Insights into Mechanisms and Models for Studying Neurological Adverse Events Mediated by Pharmacokinetic Interactions between Clinical Drugs and Illicit Substances of Herbal and Fungal Origin

Coadministration of herbs and fungi with clinical drugs can result in herb–drug and fungi–drug interactions, leading to adverse effects, including neurological and related adverse events. Many of the illicit substances are derived from herbs or fungi. Hence, adverse neurological events that arise from pharmacokinetics-based interactions of illicit substances of herbal/fungal origin with clinical drugs are of significant health burden. Despite the knowledge that concomitant usage of clinical drugs with illicit substances can often result in neurological and related adverse events, the underlying pharmacokinetics-based mechanisms of these interactions are poorly understood. This chapter briefly highlights the neurological and related adverse events associated with pharmacokinetics-based interactions between clinical drugs and commonly used illicit substances of herbal or fungal origin, such as ayahuasca, cannabis (marijuana), cocaine, psilocybin, khat, salvia, kratom, and mescaline. This chapter discusses a great deal of novel insights into the potential mechanisms of pharmacokinetics-based interactions between clinical drugs and illicit substances of herbal/fungal origin that may be responsible for neurological and related adverse events. Finally, this chapter provides insights into potential experimental models that can be used in studying these pharmacokinetic interactions that lead to neurological adverse events.