Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal
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Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies characterizing (1) SCs acute effects, (2) withdrawal upon cessation of use, and (3) effective treatment strategies for SC use disorder are urgently needed.
KeywordsSpice K2 Synthetic cannabinoid Adverse effects Dependence Withdrawal Cannabis
This research was supported by the US National Institute on Drug Abuse Grants DA039123, DA036809, and DA02775. The authors acknowledge and appreciate Dr. Margaret Haney for the discussion and feedback throughout manuscript preparation and the exceptional assistance of Damaris Rocha, Vivian Mao, Nicole Ann Borchard, Ursula Rogers, Olivia Derella, Bennett Wechsler, Stephanie Rivera, Chananda Thavisin, Divya Ramesh, and Jorge Ginory-Perez for interviewing participants and data collection.
Compliance with Ethical Standards
All study procedures were approved by the Institutional Review Board of the New York State Psychiatric Institute and were in accord with the Declaration of Helsinki.
Conflict of Interest
Ziva D. Cooper is a non-compensated board member of KannaLife, Inc. and has received consultancy fees from PharmaCann, LLC. Dr. Cooper has received research funds from Insys Therapeutics.
Human and Animal Rights and Informed Consent
This manuscript does include data obtained from human subjects.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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