Section Summary

Factors such as the route of administration and the rate of absorption, metabolism, and excretion can impact the ultimate concentration of a drug that ends up in the circulatory system. Drugs that can cross the blood-brain barrier can interact with neurotransmitters and receptors in the brain through a variety of mechanisms that can ultimately impact neuronal signaling. Understanding the pharmacodynamic and pharmacokinetic profile of drugs is essential for predicting their effects on mood, cognition and behavior.

Psychotherapeutics are prescription drugs used for the treatment of mental disorders. Benzodiazepines, a class of drugs commonly used to treat anxiety, alleviate symptoms by increasing GABAergic signaling in the brain. SSRIs are first-line treatments for depression that increase serotonin levels by blocking the reuptake of serotonin, though their therapeutic effects likely involve other neurotransmitter systems. Recent research investigating the therapeutic effects of psychedelics has revealed novel mechanisms for antidepressant effects. Antipsychotics that block dopamine D2 receptors reduce positive symptoms of schizophrenia, whereas the modulation of multiple neurotransmitter systems appears to be more effective in treating negative symptoms. Lastly, psychostimulants help increase attention and focus in patients with ADHD by enhancing dopamine signaling in the prefrontal cortex.

The mesocorticolimbic dopamine reward pathway plays a crucial role in the reward-related cognitive processes that reinforce pleasurable stimuli and experiences. Consequently, the anticipation of these positive emotions contributes to motivation to seek out the rewarding stimulus. The majority of commonly used psychoactive drugs activate the mesocorticolimbic dopamine system in some manner. Enhanced dopamine release in the nucleus accumbens is believed to underlie the reinforcing effects of these drugs.

There are many different reasons why an individual may initiate drug use. However, a single or even a few exposures to a drug rarely result in a SUD. The transition from controlled to compulsive drug use is likely mediated by drug-induced neuroplastic changes in brain reward and stress response circuits that enhance incentive salience for drug-related cues and generate negative emotional states in the absence of the drug. Although the neurobiological framework for studying addiction has helped to advance our understanding of the biological mechanisms that mediate drug-seeking behavior, it is important to also consider the societal, social, psychological, and environmental factors that contribute to the overall risk of developing a SUD.