Tetrahydrocannabivarin (THCV) Dose Dependently Blocks or Substitutes for Tetrahydrocannabinol (THC) in a Drug Discrimination Task in Rats
Hakan Kayır, Larissa Kouroukis, Iman Aziz, Jibran Y. Khokhar
Biomolecules September 18, 2025 DOI: 10.3390/biom15091329 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Male Sprague-Dawley rats |
| Interventions | Delta-9-Tetrahydrocannabivarin (THCV) THC |
| Dose | THC 0.325-3 mg/kg, THCV 0.75-6 mg/kg |
| Topics | Cannabis |
| Keywords | Cannabinoid receptor Δ9-tetrahydrocannabinol Drug Delta-9-tetrahydrocannabinol Partial agonist Blockade Pharmacology Rimonabant Antagonist Dronabinol Stimulus control Substitution logic |
| Citations | 2 |
| Key points | THCV partially substitutes for THC at 3 mg/kg and reverses THC-induced responding at 6 mg/kg, suggesting a dose-dependent partial agonist/antagonist profile at CB1 receptors. |
Abstract
Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats (n = 16, 300–340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325–3 mg/kg), THCV (0.75–6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle (p = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, p = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV (p = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding (p = 0.040), with no significant change in response rate (p = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates (p = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg (p = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC’s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 6
- The Relationship Between Cannabis, Cognition, and Schizophrenia: It’s Complicated Current Topics in Behavioral Neurosciences 2022
- Evaluation of the Modulatory Effects of Minor Cannabinoids and Terpenes on Delta-9-Tetrahydrocannabinol Discrimination in Rats. Cannabis and Cannabinoid Research September 2023
- Evaluating Potential Anxiolytic Effects of Minor Cannabinoids and Terpenes After Acute and Chronic Oral Administration in Rats. Cannabis and Cannabinoid Research September 2023
- Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Scientific Reports December 14, 2021
- In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa Scientific Reports November 23, 2020
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