THCV use triggers false THC positives on standard drug tests

Metabolite patterns in human urine after oral administration of highly purified Δ8-THCV.

Forensic toxicology • • Moderately Relevant
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AI Summary

Researchers validated a sophisticated laboratory method to track how the body processes THCV (tetrahydrocannabivarin), a lesser-known cannabinoid gaining attention for potential therapeutic uses. After healthy participants took oral Δ8-THCV, scientists analyzed urine samples collected within 8 hours to identify its metabolites—the chemical compounds the body creates as it breaks down the cannabinoid. The study identified three main metabolites: Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV, and Δ9-THCV-COOH, with Δ8-THCV-COOH being the predominant one. Notably, these metabolites are extensively glucuronidated (chemically modified for easier elimination), which has important implications for how the body processes and eliminates THCV.

The most striking finding reveals a significant problem with current drug testing practices: 70 out of 80 urine samples tested positive for THC using standard cannabinoid immunoassays, despite laboratory confirmation showing these samples contained no Δ9-THC and were primarily positive for THCV metabolites instead. This cross-reactivity phenomenon means that people who consume THCV could generate false positive results on conventional drug tests designed to detect Δ9-THC (the primary psychoactive component of cannabis). This discovery has serious real-world implications for anyone subject to drug testing—employment screenings, legal monitoring, or clinical settings—as their THCV use could trigger false positives that can't be distinguished from actual THC exposure using standard testing methods.

📄 Original Abstract

The interest in therapeutic applications of tetrahydrocannabivarin (THCV) recently increased. For this reason, we validated an online extraction liquid chromatography- tandem mass spectrometry (LC-MS/MS) method to investigate the formation of urinary metabolites and understand potential cross-reactivity of THCV metabolites in cannabinoid immunoassays. Urine samples were obtained after oral administration of Δ8-THCV to healthy participants. The protocol was approved by the Advarra Institutional Review Board (Pro00059879; approved December 20, 2021) and the trial was registered on clinicaltrials.gov (NCT05210634). Urine samples were collected pre-dose and pooled 0-8 hours post-dose. Urine samples were extracted using a simple one-step protein precipitation procedure and the extracts analyzed using online trapping LC-MS/MS in positive multiple reaction monitoring mode. All compounds passed validation criteria in urine. In the clinical samples, 11-nor-9-carboxy-Δ8-THCV (Δ8-THCV-COOH) was the main metabolite detected before and after incubation with glucuronidases. Of the urine pooled 0-8 hours post-dose, 70 out of 80 were reported positive by a cannabinoid immunoassay targeting Δ9-THC-COOH, despite being negative for Δ9-THC-COOH and positive mainly for Δ8-THCV-COOH in the LC-MS/MS analysis. The major metabolites of Δ8-THCV in urine were Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH that were extensively glucuronidated and cross-react with immunoassay routinely used for toxicology testing resulting in false positive results for Δ9-THC exposure.

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