This chapter offers a detailed examination of the neurophysiological mechanisms underlying neural activity, emphasizing the roles of neurotransmitters, neuroplasticity, and the effects of psychoactive substances. It starts with a discussion of fundamental neuronal functions, including action potentials and synaptic transmission. The chapter then explores long-term potentiation (LTP) and long-term depression (LTD) as critical mechanisms of synaptic plasticity. It further investigates the involvement of neurotransmission systems in various brain circuits related to inhibitory control, decision-making, and reward processing. The impact of psychoactive substances on these systems is analyzed, highlighting changes in neurotransmitter balance and subsequent neuroplastic adaptations. Particular attention is given to the mesocorticolimbic pathway and its modulation by drugs of abuse, as well as the roles of glutamate and GABAergic systems. The chapter concludes by examining the effects of substance use on brain function and behavior, particularly how these alterations persist during withdrawal and influence overall neuroadaptation.