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After studying this chapter, the student should be able to:

  • Recognize common drugs of abuse, associated symptoms of substance use disorders, and physiologic pathways associated with addiction.

  • Understand the prevalence and common medical comorbidities associated with substance use disorders.

  • Identify treatment approaches for each class of substance use disorders.


Approximately 20.2 million adults (8.4%) had a substance use disorder in the past year, making substance use disorders one of the most prevalent mental health disorders in the United States. Nicotine use disorder is the most prevalent, with an estimated lifetime prevalence of 27%. Alcohol use disorder is also common, with an estimated 8% of adults meeting criteria during their lifetime. Lifetime prevalence of an illicit drug use disorder is approximately 2% to 3%. The National Institute on Drug Abuse estimates the total cost of substance use to our country to be $740 billion annually. This includes not only associated healthcare cost, but also lost productivity and crime-related costs.


It is important to understand the role of the reward pathway and the effects of drugs on this part of the brain. The reward pathway of the brain increases pleasurable behaviors that enhance our survival. For example, on a more basic level, drinking a bottle of water after a run or eating meal when hungry activates the reward pathway to create the feeling of satiation. The reward pathway also plays a role in more complex behaviors such as forming relationships, sexual intercourse, and child rearing.

The reward pathway is also known as the mesolimbic pathway. It originates in a portion of the midbrain called the ventral tegmental area (VTA). From the VTA, dopaminergic neurons project into an area of the ventral striatum called the nucleus accumbens (NAcc) (Figure 43–1). When dopamine is released at the NAcc, it causes pleasure, partially through the release of endorphins. Generally, the more dopamine a given stimulus releases at the NAcc, the more pleasurable is the experience. The NAcc is able to assign various stimuli differing amounts of salience. This stimulus–reward phenomenon plays a vital role in both classical and operant conditioning (Figure 43–2).


Neuropharmacologic classification of addictive drugs by primary target. DA, dopamine; GABA, γ-aminobutyric acid; GHB, γ-hydroxybutyric acid; GPCRs, G-protein–coupled receptors; THC, Δ9-tetrahydrocannabinol. (Reproduced with permission from Katzung BG: Basic and Clinical Pharmacology, 14th ed. New York, NY: McGraw Hill; 2018.)


Major connections of the mesolimbic dopamine system in the brain. Schematic diagram of the brain illustrating that the dopamine projections (red) originate in the ventral tegmental area (VTA) and target the nucleus accumbens (NAc), prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral pallidum (VP). Neurons in the NAc fall into 2 classes, ...

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