Abstract
Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.
Highlights
Synthetic cannabinoid receptor agonists (SCRAs) were first identified in branded herbal smoking mixtures in 2008 (Auwärter et al 2009)
For all types of SCRA, the median amount used per session was 0.5 grams (IQR 1.4) and 45.4% of participants reported using between 11–50 times in the past 12-months, 27.1% between 51–100 times, and 27.5% >100 times
This is the first study to examine the contribution of quantity and frequency of SCRA use to withdrawal symptoms, and our findings suggest that people who use SCRAs more frequently and in greater amounts are significantly more likely to experience a greater number of withdrawal symptoms upon cessation, consistent with those reported within clinical settings (Macfarlane and Christie 2015; Nacca et al 2013)
Summary
Synthetic cannabinoid receptor agonists (SCRAs) were first identified in branded herbal smoking mixtures in 2008 (Auwärter et al 2009). Extended author information available on the last page of the article psychoactive component of cannabis—showing activity at both cannabinoid type 1 receptors (CB1Rs) and cannabinoid type 2 receptors (CB2Rs), structurally, SCRAs are a diverse group of chemicals varying widely in potency, receptor affinity, and effect profile (EMCDDA 2017). Whilst there are licenced cannabinoid-based medicinal products which are produced synthetically (e.g. Dronabinol and Nabilone), these are not typically classified as SCRAs, which, by contrast, are used exclusively for recreational purposes and do not fall under descriptions of medicinal products (e.g. under common EU Law; UNODC 2015). Manufactured by groups of clandestine chemists or chemical companies based in China, SCRAs are typically synthesised as powders, dissolved in solvent (e.g. acetone), and sprayed onto inert herbal material
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