Alcohol consumption can also act as a stressor
Many people drink alcohol for its anxiety-reducing and stress relieving effects. However, alcohol consumption can also act as a stressor, triggering the body’s stress response system. Research has shown that alcohol can activate and, over time, disrupt the hypothalamic-pituitary-adrenal, or HPA axis.
HPA Axis Stress Response
When a stressor is detected, neurons in the paraventricular nucleus (PVN) of the hypothalamus release hormones called corticotropin-releasing factor (CRF) and vasopressin into the blood vessels connecting the hypothalamus and the pituitary gland. These hormones stimulate the pituitary to make and secrete adrenocorticotropic hormone (ACTH). ACTH causes glucocorticoid synthesis and release from the adrenal glands. Cortisol is the main glucocorticoid in humans, often referred to as “the stress hormone.” Too much stimulation can be harmful to health. Therefore, cortisol eventually signals back to the hypothalamus and pituitary gland to decrease CRF and vasopressin release; this is a negative feedback loop to help modulate the stress response and return the body to homeostasis. Neurotransmitters of the central nervous system (CNS) are also a part of the HPA axis; the neurotransmitter and hormone systems are closely connected to influence many body processes. [2, 6, 13, 16, 17]
Cortisol and CRF
As mentioned above, although many people use alcohol for its relaxing effects, alcohol can act as a stressor to upregulate the HPA axis. Chronic alcohol use, alcohol dependence, and alcohol withdrawal all cause dysregulation of the HPA axis. Altered function of the stress response and related CNS neurotransmitters may result in serious health consequences. [2, 3, 5, 6, 12, 15, 17]
At low and moderate intake, alcohol may reduce, leave unchanged, or increase cortisol levels.  Increased alcohol consumption over time can alter the circadian rhythm of cortisol. [2, 5] Initially, cortisol levels are elevated. However, following chronic alcohol exposure, there is often seen a diminished HPA response to stress, as measurements during this time show lower cortisol levels. 
CRF activity may become altered through chronic alcohol exposure. Altered CRF function and/or a reduced number of neurons in the PVN of the hypothalamus that release CRF may be responsible for lower cortisol values. Changes in CRF have been associated with withdrawal susceptibility and the capability of stress to cause relapse. 
Research has shown that these HPA axis alterations can be long-lasting and difficult, if not impossible, to heal. Additionally, the consequences may be more significant in females, particularly when estrogen levels are low. [2, 5, 15]
Alcohol consumption can also affect DNA methylation. Research has shown that alcohol affects two genes that are important in the HPA axis, NR3C1 and FKBP5. These genes become increasingly demethylated with increasing exposure to alcohol. We know that the genes play a role in hormone receptor complexes, including cortisol. Studies have also shown one of these genes (FKBP5), in particular, is associated with PTSD, depression, and anxiety. 
Norepinephrine and Dopamine
Alcohol consumption, as well as other drugs, stress, and anxiety, can influence dopamine and norepinephrine activity in the nucleus accumbens (NAc), part of the brain’s reward system.  Alcohol can increase both dopamine and taurine levels in the NAc; taurine participates in activating the reward system and dopamine release. Disturbances in the reward system are an underlying issue in people with alcohol dependence. 
Research has also shown that alcohol may cause an increase in tryptophan in the hippocampus, serotonin in the hippocampus and amygdala, and serotonin turnover. On the other hand, withdrawal from alcohol may decrease tryptophan, serotonin, and serotonin turnover. This may lead to difficulty in modulating corticosteroid levels, resulting in low mood, as well as other withdrawal signs and symptoms. 
GABA and Glutamate
Studies have shown that both acute and chronic alcohol consumption can increase GABAergic transmission and alter GABA synapses in the central amygdala. 
Acute alcohol intake can enhance inhibitory neurotransmission through GABAa receptors, which are found in 40% of the synapses in the brain. This leads to an overall increased functional connectivity in the brain.  Over time, however, the brain will try to restore balance. Chronic alcohol intake may change the GABAa receptors, leading to reduced GABA receptor function. The altered GABA receptor function may be related to alcohol sensitivity, tolerance, and dependence.  While short-term alcohol intake increases the brain’s functional connectivity, the functional connectivity is lowered in chronic alcohol consumption. 
Alcohol increases GABA to limit excitatory neurotransmission, particularly through GABA inhibiting the excitatory neurotransmitter glutamate. Following chronic alcohol exposure with reduced GABA function, glutamate levels may increase without GABA’s inhibitory effect. Higher glutamate levels may be partially responsible for some withdrawal symptoms. This increase of glutamate and its consequential effects have been shown to continue two weeks into abstinence [4, 14]
HPA axis balance is essential for optimal wellness, from sleep to the stress response, mood to cognitive function, and more. Each person’s HPA axis – as understood through the individual’s symptoms, lifestyle factors, and laboratory measurements such as hormones and neurotransmitters – is a reflection of their health. Alcohol consumption, whether chronic or acute, can alter the HPA axis, contributing to a variety of health concerns. If you’re a heavy drinker, recovering from chronic alcohol use, or even have just one drink on occasions, monitoring and modulating HPA axis function may help you and your healthcare practitioner understand and address imbalances and health concerns, preparing your way for a healthier future!
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