Baseline Endocannabinoids Correlated With Cannabis Responses Without Becoming an Impairment Test

Circulating endocannabinoids may be associated with how people respond to cannabis, but an association is not an individual impairment test. A small human study reported baseline correlations even though acute cannabis exposure did not significantly change the measured endocannabinoid levels.

What the study measured

Twenty-six cannabis users smoked part of a cannabis cigarette. Researchers measured plasma anandamide, 2-arachidonoylglycerol and THC, together with subjective ratings and cardiovascular measures before and after smoking. These endogenous signaling molecules are different analytes from plant-derived THC.

Acute changes and baseline correlations diverged

Intoxication ratings, heart rate and plasma THC increased relative to baseline. The abstract reports no acute effect on the measured endocannabinoid levels. Nevertheless, baseline anandamide correlated positively with peak ratings of high and good drug effect, while baseline 2-arachidonoylglycerol correlated negatively with reported use frequency and baseline metabolite levels.

A biomarker hypothesis requires more evidence

Those correlations do not establish that endocannabinoid differences caused tolerance or predict driving performance. They also do not provide sensitivity, specificity or an externally validated cutoff for classifying a particular person. The study's selected cannabis-user sample limits broader inference.

The practical lesson is to keep baseline biology, drug exposure and functional effects separate. A laboratory can accurately measure a molecule without establishing a validated interpretation for impairment. The investigators' proposal for further biomarker research remains a research question, not a finished forensic instrument.

Related: interpreting cannabis tolerance claims.

Research cited

Kearney-Ramos T; Herrmann ES; Belluomo I; Matias I; Vallée M; Monlezun S; Piazza PV; Haney M. The Relationship Between Circulating Endogenous Cannabinoids and the Effects of Smoked Cannabis. Cannabis and cannabinoid research (2023). doi:10.1089/can.2021.0185. Findings discussed from the study abstract.

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