Ketamine derivatives identified as dangerous drugs with a significant risk of overdose by the ANSM
In France, concerns over the rise in poisonings linked to ketamine derivatives have been escalating. Specifically, cases of poisoning from O-PCE and DCK have been on the rise, resulting in six deaths between 2020 and 2023.
O-PCE and DCK, two newly banned ketamine derivatives in France, share a pharmacological similarity to ketamine, but with important variations in their metabolism and potential toxicity. These substances, classified as arylcyclohexylamines, act as dissociative anesthetics, similar to ketamine. Their effects include sedation, dissociation, hallucinations, and potential analgesia, but often with greater potency and longer duration than ketamine itself.
Recent forensic research indicates that these substances undergo distinct metabolic pathways. For instance, O-PCE undergoes significant N-deethylation and carbonyl hydrogenation, producing metabolites detectable in blood, liver, and urine. This active and possibly variable metabolism could affect potency and toxicity.
Specific health risks associated with O-PCE and DCK include unpredictable psychoactive effects, potential neurotoxicity, and risks of overdose, similar to ketamine but potentially exacerbated by the metabolites and longer half-life. Due to their newer status, the full profile of adverse effects is not completely established, but concerns exist about acute dissociative crises, cognitive impairment, and bladder toxicity.
These substances are often unregulated, leading to high risk due to unknown purity, dosage inconsistencies, and lack of clinical supervision. The National Agency for Medicines Safety (ANSM) has placed O-PCE and DCK on the list of narcotics in France on July 31, 2023, reflecting concerns about these risks and their emerging appearance in forensic and toxicological reports of intoxication and possible fatalities.
Ketamine, a powerful anesthetic, is also being trafficked in France, despite its marginal consumption. While primarily used for veterinary and human anesthesia, it is also diverted for recreational purposes due to its hallucinogenic properties. The actor who played Chandler in the TV series Friends, Matthew Perry, died from a ketamine overdose in late 2023, highlighting the overdose risk associated with these substances.
These derivatives are sold on the internet as white powder, crystals, or sprays. Users may experience severe dissociation, psychosis-like effects, and dangerous cardiovascular or neurological outcomes. Thus, the key risks associated with O-PCE and DCK involve their potent dissociative effects, unpredictable metabolism leading to toxic metabolites, and increased likelihood of overdose or adverse neuropsychiatric reactions, justifying their regulatory bans.
[1] Reference for metabolic studies [3] Reference for structural similarity to ketamine derivatives
French authorities are raising concerns about the increasing cases of health issues related to the use of the arylcyclohexylamines, O-PCE and DCK, in the realm of health-and-wellness and mental-health. These substances, often unregulated, pose risks of unpredictable psychoactive effects, potential neurotoxicity, and mental health complications, similar to ketamine but possibly exacerbated by their metabolites and longer duration of action.
