Supplementary Material for: Synthetic cannabinoid withdrawal: A systematic review of case reports

Abstract
Introduction: Synthetic cannabinoids are novel psychoactive substances with potential for abuse and severe withdrawal symptoms. Despite widespread use, research on withdrawal is limited. We conducted a systematic review of case reports describing SC withdrawal symptoms.
Methods: Literature searches were conducted across databases, including PubMed/Medline, Scopus, EMBASE, and PsycINFO, to identify case reports from inception to March 2025. Eligible studies involved human cases with confirmed SC use and clearly described withdrawal symptoms. Study quality was assessed using the CARE guidelines checklist.
Results: N=11 eligible case reports on SC withdrawal identified. Predominantly male (82%), mean age of 28.08 (SD 7.78). Most frequent withdrawal symptoms: psychosis (n=9), agitation/irritability (n=8), nausea/vomiting (n=6), seizures (n=5), tachycardia (n=4), and insomnia (n=3). Rarer effects like delirium, rhabdomyolysis, and auditory/visual hallucinations were also documented. Symptoms emerged within 24-48 hours (62%) and resolved within one week. Case report quality was variable, with an average of 8 out of 13 CARE checklist items reported.
Conclusion: SC withdrawal manifests with a broad spectrum of physiological and psychological symptoms that can rapidly escalate and require prompt medical management in certain cases. SC withdrawal symptoms are more severe and unpredictable compared to natural cannabinoids, particularly among daily and frequent users. The findings highlight SC withdrawal as an understudied yet clinically important syndrome, necessitating further research to elucidate neurobiological mechanisms and develop evidence-based treatment protocols.

摘要

引言：合成大麻素（Synthetic cannabinoids）是一类具有滥用潜力及严重戒断症状的新型精神活性物质。尽管其滥用范围广泛，但针对其戒断反应的研究仍较为有限。本研究针对描述合成大麻素戒断症状的病例报告开展了系统综述。

方法：本研究于PubMed/Medline、Scopus、EMBASE及PsycINFO等数据库中进行文献检索，检索时限为建库至2025年3月，旨在筛选符合要求的病例报告。纳入研究需包含经确认的合成大麻素使用史人类病例，并清晰描述戒断症状。研究质量采用CARE指南清单（CARE Guidelines Checklist）进行评估。

结果：共筛选得到11篇符合纳入标准的合成大麻素戒断相关病例报告。研究对象以男性为主（占比82%），平均年龄为28.08岁（标准差SD 7.78）。最常见的戒断症状包括精神病性症状（n=9）、激越/易怒（n=8）、恶心/呕吐（n=6）、癫痫发作（n=5）、心动过速（n=4）及失眠（n=3）；此外还记录到谵妄、横纹肌溶解、视听幻觉等罕见不良反应。62%的病例中，戒断症状于用药后24~48小时内出现，并在一周内缓解。病例报告的质量参差不齐，平均仅完成13项CARE指南清单条目中的8项。

结论：合成大麻素戒断可表现为涵盖生理与心理的多维度症状谱系，部分病例中症状可快速进展，需及时予以医学干预。与天然大麻素相比，合成大麻素的戒断症状更为严重且难以预判，这在每日或高频使用者中尤为显著。本研究结果提示，合成大麻素戒断是一类尚未被充分研究却具有重要临床意义的综合征，亟需开展进一步研究以阐明其神经生物学机制，并制定基于循证依据的治疗方案。