Terpenes activate cannabinoid CB1 receptors, just like THC

This study's goal was to determine if, and how much, different terpenes affect cannabinoid CB1 receptors. It was published in the journal Biochemical Pharmacology in June 2023.

Their experiments used a "controlled in vitro heterologous expression system" (a type of laboratory model - not in humans or animals) to quantify the activation of CB1 receptors by sixteen cannabis terpenes individually, by tetrahydrocannabinol (THC) alone, and by THC-terpenes mixtures. The CB1 receptors are what most experts believe contribute to the euphoric effects of cannabinoids, as they are located near the brain and neurological components in mammals.

The terpenes that were included: α-pinene, β-pinene, limonene, myrcene, ocimene, sabinene, terpinolene, borneol, eucalyptol, geraniol, linalool, terpineol, β-caryophyllene, humulene, bisabolol and nerolidol. However, for most of the tests, β-caryophyllene, bisabolol, humulene and nerolidol were excluded "as their solubility is below the tested concentration range".

An increase in CB1 receptor activity was seen in 12 terpenes when THC was co-applied in ratios above what is usually found in cannabis plants: α-pinene, β-pinene, borneol, eucalyptol, geraniol, limonene, linalool, myrcene, ocimene, sabinene, terpineol and terpinolene.

Borneol, geraniol, limonene, linalool, ocimene, sabinene and terpineol were shown to significantly improve the CB1 receptor activation versus THC alone in ratios (Terpene:THC) similar to those found naturally in the cannabis plant.

Overall, the tests show that combining THC and most of these terpenes increased CB1 receptor activation significantly above the activation levels shown by THC alone.

An important observation was that the highest CB1 receptor activity was shown with a ratio of terpenes to THC that is NOT found naturally in most cannabis cultivars. The authors stated that the greatest therapeutic effect will likely be achieved by mixing terpenes with THC extract to achieve ratios that are not found naturally in cannabis flower.

Results in the authors' words:

all terpenes, when tested individually [without THC], activate CB1 receptors, at about 10–50% of the activation by THC alone

The combination of some of these terpenes with THC significantly increases the activity of the CB1 receptor, compared to THC alone. In some cases, several fold. 

the addition of borneol, geraniol, limonene, linalool, ocimene, sabinene and terpineol at this ratio (Terpene:THC ratio = 1:10) significantly enhances the potency of THC in CB1 receptor activation

For some terpenes, the activation obtained by THC + terpene mixtures is notably greater than the sum of the activation by the individual components, suggesting a synergistic effect [entourage, or ensemble effect].


Authors' conclusions:

As the most effective terpenes are not necessarily the most abundant ones in the cannabis plant, reaching “whole plant” or “full spectrum” composition is not necessarily an advantage.

For enhanced therapeutic effects, desired compositions are attainable by enriching extracts with selected terpenes. 


The full text article is here at ScienceDirect.com.