Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review

Abstract

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings.

New Psychoactive Substances: Health and Legal Challenges

“…The use of synthetic and semi-synthetic cannabinoids has been associated with a variety of adverse effects, including anxiety, agitation, hallucinations, seizures, and, in extreme cases, severe risks to life. However, the long-term effects of repeated use are poorly understood [39]. Fatalities associated with synthetic cannabinoids have been reported [40,41].…”

Fatal Overdose with the Cannabinoid Receptor Agonists MDMB-4en-PINACA and 4F-ABUTINACA: A Case Report and Review of the Literature

“…Its chemical structure is most similar to APINACA (AKB48) and 5F-APINACA (5F-AKB48), which are potent agonists of both the CB1 receptor and the CB2 receptor [ 16 ]. 4F-ABUTINACA appeared in Asia in 2020, but no data are available about its pharmacological properties [ 17 , 18 , 19 ].…”

“…Its chemical structure is most similar to APINACA (AKB48) and 5F-APINACA (5F-AKB48), which are potent agonists of both the CB1 receptor and the CB2 receptor [16]. 4F-ABUTINACA appeared in Asia in 2020, but no data are available about its pharmacological properties [17][18][19]. Based on in vitro biological activity assessment at cannabinoid type 1 (CB1) receptor via its interaction with β-arrestin 2, the potency and efficacy of MDMB-4en-PINACA is similar to that of their structural analogs 4F-MDMB-BINACA and 5F-MDMB-PINACA.…”

Advances in Neuropsychology: Top Papers Published in Brain Sciences in 2022–2023

“…Crucial information about these substances that is typically lacking in the early periods of use regards their potential toxic effects. The systematic review by de Oliveira et al [ 7 ] focuses on synthetic cannabinoids. Originally synthesized for research purposes, these authors found that their main use was as drugs of abuse mixed with other various substances and herbs.…”