Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Sep;2(3):R1-R14.
doi: 10.1530/EC-13-0028. Epub 2013 May 31.

Addiction and the Adrenal Cortex

Affiliations
Free PMC article

Addiction and the Adrenal Cortex

Gavin P Vinson et al. Endocr Connect. .
Free PMC article

Abstract

Substantial evidence shows that the hypophyseal–pituitary–adrenal (HPA) axis and corticosteroids are involved in the process of addiction to a variety of agents, and the adrenal cortex has a key role. In general, plasma concentrations of cortisol (or corticosterone in rats or mice) increase on drug withdrawal in a manner that suggests correlation with the behavioural and symptomatic sequelae both in man and in experimental animals. Corticosteroid levels fall back to normal values in resumption of drug intake. The possible interactions between brain corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC) products and the systemic HPA, and additionally with the local CRH–POMC system in the adrenal gland itself, are complex. Nevertheless, the evidence increasingly suggests that all may be interlinked and that CRH in the brain and brain POMC products interact with the blood-borne HPA directly or indirectly. Corticosteroids themselves are known to affect mood profoundly and may themselves be addictive. Additionally, there is a heightened susceptibility for addicted subjects to relapse in conditions that are associated with change in HPA activity, such as in stress, or at different times of the day. Recent studies give compelling evidence that a significant part of the array of addictive symptoms is directly attributable to the secretory activity of the adrenal cortex and the actions of corticosteroids. Additionally, sex differences in addiction may also be attributable to adrenocortical function: in humans, males may be protected through higher secretion of DHEA (and DHEAS), and in rats, females may be more susceptible because of higher corticosterone secretion.

Figures

Figure 1
Figure 1
The expanded HPA axis. From and see text. BNST, bed nucleus of stria terminalis; PFC, pre-frontal cortex; PVN, paraventricular nucleus; VTA, ventral tegumental area (associated with reward responses); CRH, corticotrophin releasing hormone; POMC, proopiomelanocortin; +, stimulatory; −, inhibitory. Solid arrows show proven regulation, and dotted arrows show postulated actions. Secreted CRH is indicated in blue lettering, and sites of CRH and POMC signalling are indicated in red and green respectively: here, arrows indicate regulatory pathways that are unquestionably multifactorial but may include actions of CRH and POMC peptides. The inhibitory effect of neural POMC peptides on PVN CRH is particularly interesting, and, by comparison with other systems, might suggest a negative feedback mechanism; however, there is little evidence for reciprocal feedback of CRH on POMC in the brain. Instead, regulation of neural POMC is multifactorial (e.g. , and this is primarily linked to its role in energy balance and nutrition, see text. There is, however, much evidence to show the feedback of glucocorticoids on CRH expression in several brain regions. Mostly, this is negative, except in the amygdala, a key region in addiction , where it is positive.

Similar articles

See all similar articles

Cited by 4 articles

References

    1. Lewis JT. Sensibility to intoxication in albino rats after double adrenalectomy. American Journal of Physiology. 1923;64:506–511.
    1. Mackay EM, Mackay LL. Susceptibility of adrenalectomized rats to intoxication. Journal of Pharmacology and Experimental Therapeutics. 1929;35:67–74.
    1. Mackay EM. The relation of acquired morphine tolerance to the adrenal cortex. Journal of Pharmacology and Experimental Therapeutics. 1931;43:51–60.
    1. Sung CY, Way EL, Scott KG. Studies on the relationship of metabolic fate and hormonal effects of d,l-methadone to the development of drug tolerance. Journal of Pharmacology and Experimental Therapeutics. 1953;107:12–23. - PubMed
    1. Boswell WH. Narcotic addiction. Management of withdrawal symptoms with cortisone. United States Armed Forces Medical Journal. 1951;2:1347–1351. - PubMed
Feedback