{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:09:21Z","timestamp":1790647761002,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","doi-asserted-by":"publisher","award":["RGPIN-2019-05121"],"award-info":[{"award-number":["RGPIN-2019-05121"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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\u2013340 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\u20133 mg\/kg), THCV (0.75\u20136 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% \u00b1 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\u2019s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.<\/jats:p>","DOI":"10.3390\/biom15091329","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T09:32:32Z","timestamp":1758187952000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tetrahydrocannabivarin (THCV) Dose Dependently Blocks or Substitutes for Tetrahydrocannabinol (THC) in a Drug Discrimination Task in Rats"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-4207","authenticated-orcid":false,"given":"Hakan","family":"Kayir","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Kouroukis","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-2275","authenticated-orcid":false,"given":"Jibran Younis","family":"Khokhar","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-57369-0_1","article-title":"Constituents of Cannabis Sativa","volume":"1264","author":"Rock","year":"2021","journal-title":"Adv. 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