Discriminative stimulus properties of Cannabis sativa terpenes in rats.

Terpenes found in cannabis, such as linalool, limonene, γ-terpinene, and α-humulene, do not produce effects similar to THC or enhance THC's effects in rats. Rats trained to discriminate THC from a vehicle did not respond to terpenes alone as if they were THC, and terpenes did not increase THC's potency; α-humulene actually decreased it. In the tetrad assay, which screens for cannabinoid-like activity, none of the terpenes produced effects in all four components as THC did. The results suggest these terpenes do not act as CB1 receptor agonists in the brain.

Study at a glance

Abstract

Cannabis is a pharmacologically complex plant consisting of hundreds of potentially active compounds. One class of compounds present in cannabis that has received little attention are terpenes. Traditionally thought to impart aroma and flavor to cannabis, it has become increasingly recognized that terpenes might exert therapeutic effects themselves. Several recent reports have also indicated terpenes might behave as cannabinoid type 1 (CB1) receptor agonists. This study aimed to investigate whether several terpenes present in cannabis produce discriminative stimulus effects similar to or enhance the effects of Δ 9 -tetrahydrocannabinol (THC). Subsequent experiments explored other potential cannabimimetic effects of these terpenes. Rats were trained to discriminate THC from vehicle while responding under a fixed-ratio 10 schedule of food presentation. Substitution testing was performed with the CB receptor agonist JWH-018 and the terpenes linalool, limonene, γ-terpinene and α-humulene alone. Terpenes were also studied in combination with THC. Finally, THC and terpenes were tested in the tetrad assay to screen for CB1-receptor agonist-like effects. THC and JWH-018 dose-dependently produced responding on the THC-paired lever. When administered alone, none of the terpenes produced responding predominantly on the THC-paired lever. When administered in combination with THC, none of the terpenes enhanced the potency of THC, and in the case of α-humulene, decreased the potency of THC to produce responding on the THC-paired lever. While THC produced effects in all four tetrad components, none of the terpenes produced effects in all four components. Therefore, the terpenes examined in this report do not have effects consistent with CB1 receptor agonist properties in the brain.