Monoamine Oxidase Inhibitors

Monoamine Oxidase Inhibitors (MAOI's) are drugs than inhibit the enzyme Monoamine Oxidase (MAO) which breaks down monoamines, and thus potentiate the effects of many tryptamines, phenethylamines, and other monoamine neurotransmitters. In medicine, MAOIs are a class of drugs indicated primarily for the treatment of depression and Parkinson's, although some are also used to treat conditions such as social anxiety.

Using MAOI's

MAOI's are found in various plant sources, among them Syrian Rue and Banisteriopsis caapi which both contain Harmal and Harmaline, which inhibits MAO-A. MAO's come in two isoforms, MAO-A and MAO-B.

MAO-A breaks down serotonin, epinephrine, and norepinephrine.
MAO-B breaks down phenethylamine.
Both break down dopamine.

Ways of administration:

Syrian Rue seeds or B. Caapi are common plant sources of MAOI-A. They can be ground up and consumed.

Effects of MAOI's

Consumption of MAOI's stimulates the central nervous system and lifts mood.

Combinations with Psychedelics

Combination of MAOI's and psychedelic drugs can notably prolong and intensify the experience.

It has been reported that roughly 3 grams of powdered Syrian rue seeds is enough for full MAOI-A inhibition, which in turn doubles the length of a psylocybin mushroom trip.

The dangers of MAOI's

There are two major conditions that can arise during the use of MAOIs, namely a hypertensive crisis and serotonin syndrome.

Hypertensive crisis:
In humans, MAO enzymes are found both centrally (i.e. in the brain) and peripherally (e.g. in the liver and intestines). It's the inhibition of central MAO that produces both clinical effects and potentiation of recreational drugs, but orally administered MAOIs inhibit peripheral MAO as well. Peripheral MAO breaks down monoamines, such as tyramine, contained in ingested food. In doing so, it protects the body from health risks posed by the consumption of spoiled food, which often times has a particularly high tyramine content. The consequence of inhibition of peripheral MAO is that monoamines in food are broken down at a much slower pace, resulting in higher monoamine concentrations in the body. High concentrations of tyramine in the body produce a so-called 'tyramine pressor response', referring to a significant rise in blood pressure. By inhibiting monoamine degradation, MAOIs significantly lower the amount of ingested tyramine necessary to produce a rise in blood pressure and therefore lowers the threshold for a hypertensive crisis. Thus, when taking an MAOI, one has to be careful to avoid eating tyramine-rich foods (see MAOI Diet below). Consequences of a severe hypertensive crisis can be irreversible organ damage and death.

Serotonin syndrome:
The inhibition of central MAO enzymes raises the concentrations of monoamines, including serotonin, in the brain, and more specifically, in the synaptic cleft. When combined with serotonin precursors or other serotonergic agents (see Drugs to Avoid below), an overstimulation of serotonin receptors, called serotonin syndrome, can occur. This, too, is a serious and potentially fatal condition.

Drugs to Avoid

Really important - Never mix MAOI's with other drugs for depression such as 5htp, st johns wort, SSRI's, SNRI's etc. on cause death.

Talk to your doctor about these drugs if taking them:
  • alcohol
  • allergy/cold remedies
  • anesthetics
  • anxiety pills
  • asthma medications
  • barbiturates
  • blood pressure medications
  • cocaine
  • cough or cold medications
  • diabetes medications
  • heart medications
  • migraine medications
  • muscle relaxants
  • narcotics or other pain medications
  • seizure medications
  • stimulant medications
  • sulfur medications
  • tremor medications
  • weight reduction pills

MAOI Diet

FOODS TO AVOID
Alcoholic beverages Avoid Chianti wine and vermouth.
Consumption of red, white, and port wine in quantities less than 120 mL present little risk (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).
Beer and ale should also be avoided (McCabe, 1986), however other investigators feel major domestic (US) brands of beer is safe in small quantities (½ cup or less than 120 mL) (Anon, 1989; Da Prada, 1988), but imported beer should not be consumed unless a specific brand is known to be safe.
Whiskey and liqueurs such as Drambuie and Chartreuse have caused reactions.
Nonalcoholic beverages (alcohol-free beer and wines) may contain tyramine and should be avoided (Anon, 1989; Stockley, 1993).

Banana peels A single case report implicates a banana as the causative agent, which involved the consumption of whole stewed green banana, including the peel. Ripe banana pulp contains 7 µg/gram of tyramine compared to a peel which contains 65 µg/gram and 700 µg of tyramine and dopamine, respectively (McCabe, 1986).

Bean curd Fermented bean curd, fermented soya bean, soya bean pastes contain a significant amount of tyramine (Anon, 1989).

Broad (fava) bean pods These beans contain dopa, not tyramine, which is metabolized to dopamine and may cause a pressor reaction and therefore should not be eaten particularly if overripe (McCabe, 1986; Anon, 1989; Brown & Bryant, 1988).

Cheese Tyramine content cannot be predicted based on appearance, flavor, or variety and therefore should be avoided.
Cream cheese and cottage cheese have no detectable level of tyramine (McCabe, 1986; Anon, 1989, Brown & Bryant, 1988).

Fish Fresh fish (Anon, 1989; McCabe, 1986) and vacuum-packed pickled fish or caviar contain only small amounts of tyramine and are safe if consumed promptly or refrigerated for short periods; longer storage may be dangerous (Anon, 1989).
Smoked, fermented, pickled (Herring) and otherwise aged fish, meat, or any spoiled food may contain high levels of tyramine and should be avoided (Anon, 1989; Brown & Bryant, 1988).

Ginseng Some preparations have resulted in a headache, tremulousness, and manic-like symptoms (Anon, 1989).

Protein extracts Three brands of meat extract contained 95, 206, and 304 µg/gram of tyramine and therefore meat extracts should be avoided (McCabe, 1986).
Avoid liquid and powdered protein dietary supplements (Anon, 1989).

Meat non-fresh or liver
no detectable levels identified in fresh chicken livers
high tyramine content found in spoiled or unfresh livers (McCabe, 1986).
Fresh meat is safe, caution suggested in restaurants (Anon, 1989; Da Prada et al, 1988).
Sausage, bologna, pepperoni and salami contain large amounts of tyramine (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).
No detectable tyramine levels were identified in country cured ham (McCabe, 1986).

Sauerkraut Tyramine content has varied from 20 to 95 µg/gram and should be avoided (McCabe, 1986).

Shrimp paste Contain a large amount of tyramine (Anon, 1989).

Soups Should be avoided as protein extracts may be present; miso soup is prepared from fermented bean curd and contain tyramine in large amounts and should not be consumed (Anon, 1989).

Yeast Brewer's or extracts - yeast extracts (Marmite) which are spread on bread or mixed with water,
Brewer's yeast, or Yeast vitamin supplements should not be consumed.
Yeast used in baking is safe (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).

The foods to use with caution list categorizes foods that have been reported to cause a hypertensive crisis if foods were consumed in large quantities, stored for prolong periods, or if contamination occurred. Small servings (½ cup, or less than 120 mL) of the following foods are not expected to pose a risk for patients on MAOI therapy (McCabe, 1986).

FOODS TO USE WITH CAUTION
(½ cup or less than 120 mL)
Alcoholic beverages - see Foods to Avoid.

Avocados - contain tyramine, particularly overripe (Anon, 1989) but may be used in small amounts if not overripened (McCabe, 1986).

Caffeine - contains a weak pressor agent, large amounts may cause a reaction (Anon, 1989).

Chocolate - is safe to ingest for most patients, unless consumed in large amounts (Anon, 1989; McCabe, 1986).

Dairy products - Cream, sour cream, cottage cheese, cream cheese, yogurt, or milk should pose little risk unless prolonged storage or lack of sanitation standards exists (Anon, 1989; McCabe, 1986). Products should not be used if close to the expiration date (McCabe, 1986).

Nuts - large quantities of peanuts were implicated in a hypertensive reaction and headache. Coconuts and brazil nuts have also been implicated, however no analysis of the tyramine content was performed (McCabe, 1986).

Raspberries - contain tyramine and small amounts are expected to be safe (McCabe, 1986).

Soy sauce - has been reported to contain large amounts of tyramine and reactions have been reported with teriyaki (Anon, 1989), however analysis of soy sauce reveals a tyramine level of 1.76 µg/mL and fermented meat may have contributed to the previously reported reactions (McCabe, 1986).

Spinach, New Zealand prickly or hot weather - large amounts have resulted in a reaction (Anon, 1989; McCabe, 1986).

More than 200 foods contain tyramine in small quantities and have been implicated in reactions with MAOI therapy, however the majority of the previous reactions were due to the consumption of spoiled food. Evidence does not support the restriction of the following foods listed if the food is fresh (McCabe, 1986).

FOODS WITH INSUFFICIENT EVIDENCE FOR RESTRICTION (McCabe, 1986)
  • anchovies
  • beetroot
  • chips with vinegar
  • Coca Cola
  • cockles
  • coffee
  • corn, sweet
  • cottage cheese
  • cream cheese
  • cucumbers
  • egg, boiled
  • figs, canned
  • fish, canned
  • junket
  • mushrooms
  • pineapple, fresh
  • raisins
  • salad dressings
  • snails
  • tomato juice
  • wild game
  • Worcestershire sauce
  • yeast-leavened bread

Serotonin Syndrome

The combination of MAOI-A's and tryptophan can cause Serotonin Syndrome, or Serotonin Toxicity which is a life-threatening adverse drug reaction. Mild symptoms may only consist of increased heart rate, shivering, sweating, dilated pupils, myoclonus (intermittent tremor or twitching), as well as over-responsive reflexes.[1] Moderate intoxication includes additional abnormalities such as hyperactive bowel sounds, high blood pressure and hyperthermia; a temperature as high as 40 °C (104 °F) is common in moderate intoxication.

History of MAOI's

MAOIs started off due to the serendipitous discovery that iproniazid was a potent MAO inhibitor (MAOI). Originally intended for the treatment of tuberculosis, in 1952, iproniazid's antidepressant properties were discovered when researchers noted that the depressed patients given iproniazid experienced a relief of their depression. Subsequent in vitro work led to the discovery that it inhibited MAO and eventually to the monoamine theory of depression.

More MAOI Sections

MAOI and Psilocybin Experiences Post & read experiences with this combination.

References

1. Erowid MAOI Vault, accessed April 29 2009: http://www.erowid.org/chemicals/maois/
2. Wikipedia MAOI article, accessed April 29 2009: http://en.wikipedia.org/wiki/Monoami...dase_inhibitor

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