MAOI

For reversible inhibitor of monoamine oxidase A, see RIMA.

Monoamine oxidase inhibitors (also known as MAOIs) are a class of drugs which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression and are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders.

Mechanism of action

MAOIs act by inhibiting the activity of monoamine oxidase, preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B.

MAOA preferentially deaminates norepinephrine (NE), serotonin (5-HT) and epinephrine (E), while MAOB preferentially deaminates benzylamine and phenylethylamine (PEA). Dopamine (DA) and tyramine are equally catabolized by both forms of MAO.

Reversibility

Further information: RIMA

The early MAOIs inhibit monoamine oxidase irreversibly, meaning they permanently deactivate it and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, known as reversible inhibitors of monoamine oxidase A (RIMAs), are reversible. This means that they are able to detach from the enzyme to facilitate usual catabolism of the substrate.

Poly drug use

• Ayahuasca: The tryptamine DMT will break down without MAOIs when taken orally.

Interactions

Check if your MAOIs also inhibits other substances. Most MAOIs are also cytochrome P450 inhibitors (and tyramine and many other substances are cytochrome P450 substrates) and some are also acetylcholinesterase inhibitors (AChEIs)!

Substances that inhibits the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times. When the CYP450 system is impacted in this way, it leads to higher levels of certain drugs in your system at one time. This can cause unwanted side effects, and sometimes, an overdose.

This section will never be complete since too many substances interact with MAOIs. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption. However, not everything is documented and animal studies is not always reliable, so always start with microdoses.

Tyramine

Tyramine causes hypertensive crises after MAO inhibition aka the "cheese effect" or "cheese crisis". Using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction. Tyramine rich food should also be avoided by people prone to headache and migraine.

Psychoactive substances

Naturally occurring sources with tyramine.

• Psychedelic cacti. The cacti contain contain a bunch of phenethylamines, not just tyramine (but also 3-Methoxytyramine, methyltyramine, hordenine (aka dimethyltyramine), mescaline, etc) and should thus be avoided with MAOIs. However, tyramine has been identified in these species:
  • Peruvian torch cactus (Echinopsis peruviana (syn. Trichocereus peruvianus))
  • San Pedro cactus (Echinopsis pachanoi (syn. Trichocereus pachanoi))
  • Other cactis:

Specie	Tyramine (mg/gram of alive plant)
L. williamsii	0.5 - 1
L. jourdaniana	0.6
L. diffusa	0.1
L. fricii	0.1
L. koehresii	0.1

Food

Specific foods with high amounts of tyramine:

• Aged cheese (gouda, camembert, cheddar) -- Few cheeses (even. 'mature' cheeses) contain more than 25 mg of tyramine in 100 grams. However, Stilton (a blue cheese) contains up to 217 mg tyramine per 100 grams.
• Aged, smoked or pickled meats
• Aged or fermented soy and yeast products (soy sauce, teriyaki sauce, home baked yeast bread, sourdough bread)
• Overripe fruits
• High amounts of nuts

Candy, and dried fruit:

• Cocoa
  • Chocolate, especially dark chocolate
  • Dried and/or candied fruit rolled in cocoa powder
• Licorice (isoliquiritigenin and liquiritigenin are non-selective MAOIs).
  • Licorice candy
  • Dried and/or candied fruit rolled in licorice powder

Tyramine formation has been associated with bacterial contamination of foods or temperature abuse conditions, but can also occur as a side effect of generally desired ripening processes. Tyramine is a breakdown product of the amino acid L-tyrosine.

Psychoactive substances

The MAOIs are well-known for their numerous drug interactions, including the following kinds of substances:

• Substances that are metabolized by monoamine oxidase, as they can be boosted by up to several-fold
• Substances that increase serotonin, noradrenaline, or dopamine activity as too much of any of these neurotransmitters can result in severe acute consequences including serotonin syndrome, hypertensive crisis, and psychosis.
• Long-term use with psychoactive substances that interact with MAOIs must be gradually discontinued to avoid discontinuation syndrome. Examples:
  • Cannabinoids: Cannabinoids are lipophilic. For example, THC has been detected in heavy cannabis users after 77 days of drug abstinence (Ellis et al., 1985).
  • SSRIs: Because of the extended half-life of norfluoxetine, a minimum of 5 weeks should lapse between stopping fluoxetine (20 mg/day) and starting an MAOI. With higher doses the interval should be longer. For example, a serotonin syndrome was reported following a 6-weeks washout in a patient who had been given fluoxetine (80 mg/day).

By chemicals

• Adrenergics
• Lysergamides
• Monoaminergics (MA)
  • Cholinergics (see also MAOIs that act as acetylcholinesterase inhibitors (AChEIs)), certain substances, examples: alpha-GPC (suspected monoaminergic), centrophenoxine, citicoline (suspected monoaminergic)
  • MAOIs, avoid mixing pure MAOIs. Plants with multiple MAOIs like Peganum harmala are fine since they have been evaluated.
    • RIMAs
• Disinhibitors
  • Norepinephrine and dopamine disinhibitors (NDDIs): Fluoxetine
• Neurotransmitter precursors
  • Dopamine: L-DOPA, L-tyrosine (L-DOPA precursor)
  • Epinephrine (adrenaline): L-DOPA, SAM-e
  • Melatonin: L-tryptophan
  • Norepinephrine (noradrenaline): L-DOPA
  • Serotonin: 5-HTP, L-tryptophan
• Opioids: Some opioid analgesics are associated with a risk of serotonin syndrome in combination with MAOIs due to their serotonergic properties. Other combinations may result in opioid toxicity due to CYP450 enzyme inhibition by the MAOI. Given the widespread availability of several suitable alternative drugs, the combination of dextromethorphan, methadone, pethidine, tramadol, fentanyl or tapentadol with an MAOI should usually be avoided, including in the 14 day period following the withdrawal of an irreversible MAOI. Morphine, codeine, oxycodone and buprenorphine are alternative opioids for patients receiving MAOIs, though starting at a low dose and titrating cautiously against clinical response is advised.
• Racetams: Aniracetam, piracetam
• Receptor agonists
  • Serotonin receptor agonist
    • 5-HT_1A: CBD
  • Dopamine receptor agonist, examples: amphetamines (amphetamine, lisdexamfetamine, methamphetamine), cathinone, cocaine, PCP, phenethylamine, salvinorin A (found in Salvia divinorum), tyramine
    • D2: CBD, lysergamides (LSD)
• Releasing agents and monoamine releasing agent (MRA) (or monoamine releaser)
  • Dopamine releasing agent (DRA)
  • Norepinephrine releasing agent (NRA) (or adrenergic releasing agent), examples: Adrenaline, ephedrine, pseudoephedrine
  • Norepinephrine-dopamine releasing agents (NDRAs), examples: Amphetamine, cathinone, phenethylamine, tyramine, methamphetamine
  • Serotonin releasing agent (SRA)
    • Dextropropoxyphene
    • Diphenhydramine
    • DXM
    • Selective serotonin releasing agent (SSRA), examples: MDAI, PMA, PMMA
  • Serotonin–norepinephrine-dopamine releasing agent (SNDRA) (also known as a triple releasing agent (TRA)), examples:
    • Amphetamines: MDA, MDMA, methamphetamine
    • Substituted benzofurans: 5-APB, 6-APB
    • Substituted cathinones: mephedrone
    • Tryptamines: αET, αMT
• Reuptake inhibitors and monoamine reuptake inhibitors (MRIs)
  • Dopamine reuptake inhibitors (DRI), examples: Armodafinil, ethylphenidate, methylphenidate, modafinil
  • Norepinephrine reuptake inhibitor (NRI, NERI) (or adrenergic reuptake inhibitor (ARI)), example: Tapentadol
  • Norepinephrine-dopamine reuptake inhibitors (NDRI), examples: Ethylphenidate, methylphenidate, prolintane. Suspected: A-PVP, desoxypipradrol, MDPV
  • Serotonin reuptake inhibitor (SRA)
    • Selective serotonin reuptake inhibitors (SSRI), examples: Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
  • Serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), examples:
    • 6-APB
    • Cocaine
    • Ketamine
    • PCP
    • St. Johnswort (Hypericum perforatum)
• Serotonin modulator and stimulator (SMS)
• Substituted cathinones, examples: a-PVP, MDPV, methylone, mephedrone
• Substituted phenethylamines
  • Amphetamines, examples: Amphetamine, dextroamphetamine, methamphetamine
  • Psychedelic phenethylamines, examples: 2C-x (and NBs for example 25x-NBOH, 25x-NBOMe), DOx, MDMA, mescaline (psychedelic cacti)
• Substituted tryptamines, examples:
  • 5-MeO-xxT: 5-MeO-AMT, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-MiPT
• Tetracyclic antidepressants (TeCA), example: Mirtazapine
• Tricyclic antidepressants (TCA), example: Tianeptine
• Xanthines: Caffeine

By pharmacotherapy

• Antibiotics
  • Linezolid
• Antihistamines (allergy medicines), example but not limited to:
  • Desloratadine -- hay fever medicine.
  • Loratadine -- hay fever medicine.
• Antitussives
  • Cold medicine
• Decongestants, example but not limited to:
  • Naphazoline (brand name Clear Eyes, Cleari) -- eye drops relieve dry, red, itchy eyes.
• Essential nutrients
  • Choline
    • Certain cholinergics (see "Cholinergics")
• Local and general anesthetic

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when taken with other substances. The following lists some known dangerous combinations, but cannot be guaranteed to include all of them. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

• 2c-t-x - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably, which could be dangerous given the unpredictability of the 2C-T-x series
• 2c-x - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
• dox - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
• ketamine - MAO-B inhibitors appear to increase the potency of Ketamine. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available
• mescaline
• nbomes - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
• opioids - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
• alcohol - Tyramine found in many alcoholic beverages can have dangerous reactions with MAOIs, causing an increase in blood pressure.
• mxe - MAO-B inhibitors appear to increase the potency of MXE. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available
• 5-meo-xxt
• amphetamines - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.
• amt - aMT is an MAOI on its own. Using enzyme inhibitors can greatly reduce predictability of effects.
• cocaine - This combination is poorly explored
• dxm - High risk of serotonin syndrome
• mdma - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with MDMA will lead to hypertensive crises.
• pcp - This combination is very poorly explored
• ssris
• tramadol

Reduced bio-availability

Essential vitamins and minerals

• Vitamin B6: MAOIs may reduce blood levels of vitamin B6.

List of MAOIs

See also: RIMA § List of RIMAs

Nonselective MAO-A and MAO-B inhibitors

• Naturally occurring sources

Natural occuring source	Chemical	MAOI
Yangonin (ayahuasca, caapi or yagé)	(−)-epicatechin	MAO-B
Banisteriopsis caapi (ayahuasca, caapi or yagé)	(−)-epicatechin	MAO-B
Banisteriopsis caapi (ayahuasca, caapi or yagé)	(−)-procyanidins	MAO-B
Banisteriopsis caapi (ayahuasca, caapi or yagé)	Harmaline	RIMA
Banisteriopsis caapi (ayahuasca, caapi or yagé)	Harmine	MAO-A, MAO-B
Black pepper (Piper nigrum)	Piperine	MAO-A, MAO-B
Cannabis, Cannabis extract		MAO-A, MAO-B
Cocoa bean (from Theobroma cacao)	Caffeine	MAO-A, MAO-B
Cocoa bean (from Theobroma cacao)	Catechin	MAO-B
Cocoa bean (from Theobroma cacao)	Epicatechin	MAO-B
Cocoa bean (from Theobroma cacao)	Tetrahydro-beta-carbolines
Coffee (Coffea arabica, Coffea canephora)	Caffeine	MAO-A, MAO-B
Coffee (Coffea arabica, Coffea canephora)	Harman	MAO-A
Coffee (Coffea arabica, Coffea canephora)	Norharman	MAO-A
Liquorice/licorice (Glycyrrhiza Glabra)	Isoliquiritigenin	MAO-A, MAO-B
Liquorice/licorice (Glycyrrhiza Glabra)	Liquiritigenin	MAO-A, MAO-B
Long pepper (Piper longum)	Piperine	MAO-A, MAO-B
Nutmeg (Myristica fragrans)	Kaempferol	MAO-A
Nutmeg (Myristica fragrans)	Myristicin	MAO-A, MAO-B?
Nutmeg (Myristica fragrans)	Quercetin	MAO-A
Passionflower (Passiflora incarnata), weak MAOI	Apigenin	MAO-A
Passionflower (Passiflora incarnata), weak MAOI	Harmine	MAO-A, MAO-B
Passionflower (Passiflora incarnata), weak MAOI	Kaempferol	MAO-A
Passionflower (Passiflora incarnata), weak MAOI	Quercetin	MAO-A
Rhodiola rosea		MAO-A, MAO-B
Syrian rue (Peganum harmala)	Desoxypeganine	MAO-A
Syrian rue (Peganum harmala)	Harmaline	RIMA
Syrian rue (Peganum harmala)	Harman	MAO-A
Syrian rue (Peganum harmala)	Harmine	MAO-A, MAO-B
Tobacco	1,2,3,4-tetrahydro-b-carboline (THbC)	MAO-A, MAO-B
Tobacco	1,2,3,4-tetrahydroisoquinoline	MAO-A, MAO-B
Tobacco	Harman	MAO-A
Tobacco	Norharman	MAO-B

• Psychedelics
  • AET
  • AMT
• Pharmaceuticals
  • Hydrazine (antidepressant)
    • Isocarboxazid (Marplan)
    • Nialamide (Niamid)
    • Phenelzine (Nardil, Nardelzine)
    • Hydracarbazine
  • Non-hydrazines
    • Tranylcypromine (Parnate, Jatrosom)

Selective MAO-A inhibitors

For safer MAO-A inhibitors, see RIMA.

• Naturally occurring sources
  • Yohimbe (Pausinystalia johimbe): Yohimbine
• Psychedelics
  • 2C-T-2 (suspected, weak)
  • 2C-T-7 (suspected, strong)
  • Bromo-DragonFLY (suspected, very strong)
• Pharmaceuticals
  • Bifemelane (Alnert, Celeport) (available in Japan)
  • Isocarboxazid (common brand name Marplan)
  • Phenelzine (common brand name Nardil)
  • Pirlindole (Pirazidol) (available in Russia)
  • Tranylcypromine (common brand name Parnate)

Unknown selectivity

• Psychedelics
  • 5-MeO-AET
  • 5-MeO-AMT
  • 5-Fluoro-AMT
• Stimulants
  • 4-MTA
  • 5-IT
  • PMA
  • PMMA
  • PMEA

Selective MAO-B inhibitors

• Naturally occurring sources
  • Betel nut (Areca catechu): MAO-A inhibitor.
  • Kava (Piper methysticum): Yangonin. Kava pyrones: The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain.
  • Olives (Olea europaea), fresh, olive leaf extract: The selective MAO-B inhibitor hydroxytyrosol.
• Pharmaceuticals
  • Rasagiline (Azilect)
  • Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)
  • Safinamide (Xadago)

Research

• Naturally occurring sources
  • Mimosa tenuiflora: As there have been no MAO inhibitors detected in M. tenuiflora, there is ongoing interest into how yurema exerts its visionary effects.

See also

• Responsible use
• RIMA
• Monoamine
• Ayahuasca

External links

• Monoamine oxidase inhibitor (Wikipedia)
• Monoamine oxidase A (Wikipedia)
• Monoamine oxidase B (Wikipedia)
• MAOIs (Erowid Vault)
• Erowid MAOI Vault : Food & Drug Interactions with MAOIs
• Agents That Are Contraindicated With MAOIs and the Corresponding Adverse Events

References

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