Drug–toxin interactions in the brain: An overlooked dimension of psychopharmacology

This study aimed to suggest a new research field called ‘environmental psychopharmacology’ that will investigate the role of environmental chemical stressors in interfering with psychiatric drugs and in treatment resistance. This narrative review synthesizes knowledge on pharmacological, toxicological and environmental health data regarding the pharmacokinetic and pharmacodynamic mechanisms involved in the action of psychotropic drugs, including blood–brain barrier (BBB) integrity, cytochrome P450 (CYP450) metabolism, P‐glycoprotein (P‐gp) efflux, neuroinflammation and mitochondrial oxidative stress. Environmental contaminants can affect the bioavailability of drugs in the central nervous system (CNS) by interfering with BBB integrity, changing the metabolism of the CYP450 family and increasing the activity of P‐gp efflux pumps. A more complex picture may be presented, resulting in apparent ‘pseudo‐resistance’ due to neuroinflammation and oxidative stress, which further diminishes drug‐induced neuroplasticity. Drug–toxin interactions (DTIs) can occur either by direct interaction with a common molecular target or indirectly by modifying the biological environment. Bidirectional interactions between psychotropics and neurotoxic proteins may also be attributed to glymphatic clearance. Children, older adults and socio‐economically disadvantaged groups are vulnerable populations. Environmental history‐taking, toxicological screening and omics‐based predictive modelling could become a powerful tool in the management of treatment‐resistant psychiatric conditions.