MAOI

Monoamine oxidase inhibitors, or MAOIs, alter consciousness not through direct receptor activation but by preventing the breakdown of monoamine neurotransmitters, thereby increasing their concentration in the synaptic cleft. The subjective experience of MAOIs varies depending on whether they are taken alone or in combination with other substances.

When taken alone, MAOIs at therapeutic doses produce a gradual mood elevation over days to weeks rather than an acute subjective experience. There may be a subtle increase in energy, emotional resilience, and interest in activities. The effects integrate seamlessly into normal functioning and are most apparent in their absence: the lifting of depressive symptoms rather than the creation of positive symptoms.

In combination with tryptamine psychedelics, MAOIs serve as potentiators, dramatically extending and intensifying the psychedelic experience. Ayahuasca is the prototypical example. The MAOI component prevents the rapid breakdown of DMT, allowing it to produce extended visionary experiences that would not be possible with DMT alone. The critical safety concern with MAOIs is their interaction potential: the combination with serotonin releasers or serotonin-rich foods can trigger life-threatening serotonin syndrome or hypertensive crisis.

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.

Monoamine oxidase A (MAOA) generally metabolizes tyramine, norepinephrine (NE), serotonin (5-HT), and dopamine (DA) (and other less clinically relevant chemicals). In contrast, monoamine oxidase B (MAOB) mainly metabolizes dopamine (DA) (and other less clinically relevant chemicals).

• Reversibility

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monoamine oxidase irreversibly, meaning they permanently deactivate it and the enzyme cannot function until it has been replaced by the body, which can take about two weeks.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.

Not only avoid the consumption but also the handling of substances with dangerous MAOI interactions (in case they are absorbed unintentionally, e.g. via breathing, skin absorption, or contaminated fingers to mouth, nose, eyes, etc).

• Before MAOI consumption
• Substances with slow elimination
• Methamphetamine: Because of its slow elimination, low concentrations of Methamphetamine can be detected in urine for up to 7 days after a single oral dose of 30 mg (Valentine et al., 1995) or up to 60 h after a single 15-mg smoked or intravenous dose (Cook et al., 1993). A chronic meth user might still test positive seven to 10 days after consuming the drug.
• Pharmacotherapy 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).
• Tolerance from heavy substance use or therapy may cause post-acute-withdrawal syndrome (PAWS). The condition gradually improves over a period of time which can range from six months to several years in more severe cases.
• After MAOI consumption

MAOIs cause dangerous interactions with many substances, they must be avoided during or within 14 days of administration of monoamine oxidase inhibitors.

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

Party pills (sometimes called "herbal highs") often contain MAOIs.

• Nonselective MAOIs/RIMAs

See also naturally occurring RIMA sources.

• Naturally occurring sources
• Psychedelics
• AET
• AMT
• Selective MAO-A inhibitors
• Naturally occurring sources
• Betel nut (Areca catechu): MAO-A inhibitor.
• Psychedelics
• 2C-T-2 (suspected, weak)
• Substituted phenethylamines are dangerous to combine with MAOIs.
• 2C-T-7 (suspected, strong)
• Dangerous to combine with MAOIs.
• Pharmaceuticals
• Bifemelane (Alnert, Celeport) (available in Japan)
• Isocarboxazid (common brand name Marplan)
• Methylthioninium chloride (Urelene blue, Provayblue, Proveblue), commonly called methylene blue. — Pure methylene blue is frequently sold as a dying agent and thus easy to obtain.
• Phenelzine (common brand name Nardil)
• Pirlindole (Pirazidol) (available in Russia)
• Tranylcypromine (common brand name Parnate)
• Selective MAO-B inhibitors
• Naturally occurring sources
• 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)
• Unknown selectivity
• Psychedelics
• 5-MeO-AET
• 5-MeO-AMT
• 5-Fluoro-AMT
• Stimulants
• 4-MTA
• 5-IT
• PMA
• PMMA
• PMEA
• 4-HO-DTBT

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.

• Psychoactive naturally occurring sources with high tyramine content
• 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:
• 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.
• By chemicals
• Amino acids, and amino acid metabolism metabolic intermediates
• Monoamine precursors
• 5-HTP → serotonin
• L-DOPA → dopamine, and epinephrine (adrenaline)
• L-phenylalanine → L-tyrosine, and phenethylamine: Use with caution, taking phenylalanine while taking MAOIs may cause a severe increase in blood pressure (hypertensive crisis).
• L-tryptophan → 5-HTP, and melatonin: May result in short-term serotonin syndrome.
• L-tyrosine → L-DOPA, and tyramine: It is unknown if MAOIs interact with tyrosine, so use with caution.
• Amino acid metabolism metabolic intermediates
• SAM-e → epinephrine (adrenaline)
• Adrenergics
• Lysergamides: LSA (morning glory: (Argyreia nervosa, Ipomoea tricolor, etc)
• Monoaminergics (MA)
• Cholinergics (see also MAOIs that act as acetylcholinesterase inhibitors (AChEIs)), certain substances, examples: alpha-GPC (suspected monoaminergic), centrophenoxine,
• 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
• 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
• Dopamine receptor agonist, examples: amphetamines (amphetamine, lisdexamfetamine, methamphetamine), cathinone, cocaine, PCP, phenethylamine, salvinorin A (found in Salvia divinorum), tyramine
• D2: CBD,
• 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
• Tropane alkaloids
• Anticholinergics (found in (Datura spp., Hyoscyamus niger, etc))
• Atropine
• Hyoscyamine
• Scopolamine
• Stimulants
• Cocaine
• RTI-111
• Xanthines: Caffeine
• By pharmacotherapy
• Antibiotics
• Linezolid
• Anticholinergics
• Hyoscine, also known as scopolamine: The transdermal patch (e.g., Transderm Scōp) for prevention of nausea and motion sickness employs hyoscine base, and is effective for up to three days.
• Antihistamines (allergy medicines used to treat allergic conjunctivitis most often caused by hay fever), for example desloratadine, and loratadine. MAOI safe alternative: Cromoglicic acid eye drops.
• Antitussives
• Cold medicine
• Decongestants
• Naphazoline
• Essential nutrients
• Choline
• Certain cholinergics (see "Cholinergics")
• Local and general anesthetic
• Vasoconstrictors
• Naphazoline (brand name Clear Eyes, Cleari -- Eye drops used to treat red eyes, caused by for example cannabis that induces corneal vasodilation)
• Over-the-counter (OTC) medicines
• Tyramine

Tyramine is physiologically metabolized by monamine oxidases (primarily MAO-A), FMO3, PNMI, DBH and CYP2D6. Tyramine and dopamine are metabolized by both MAO-A and MAO-B. It has been established that hypertensive crises are a consequence of MAO-A inhibition (Youdim et al. 1988; Laux et al. 1995). However, eating foods rich in tyramine while taking high doses of MAO-B inhibitors can cause a sudden increase in blood pressure.

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.

• Tyramine rich foods

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. Tyramine is a breakdown product of the amino acid L-tyrosine.

• Essential vitamins and minerals

• Vitamin B6: MAOIs may reduce blood levels of vitamin B6. Not studied on harmalas. But on tranylcypromine (a cyclopropane), and phenelzine (a hydrazine), two pharms with distinct chemical groups.

• Substances

• Lysergamides: LSD. MAOIs seem to cause a greater reduction in the effects of LSD than SSRIs.

• 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.

• Responsible use

• RIMA

• Monoamine

• Ayahuasca

• 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

The knowledge of MAOIs began with 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. MAOIs became widely used as antidepressants in the early 1950s. The discovery of the 2 isoenzymes of MAO has led to the development of selective MAOIs that may have a more favorable side-effect profile.

The older MAOIs' heyday was mostly between the years 1957 and 1970. The initial popularity of the 'classic' non-selective irreversible MAO inhibitors began to wane due to their serious interactions with sympathomimetic drugs and tyramine-containing foods that could lead to dangerous hypertensive emergencies. As a result, the use by medical practitioners of these older MAOIs declined. When scientists discovered that there are two different MAO enzymes (MAO-A and MAO-B), they developed selective compounds for MAO-B, (for example, selegiline, which is used for Parkinson's disease), to reduce the side-effects and serious interactions. Further improvement occurred with the development of compounds (moclobemide and toloxatone) that not only are selective but cause reversible MAO-A inhibition and a reduction in dietary and drug interactions. Moclobemide, was the first reversible inhibitor of MAO-A to enter widespread clinical practice.

A transdermal patch form of the MAOI selegiline, called Emsam, was approved for use in depression by the Food and Drug Administration in the United States on 28 February 2006.