Challenging CBD protective effect against THC-related outcomes: a call for robust clinical trials.

Abstract

Cannabis is consumed by more than 182 million people worldwide [1] and research on cannabinoids is booming, with the potential of supporting public health initiatives that promote safer cannabis use. It has been proposed that cannabidiol (CBD) can guard against adverse effects of tetrahydrocannabinol (THC), which has led governmental and academic bodies to recommend the use of cannabis products with high CBD : THC ratios (e.g. [2]). We believe that the evidence for this is weak. Observational studies have demonstrated a possible protective effect of CBD on memory and psychotic symptoms [3-5]. However, this type of study has a high risk of selection bias and limited capacity to distinguish between the various doses and ratios of THC and CBD contained in cannabis. Experimental studies supporting the protective effect of CBD have typically used dosages that are not found in real-world contexts [6]. To reflect such conditions, studies should use cannabis products containing CBD levels found in the recreational market (e.g. below 100 mg), not only assessing oral, but also smoked and vaporized administration methods. Well-designed randomized trials have actually yielded a mixed and complex pattern of results [6]. For example, when compared to THC alone, vaporized THC combined with high-dose CBD (400 mg) reduced intoxication, while low-dose CBD (4 mg) enhanced intoxication [7]. Although vaporized CBD may attenuate THC impairment on emotional affect recognition [8], it has not been clearly found to mitigate psychotic symptoms and memory impairment [9]. Equivalent doses of vaporized CBD and THC may worsen attention and working memory compared with THC alone [10]. Despite conflicting evidence, users are currently encouraged to favour products containing CBD which, if most probably not harmful, may not provide the protective effects advertised thus far. Consequently, there is an urgent need for well-designed clinical trials in ecologically valid conditions. These conditions include naturalistic dosage corresponding to recreational market products. InSYS therapeutics provided cannabidiol to D.J.-A's team for a clinical trial funded by the Canadian Institute of Health Research. The Quebec government funded D.J.-A.'s work, but had no role in writing or deciding to publish this letter. Violaine Mongeau-Pérusse: Conceptualization; formal analysis; methodology. Didier Jutras-Aswad: Conceptualization; formal analysis; methodology; supervision.