Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley Rats: A Pharmacokinetic and Behavioral Assessment.
Samantha L Penman, Erin C. Berthold, Abrianna Mihalkovic, Nikki Hammond, Christopher R Mccurdy, Kenneth Blum, Rina D Eiden, Abhisheak Sharma, Panayotis K Thanos
Current Pharmaceutical Design 2023 DOI: 10.2174/1381612829666230419093809 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Adult female rats |
| Interventions | Delta-9-tetrahydrocannabinol (THC) inhaled THC |
| Dose | 2 mg/kg THC intraperitoneally; 0.25 mL of 40 or 160 mg/mL THC via inhalation |
| Topics | Cannabis |
| Keywords | Delta-9-Tetrahydrocannabinol THC Liquid-chromatography/mass-spectrometry Locomotor activity. Rodent Serum |
| Key points | Inhaled THC produced lower peak serum concentrations than intraperitoneal injection in female rats: 43.3 and 71.6 ng/mL for the two inhaled doses versus 107.7 ng/mL for 2 mg/kg injected THC. The lower inhaled dose and the injected dose both significantly reduced vertical locomotor activity compared with vehicle. The authors propose this as a simple rodent model of inhaled THC exposure. |
Abstract
Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 4
- Vaporized Δ9-tetrahydrocannabinol exposure in utero has negative effects on attention in a dose- and sex-dependent manner. Pharmacology, Biochemistry, and Behavior September 1, 2024
- Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects bioRxiv (Cold Spring Harbor Laboratory) September 29, 2024
- Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats Psychopharmacology February 7, 2025
- FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice. Pharmacology, Biochemistry, and Behavior October 2023
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