Can Terpenoids Modulate the Actions of Cannabinoids on Endogenous Channels?

Can Terpenoids Modulate the Actions of Cannabinoids on Endogenous Channels?

Medicinal cannabis is widely acknowledged for its therapeutic effects in treating pain. The two most widely studied components of the plant, Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are commonly prescribed separately or together for the relief of pain. CBD and THC are referred to as cannabinoids as they act via the human body’s own cannabinoid receptors, in addition to other targets. Over 110 individual cannabinoids have been identified within the cannabis plant.

In addition to cannabinoids, there are hundreds of other compounds with widely touted medicinal properties, with varying levels of evidence to support these claims. One such group of compounds is terpenoids which form part of the essential oils within the cannabis plant.

Whilst some forms of medicinal cannabis contain just CBD, THC or a combination of the two, others take the form of full-spectrum extracts or unprocessed flower. These contain a wide variety of cannabinoids and terpenoids, as well as other compounds. Much like when taking two or more medications at the same time, changes in the proportions of these compounds are thought to alter both the positive and adverse effects of the medication. The process of different compounds working together in the context of medicinal cannabis is widely referred to as the ‘Entourage Effect’.

Existing Evidence of the Entourage Effect

Existing research into the Entourage Effect is controversial in nature due to the wide variety of outcomes that have been achieved in studies to date both refuting and supporting its existence.

Some suggest that terpenoids may play a role in the Entourage Effect when treating pain. Whilst there are many touted therapeutic properties of terpenoids few studies have examined their benefits in full within human participants, particularly regarding the Entourage Effect.

Terpenoids in the Modulation of Cannabinoids

Researchers from the Lambert Institute in Sydney set out to examine this further by assessing the impact of commonly found terpenoids on the signals produced on TRPA1 and TRPV1 channels, which form part of the body’s mechanism for sensing and controlling pain.

Terpenoids have been thought to be an integral part of the Entourage Effect. The study’s results, however, demonstrate that terpenoids have no additional activity at TRPA1 and TRPV1 channels. They also do not affect the activity of cannabinoids at these receptors. Results found in a previous study conducted by the same research group demonstrated that terpenoids also did not affect the signaling of THC at specific cannabinoid receptors (CB1 and CB2). These results suggest that any role of terpenoids in pain modulation might be outside these four receptors.

The study authors stress that future research should be carried out in order to better understand the potential contribution of terpenoids to the Entourage Effect in human cells before any definitive conclusions are made, yet these results would suggest that if an ‘Entourage Effect’ exists then its mechanism lies elsewhere.