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.
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions 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
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:
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.
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, 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
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-HT1A: CBD
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
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)
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.
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 milk
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.
