FAAH Inhibition Reduced Alcohol-Withdrawal Anxiety Without Changing Every Drinking Outcome
An experimental treatment can reduce an anxiety-like response during alcohol withdrawal without reducing alcohol self-administration or reinstatement. A review of endocannabinoid research describes this separation for the FAAH inhibitor URB597.
The enzyme target changes endogenous signaling
FAAH helps break down anandamide, an endogenous cannabinoid. Inhibiting FAAH is pharmacologically different from administering THC or a cannabis preparation, even when CB1 signaling contributes to an observed effect.
Kunos’s 2020 review describes a rat study in which URB597 robustly suppressed withdrawal-induced anxiety-like behavior. In the same account, it did not increase voluntary drinking in alcohol-preferring rats or facilitate operant alcohol self-administration in Wistar rats.
The null reinstatement findings also matter
URB597 failed to alter cue- or stress-induced reinstatement in the study summarized by the review. An anxiety-related result therefore cannot be relabeled as demonstrated relapse prevention.
Other experiments discussed in the review found different effects of FAAH manipulation on alcohol preference. The evidence needs its strain, exposure history, treatment timing and behavioral test rather than a single claim that increasing anandamide either helps or worsens every alcohol-related outcome.
Symptom relief and behavior change need separate evidence
Anxiety-like behavior in a rodent task is not a patient’s clinical anxiety diagnosis. Alcohol self-administration and experimentally reinstated responding likewise model defined aspects of behavior rather than the complete human disorder.
The useful conclusion is endpoint-specific: this research separated withdrawal-related affect from several drinking outcomes. It supplies a reason to investigate the pathway, while leaving human efficacy and the connection between symptom improvement and reduced drinking to direct clinical study.
Related reading: Alcohol–Endocannabinoid Reviews Need to Keep Stages of Dependence Separate.
Research cited
Kunos G. Interactions Between Alcohol and the Endocannabinoid System (2020). This analysis draws on the review’s discussion of the cited experiments.
