“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.”
https://pubmed.ncbi.nlm.nih.gov/41008636/
“Taken together, our findings highlight THCV’s unique pharmacological profile, characterized by partial agonism dose-dependent substitution for THC, and antagonism at higher doses. Importantly, THCV substituted for THC in a graded manner without evidence of pharmacokinetic interactions, and it also produced stimulant-like effects that distinguish it from THC. These results suggest that THCV may act as a dose-dependent modulator of cannabinoid receptor activity, capable of both mimicking and opposing THC’s discriminative stimulus effects. Such bidirectional properties are consistent with its complex receptor pharmacology and underscore the importance of dose in determining behavioral outcomes. Future studies should expand on these findings by examining sex- and strain-dependent variability, assessing the role of CB1 and CB2 receptor mechanisms using antagonist approaches, and exploring THCV’s actions across a broader range of behavioral paradigms, including those related to reward, cognition, and feeding behavior. Together, these efforts will help to clarify the pharmacology of THCV and further delineate its position within the cannabinoid spectrum.”