Modulation of Nicotinic Receptors by Cannabinoids

Abstract

The legalization of medicinal and recreational use of marijuana by many states in the USA, has resulted in an increase in its use. The two most abundant phytocannabinoids in marijuana Δ9‐Tetrahydrocannabinol (THC) and cannabidiol (CBD) have been shown to have tremendous therapeutic potential in many neurological disorders such as anxiety, seizures, post‐traumatic stress disorder and pain. One study showed that CBD use reduces cigarette consumption by 40%. However, little is known about the effects that these phytocannabinoids have on the function of nicotinic acetylcholine receptors (nAChRs). Published results showed that CBD reduces the response of the α7 nAChR to acetylcholine (ACh). Through this project we are characterizing the effects of CBD and THC on the function of the α7 nAChR. Our results indicate that CBD reduces the response of the α7 nAChR to ACh by 49% (p value=0.0003); and that CBD alone does not activate the receptor. Interestingly, THC seems to have the opposite effect, it appears to increase the response of the α7 nicotinic receptor to ACh by a 128% (pvalue=0.44). When both drugs were combined at a 1:1 ratio, the observed effect was an inhibition. The effect was intermediate to the effect seem with either drug alone, the observed response was 62% of the normal response (pvalue=0.007). The response of the α7 nicotinic receptor to CBD and THC seems to be independent of the concentration of ACh applied. Which suggests that neither CBD nor THC compete with ACh for the binding site. Dissecting the effects of phytocannabinoids found in marijuana on the nervous system is critical to increase our chances of using it successfully in the clinic.Support or Funding InformationNIH‐Maximizing Access to Research Careers (Grant # 5T34GM007821‐38)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.