Addiction involves complex interactions between the brain’s reward circuitry and stress systems. The adrenal cortex and its hormones are emerging as key players.
Key Facts:
- The hypothalamic-pituitary-adrenal (HPA) axis regulates adrenal cortex hormone secretion.
- Adrenal hormones like cortisol influence mood, cravings, and withdrawal symptoms.
- Disrupting adrenal hormone signaling reduces addictive behaviors in animal studies.
- There are sex differences in adrenal hormones that may contribute to addiction risk.
The Adrenal Cortex: At the Intersection of Stress and Reward
The adrenal glands sit atop the kidneys and contain an outer cortex layer that produces vital hormones.
When stimulated by the brain’s hypothalamus and pituitary gland, the adrenal cortex secretes cortisol along with other hormones like androgens.
Cortisol is often called the “stress hormone” due to its role in the body’s stress response.
It increases blood sugar, suppresses the immune system, and influences cognition and emotion.
Chronic stress leads to excessive cortisol exposure which can be detrimental.
Interestingly, cortisol also affects the brain’s reward system and pathways involved in drug addiction.
Many addictive substances like alcohol, nicotine, and cocaine activate the HPA axis, increasing cortisol release.
The mood-altering properties of cortisol likely contribute to the development of substance use disorders.
In the short term, cortisol boosts euphoria.
But over time, high cortisol levels are linked to depression, psychosis, and impaired cognition.
Studies also show that blocking cortisol synthesis reduces addictive behaviors like drug self-administration and reinstatement in animal models.
This suggests cortisol signaling is necessary for key aspects of addiction.
The Adrenal Cortex and Brain Stress Systems Are Linked
The hypothalamus contains corticotropin releasing hormone (CRH) neurons that control cortisol release by signaling the pituitary.
But CRH is also found throughout the brain, where it acts as a neurotransmitter.
While brain CRH systems regulate mood and addiction behaviors independently, evidence shows they interact with the HPA axis.
For example, drugs like morphine inhibit HPA activity by suppressing hypothalamic CRH release.
Proopiomelanocortin (POMC) is another HPA hormone precursor that’s expressed in the pituitary gland and brain. POMC breakdown produces adrenocorticotropic hormone (ACTH) to stimulate cortisol release, along with natural opioids like β-endorphin.
In the brain, POMC neurons interact with CRH and also bind to opioid receptors involved in addiction.
So HPA-linked POMC has central nervous system effects beyond the adrenal cortex.
Together, this suggests CRH and POMC form an “expanded HPA axis” where the adrenal gland remains the key endpoint.
Multiple brain regions process addiction cues, but they rely on adrenal hormones like cortisol to influence behavior.
How Adrenal Hormones Impact the Brain
The mood and cognitive effects of cortisol originate from its ability to access the brain and bind neuronal glucocorticoid receptors (GRs).
Animal studies show that disrupting GR signaling reduces stimulant self-administration, reward responses, and reinstatement.
This suggests cortisol action on GRs is essential for acquiring and relapsing to drug addiction.
Since GRs are found throughout the brain, cortisol likely impacts reward and executive function areas simultaneously.
The adrenal gland also produces neuroactive steroids like DHEA that bind distinct receptors in the brain, reducing addictive behaviors.
But animal data indicates these steroids still depend on adrenal gland substrates.
Together, this means the adrenal cortex provides precursors for hormones that either enhance addiction pathways or protect against them.
The ultimate effects depend on complex dose and receptor interactions. But the adrenal cortex sits at the center of it all.
Sex Differences in Addiction Risk
There are well known sex differences in addiction risk and severity in both humans and animals.
Females tend to progress more rapidly and have worse outcomes.
Adrenal hormones likely contribute to this dichotomy.
In humans, DHEA levels are significantly higher in men. Since DHEA is protective against addiction, lower levels in women may increase their risk.
In rats, there’s an opposite effect – females have higher corticosterone levels, which enhances addiction behaviors in models.
This suggests unique adrenal cortex profiles in each sex mediate differences in addiction vulnerability.
Adrenal glands & the circadian rhythm: cortisol release
The adrenal gland secretes hormones in a circadian rhythm.
Cortisol peaks in the morning then declines throughout the day. Disrupting this cycle impairs health and brain function.
Like stress, the time of day also impacts addiction risk.
Animal studies find addictive behaviors and drug sensitivity vary over a 24 hour period based on clock gene expression.
Though less explored in research, the circadian nature of adrenal hormones likely contributes to time-of-day effects on addiction as well.
Therapies aimed at stabilizing adrenal rhythms may be an effective strategy.
The Adrenal Cortex As A New Frontier
Despite early clues linking the adrenal glands to addiction, this important relationship was overlooked for many years.
Now, a converging body of research in humans and animal models demonstrates that the adrenal cortex and its hormones are essential drivers of addictive processes through complex brain pathways.
These findings open promising new possibilities for predicting addiction vulnerability, understanding sex differences and circadian effects, and developing more targeted treatments.
With further study, the untapped potential of the adrenal cortex as a key player in the neurobiology of addiction will continue to be revealed.
References
- Study: Addiction and the adrenal cortex
- Authors: Gavin P Vinson & Caroline H Brennan (2013)
