Study Points to Analgesic Potential of Terpenes Found in Cannabis

By João R. Negromonte

The terpenes found in cannabis and other plants may reduce chronic pain by uniquely interacting with cannabinoids and other receptors in the brain.

This, according to a study published in Pubmed (a free access search engine for the MEDLINE database of citations and abstracts of biomedical research articles, provided by the U.S. National Library of Medicine), which found that the terpenes α-terpineol, ß-caryophyllene, and γ-terpinene activate cannabinoid receptors CB1 and CB2 in a way that reduces chronic pain caused by nerve damage, known as neuropathic pain.

The terpenes were particularly effective in reversing mechanical allodynia, characterized by extreme sensitivity to touch, as well as thermal hyperalgesia, a heightened sensitivity to temperature. These are common conditions among people with neuropathic pain.

The results suggest that new safe analgesics could be made by combining these terpenes in high doses, scientists explain.

By conducting experiments on genetically modified mice, researchers at the University of Florida found that ß-caryophyllene helped alleviate symptoms by activating CB2 receptors. They found that γ-terpinene calmed symptoms by activating CB1 receptors.

Surprisingly, α-terpineol did not need to interact with cannabinoid receptors to have positive effects. Researchers say that further investigations are needed to measure the effects on other unexamined receptors in this study.

Another research showed that substances specifically targeting CB2 receptors do not produce immediate pain relief, nor do they decrease body temperature or movement, but ß-caryophyllene produced all three effects. This means that the terpene has multiple receptor targets, researchers explain.

Overall, the terpenes were better at treating thermal hyperalgesia than mechanical allodynia - α-terpineol produced the best results, followed by β-caryophyllene and γ-terpinene.

γ-terpinene gives a citrus scent to cannabis, β-caryophyllene gives a spicy and peppery scent, while α-terpineol gives a woody scent.

For the study, researchers compared results between 156 genetically modified mice and 36 non-genetically modified ones. Among the genetically modified mice, 78 of them lacked CB1 receptors, while the other 78 lacked CB2 receptors.

Previous research shows that CB1 receptors are abundant in the peripheral and central nervous systems, while CB2 receptors are located in immune cells and other areas of the brain involved in memory and learning, but primarily in the hippocampus.

To test the relationship between terpenes and neuropathic pain, researchers performed surgery to create pain in the limbs of the mice.

After recovery, the mice were injected with each terpene, and different pain induction tests were conducted to test the efficacy of each.

The mice that lacked CB2 receptors and received γ-terpinene showed the same decrease in touch hypersensitivity as those with the receptor and the non-genetically modified mice.

“Thus, it seems that these findings suggest that α-terpineol, β-caryophyllene, and γ-terpinene may have differential cannabinoid receptor activity and a pharmacological profile that could yield more effective analgesics in the future,” says the study.