies—but how it works remains unclear.

Methods

Researchers at UCLA investigated myrcene’s pain-relieving effects in male and female mice with nerve injury-induced pain (a model of neuropathic pain). Mice received various doses of myrcene (1–200 mg/kg) and were tested for mechanical pain sensitivity using von Frey filaments. They also assessed side effects typical of cannabinoid drugs (e.g., reduced movement or body temperature) and used conditioned place preference tests to see whether myrcene had rewarding or aversive properties. Finally, cell-based assays were used to determine whether myrcene directly activates cannabinoid receptor 1 (CB1).

Results

Myrcene significantly reduced pain sensitivity in a dose-dependent and sex-specific manner—females responded at lower doses than males. The effect was blocked by a CB1 antagonist, suggesting CB1 involvement. However, myrcene did not directly activate CB1 receptors in vitro, nor did it enhance the effects of known CB1 agonists or endocannabinoids like anandamide. Myrcene did not cause sedation or hypothermia, unlike THC, but female mice developed an aversion to myrcene in behavioral tests.

Discussion

These findings suggest that myrcene relieves pain by indirectly engaging the endocannabinoid system, possibly by increasing natural cannabinoid levels or acting on upstream targets. Importantly, it does so without producing THC-like side effects. However, the observed aversion in female mice raises questions about dose and tolerability. Future studies should clarify how myrcene interacts with the broader pain and cannabinoid signaling networks—and whether its effects translate to humans.

Read the full study here.

Citation: Alayoubi, Myraa,b; Rodrigues, Akeeshab; Wu, Christineb; Whitehouse, Ellab; Nguyen, Jessicab; Cooper, Ziva D.b,c,d,e; O'Neill, Patrick R.b,c; Cahill, Catherine M.b,c,d,*. Elucidating interplay between myrcene and cannabinoid receptor 1 receptors to produce antinociception in mouse models of neuropathic pain. PAIN ():10.1097/j.pain.0000000000003558, March 18, 2025. | DOI: 10.1097/j.pain.0000000000003558