In a placebo-controlled crossover trial conducted in healthy adults who infrequently use cannabis, a comparison of acute effects of smoked vs vaporized cannabis at 2 different doses is reported, with greater effects and higher blood cannabinoid concentrations achieved from vaporization.
We are living in an era of unprecedented rapid change to cannabis use legislation across jurisdictions worldwide. Increased availability of cannabis, and inherent perceived endorsement of its apparent harmlessness, will inevitably lead to some increase in uptake by novice or infrequent users.1,2 Missives around potential safety of delivery by 1 method vs another circulate, yet like much of the anecdotal information that abounds, there is little scientific examination of concomitant consequences. In a placebo-controlled crossover trial conducted in healthy adults who infrequently use cannabis, Spindle and colleagues3 report a comparison of acute effects of smoked vs vaporized cannabis at 2 different doses. Dose-orderly subjective drug effects, cardiovascular effects, and impaired cognitive and psychomotor function were observed, with greater effects and higher blood cannabinoid concentrations achieved from vaporization. The authors warn that even relatively low-potency cannabis can adversely affect inexperienced users. Acute cannabis or cannabinoid administration studies have typically shown impairment across the domains of memory, attention, and psychomotor function.4 The literature indicates that intravenous, smoked, and vaporized administration exerts more immediate but shorter-lasting effects than oral or sublingual routes. Spindle et al3 extend these observations by distinguishing further between smoked and vaporized routes. Of note, the same low dose of 10 mg of Δ9-tetrahydrocannabinol (THC) in cannabis resulted in significant differences relative to placebo on 16 of a total 33 pharmacodynamic outcome measures following vaporized cannabis administration, but only 8 after smoking. The higher dose of 25 mg of THC resulted in 21 and 15 significant outcomes for vaporized and smoked cannabis, respectively. Hence, vaporized low-dose cannabis produced a greater number of measurable impairments than smoked high-dose cannabis in this sample of infrequent users. These findings have implications for novice users, trying for the first time the multitude of products available legally in some US states, and believing vaporization to be a safer route of administration. Similarly, medicinal users and doctors advising patients need to be aware of the potential for vaporization to induce stronger effects, including adverse effects, and if choosing this route of administration, commence with lower doses. Beyond an early phase of initiation, if use was continued to become frequent, tolerance may develop to some of the cognitive and subjective effects as observed in acute administration studies in frequent users; however, tolerance generally manifests as a blunted effect rather than an absence of observable effects.4 Not many studies have directly compared acute administration effects in frequent and infrequent users; it would be interesting to see whether vaporization relative to smoking also produces stronger effects in frequent cannabis users, particularly on the range of outcomes examined by Spindle and colleagues.3 The cannabis plant matter used in the study by Spindle and colleagues3 contained a very low proportion of cannabidiol (CBD) relative to THC. There is significant interest in the potential for CBD to ameliorate adverse effects of THC (among a range of clinical therapeutic applications) and a few vaporization studies have begun to investigate higher doses of CBD delivered by these means.5 It appears important to determine whether higher proportional concentrations of CBD in plant matter may protect against the greater adverse effects observed in the study by Spindle and colleagues,3 and indeed whether protection may be conferred for frequent and infrequent users alike. This evidence may be used toward informing public health policies, including recommendations to + Related article