Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

TLDR: Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels, and each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females.

Abstract: Adolescents are regularly exposed to Δ9-tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference. Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl self-administration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood.