MDMA (ecstasy) and its major metabolite MDA did not directly damage heart cells from adult rats in the lab, but two further metabolites, N-Me-alpha-MeDA and alpha-MeDA, caused significant toxicity. These catechol metabolites triggered a loss of normal cell shape, depletion of the antioxidant glutathione, sustained increases in intracellular calcium, drops in ATP, and reduced activity of antioxidant enzymes. N-Me-alpha-MeDA was the most toxic. The findings suggest that MDMA must be metabolized into these catechol compounds for cardiotoxicity to occur in isolated heart cells.
An aqueous extract of the aerial parts of Calea zacatechichi, a plant traditionally used for its dream-inducing effects, interferes with the cholinergic and dopaminergic systems by inhibiting acetylcholinesterase and tyrosinase, but does not affect monoamine oxidase A. The extract also shows notable cytotoxicity in neuronal and microglial cells at low concentrations, with evidence of apoptosis and necroptosis, though it scavenges free radicals and inhibits lipid peroxidation. Twenty-eight phenolic constituents were identified, 24 previously unreported in this species. The findings highlight the need for a regulatory framework for recreational use and help clarify the plant's psychopharmacological mechanisms.