Spice and K2: clinical effects, toxicity, and three cases of cannabis-dependent users switching to synthetics | Research

The takeaway

A systematic review of synthetic cannabinoid reports found mostly acute anxiety and psychosis as adverse effects, while three case studies showed cannabis-dependent users found synthetics effectively relieved their cannabis withdrawal.

Read this if you want to understand the health risks of synthetic cannabinoid products.

Three cannabis-dependent users found synthetic cannabinoids relieved their withdrawal

What the researchers found

The researchers conducted a systematic review of published reports on clinical effects of synthetic cannabinoids (SCs) in humans. Most reports highlighted potential toxicity, particularly acute anxiety and psychosis episodes.

The three documented cases were notable: experienced marijuana users with confirmed cannabis dependence and physical withdrawal began using SC products ("Spice/K2") regularly. They reported effects similar to marijuana and found them well tolerated. All three reported that SC products effectively alleviated their cannabis withdrawal symptoms.

The biopsychosocial factors behind SC initiation included drug testing avoidance (SCs were not detected on standard tests), legal status, curiosity, and self-medication of withdrawal. These factors helped explain the rapid adoption of SCs among cannabis-dependent populations.

Why it matters

The finding that SC products could relieve cannabis withdrawal confirmed their pharmacological overlap with THC. But the reports of acute anxiety and psychosis, combined with unknown long-term effects and rapidly changing formulations, raised serious public health concerns.

The numbers in context

Three documented cases of cannabis-dependent users switching to SCs. All reported cannabis withdrawal relief. Most published reports highlighted anxiety and psychosis as adverse effects. SCs not detected on standard drug tests at the time.

How the study worked

Systematic review of published reports on synthetic cannabinoid clinical effects, plus detailed documentation of three case studies of cannabis-dependent individuals who regularly used SC products.

What this study cannot tell us

Case series (3 cases) is very limited evidence. Systematic review found mostly case reports and anecdotal data. SC products varied enormously in composition and potency. The rapidly evolving SC landscape meant findings quickly became outdated.

How to read the evidence

Systematic review of mostly case-level evidence plus three documented cases. Very limited but represented the state of knowledge for a rapidly emerging problem.

When this study was published

Published in 2012. The synthetic cannabinoid landscape has changed dramatically, with many compounds now scheduled and new ones constantly emerging.

The bigger picture

The SC phenomenon illustrated what happens when prohibition drives users toward unregulated alternatives. Products designed to evade drug testing and legal restrictions ended up being potentially more dangerous than the substance users were trying to avoid.

Questions still open

Are SCs more dangerous than natural cannabis? Do SC users develop novel dependence syndromes? Would legalizing cannabis reduce SC use? How can healthcare providers screen for SC use?

Common questions

Are synthetic cannabinoids safe?

No. While the three case study users found them well-tolerated, the broader literature showed reports of acute anxiety, psychosis, and other serious adverse effects. SC products have unpredictable compositions and potencies, making them considerably more risky than natural cannabis.

Why did people switch from marijuana to synthetics?

The main reasons were: standard drug tests could not detect SCs, they were legally available in many places, and as this study showed, they effectively relieved cannabis withdrawal. These factors drove adoption despite potential dangers.

Read the original research

"Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans.

The American journal on addictions, 21(4), 320-6

View on PubMed ↗Publisher’s paper ↗

Citation

Gunderson, Erik W; Haughey, Heather M; Ait-Daoud, Nassima; Joshi, Amruta S; Hart, Carl L. (2012). "Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans.. The American journal on addictions, 21(4), 320-6. https://doi.org/10.1111/j.1521-0391.2012.00240.x