Synthetic cannabinoids can trigger new-onset psychosis and psychotic relapses, and their effects are more complex than natural cannabis | Research

The takeaway

A review of clinical reports found that synthetic cannabinoids induce psychotic symptoms including new-onset psychosis and relapses, with effects that are more complex and potentially more dangerous than those of natural cannabis.

Read this if you want to understand why synthetic cannabinoids carry different and potentially greater psychosis risks than natural cannabis.

SCs are full agonists at cannabinoid receptors; THC is a partial agonist

What the researchers found

Researchers reviewed the clinical literature on psychotic symptoms following synthetic cannabinoid (SC) use.

Multiple clinical reports documented induction of psychotic symptoms after consuming SC products, including both new-onset psychosis in people with no psychiatric history and psychotic relapses in those with prior episodes.

The review found that the relationship between SCs and psychosis is more complex than any single chemical component can explain. Unlike natural cannabis, SC products contain a constantly changing mix of potent full agonists at cannabinoid receptors, compared to THC which is a partial agonist.

The authors concluded that the psychotic effects of SCs may not be a simple extension of the typical effects of cannabis or natural cannabinoids, warranting distinct clinical consideration.

Why it matters

Synthetic cannabinoids are often misleadingly marketed as cannabis alternatives, but their pharmacology is fundamentally different and more dangerous. Understanding that SC-related psychosis operates through distinct mechanisms helps clinicians recognize and treat these cases appropriately.

The numbers in context

SCs broadly impact psychological state (mood, suicidal thoughts, psychosis) and physiological functions (cardiovascular, gastrointestinal, urinary). Products have gained popularity as abused drugs over the past decade across many countries.

How the study worked

Literature review of clinical reports, case studies, and pharmacological research on synthetic cannabinoid products and their association with psychotic symptoms, including analysis of chemical mechanisms.

What this study cannot tell us

Much of the evidence comes from case reports and clinical observations rather than controlled studies. The constantly changing chemical composition of SC products makes it difficult to attribute effects to specific compounds. Confounding from polysubstance use is common in clinical reports.

How to read the evidence

This review synthesizes clinical reports and pharmacological research, providing moderate evidence on the distinct psychosis risk profile of synthetic cannabinoids.

When this study was published

Published in 2018. New synthetic cannabinoid compounds continue to emerge, and the specific products available have changed since publication.

The bigger picture

The distinction between synthetic and natural cannabinoids is clinically important. SCs are full agonists at cannabinoid receptors while THC is a partial agonist, which means SCs can produce much stronger receptor activation. This pharmacological difference likely explains why SC-related psychosis appears more severe and unpredictable than cannabis-related psychosis.

Questions still open

Which specific synthetic cannabinoid compounds carry the highest psychosis risk? Do SC-induced psychotic episodes have different long-term outcomes than cannabis-induced episodes? Should clinical guidelines for substance-induced psychosis differentiate between natural and synthetic cannabinoids?

Common questions

Are synthetic cannabinoids the same as cannabis?

No. Despite being marketed as cannabis alternatives, synthetic cannabinoids are pharmacologically different. They are full agonists at cannabinoid receptors (producing stronger activation), while THC in natural cannabis is a partial agonist.

Can synthetic cannabinoids cause psychosis in someone with no history?

Yes. The review documented cases of new-onset psychosis (first episodes in people with no prior psychiatric history) following synthetic cannabinoid use, in addition to relapses in those with previous episodes.

Read the original research

Psychosis and synthetic cannabinoids.

Psychiatry research, 268, 400-412

View on PubMed ↗Publisher’s paper ↗

Citation

Deng, Huiqiong; Verrico, Christopher D; Kosten, Thomas R; Nielsen, David A. (2018). Psychosis and synthetic cannabinoids.. Psychiatry research, 268, 400-412. https://doi.org/10.1016/j.psychres.2018.08.012