Introduction: Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses.

Methods: This was a two-phase, dose-ranging, placebo-controlled trial of the D8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n = 3). Phase 2 used a double-blind, random- ized, within-participant crossover design (n = 18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose.

Results: Most adverse events (AEs; 55/60) were mild. Euphoric mood was the most common AE. The 12.5, 25, and 200 mg doses produced significantly lower minimum times to complete the digit vigilance test ( ps = 0.01). The 25 mg dose showed elevations on mean ratings of ‘‘energetic’’ at 1-, 2-, and 4-h postdose, but the maximum postdose rating for this dose did not achieve statistical significance relative to placebo ([95% confidence inter- val] = 3.2 [􏰀0.5 to 6.9], p = 0.116). The 100 and 200 mg doses showed elevations on ratings of ‘‘feel a drug effect’’ and ‘‘like the drug effect.’’ Almost all urine drug screens (78/79) at 8 h postdose in the active THCV conditions tested positive for tetrahydrocannabinol (THC).

Conclusion: All THCV doses displayed a favorable safety profile. Several THCV doses showed a preliminary signal for improved sustained attention, but the effect was not dose dependent. Though mild and not associated with impairment, THC-like effects were observed at higher THCV doses. Oral THCV-containing products could lead to positive urine drug screens for THC.