In a groundbreaking study funded by federal agencies, researchers have discovered that terpenes, a component of marijuana, can significantly alleviate chronic neuropathic pain in mice through the activation of adenosine A2A receptors (A2AR).
Terpenes are aromatic compounds found in many plants, contributing to their flavor and scent, and are abundant in cannabis. Previous studies have hinted at the analgesic properties of terpenes, but this study provides a more focused insight into their mechanisms and effectiveness.
The research team, which included researchers from the University of Arizona and the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, utilized a mouse model to explore the effects of specific terpenes (geraniol, linalool, β-pinene, α-humulene, and β-caryophyllene) in treating chronic pain conditions, including chemotherapy-induced peripheral neuropathy (CIPN) and inflammatory pain caused by lipopolysaccharide. The terpenes were tested at a dosage of 200 mg/kg, which showed a level of pain relief comparable to standard pain medications like morphine and the synthetic cannabinoid WIN55,212.
One of the critical findings of the study is that these terpenes do not produce addictive behaviors, a significant advantage over conventional opioid treatments. Moreover, when used in lower doses alongside morphine, the terpenes enhanced the pain relief effects without increasing addictive potential.
The pivotal mechanism behind the terpenes’ effectiveness lies in their interaction with the adenosine A2A receptor. By blocking this receptor using the selective antagonist istradefylline and employing CRISPR technology for targeted genetic knockdowns in the spinal cord, the researchers pinpointed A2AR as essential for the terpenes’ antinociceptive effects.
Further in vitro and in silico studies supported the hypothesis that terpenes might act as A2AR agonists. This interaction could explain the significant reduction in pain experienced by the animal subjects, positioning marijuana terpenes as a promising new class of therapeutics for managing chronic neuropathic pain.
