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Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats.

Jacques D. Nguyen, Yanabel Grant, Tony M Kerr, Arnold Gutierrez, Maury Cole, Michael A. Taffe

Pharmacology, Biochemistry, and Behavior September 2018 DOI: 10.1016/j.pbb.2018.07.007 (opens in new tab)

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AI-extracted from the abstract
Characteristics Controlled preclinical experiment in rats Peer reviewed
Population Male and female Wistar rats
Dose 200 mg/mL THC in propylene glycol
Duration 30-minute inhalation sessions two or three times per day for four days
Measures Rectal temperature, nociception assessment, plasma THC levels
Topics Cannabis
Keywords E-cigarette Hypothermia Nociception Tolerance
Key findings Four days of twice-daily THC vapor inhalation produced tolerance to THC's hypothermic and antinociceptive effects in female rats but not males, while three daily sessions produced tolerance in both sexes. Plasma THC levels after a 30-minute session did not differ between males and females, and the authors present the results as validation of the vapor inhalation method for preclinical studies.

Abstract

A reduced effect of a given dose of ∆9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats. To determine if tolerance to these effects can be produced with repeated vapor inhalation. Groups of male and female Wistar rats were exposed to 30 min of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation. Female, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 min inhalation session did not differ between the male and female rats. Repeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.

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