What happens when you take nutmeg with MAOIs?
Nutmeg, the dried seed of Myristica fragrans, contains an essential oil rich in myristicin. A laboratory study from 1963 reported that myristicin and whole nutmeg could weakly inhibit monoamine oxidase (MAO), the enzyme that breaks down serotonin, norepinephrine, dopamine, and tyramine. MAOI antidepressants work by blocking the same enzyme, so the theoretical concern is that the two effects could stack on top of one another.
- Nutmeg may weakly block MAO. In the 1963 in-vitro work, myristicin showed mild, reversible MAO-inhibiting activity. This is far weaker than a prescription MAOI, but it points in the same direction.
- MAOIs already block MAO heavily. Prescription MAOIs are given to keep monoamines from being broken down, so synaptic levels rise. Patients are already asked to avoid tyramine-rich foods for this reason.
- Layering one on the other could, in theory, add up. If nutmeg's weak effect were added to a prescription MAOI, it might in principle make a person slightly more sensitive to tyramine, or contribute to excess serotonin signalling. Importantly, there are no documented human cases of nutmeg actually causing this with an MAOI.
So the mechanism is plausible on paper, but the real-world risk rests on a single old laboratory study and remains theoretical and dose-dependent.
Why is this important?
MAOI therapy already asks a lot of patients: aged cheeses, cured meats, fermented soy products, and a long list of cough-cold and serotonergic medicines have to be avoided. Adding anything that nudges MAO further in the same direction is, at least in principle, the wrong way to go. Because the consequences of overshooting MAO inhibition (a sharp rise in blood pressure, or excess serotonin signalling) can be serious, it is reasonable to be cautious even when the supporting evidence is thin.
At the same time, this is not a documented, well-established danger. The concern is mechanistic, not a record of people being harmed. The honest framing is: a sensible precaution for concentrated nutmeg products, not a reason for alarm about the nutmeg in your food.
What should you do?
The dividing line is between a trace of nutmeg in food and concentrated nutmeg products.
Before starting or changing an MAOI: tell your prescriber and pharmacist about any nutmeg supplement, nutmeg essential oil, or herbal sleep blend you use, and ask whether to stop it. Bring the actual product label so they can see what is in it.
While on an MAOI, day to day: keep nutmeg to the small amounts you would find in ordinary cooking and baking. Avoid concentrated nutmeg supplements and nutmeg essential oil taken internally. The same caution applies to mace, the outer covering of the nutmeg seed, which shares nutmeg's essential-oil profile.
After stopping an MAOI: irreversible MAOIs take time for the enzyme to regenerate, so don't assume restrictions lift the day you stop the pill. Ask your prescriber how long to keep any nutmeg precautions in place.
If you ever develop a severe headache, a pounding heartbeat, sweating, agitation, tremor, or confusion, seek medical care promptly rather than trying to sort out the cause yourself.
Which specific products are affected?
The concern is concentrated sources of myristicin, not the spice rack:
- Concentrated nutmeg supplements (often sold for sleep, anxiety, or "natural mood support")
- Nutmeg essential oil taken internally or used in high-dose aromatherapy
- Mace supplements and concentrated mace preparations
- Herbal sleep blends that list nutmeg as an ingredient
- Ethnobotanical preparations of Myristica fragrans
Prescription MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegiline (Eldepryl, Emsam transdermal patch), rasagiline (Azilect), and, in some non-US markets, moclobemide (Aurorix, Manerix). Note that serotonergic medicines such as SSRIs, SNRIs, tramadol, dextromethorphan, meperidine, triptans, lithium, St. John's wort, and 5-HTP are themselves generally avoided with MAOIs.
Ordinary culinary nutmeg, a sprinkle on eggnog or in a baked good, is not the target of this caution.
The science behind it
The evidence here is limited and old. The main reference is a single 1963 laboratory study reporting weak, reversible MAO inhibition by myristicin and nutmeg in vitro. There are no published human cases of nutmeg interacting with an MAOI, and no clinical trials.
- Truitt EB, Duritz G, Ebersberger EM. Evidence of monoamine oxidase inhibition by myristicin and nutmeg. Proc Soc Exp Biol Med. 1963;112:647-50. PMID 13994372. (In-vitro / animal laboratory evidence of weak MAO inhibition.)
- General pharmacology summaries of myristicin describe it as a weak MAO inhibitor and note its psychoactivity at very high doses, without documenting MAOI drug interactions in people. (Secondary summary: Myristicin pharmacology overview.)
In short, the interaction is biologically plausible but rests on minimal, dated, non-human data.
Frequently Asked Questions
Is the nutmeg in my holiday baking dangerous if I take an MAOI?
Ordinary culinary amounts are not the concern. The caution is about concentrated nutmeg supplements and nutmeg essential oil, not the small quantities used in cooking and baking.
How strong is the evidence for this interaction?
Weak. It rests largely on a single 1963 laboratory study showing mild MAO inhibition by myristicin. There are no documented human cases of nutmeg causing a problem with an MAOI.
Does mace carry the same caution?
Yes. Mace is the outer covering of the same nutmeg seed and shares its essential-oil profile, so the same precaution applies to concentrated mace products.
What about nutmeg essential oil in aromatherapy?
Essential oil taken internally is the form of most concern. High-dose aromatherapy is best discussed with your prescriber; ordinary scent exposure is a much smaller issue than internal use.
I just stopped my MAOI. Can I use a nutmeg supplement now?
Not necessarily right away. Irreversible MAOIs need time for the enzyme to recover. Ask your prescriber how long to keep nutmeg precautions before restarting any supplement.
Should I worry about serotonin syndrome from nutmeg?
This is a theoretical concern only. No human cases link nutmeg to serotonin syndrome. Still, because MAOIs already carry serotonin-related cautions, avoiding concentrated nutmeg products is a reasonable precaution.
Key takeaways
- Nutmeg's myristicin showed weak MAO-inhibiting activity in a 1963 lab study; in theory it could add to a prescription MAOI's effect.
- The interaction is theoretical and dose-dependent, with no documented human cases.
- Ordinary culinary nutmeg is not a concern; the caution is for concentrated supplements and nutmeg essential oil taken internally.
- The same caution applies to mace.
- Review any nutmeg supplement with your doctor or pharmacist before and during MAOI therapy.