Toxicology of anhydroecgonine methyl ester: A systematic review of a cocaine pyrolysis product.

ABSTRACT

Anhydroecgonine Methyl Ester (AEME), also known as methylecgonidine, is the main pyrolysis product of smoking cocaine (cocaine base paste or basuco, crack, or freebase). This review aims to synthesize the available scientific evidence on the toxicokinetic and toxicodynamic effects of AEME. A search of scientific articles published in Science Direct, SCOPUS, and MEDLINE up to May 2024 was conducted. Twenty-four articles, including 13 experimental animal studies, 2 clinical trials, and 3 observational studies, were reviewed. AEME is readily deposited in the alveoli; its absorption improves in combination with cocaine and has a broad tissue distribution. It is metabolized primarily in the liver, with a half-life of approximately one hour, and is mainly excreted through urine. Moreover, AEME acts as a partial agonist of M1 and M3 muscarinic cholinergic receptors, influences dopaminergic system neuroadaptation, increases the production of reactive oxygen species, imbalances the activity of glutathione-associated enzymes, and reduces melatonin levels, affecting its antioxidant regulatory properties. When combined with cocaine, AEME activates the non-apoptotic pathway of caspase-9 and then, the apoptotic pathway via caspase-8, reducing neuronal viability in half the time of cocaine. AEME plays a significant role in cocaine toxicity and AEME itself.