Opioid–Cannabinoid Cross-Tolerance Was One-Way in a Rat Social-Play Experiment
Cross-tolerance can depend on which treatment comes first. In a rat social-play experiment, repeated morphine exposure blunted the play-enhancing effect of an endocannabinoid enzyme inhibitor, while the reverse treatment history did not remove morphine's acute effect.
The endpoint was social play
Researchers investigated social behavior and related signaling in young animals. JZL184 increases endogenous cannabinoid signaling by inhibiting breakdown of 2-arachidonoylglycerol. It is not THC and is not equivalent to smoking cannabis.
The two directions differed
Systemic JZL184 failed to produce its usual play enhancement after repeated morphine. Acute morphine still increased play after prior treatment with JZL184 or WIN55,212-2. The biochemical analyses also identified treatment-dependent changes in CB1 receptor and Akt activation in selected brain regions.
The order belongs in the conclusion
Calling the result opioid–cannabinoid cross-tolerance without specifying direction loses essential information. The experiment does not support assuming that exposure to either class will equally reduce responses to the other.
Social play is also different from analgesia, respiratory depression, drug reward or driving performance. A result in one behavior cannot establish class-wide protection from adverse effects. The study supports a specific interaction between treatment history and a social-behavior endpoint, with associated signaling findings. It does not establish a treatment for social dysfunction or determine how a person combining an opioid with cannabis would respond.
Related: interpreting cannabis tolerance claims.
Research cited
Schiavi S; Manduca A; Segatto M; Campolongo P; Pallottini V; Vanderschuren LJMJ; Trezza V. Unidirectional opioid-cannabinoid cross-tolerance in the modulation of social play behavior in rats. Psychopharmacology (2019). doi:10.1007/s00213-019-05226-y. Findings discussed from the study abstract.
