What happens when you take nutmeg with MAOIs?
Nutmeg, the dried seed of Myristica fragrans, contains essential oils rich in myristicin, elemicin, and safrole. Myristicin has long been recognized as a psychoactive substance at high doses, and laboratory work dating back to the 1960s demonstrated that myristicin and whole nutmeg can inhibit monoamine oxidase (MAO), the enzyme that breaks down serotonin, norepinephrine, dopamine, tyramine, and related monoamines. The inhibition is considered weak and reversible compared to prescription MAOIs, but it is real.
MAOIs prescribed for depression (phenelzine, tranylcypromine, isocarboxazid), Parkinson's disease (selegiline, rasagiline), or smoking cessation (the antidepressant moclobemide, in countries where it is available) work by blocking MAO so that synaptic monoamines accumulate. Patients on MAOIs are warned to avoid tyramine-rich foods because tyramine, normally cleared by MAO in the gut and liver, can flood the circulation, displace norepinephrine from sympathetic nerve terminals, and trigger a hypertensive crisis with severe headache, blood pressure surge, sweating, chest pain, and the risk of intracranial hemorrhage.
When myristicin's weak MAO inhibition is layered on top of a prescription MAOI, two related risks emerge. First, the additive enzyme blockade can make the patient even more vulnerable to dietary tyramine. Second, myristicin and other nutmeg constituents may exert mild serotonergic activity, raising the theoretical risk of serotonin syndrome, a constellation of agitation, hyperreflexia, clonus, autonomic instability, and hyperthermia that can be fatal.
Why is this important?
MAOI therapy already requires considerable patient effort: aged cheeses, cured meats, fermented soy products, draft beer, and several other tyramine sources have to be avoided, and a long list of cough-cold remedies and serotonergic drugs are off-limits. Adding a herb that further inhibits MAO is exactly the wrong direction. Hypertensive crisis is a medical emergency, and serotonin syndrome can progress quickly enough that timely recognition is critical.
The risk is dose-dependent. A pinch of nutmeg in a holiday eggnog or sprinkled on a latte is unlikely to deliver enough myristicin to matter. Large doses, on the order of one tablespoon or more of ground nutmeg, are also independently dangerous because of nutmeg's own neurotoxic and anticholinergic effects (the so-called 'nutmeg high' is rarely pleasant and can cause tachycardia, hallucinations, severe nausea, and prolonged anxiety). Nutmeg essential oil used internally or in concentrated tincture form carries the highest concern.
What should you do?
If you take a prescription MAOI, treat nutmeg like any other restricted substance: trace amounts in food are generally fine, but avoid concentrated nutmeg supplements, nutmeg essential oil taken internally, and large therapeutic doses. The same caution applies to mace, which is the outer covering of the nutmeg seed and shares its essential oil profile. Watch for the warning signs of hypertensive crisis (severe occipital or temporal headache, palpitations, blood pressure spike, nausea, sweating, photophobia) and serotonin syndrome (restlessness, tremor, muscle twitching, fever, confusion). Both warrant emergency care.
If you are also taking serotonergic medications alongside an MAOI (which is itself usually contraindicated), the combined risk with nutmeg climbs even higher. SSRIs, SNRIs, tramadol, dextromethorphan, meperidine, triptans, lithium, St. John's wort, and 5-HTP should all be avoided with MAOI therapy, and nutmeg simply adds another small risk to a list that is already long.
Which specific products are affected?
Concerning sources of myristicin include: whole nutmeg or freshly ground nutmeg in large amounts; mace; nutmeg essential oil (both internal use and high-dose aromatherapy); concentrated nutmeg supplements marketed for sleep, anxiety, or 'natural mood support'; some commercial herbal sleep blends; and certain ethnobotanical preparations. Prescription MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegiline (Eldepryl, Emsam transdermal patch), rasagiline (Azilect), and in non-US markets, moclobemide (Aurorix, Manerix).
The 'cheese effect' washout period after stopping an irreversible MAOI is typically 14 days, during which MAO must regenerate. Nutmeg restrictions should be maintained throughout that interval and not relaxed simply because the daily pill has stopped.
The bottom line
Culinary nutmeg in normal amounts is unlikely to interact dangerously with MAOIs, but concentrated nutmeg supplements, essential oil, and large doses can add to MAOI activity and tip patients into hypertensive crisis or serotonin syndrome. If you take an MAOI, avoid nutmeg supplements entirely and keep dietary nutmeg to the levels you would find in a typical recipe.