Uma revisão de escopo das evidências sobre mecanismos de toxicidade do canabinoide sintético JWH-018, efeitos adversos e risco à saúde pública

Abstract

Introduction: New psychoactive substances (NPS) constitute a major public health problem due to the rapid expansion of synthetic compounds developed to mimic the effects of traditional drugs. Among these, the synthetic cannabinoid JWH-018 stands out; it is widely found in products marketed as "Spice" or "K2" and is associated with severe intoxications and toxic effects superior to those observed with natural cannabis. Objective: To map and synthesize the available scientific evidence on the mechanisms of toxicity, adverse effects, and public health impacts related to exposure to the synthetic cannabinoid JWH-018. Methodology: A scoping review of a descriptive and exploratory nature was conducted in accordance with the recommendations of the Joanna Briggs Institute (JBI) and the PRISMA-ScR guidelines. The bibliographical search was performed in the PubMed (MEDLINE) database, complemented by strategies adapted for other databases, including studies published between 2022 and 2026. Original articles, reviews, and case reports related to JWH-018 and its toxicological effects were included. Results: The evidence demonstrated that JWH-018 acts as a full agonist of CB1 cannabinoid receptors, presenting greater pharmacological potency than Δ9- tetrahydrocannabinol (THC). Its high affinity for cannabinoid receptors promotes neurochemical alterations associated with neurotoxicity, seizures, cognitive deficits, psychotic episodes, anxiety, aggressiveness, and dependence potential. Furthermore, significant cardiovascular effects were observed, including arrhythmias, hemodynamic changes, myocardial injury, and an increased risk of ischemic events. Hepatic metabolism, mediated primarily by the CYP2C9 enzyme, generates biologically active metabolites capable of prolonging toxic effects and increasing clinical variability among individuals. Significant impacts on public health were also identified, such as an increase in acute intoxications, diagnostic difficulties, limitations in epidemiological surveillance, and regulatory challenges arising from the constant introduction of new synthetic analogs. Conclusion: JWH-018 presents a complex toxicological profile that is significantly more severe than that of natural cannabis, representing a relevant threat to public health. Its neurotoxic, psychiatric, and cardiovascular effects, associated with the formation of active metabolites and the difficulty of laboratory monitoring, reinforce the need to expand toxicological research, strengthen epidemiological surveillance, and develop more effective regulatory and preventive strategies to address the risks related to synthetic cannabinoids.