Work

Neurotoxic potential of synthetic cannabinoids’ pyrolysis products

Year: 2025

Type: article

Abstract: Synthetic cannabinoids (SCs) represent a prominent class of new psychoactive substances (NPS), primarily consumed via inhalation methods such as smoking or vaping. Although the direct neurotoxic effects of SCs are well established, the pyrolysis process that occurs during smoking induces structural alterations that generate novel, frequently unidentified toxicants with potentially severe neurobiological consequences. This review addresses the neurotoxicity associated with parent SC compounds and their pyrolysis products, with particular emphasis on mechanisms, including oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. A PRISMA-guided systematic review identified only nine studies specifically investigating the neurotoxic effects of SC pyrolysis products, revealing a significant gap in the literature and underscoring the urgent need for targeted research in this domain. The review further highlights that additional constituents, such as plant materials incorporated into SC formulations, can contribute to the generation of harmful byproducts and complicate forensic interpretation. The structural heterogeneity of SCs, in conjunction with variables such as polydrug use and chronic exposure, further exacerbates their toxicological profile. Future research should prioritise the identification and characterisation of pyrolysis-derived toxicants, the advancement of analytical methodologies for their detection, and the implementation of evidence-based public health strategies aimed at risk mitigation. • Synthetic cannabinoids are potent neurotoxic drugs. • Smoking generates pyrolysis byproducts with even higher toxicity. • Neurotoxicity is driven by excitotoxicity, oxidative stress, and neuroinflammation. • Pyrolysis products remain largely uncharacterized, posing unknown risks. • Forensic detection and public health responses remain critically challenged.

Source: Toxicology

DOI: 10.1016/j.tox.2025.154374

Authors: Filipa Pita, Ricardo Jorge Dinis-Oliveira, João Pedro Silva, Paula Guedes de Pinho, Félix Carvalho

Institutions: Universidade do Porto, Unidade em Ciências Biomoleculares Aplicadas, Cooperativa de Ensino Superior Politécnico e Universitário, Unidade de Investigação em Toxicologia & Uma Só Saúde

Language: English

Topic: Forensic Toxicology and Drug Analysis

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,250