Drug addiction co-morbidity with alcohol: Neurobiological insights

Abstract

Addiction is a chronic disorder that consists of a three-stage cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages involve, respectively, neuroadaptations in brain circuits involved in incentive salience and habit formation, stress surfeit and reward deficit, and executive function. Much research on addiction focuses on the neurobiology underlying single drug use. However, alcohol use disorder (AUD) can be co-morbid with substance use disorder (SUD), called dual dependence. The limited epidemiological data on dual dependence indicates that there is a large population of individuals suffering from addiction who are dependent on more than one drug and/or alcohol, yet dual dependence remains understudied in addiction research. Here, we review neurobiological data on neurotransmitter and neuropeptide systems that are known to contribute to addiction pathology and how the involvement of these systems is consistent or divergent across drug classes. In particular, we highlight the dopamine, opioid, corticotropin-releasing factor, norepinephrine, hypocretin/orexin, glucocorticoid, neuroimmune signaling, endocannabinoid, glutamate, and GABA systems. We also discuss the limited research on these systems in dual dependence. Collectively, these studies demonstrate that the use of multiple drugs can produce neuroadaptations that are distinct from single drug use. Further investigation into the neurobiology of dual dependence is necessary to develop effective treatments for addiction to multiple drugs.

Keywords: Addiction; Alcohol or substance use disorder; Alcoholism; Co-morbidity; Compulsive drug use; Neurobiological interactions; Self-medication.

Fig. 1

The three stages of the addiction cycle and associated brain regions. Modified with permission from Koob, G. F., Arends, M. A., & Le Moal, M. (2014). Drugs, addiction, and the brain. Academic Press.

Fig. 2

Prevalence rates of alcohol and drug use or alcohol use disorder and other substance use disorders from the National epidemiologic Survey on Alcohol and Related Conditions-III. Left graph: the prevalence of light, moderate, or heavy drinking among respondents who reported past-year alcohol or alcohol and drug consumption. Right graph: the prevalence of mild, moderate, or severe DSM-5 diagnosis among respondents who reported an alcohol use disorder only or alcohol use disorder and another concurrent substance use disorder diagnosis. Alcohol use disorder (AUD), nicotine use disorder (NUD), cannabis use disorder (CUD), substance use disorder (DUD). Modified from Saha, T. D., Grant, B. F., Chou, S. P., Kerridge, B. T., Pickering, R. P., & Ruan, W. J. (2018). Concurrent use of alcohol with other drugs and DSM-5 alcohol use disorder comorbid with other drug use disorders: Sociodemographic characteristics, severity, and psychopathology. Drug and Alcohol Dependence, 187, 261–269, with permission.

Fig. 3

The converging effects of different drugs of abuse on the DA system in the VTA and NAc. From Juarez, B., & Han, M. H. (2016). Diversity of dopaminergic neural circuits in response to drug exposure. Neuropsychopharmacology, 41(10), 2424–2446, with permission.

Fig. 4

Expression of μ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and nociception/orphanin FQ receptor (N/OFQ) in brain regions involved in affective states. From Browne, C. A., & Lucki, I. (2019). Targeting opioid dysregulation in depression for the development of novel therapeutics. Pharmacology & Therapeutics, 201, 51–76, with permission.

Fig. 5

Effect of alcohol-induced neuroinflammation on astrocytes. From Erickson, E. K., Grantham, E. K., Warden, A. S., & Harris, R. A. (2019). Neuroimmune signaling in alcohol use disorder. Pharmacology, Biochemistry, and Behavior, 34–60, with permission.