Amphetamine induced activation of the opioid system: a focused review of animal and human studies

Stimulants are commonly prescribed as first line medications for ADHD and also used as adjunct treatment in other psychiatric conditions. While much is known about stimulants’ influence on brain neurochemistry, particularly on the dopaminergic neurotransmission, there has been less research into prescription stimulants’ effects on the endogenous opioid system. What we know about the mechanisms underlying the effects of stimulants on the opioid system come predominantly from animal studies and a relatively small number of studies in humans using positron emission tomography (PET) to examine the activation of the endogenous opioid system as evidenced by radioligand binding to opioid receptors. This paper is a focused review of the currently available literature on both animal and human studies examining the effects of stimulant administration on the endogenous opioid system, which suggest that stimulant administration results in increased occupancy of the opioid receptors in a widespread network of brain regions. We discuss the possible underlying mechanisms of this interaction, it’s potential impact on our understanding of substance abuse and addiction, particularly as viewed through the model of behavioral sensitization, and possible clinical implications