Informal breeding practices have led to the proliferation of Cannabis sativa chemovars with undocumented parentage and overlapping phytochemical profiles. Despite diverse strain nomenclature in legal and illicit markets, many chemovars exhibit similar cannabinoid and terpene compositions. Emerging anecdotal evidence suggests pharmacological interactions between these metabolite classes, yet systematic investigations remain limited. This study aimed to identify correlations between cannabinoids and terpenes in commercially cultivated Cannabis chemovars using a chemometric data fusion model, with implications for understanding domestication effects on phytochemical expression. Cannabis chemovars (n=33) were profiled for 32 cannabinoids, 29 monoterpenes, and 38 sesquiterpenes using targeted metabolomics. A data fusion model was applied to uncover cross-class relationships. The analysis revealed a distinct association between terpinolene and nine monoterpenes with three minor, previously unidentified cannabinoids. The most abundant and strongly correlated compound was isolated and structurally characterized as THCA-C4. These findings suggest that selection for high cannabinoid content induces overexpression of biosynthetic precursors, activating terpinolene biosynthesis. In contrast, wild-type or low-cannabinoid chemovars do not exhibit this monoterpene profile, indicating a domestication-driven shift in metabolic regulation. Chemometric data fusion enabled the discovery of novel correlations between cannabinoids and terpenes in Cannabis sativa, highlighting the impact of selective breeding on phytochemical diversity. These insights may inform future strategies for optimizing therapeutic efficacy in medical cannabis formulations.
Mudge et al. (Wed,) studied this question.