Study Design and Procedure

This within-individuals, double-blind, crossover study was conducted at the Johns Hopkins Behavioral Pharmacology Research Unit and followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline (Trial Protocol in Supplement 1). A double-dummy procedure to blind participants and research staff to inhalation method was not used in order to equally capture peak drug effects that occur immediately after inhalation. All participants completed six 8.5-hour outpatient sessions that differed only by inhalation method (smoked vs vaporized) and THC dose (0 mg, 10 mg, or 25 mg). All participants were compensated for their time. Sessions were separated by at least 1 week and clustered by inhalation method (ie, cannabis was smoked for the first 3 sessions and vaporized the final 3 sessions or vice versa). The order of inhalation method was counterbalanced across participants (ie, half of participants completed smoked sessions first and the other half completed vaporized sessions first). The THC dose order was randomized within each inhalation method cluster (Figure 1).

THC indicates Δ9-tetrahydrocannabinol.

At the start of each session, participants completed a urine drug screening and alcohol breathalyzer to confirm compliance with instructions to not use illicit drugs or alcohol; female participants also completed a urine pregnancy test. An intravenous catheter was placed in a forearm vein of the nondominant arm and a baseline blood sample was collected. Additional baseline assessments of heart rate (HR), blood pressure (BP), cognitive and psychomotor performance, and subjective drug effects were obtained. Following baseline assessments, participants self-administered the assigned cannabis dose by inhaling the study product ad libitum within a 10-minute period. During vaporized cannabis sessions, the Volcano Medic (Storz & Bickel, Oakland, California) was used to heat and aerosolize the cannabis, which was then trapped in a balloon and given to participants to inhale ad libitum until the balloon was empty. To ensure complete vaporization of the highest dose, participants inhaled 3 balloons within the designated 10-minute period. A new balloon was used for each experimental session to avoid contamination from prior doses. During smoked cannabis sessions, participants were given a small handheld pipe prefilled with cannabis and given 10 minutes to self-administer the entire dose by igniting the plant material with a lighter and inhaling the resulting smoke. To more effectively blind participants and study staff, an opaque bag was used to cover the vaporizer balloons and thus decrease the visibility of the vapor inside, and the pipe was fitted with a metal top to conceal the plant material; the metal top also minimized drug loss owing to sidestream smoke. Unblinded research pharmacy staff visually inspected the contents of the pipe to ensure complete dose consumption.