Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats
Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation.
To compare thermoregulatory and locomotor responses to inhaled ∆9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based model in male and female rats
Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5–200 mg/mL) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10–40 min). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content.
THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex.
In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.
Keywordse-cigarette Cannabidiol Hypothermia Locomotor activity Sex differences
The authors are grateful to Mr. Howard Britton for prototyping and fabrication of inhalation equipment and to Arnold Gutierrez, Ph.D., for comments on the manuscript draft. This is manuscript #29416 from The Scripps Research Institute.
This work was funded by support from the United States Public Health Service National Institutes of Health (R01 DA024105, R01 DA035482, and R44 DA041967) which had no direct input on the design, conduct, analysis, or publication of the findings.
Compliance with ethical standards
All procedures were conducted in the animals’ dark (active) cycle under protocols approved by the Institutional Care and Use Committee of The Scripps Research Institute and in a manner consistent with the Guide for the Care and Use of Laboratory Animals (National Research Council (U.S.). Committee for the Update of the Guide for the Care and Use of Laboratory Animals. et al. 2011).
Conflict of interest
MJP was supported in part by T32 AA007456. MC is proprietor of La Jolla Alcohol Research, Inc. and PI of the SBIR grant (R44 DA041967) supporting further commercialization of the inhalation equipment. The other authors declare that they have no competing interests.
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