3-CMC

cardiac arrhythmias, coronary artery disease, uncontrolled hypertension, cardiomyopathy

Pre-existing cardiac arrhythmias, coronary artery disease, uncontrolled hypertension, or cardiomyopathy represent absolute contraindications. Cardiac arrhythmias and thoracic pain are documented in human intoxication cases, and computational ADMET modelling predicts cardiotoxicity risk.

epilepsy, seizure history

Seizure threshold reduction is a documented class-level effect of synthetic cathinones. Individuals with epilepsy or seizure history face increased risk. No 3-CMC-specific seizure data exist.

psychotic disorders, bipolar disorder, severe anxiety disorders

Psychosis is documented in human intoxication cases at the Italian Poison Control Centre. Prepulse inhibition disruption at high doses in mice provides an animal correlate. Pre-existing psychotic disorders, bipolar disorder, or severe anxiety disorders increase vulnerability to psychiatric destabilization.

hepatic impairment, liver disease, CYP2D6 poor-metaboliser phenotype

Liver histopathological changes were observed at both doses in the rat study (Langa 2026). Hepatic impairment could reduce metabolic clearance and prolong exposure. CYP2D6 poor-metaboliser phenotype may represent an additional risk factor.

chronic kidney disease, renal impairment

Nephrotoxicity was observed in Wistar rats at high dose (20 mg/kg i.p.) including histopathological kidney changes and elevated urea. Pre-existing renal impairment may increase vulnerability to kidney damage and reduce metabolic clearance.

CYP2D6 poor-metaboliser phenotype, CYP2D6 inhibitor co-administration

CYP2D6 poor-metaboliser phenotype may lead to elevated 3-CMC exposure due to reduced metabolism. Olesti et al. (2019) demonstrated CYP2D6-mediated mephedrone metabolism in a Phase I clinical trial, with poor metabolisers at elevated toxicity risk. This prediction is structural-analog inference for 3-CMC.

pregnancy, lactation

No reproductive toxicity data exist for 3-CMC. Sympathomimetic stimulants carry class-level risks including placental vasoconstriction, fetal tachycardia, and potential developmental effects. Absolute contraindication by class inference.

MAOI use, reversible MAOI use

Concurrent use of monoamine oxidase inhibitors (MAOIs) with 3-CMC carries class-level risk of hypertensive crisis and serotonin syndrome. No 3-CMC-specific data exist, but this is a safety-critical contraindication for all monoamine releasing agents.

SSRI use, SNRI use, triptan use

Serotonin syndrome risk when combined with SSRIs, SNRIs, triptans, or other serotonergic agents. Daziani et al. (2023) documented serotonin syndrome in the broader synthetic cathinone class. Additional pharmacokinetic interaction if co-administered serotonergic agent is also a CYP2D6 inhibitor.