Cannabinoids, interoception, and anxiety

The use of cannabis is rapidly gaining legal status across North America. Such dramatic legislative shifts have prompted an urgency in elucidating the stimulus effects of cannabis consumption. Cannabis use, though relatively safe compared to other drugs of abuse, has been associated with greater risk of mental health disorders, possibly via its primary psychoactive constituent, Δ-9-tetrahydrocannabinol (THC). In this review, we discuss endocannabinoid activation and cannabis constituents from the perspective of subjective interoceptive (internally-perceived) states and how that relates to anxiety. Human studies have examined these subjective effects through use of self-report questionnaires. However, non-human studies use proxy methods of assessing anxiety states, such as elevated plus maze and fear conditioning paradigms. So far, this body of research has demonstrated that both endogenous and exogenous cannabinoid activation generally elicits biphasic effects on expression of the subjective state, with lower doses appearing to have anxiolytic properties and higher doses perceived as anxiogenic. Unfortunately, research with these compounds has been historically limited due to excessively tight regulatory control. Therefore, much work remains regarding the investigation of interactions between cannabinoid receptor activity and cannabis constituents on anxiety. Ongoing changes in legal status will hopefully mitigate the challenges faced by researchers attempting to access cannabis and THC that is inherently built in by federal and international classifications.