Persistent Exposure to Δ⁹-Tetrahydrocannabinol during Adolescence Does Not Affect Nociceptive Responding in Adult...

Evidence suggests that Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the intoxicating component of cannabis, causes enduring changes in the structure and function of adolescent brain circuits implicated in nociceptive responding. However, whether such changes might persistently disrupt nociceptive behaviors remains unknown. In the present study, we subjected C57BL6/J mice of both sexes to once-daily injections of Δ⁹-THC (5 mg-kg^-1, i.p.) or vehicle throughout adolescence (PND 30-43) and, when the animals had reached adulthood (PND 70), assessed nociceptive behavior using the formalin and chronic constriction injury tests. We also investigated, using the tail immersion test, the antinociceptive effects of morphine and the development of tolerance to such effects. The results show that adolescent Δ⁹-THC exposure does not significantly impair nociceptive responding or morphine-related antinociception and tolerance. The findings suggest that frequent exposure to a moderate dose of Δ⁹-THC during adolescence does not permanently alter nociceptive circuits in male or female mice. SIGNIFICANCE STATEMENT: The endocannabinoid system serves critical functions in the central and peripheral nervous systems, including regulation of pain, and can be modified by prolonged exposure to the intoxicating constituent of cannabis, Δ⁹-tetrahydrocannabinol (Δ⁹-THC). This raises the possibility that regular use of Δ⁹-THC-containing cannabis during adolescence might cause changes in nociception that persist into adulthood. This study found that frequent early-life exposure to a moderate dose of Δ⁹-THC does not permanently alter nociceptive function in male or female mice.