MAO stands for monoamine oxidase, an enzyme your body uses to break down certain brain chemicals and dietary compounds. It exists in two forms, MAO-A and MAO-B, and it plays a central role in regulating mood, energy, and nervous system function. You’ve probably encountered the term because of MAO inhibitors (MAOIs), a class of medications used to treat depression and Parkinson’s disease.
What MAO Does in Your Body
Monoamine oxidase sits on the surface of mitochondria, the energy-producing structures inside your cells. Its job is to break down a group of chemical messengers called monoamines. These include serotonin (which influences mood and sleep), norepinephrine (involved in alertness and stress responses), and dopamine (tied to motivation and pleasure). MAO also breaks down trace amines and dietary amines like tyramine, which is found in aged cheeses, cured meats, and fermented foods.
The chemical reaction itself is called oxidative deamination. MAO strips an amine group off the neurotransmitter molecule, producing an aldehyde, ammonia, and hydrogen peroxide as byproducts. The aldehyde is then further converted into harmless acids or alcohols by other enzymes. This process is how your body clears used neurotransmitters from the system, keeping their levels in balance. Without MAO, these chemicals would accumulate and overstimulate the nervous system.
MAO-A vs. MAO-B
The two forms of the enzyme have different preferences. MAO-A primarily breaks down serotonin and norepinephrine, while MAO-B preferentially targets a trace amine called phenylethylamine. Dopamine is broken down by both. The difference between the two comes down to a single amino acid in their structure. When researchers swapped that one amino acid in lab experiments, MAO-A started behaving like MAO-B and vice versa.
Their distribution in the body also differs. In the brain, about 80% of total MAO activity comes from MAO-B and roughly 20% from MAO-A. Both forms are found at their highest concentrations in the frontal cortex and a brainstem region called the locus coeruleus. Outside the brain, both are expressed across most tissues, including the liver, gut, and heart. MAO in the gut wall serves as a first line of defense, breaking down tyramine and other amines in food before they reach your bloodstream.
Why MAO Matters for Depression
Because MAO breaks down serotonin, norepinephrine, and dopamine, blocking it causes these neurotransmitters to build up. That’s the principle behind MAO inhibitors, one of the earliest classes of antidepressants. By preventing MAO from clearing these chemicals, MAOIs increase the amount available in the brain, which can relieve depression symptoms.
The FDA has approved several oral MAOIs for depression: isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate). A fourth, selegiline (Emsam), is available as a skin patch and tends to cause fewer side effects than the oral versions. These older MAOIs are irreversible and nonselective, meaning they permanently disable both MAO-A and MAO-B until your body produces new enzyme molecules. That potency is a double-edged sword: they’re effective antidepressants, but they come with significant dietary restrictions.
A newer class called RIMAs (reversible inhibitors of MAO-A) was developed to address those limitations. The most well-known is moclobemide, which selectively and temporarily blocks MAO-A. Because its effects are reversible, tyramine from food can still be broken down to some extent, and dietary restrictions are generally unnecessary. The tradeoff is that RIMAs appear to be somewhat less potent as antidepressants than the older irreversible options.
The Tyramine Problem
The most notable risk of taking traditional MAOIs is the “cheese effect.” Normally, MAO in your gut and liver breaks down tyramine from food before it can affect your cardiovascular system. When that enzyme is blocked by medication, tyramine passes into the bloodstream unchecked. Tyramine triggers the release of norepinephrine, which constricts blood vessels and raises blood pressure. At high enough levels (9 mg or more over 24 hours), this can cause a dangerous spike in blood pressure called a hypertensive crisis. In rare cases, this can lead to a cerebral hemorrhage.
People taking irreversible MAOIs need to avoid tyramine-rich foods, including aged cheeses, sauerkraut, soy sauce, cured meats, and certain alcoholic beverages. These restrictions continue for two weeks after stopping the medication, because the body needs time to produce fresh MAO enzyme. The lowest-dose selegiline patch may not require these precautions, since it primarily affects MAO in the brain rather than the gut.
MAO-B Inhibitors and Parkinson’s Disease
In Parkinson’s disease, dopamine-producing neurons in the brain progressively die. Since MAO-B is responsible for most dopamine breakdown in the brain, blocking it helps preserve whatever dopamine is still being produced. Selective MAO-B inhibitors like selegiline and rasagiline cross the blood-brain barrier and reduce dopamine degradation at the synapse, the gap between nerve cells where signaling happens.
There may also be a neuroprotective angle. When MAO-B breaks down dopamine, the hydrogen peroxide it generates can damage neurons through oxidative stress. MAO-B inhibitors reduce that toxic byproduct. Animal studies have also shown that these drugs can block the conversion of certain environmental toxins into compounds that kill dopamine neurons. By reducing both dopamine loss and oxidative damage, MAO-B inhibitors serve as one piece of the Parkinson’s treatment puzzle, often used alongside other dopamine-boosting therapies.
The “Warrior Gene” and Behavior
The gene that codes for MAO-A has attracted attention outside of pharmacology. People carry different versions of this gene: a low-activity variant (MAOA-L) that produces less of the enzyme, and a high-activity variant (MAOA-H) that produces more. Less MAO-A means slower breakdown of serotonin, norepinephrine, and dopamine, which changes how the brain processes emotions.
MAOA-L has been nicknamed the “warrior gene” because of its association with aggression in research studies. Brain imaging shows that men with the low-activity variant have stronger reactions in the amygdala (the brain’s threat-detection center) and weaker activity in prefrontal areas that regulate impulses during emotional situations. In controlled experiments, people with MAOA-L showed higher aggression after being provoked, with 75% retaliating in one study compared to 62% of those with the high-activity variant.
Context matters enormously, though. The link between MAOA-L and antisocial behavior is strongest in people who experienced childhood abuse or trauma. Children with both the low-activity gene and a history of maltreatment were significantly more likely to develop behavioral problems as adults. Without that environmental trigger, the genetic variant alone doesn’t predict aggression in any meaningful way. It’s a textbook example of gene-environment interaction: the gene loads the gun, but experience pulls the trigger.