A within-subject cross-over trial comparing the acute effects of vaporized delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in healthy adults.
Tory R Spindle, C Austin Zamarripa, Destiny Schriefer, Edward J. Cone, Ruth Winecker, Ronald Flegel, Eugene Hayes, Lisa S. Davis, David Kuntz, Ryan Vandrey
Drug and Alcohol Dependence July 1, 2025 DOI: 10.1016/j.drugalcdep.2025.112684 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, within-subjects crossover trial Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy adults with no past-month cannabis exposure |
| Interventions | Δ8-tetrahydrocannabinol (Δ8-THC) Δ9-tetrahydrocannabinol (Δ9-THC) placebo (distilled water) |
| Dose | Δ8-THC 10, 20, 40 mg; Δ9-THC 20 mg |
| Duration | Five randomized outpatient sessions |
| Measures | DRUID |
| Topics | Cannabis |
| Keywords | Cannabinoids δ8-THC Δ8-tetrahydrocannabinol δ9-THC Δ9-tetrahydrocannabinol |
| Key findings | Vaporized Δ8-THC at 10, 20, and 40 mg and Δ9-THC at 20 mg all produced subjective drug effects differing from placebo. 20 mg Δ9-THC elicited stronger "drug effect" and "unpleasant" ratings than 10 mg Δ8-THC and impaired DRUID performance versus placebo, while no other cognitive or subjective differences were significant between cannabinoids. Blood data indicated less psychoactive 11-OH metabolite formation after Δ8-THC, and compensatory puffing (longer/larger puffs) occurred at lower Δ8-THC doses and placebo. |
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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cites 3
- Review of delta‐8‐tetrahydrocannabinol (Δ8‐THC): Comparative pharmacology with Δ9‐THC British Journal of Pharmacology August 1, 2022
- Weed Light: An Exploratory Study of Delta-8 THC Conversations on Reddit June 8, 2022
- Delta-8-THC: Delta-9-THC’s nicer younger sibling? Journal of Cannabis Research January 4, 2022