MAO-A inhibition
MAO-A inhibition. Blocks monoamine oxidase A, the enzyme that breaks down serotonin, noradrenaline and dietary tyramine. Two separate hazards come off one enzyme: serotonin accumulates (toxicity) and dietary tyramine is no longer destroyed in the gut wall (pressor response).
MAO-B inhibition. Blocks monoamine oxidase B, which preferentially handles dopamine and phenylethylamine. At low, B-selective doses the tyramine hazard is much smaller; selectivity is lost as dose rises.
What acts on it
- Phenelzine
— inhibits, strong
Irreversible; enzyme activity returns only as new enzyme is synthesised, over about two weeks. - Tranylcypromine
— inhibits, strong
Irreversible and non-selective, and unlike phenelzine it additionally releases noradrenaline in the manner of an amphetamine. That second property is why its pressor reactions can be more abrupt, and why it is the MAOI with the most stimulant-like adverse-effect profile. - Isocarboxazid
— inhibits, strong
Irreversible and non-selective. The same two-week enzyme-resynthesis rule applies to it as to phenelzine and tranylcypromine, so both the dietary restriction and the washout interval before any serotonergic drug are measured in weeks rather than days. - Moclobemide
— inhibits, moderate
Reversible and competitive — tyramine displaces it. The tyramine pressor dose is raised only about 2–4 fold, versus roughly 10–50 fold for irreversible MAOIs, and the classic diet is not generally required at standard doses. - Selegiline (oral) — inhibits, strong
- Selegiline transdermal system
— inhibits, moderate
Central MAO-A inhibited; INTESTINAL MAO-A largely spared, which is the mechanistic reason the diet is not required at 6 mg/24 h. - Rasagiline — inhibits, strong
- Linezolid
— inhibits, moderate
Reversible. Serotonin toxicity has been reported repeatedly when it is started in someone already on a serotonergic antidepressant. - Methylene blue (methylthioninium chloride)
— inhibits, strong
Given intravenously in theatre for vasoplegia and parathyroid localisation, and for methaemoglobinaemia — settings where nobody is reviewing the patient's antidepressant. Serotonin toxicity following intraoperative methylene blue in a patient on an SSRI is a recognised event, and the exposure is a single dose nobody wrote on a medication list. - Harmala alkaloids (harmine, harmaline, tetrahydroharmine)
— inhibits, strong
Harmine and harmaline are potent competitive MAO-A inhibitors in human tissue; tetrahydroharmine additionally inhibits serotonin reuptake. - Ayahuasca (hoasca, daime)
— inhibits, strong
The brew delivers MAO-A inhibition and a direct 5-HT agonist in the same cup, by design — that is what makes it orally active. It therefore carries the serotonergic hazard from both directions at once, which is the specific reason the ayahuasca harm-reduction literature is emphatic about SSRI washout before a session. - Nutmeg (myristicin, elemicin)
— inhibits, weak
Truitt et al. (1963) demonstrated MAO inhibition by myristicin and nutmeg. The evidence is old and largely non-human; treat it as a documented signal of uncertain human magnitude, not as an equivalent of a prescribed MAOI. Marked here deliberately as WEAK rather than dropped, because a weak documented signal in a kitchen spice is worth a reader knowing about. - Kava
— inhibits, weak
All six major kavalactones inhibit MAO-B reversibly in vitro. B-selective and reversible inhibition carries a much smaller dietary-tyramine hazard than a non-selective irreversible MAOI, which is why this is scored weak rather than dropped. - Passionflower
— inhibits, weak
Harmine and harmaline content in Passiflora preparations is variable and generally low, and the inhibition is reversible, so this is scored weak. It is listed rather than omitted because a weak reversible MAO-A inhibitor in a stack that also contains a serotonergic drug or a dietary L-dopa load is exactly the combination the serotonin and tyramine rules exist to catch.
What is affected by it
- Nothing in this dataset.
Recognising serotonin toxicity
Hunter Serotonin Toxicity Criteria
In the presence of a serotonergic agent, serotonin toxicity is present if ANY ONE of the following holds.
- Spontaneous clonus.
- Inducible clonus AND (agitation OR diaphoresis).
- Ocular clonus AND (agitation OR diaphoresis).
- Tremor AND hyperreflexia.
- Hypertonia AND temperature above 38 °C AND (ocular clonus OR inducible clonus).
Reported sensitivity 84% and specificity 97% against a gold standard of clinical toxicologist diagnosis, in 2222 overdose admissions — better than the older Sternbach criteria, which are more sensitive to mild cases but far less specific.
CLONUS is the discriminating sign. It is what separates serotonin toxicity from neuroleptic malignant syndrome, anticholinergic delirium and sympathomimetic toxicity, and it is more marked in the legs than the arms.
Severe cases progress over hours: rigidity, hyperthermia above 38.5 °C, rhabdomyolysis, disseminated intravascular coagulation. Hyperthermia in this setting is a medical emergency — it is muscular in origin, so antipyretics do not treat it.
What a clean result means here
A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.
In this dataset
- Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
- Serotonergic drugs and the serotonin-toxicity mechanism
- Dietary tyramine and L-dopa loads
- The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
- P-glycoprotein inhibition and induction
- 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
- QT prolongation as an additive pharmacodynamic axis
- Culinary seasonings and common foods with documented pharmacological activity
- A selected set of narrow-therapeutic-index drugs where those shifts matter most
- The endocannabinoid enzymes and transport: FAAH, MAGL, endocannabinoid membrane transport, CB1 and CB2
- Additive CNS depression and GABA-A positive modulation — the alcohol / benzodiazepine / opioid / kava axis
- The phytocannabinoids delta-9-THC, cannabidiol and the converted cannabinoids, as both substrates and inhibitors
- Synthetic full CB1 agonists as a class, and why they are pharmacologically unlike cannabis
- CYP2E1, and phase-2 glucuronidation and sulfation where a specific entry names them
- The sedative and potentiator botanicals of the kava literature, and dietary L-dopa from Mucuna
Not in this dataset
- Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
- Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
- Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
- Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
- Renal and hepatic impairment, age, pregnancy, and body composition.
- Bleeding and antiplatelet risk, hypoglycaemia, anticholinergic load, and most other pharmacodynamic axes beyond the ones listed above. Additive CNS depression and GABA-A modulation ARE now modelled — see the covers list — but the absence of a sedation finding still only means the agents you named are not on that axis in this dataset.
- Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
- Allergy, intolerance, and contamination or adulteration of unregulated products.
- Anything published after the last-reviewed date below.
- Bleeding and antiplatelet risk, which is the mechanism that matters most for garlic, ginkgo and several other common supplements. It is not modelled at all, so a clean result says nothing about it.
- Whether any of the natural FAAH, MAGL or transport inhibition reported in vitro occurs at all at a dose a person would take. For most of these compounds nobody has measured it.
- The actual contents of an unregulated cannabinoid product. This engine models named compounds; an unidentified isomer or side-product in a converted-cannabinoid product is outside it by construction.
- Dose. Every cannabinoid interaction here scales with dose, and consumer product labelling for this category is repeatedly found inaccurate in published surveys.
- Inhalation-specific hazards — thermal degradation products, diluents chosen for rheology rather than for inhalation toxicology, and carrier and adulterant contamination.
101 substances, 33 mechanisms, 101 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.
References
- Gillman PK (2011). Advances Pertaining to the Pharmacology and Interactions of Irreversible Nonselective Monoamine Oxidase Inhibitors. Journal of Clinical Psychopharmacology. doi:10.1097/JCP.0b013e31820469ea
- Gillman PK, Feinberg SS, Fochtmann LJ (2018). A reassessment of the safety profile of monoamine oxidase inhibitors: elucidating tired old tyramine myths. Journal of Neural Transmission. doi:10.1007/s00702-018-1932-y
- Bonnet U (2003). Moclobemide: Therapeutic Use and Clinical Studies. CNS Drug Reviews. doi:10.1111/j.1527-3458.2003.tb00245.x
- Azzaro AJ, VanDenBerg CM, Blob LF, et al. (2006). Tyramine Pressor Sensitivity During Treatment With the Selegiline Transdermal System 6 mg/24 h in Healthy Subjects. The Journal of Clinical Pharmacology. doi:10.1177/0091270006289852
- Gillman PK (2003). Linezolid and Serotonin Toxicity. Clinical Infectious Diseases. doi:10.1086/378895
- Quinn DK, Stern TA (2009). Linezolid and Serotonin Syndrome. The Primary Care Companion to The Journal of Clinical Psychiatry. doi:10.4088/PCC.09r00853
- Lawrence KR, Adra M, Gillman PK (2006). Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data. Clinical Infectious Diseases. doi:10.1086/503839
- Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H (2010). β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food and Chemical Toxicology. doi:10.1016/j.fct.2009.12.019
- Callaway JC, McKenna DJ, Grob CS, et al. (1999). Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of Ethnopharmacology. doi:10.1016/S0378-8741(98)00168-8
- Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (2003). Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics. The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.103.049882
- Truitt EB Jr, Duritz G, Ebersberger EM (1963). Evidence of Monoamine Oxidase Inhibition by Myristicin and Nutmeg. Proceedings of the Society for Experimental Biology and Medicine. doi:10.3181/00379727-112-28128
- Mathews JM, Etheridge AS, Black SR (2002). Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metabolism and Disposition. doi:10.1124/dmd.30.11.1153
- Dhawan K, Dhawan S, Sharma A (2004). Passiflora: a review update. Journal of Ethnopharmacology. doi:10.1016/j.jep.2004.02.023
Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.
Last reviewed . All interaction pages.