Emerging Hemp-Derived Semi-Synthetic Cannabinoids, Absent Regulations: Patterns of Use and Adverse Effects Among a Sample of U.S. Cannabis Consumers

<b>Introduction:</b> Hemp-derived semi-synthetic cannabinoids are marketed as legal alternatives to cannabis containing ≥0.3% Δ⁹-tetrahydrocannabinol (THC) but remain unregulated at the federal and state levels. Their growing availability underscores the urgent need to investigate patterns of use and associated health risks. <b>Methods:</b> Data were collected <i>via</i> an online survey on self-reported patterns and associations of semi-synthetic cannabinoid use, as well as related factors and effects, from a sample of U.S. adults (≥18 years old) who reported past-year cannabis use. <b>Results:</b> In the sample (<i>N</i> = 229; 55.5% male, 63.8% White, 80.3% not Hispanic/Latino), nearly half (44.5%) reported using at least one semi-synthetic cannabinoid in the past year. Patterns of use varied by cannabinoid: Δ⁷-THC (10.0%), Δ⁸-THC (21.8%), Δ¹⁰-THC (14.0%), THC-O-acetate (5.2%), THC homologue tetrahydrocannabiphorol (24.4%), and hydrogenated derivative hexahydrocannabinol (3.5%). Older individuals had lower odds of reporting past-year semi-synthetic cannabinoid use (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI] = 0.94, 0.99, <i>p</i> = 0.004); factors associated with higher odds of reporting semi-synthetic cannabinoid use included reporting 101-1,000 lifetime cannabis uses (vs. <100 times; aOR = 2.55, 95% CI = 1.02, 6.38, <i>p</i> = 0.046), reporting 1,001-10,000 lifetime cannabis uses (vs. <100 times; aOR = 4.40, 95% CI = 1.57, 12.33, <i>p</i> = 0.005), and reporting non-inhaled forms of cannabis as the most frequent route of administration in the past year (vs. smoking; aOR = 2.98, 95% CI = 1.18, 7.53, <i>p</i> = 0.021). Adverse effects were reported across all semi-synthetic cannabinoids. <b>Discussion:</b> Semi-synthetic cannabinoid use was prevalent among this sample, especially among younger individuals. Despite their popularity, adverse effects underscore the need for regulation and research to address these products' safety and public health implications.