Synthetic Cannabinoid Withdrawal Included Psychosis, Seizures, and Rhabdomyolysis | Research

The takeaway

A systematic review of 11 case reports found synthetic cannabinoid withdrawal produced more severe symptoms than natural cannabis withdrawal, including psychosis (82% of cases), seizures (45%), and rhabdomyolysis, typically emerging within 24-48 hours.

Emergency physicians, addiction medicine specialists, and toxicologists managing synthetic cannabinoid users.

What the researchers found

Most frequent withdrawal symptoms were psychosis (n=9, 82%), agitation/irritability (n=8, 73%), nausea/vomiting (n=6, 55%), seizures (n=5, 45%), tachycardia (n=4, 36%), and insomnia (n=3, 27%). Rarer effects included delirium, rhabdomyolysis, and hallucinations. Symptoms emerged within 24-48 hours in 62% of cases and resolved within 1 week. Cases were predominantly male (82%), mean age 28.

Why it matters

Synthetic cannabinoids are often marketed as legal alternatives to cannabis, but their withdrawal profile is dramatically different and more dangerous. Psychosis in 82% of cases and seizures in 45% highlight the need for clinical awareness and prompt medical management.

The numbers in context

11 case reports. 82% male. Mean age 28.08 (SD 7.78). Psychosis: 82%. Agitation: 73%. Nausea/vomiting: 55%. Seizures: 45%. Tachycardia: 36%. Insomnia: 27%. Onset: 24-48 hours (62%). Resolution: within 1 week. Average CARE checklist score: 8/13.

How the study worked

Systematic review of PubMed/Medline, Scopus, EMBASE, and PsycINFO from inception to March 2025 for case reports describing synthetic cannabinoid withdrawal. 11 eligible case reports identified. Quality assessed using CARE guidelines checklist (average 8/13 items).

What this study cannot tell us

Only 11 case reports available worldwide, reflecting both rarity and underreporting. Case reports are the lowest level of evidence. No standardized withdrawal assessment tools were used across cases. Variable quality of reporting. Cannot determine incidence of withdrawal among synthetic cannabinoid users.

How to read the evidence

Systematic search with quality assessment, but limited to case reports (lowest evidence level) with only 11 cases worldwide, likely underrepresenting the true scope.

When this study was published

Published 2025, searching through March 2025.

The bigger picture

Natural cannabis withdrawal is generally mild (irritability, insomnia, decreased appetite). Synthetic cannabinoid withdrawal can be life-threatening. This stark difference reflects the much higher potency and different pharmacology of synthetic cannabinoids, which are full agonists at CB1 receptors compared to cannabis's partial agonism.

Questions still open

What percentage of regular synthetic cannabinoid users experience withdrawal symptoms
Whether benzodiazepine or antipsychotic protocols are more effective for managing synthetic cannabinoid withdrawal

Common questions

How is synthetic cannabinoid withdrawal different from marijuana withdrawal?

Natural cannabis withdrawal typically causes mild irritability, insomnia, and appetite changes. Synthetic cannabinoid withdrawal can cause psychosis, seizures, rhabdomyolysis, and delirium, often requiring emergency medical care. The difference reflects synthetic cannabinoids' much higher potency at brain receptors.

Why are synthetic cannabinoids more dangerous?

Unlike THC (a partial agonist), synthetic cannabinoids are full agonists at CB1 receptors with much higher binding affinity. This means they cause stronger receptor activation, leading to more severe dependence and more dangerous withdrawal when stopped abruptly.

Read the original research

Synthetic Cannabinoid Withdrawal: A Systematic Review of Case Reports.

European addiction research, 31(4), 274-285

View on PubMed ↗Publisher’s paper ↗

Citation

Sharma, Rishi; Weinstein, Aviv. (2025). Synthetic Cannabinoid Withdrawal: A Systematic Review of Case Reports.. European addiction research, 31(4), 274-285. https://doi.org/10.1159/000546633