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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 &gt;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 (<jats:italic>n<\/jats:italic>\u2009=\u2009284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for &gt;1\u00a0day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (&gt;51 vs. 11\u201350 times per year: IRR\u2009=\u20091.43, 95% CI: 1.16, 1.77, <jats:italic>p<\/jats:italic>\u2009=\u20090.005) and quantity (grams per session: IRR\u2009=\u20091.13, 95% CI: 1.05, 1.22, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) 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 (<jats:italic>p<\/jats:italic>\u2019s\u2009&lt;\u20090.001). 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.<\/jats:p>","DOI":"10.1007\/s00213-021-05945-1","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T10:03:21Z","timestamp":1631873001000},"page":"1349-1357","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis"],"prefix":"10.1007","volume":"239","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-2731","authenticated-orcid":false,"given":"Sam","family":"Craft","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Ferris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica J.","family":"Barratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa J.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Lynskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Winstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom P.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"5945_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1177\/0269881119826592","volume":"33","author":"H Akram","year":"2019","unstructured":"Akram H, Mokrysz C, Curran HV (2019) What are the psychological effects of using synthetic cannabinoids? 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