Stress-Related Analgesia and Cannabinoid Exposure Adapted Asymmetrically in Rats

Repeated activation of the cannabinoid system did not produce the same adaptation when driven by a drug and by a stressor. A rat study found differences between repeated cannabinoid treatment and repeated footshock exposure.

The comparison used a pain-response test

Researchers measured tail-flick antinociception after stress or cannabinoid administration and assessed movement separately. Acute stress increased sensitivity to tested cannabinoid effects, while acute cannabinoids also enhanced stress-related antinociception.

The repeated-treatment findings differed

Stress-related antinociception was attenuated after chronic cannabinoid treatment. Repeated footshock exposure, however, did not attenuate the reported responses to stress or WIN55,212-2 in the same way.

A motor control addressed one alternative

At a dose that blocked stress antinociception, rimonabant did not change measured locomotor behavior in similarly stressed rats. That finding argued against explaining the blocked antinociception simply as altered movement under those conditions.

These were animal stress and reflex procedures, not a study of how a human's emotional state changes driving impairment. The result also does not establish that stress makes cannabis beneficial or safe. Its value is in distinguishing acute sensitization, repeated-drug tolerance and repeated-stressor adaptation instead of treating all cannabinoid-system activation as equivalent.

Related: interpreting cannabis tolerance claims.

Research cited

Suplita RL; Eisenstein SA; Neely MH; Moise AM; Hohmann AG. Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia. Neuropharmacology (2008). doi:10.1016/j.neuropharm.2007.07.006. Findings discussed from the study abstract.