In our last blog post, we discussed the ‘feel good’ and motivation neurotransmitter Dopamine. Today, we'll introduce two other neurotransmitters involved in the neurobiology of alcohol addiction: Gamma-aminobutyric acid (GABA) and glutamate.
The Role of GABA and Glutamate
Alcohol exerts its effects on the brain by modulating both GABA and glutamate systems. The effects felt when drinking alcohol, caused by these neurotransmitters’ reactions, include stress relief, relaxation, sedation, and sleepiness.
GABA is the primary inhibitory neurotransmitter in the brain, meaning it reduces neuronal excitability; it reduces the activity in the cells and therefore has sedative effects. GABA is the neurotransmitter that makes you feel relaxed and calm. In other words, it's the one that makes you feel less stressed from your week on Friday when you want to take the edge off. GABA receptors react to a few substances: ethanol (alcohol), benzodiazepines (diazepam, alprazolam, oxazepam, lorazepam, also known under brands like Xanax, Valium, Klonopin, Ativan), and barbiturates. This results in the characteristic sedative and anxiolytic (anxiety-reducing) effects of alcohol.
Concurrently, alcohol inhibits the activity of NMDA (N-methyl-D-aspartate) receptors, a subtype of glutamate receptor, reducing excitatory signalling in the brain. Glutamate is the main excitatory neurotransmitter, promoting neuronal activity, but alcohol reduces its activity, doubling the sedative calming effects when drinking alcohol.
The interplay between these two neurotransmitter systems contributes to the overall depressant effects of alcohol on the central nervous system. Here depressant means: lowering vital activities.
Neuroadaptive Changes and Homeostasis
The brain is quite smart and tries to recalibrate and rebalance itself, a process called homeostasis. Chronic alcohol use leads to neuroadaptive changes: the brain reduces the number of GABA receptors and increases the number of NMDA receptors to compensate for the prolonged presence of alcohol. With fewer GABA receptors, the brain's inhibitory (calming) effect is diminished, making it harder for the brain to regulate stress and anxiety. Additionally, the increase in NMDA receptors leads to heightened excitatory activity in the brain, contributing to feelings of anxiety and hyperexcitability.
To simplify, prolonged alcohol use tells your brain: “Hey, we don’t need to produce as much GABA to calm down because alcohol does it for us.” More alcohol, less GABA equals more stress and anxiety a few hours after intake. Hello, anxiety at 3 am!
Additionally, alcohol makes you sleepy and sedated, so the brain responds: “Hey, we need more excitation to shake this sleepy head, so let's increase NMDA receptors to get more excitation.” A few hours after your last drink, with anxiety, you now feel nervousness, agitation, and some sort of anxious excitation. Welcome to a hangover, jacking up the anxiety for a few hours but usually days. But it is also what would cause seizures to an individual after chronic alcohol exposure.
Important note: If you're alcohol consumption is frequent, chronic, and you think you may have a physical dependance, please consult a medical practitioner before stopping abruptly as it can be LETHAL and it can cause DEATH.
Tolerance, addiction and conclusion
These adaptations contribute to tolerance, where increasing amounts of alcohol are needed to achieve the same effects, and to withdrawal symptoms when alcohol consumption is reduced or stopped.
The neurobiology of alcohol addiction involves a complex interplay of neurotransmitter systems, brain regions, and neuroadaptive changes. Dopamine and the reward system play a central role in the reinforcing effects of alcohol, while GABA and glutamate contribute to its depressant effects. Chronic alcohol use leads to significant neuroplastic changes, dysregulation of the stress response, and neuroinflammation. Genetic and epigenetic factors further influence susceptibility to addiction. Understanding these mechanisms is crucial for developing effective treatments and interventions for alcohol addiction, ultimately helping individuals break the cycle of addiction and achieve lasting recovery.
To conclude, if the "hangxiety" is ruining your life, you're fed up of being tired, confused, and if alcohol takes to much space in your life, your head, your wallet, you're always welcome to get in touch and I'll provide you more information about how I could support you.