THC Vapor Tolerance Changed With Exposure Frequency in Rats

Female and male rats did not show the same tolerance pattern under a twice-daily THC-vapor schedule, but both showed tolerance with more frequent exposure. The dosing schedule was part of the explanation.

A vapor-inhalation model

Researchers used an electronic-cigarette-based system to expose male and female rats to THC in propylene glycol or vehicle. Temperature and pain-related responses were compared after early and repeated sessions. This was an animal delivery model, not a comparison of commercial vape-product safety.

The schedule changed the observed result

After four days of twice-daily exposure, tolerance was detected in females but not males on the studied hypothermic and antinociceptive outcomes. A three-times-daily regimen produced tolerance in both sexes. These results do not support a fixed statement that only one sex develops inhaled-THC tolerance.

What the plasma result adds

A post-inhalation plasma THC comparison did not show a significant sex difference. That observation makes a simple difference in measured concentration less persuasive at that time point. It does not establish identical full concentration-time profiles, metabolism or brain exposure.

The limit of the comparison

A nonsignificant concentration comparison is not a formal demonstration of pharmacokinetic equivalence. Likewise, temperature and nociception do not represent every cognitive or motor effect. The study supports specifying route, frequency, observation time and outcome before comparing tolerance. Its plasma values cannot be converted into a human impairment threshold or a safe vaping schedule.

Related analysis: evaluating cannabis tolerance claims.

Primary research

Nguyen JD; Grant Y; Kerr TM; Gutierrez A; Cole M; Taffe MA. Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats. Pharmacology, biochemistry, and behavior (2018). DOI: 10.1016/j.pbb.2018.07.007.

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