MET

Cardiovascular disease or uncontrolled hypertension is a relative contraindication due to class-typical acute sympathomimetic effects. MET's consistently reported stimulating character may increase cardiovascular risk compared to other tryptamines.

Personal or family history of schizophrenia or other psychotic disorders is an absolute contraindication for MET use. 5-HT2A agonism can trigger acute psychotic episodes in predisposed individuals, a risk documented across the serotonergic psychedelic class.

Bipolar disorder is a relative contraindication due to risk of manic episode precipitation. The serotonergic psychedelic class carries this risk at a class level, though the frequency and severity are not well quantified.

No safety data exist for MET use during pregnancy or lactation. Given the absence of any reproductive safety data and the serotonergic mechanism, use during pregnancy or breastfeeding cannot be considered safe.

Concurrent use of any monoamine oxidase inhibitor with MET carries risk of serotonin syndrome. MAOIs reduce first-pass metabolism of MET (increasing plasma levels) while simultaneously elevating synaptic serotonin, creating a dual-mechanism pathway to serotonin toxicity. This is a class-level absolute contraindication for all serotonergic tryptamines.

Concurrent use of lithium carbonate with MET carries risk of seizures and neurotoxicity. The mechanism involves lithium's effects on second messenger systems (inositol phosphate accumulation) interacting with the 5-HT2A-mediated PLC-IP signaling pathway. This is a class-level absolute contraindication for serotonergic psychedelics.

Concurrent use of tramadol with MET carries additive serotonin toxicity risk. Tramadol is a documented cause of serotonin syndrome at therapeutic doses when combined with serotonergic agents.

Concurrent use of SSRIs or SNRIs with MET may reduce psychedelic effects via 5-HT2A receptor downregulation while carrying theoretical serotonin toxicity risk in acute combination.