Two Cases of Synthetic Cannabinoid Withdrawal: More Severe Than Natural Cannabis Withdrawal | Research

The takeaway

Two patients with prolonged habitual synthetic cannabinoid use experienced withdrawal characterized by anxiety and tachycardia, more severe than typical cannabis withdrawal, and symptoms did not improve with natural THC.

Read this if you or someone you know uses synthetic cannabinoid products and is experiencing withdrawal symptoms.

Natural THC did not relieve synthetic cannabinoid withdrawal symptoms

What the researchers found

Two patients presented with withdrawal symptoms from prolonged use of synthetic cannabinoids. The withdrawal syndrome was primarily characterized by anxiety and tachycardia without neurological findings or electrolyte disturbances.

The withdrawal was described as more severe than typical delta-9-THC withdrawal, which features anxiety, muscle aches, chills, and appetite loss. Notably, natural THC did not improve the synthetic cannabinoid withdrawal symptoms, possibly because synthetic products contain multiple heterogeneous compounds, including amphetamine-like substances, or because synthetic cannabinoids have much higher receptor potency than natural THC.

Why it matters

The finding that natural THC did not improve synthetic cannabinoid withdrawal is clinically important. It means the agonist replacement strategy (using natural THC to treat synthetic cannabinoid withdrawal, analogous to methadone for heroin) may not work, likely because synthetic cannabinoids are far more potent or act differently than natural THC.

The numbers in context

2 patients with synthetic cannabinoid withdrawal. Primary symptoms: anxiety and tachycardia. No neurological findings or electrolyte disturbances. Natural THC did not help. Treatment: benzodiazepines (first line), quetiapine (possible adjunct).

How the study worked

Case report of two patients with withdrawal symptoms presumed to be from synthetic cannabinoid use. Clinical presentation and management documented.

What this study cannot tell us

Only 2 cases reported. The specific synthetic cannabinoids used were likely not identified analytically. Self-reported drug use histories. The products may have contained non-cannabinoid adulterants. No standardized assessment of withdrawal severity.

How to read the evidence

Case report of 2 patients; early clinical documentation of a novel withdrawal syndrome.

When this study was published

Published in 2013. Synthetic cannabinoid withdrawal is now better recognized, though treatment remains challenging.

The bigger picture

This was only the second report of synthetic cannabinoid withdrawal syndrome. As these products became more common, withdrawal would be increasingly recognized as a clinical entity distinct from cannabis withdrawal, requiring different management approaches.

Questions still open

What is the optimal treatment for synthetic cannabinoid withdrawal? Why does natural THC not help? How common is dependence and withdrawal among regular synthetic cannabinoid users? Should emergency departments stock specific treatments for this withdrawal syndrome?

Common questions

Is synthetic cannabinoid withdrawal different from cannabis withdrawal?

Yes. According to this report and others, synthetic cannabinoid withdrawal appears more severe, with prominent anxiety and tachycardia. Additionally, natural THC (which could theoretically substitute) did not improve symptoms, suggesting the withdrawal involves different or more intense mechanisms than natural cannabis withdrawal.

How is synthetic cannabinoid withdrawal treated?

The optimal treatment remains unknown. These authors suggested benzodiazepines as a reasonable first-line approach for anxiety and tachycardia, with quetiapine as a possible adjunct. The key challenge is that the specific compounds in synthetic products are often unknown, making targeted treatment impossible. Supportive care with symptom management is currently the standard approach.

Read the original research

The synthetic cannabinoid withdrawal syndrome.

Journal of addiction medicine, 7(4), 296-8

View on PubMed ↗Publisher’s paper ↗

Citation

Nacca, Nicholas; Vatti, Deepak; Sullivan, Ross; Sud, Payal; Su, Mark; Marraffa, Jeanna. (2013). The synthetic cannabinoid withdrawal syndrome.. Journal of addiction medicine, 7(4), 296-8. https://doi.org/10.1097/ADM.0b013e31828e1881