A within-subject cross-over trial comparing the acute effects of vaporized delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in healthy adults.

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ID: 282398
2025
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Abstract
The prevalence and accessibility of Δ8-tetrahydrocannabinol (Δ8-THC), a chemical isomer of Δ9-tetrahydrocannabinol (Δ9-THC), has increased drastically, yet no controlled studies have directly compared the effects of vaporized Δ8-THC and Δ9-THC . Twenty healthy adults with no past-month cannabis exposure completed five randomized outpatient sessions in a within-subjects, double-blind, crossover design. Participants inhaled Δ8-THC (10, 20, 40mg), Δ9-THC (20mg), or placebo (distilled water) using the Mighty Medic vaporizer. Measures included subjective drug effects, cognitive/psychomotor performance, puff topography, vital signs, and whole blood concentrations of Δ8-THC, Δ9-THC, and their metabolites. All Δ8-THC doses and Δ9-THC produced subjective drug effects that differed from placebo. 20mg Δ9-THC elicited stronger ratings of "drug effect" and "unpleasant" than 10mg Δ8-THC; no other subjective effects differed between Δ8-THC and Δ9-THC. 20mg Δ9-THC impaired DRUID performance compared with placebo; no other significant differences were observed between conditions on cognitive/psychomotor measures. Few pharmacodynamic differences were observed between Δ8-THC doses. Evidence of compensatory puffing emerged, with longer/larger puffs at lower Δ8-THC doses and placebo. Blood cannabinoid concentrations revealed that Δ8-THC metabolism differed from Δ9-THC, with less psychoactive 11-OH metabolite formed after Δ8-THC exposure. Various doses of vaporized Δ8-THC elicited comparable psychoactive effects as vaporized Δ9-THC, which is noteworthy considering Δ8-THC is less potent and generally perceived as less harmful/intoxicating than Δ9-THC. The magnitude of effects from cannabinoids is dictated by several factors including dose, route of administration, and, for inhaled methods, puffing behaviors. These data should be considered in future drug policy and public education initiatives.
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Authors Spindle, Tory R; Zamarripa, C Austin; Schriefer, Destiny; Cone, Edward J; Winecker, Ruth; Flegel, Ronald; Hayes, Eugene; Davis, Lisa S; Kuntz, David; Vandrey, Ryan
Journal Drug and alcohol dependence
Year 2025
DOI
10.1016/j.drugalcdep.2025.112684
URL
Keywords
cannabinoids Δ8-thc Δ8-tetrahydrocannabinol Δ9-thc Δ9-tetrahydrocannabinol

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