Enkephalin Deficiency Reduced THC Antinociception and Slowed Its Tolerance in Mice
Mice lacking pre-proenkephalin showed weaker initial THC antinociception and slower development of tolerance to that response. The combination matters: slower tolerance did not begin from the same acute response as in comparison mice.
The acute phenotype was selective
Researchers measured THC antinociception with a tail-immersion test. The response was reduced in mutant mice, while effects on temperature, movement and ring catalepsy did not differ between genotypes. The genetic change therefore did not reduce all acute THC effects.
Initial sensitivity and adaptation were separate findings
During chronic treatment, antinociceptive tolerance developed more slowly in mice lacking enkephalin. A smaller initial response and a different adaptation rate need separate reporting. Simply describing the animals as protected from tolerance would omit the reduced acute effect on the same endpoint.
Withdrawal signs were also attenuated
A CB1 antagonist precipitated withdrawal in THC-dependent animals, with significantly reduced manifestations in the mutant group. That finding concerns pharmacologically precipitated signs, rather than all subjective and behavioral aspects of abstinence. Enkephalin precursor deficiency also differs from selectively blocking a receptor with a medication.
The study supports involvement of the endogenous opioid peptide system in selected THC responses and withdrawal. It does not establish an analgesic strategy for patients or imply that genetically altered animals were globally less affected. The baseline response, tolerance rate and withdrawal result are three related but distinct observations.
Related: interpreting cannabis tolerance claims.
Research cited
Valverde O; Maldonado R; Valjent E; Zimmer AM; Zimmer A. Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience (2000). doi:10.1523/JNEUROSCI.20-24-09284.2000. Findings discussed from the study abstract.
