Third-generation synthetic cannabinoids caused more severe poisoning with seizures in 27% and symptoms lasting 24+ hours in 34% | Research

The takeaway

A clinical study of 44 ED patients who used AB-CHMINACA or MDMB-CHMICA found that these newer synthetic cannabinoids produced more severe neuropsychiatric symptoms than earlier generations, including seizures (27%), prolonged symptoms (34% lasting 24+ hours), and severe poisoning in 20%.

Read this if you want to understand why newer synthetic cannabinoids are more dangerous than earlier products.

27% had seizures; 34% had symptoms lasting 24+ hours

What the researchers found

Researchers prospectively studied 44 patients treated in emergency departments after using synthetic cannabinoids, with lab confirmation of AB-CHMINACA and/or MDMB-CHMICA in blood or urine.

Based on the Poison Severity Score, poisoning severity was minor in 4 cases, moderate in 31 cases, and severe in 9 cases (20%).

The most common neuropsychiatric symptoms were CNS depression (61%), disorientation (45%), generalized seizures (27%), combativeness (18%), and extreme agitation (16%). Symptoms lasted 24 hours or longer in 34% of cases.

These rates were notably higher than those previously reported for earlier-generation synthetic cannabinoids (aminoalkylindole-type like JWH-018). The authors concluded that these "third generation" synthetic cannabinoids appear to be associated with more severe clinical toxicity.

In 19 of 44 cases, more than one synthetic cannabinoid was detected, complicating attribution of effects to specific compounds.

Why it matters

As synthetic cannabinoid chemistry evolves, each new generation appears to carry increased risk. The finding that third-generation compounds produce more seizures, more severe poisoning, and longer symptom duration than earlier generations is a critical public health warning.

The numbers in context

44 patients (39 male, 5 female, ages 12-48). AB-CHMINACA detected in 20 serum samples, MDMB-CHMICA in 19. Severe poisoning: 20%. Seizures: 27%. Symptoms 24+ hours: 34%. CNS depression: 61%. Disorientation: 45%. Multiple SCs in 19 cases.

How the study worked

Prospective observational study of patients in EDs after synthetic cannabinoid use. Clinical and lab data reported to poison control centre. Serum and/or urine analyzed by LC-MS/MS. 44 patients (39 male, 5 female, ages 12-48). Severity graded by Poison Severity Score.

What this study cannot tell us

In 19 of 44 cases, multiple synthetic cannabinoids were present, making it difficult to attribute effects to specific compounds. Other psychoactive substances were found in 7 cases. Prospective design at select EDs may not capture all presentations. The sample size limits generalization about specific compounds.

How to read the evidence

Prospective observational study with analytical confirmation of specific compounds provides moderate evidence on the clinical toxicity of these third-generation synthetic cannabinoids.

When this study was published

Published in 2018. New synthetic cannabinoid compounds have continued to emerge, and toxicity profiles continue to evolve.

The bigger picture

The rapid turnover of synthetic cannabinoid compounds on the drug market means that users face an evolving and increasingly dangerous chemical landscape. Each new generation of compounds can be more potent and toxic than the last, with effects that are difficult to predict from earlier products.

Questions still open

Will fourth-generation synthetic cannabinoids be even more toxic? What specific pharmacological properties make newer compounds more dangerous? Should synthetic cannabinoid presentations be managed differently based on generation?

Common questions

Are newer synthetic cannabinoids more dangerous?

This study found that AB-CHMINACA and MDMB-CHMICA (third-generation) produced higher rates of seizures (27%), severe poisoning (20%), and prolonged symptoms than previously reported for earlier synthetic cannabinoids like JWH-018.

What are the main symptoms?

The most common were CNS depression (61%), disorientation (45%), generalized seizures (27%), combativeness (18%), and extreme agitation (16%). Over a third of patients had symptoms lasting more than 24 hours.

Read the original research

Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

Clinical toxicology (Philadelphia, Pa.), 56(6), 404-411

View on PubMed ↗Publisher’s paper ↗

Citation

Hermanns-Clausen, Maren; Müller, Dieter; Kithinji, Josephine; Angerer, Verena; Franz, Florian; Eyer, Florian; Neurath, Hartmud; Liebetrau, Gesine; Auwärter, Volker. (2018). Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.. Clinical toxicology (Philadelphia, Pa.), 56(6), 404-411. https://doi.org/10.1080/15563650.2017.1393082