Causes
There are several known causes of adrenergic storms; in the United States, cocaine overdose is the leading cause. Any stimulant drug has the capacity to cause this syndrome if taken in excess, but even non-psychotropic drugs can very rarely provoke a reaction.
MAOIs, i.e. monoamineoxidase inhibitors, are a class of drugs that inhibit the enzyme monoamine oxidase. This enzyme is responsible for breaking down many compounds; basically, anything with a primary amine moiety is likely to be oxidized by monoamine oxidase. Important substrates of the enzyme MAO include tyrosine and tyramine, which are precursors to dopamine. MAOIs inhibit the enzyme either reversibly, in which MAO is inhibited only until the drug is cleared from the system, or irreversibly, in which the substrate binds permanently to the enzyme, rendering it inactive and effectively destroying it. These types of MAOIs are more dangerous, because the body takes about two weeks to regenerate its MAO enzymes to functional levels. There are also two subtypes of MAO: MAO-A and MAO-B; this is not relevant to adrenergic storms in any known way, but there are significant differences between the two types, such as their differential expression throughout the body and brain.
Harmine and moclobemide are two examples of reversible inhibitors; the first is a mild psychedelic used by recreational or spiritual drug users to greatly increase the bioavailability of DMT, normally entirely broken down by MAO in the stomach. The latter is an antidepressant and anxiolytic which works by reversibly inhibiting MAO-A and MAO-B, with a greater effect on MAO-A (80% inhibition) than MAO-B (30% inhibition).
With this in mind, the importance of MAOIs to adrenergic storms is that these enzymes break down substances in food that are either precursors to stimulatory drugs, or that are themselves excitatory chemicals. Aged cheese; beer; red wine; some mushrooms; fermented products such as pickles; and many other seemingly innocuous foods can provoke a hypertensive crisis. The main culprit is tyramine, a derivative of the amino acid tyrosine that is a direct precursor to dopamine. However, other substances in food can also modulate or change the effects. Hypertension will always result, however, so patients on MAOIs must be careful what they eat.
Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the CNS, it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various entheogens to attain a stronger psychedelic experience, both from adrenergic storms and serotonin syndrome. Combining drugs like MDMA, 2C-B, mescaline, 2C-T-7, etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.
Subarachnoid hemorrhage is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemhorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the intracranial pressure increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space. An alternative explanation that has been proposed is that this increased in intracranial pressure transduces through the brain parenchyma through to the blood vessels producing a loss in effective cerebral perfusion. This triggers the sympathetic nervous system to secrete more norepinepherine and epinepherine increasing blood pressure and heart rate to dangerous levels in order to maintain cerebral perfusion.
Rarely, a pheochromocytoma (tumor of the medullar tissue of the adrenal glands, which are located anterior to the kidney), may result in an adrenergic storm. This type of tumor is not common to begin with, and furthermore, the subtype that can cause massive adrenaline release is rarer still. Patients with pheochromocytoma can unexpectedly fly into a rage or sink into trembling fear, possibly dangerous to themselves and others as their judgment is impaired, their senses and pain threshold are heightened, and the level of the adrenalin in their bloodstream is more than most people ever experience; pheochromocytoma can, very rarely, kill by internal adrenaline overdose. But overall, adrenergic storm is an uncommon but certainly not rare phenomenon associated with the unfortunate but also uncommon condition of pheochromocytoma.
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