Monoamine oxidase inhibitors (MAOIs) are one of the most interaction-prone drug classes in existence. They prevent the breakdown of monoamine neurotransmitters (serotonin, dopamine, norepinephrine). Combined with serotonergic drugs, they can cause fatal serotonin syndrome. Combined with tyramine-containing foods or stimulants, they can cause hypertensive crisis.
Evidence Snapshot
Last updated
Mar 16, 2026
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Safety at a Glance
High Risk- Dangerous with: Amphetamine, Cocaine, Fenfluramine, MDMA (+1 more)
- Start with a low dose and wait for onset before redosing
- Test your substance with reagent kits when possible
- Never use alone — have a sober person present
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Duration
No duration data available.
Interactions
| Substance | Status | Note |
|---|---|---|
| Amphetamine | Dangerous | MAOIs prevent the breakdown of norepinephrine and dopamine. Amphetamine causes their release. The combination can cause fatal hypertensive crisis — a sudden, extreme spike in blood pressure. |
| Cocaine | Dangerous | Cocaine blocks reuptake of catecholamines while MAOIs prevent their breakdown. This can cause hypertensive crisis and is potentially fatal. |
| Fenfluramine | Dangerous | Risk of fatal serotonin syndrome. Must wait at least 2 weeks between fenfluramine and any MAOI. |
| MDMA | Dangerous | MAOIs prevent the breakdown of serotonin while MDMA floods the synapse with it. This combination has caused multiple deaths from serotonin syndrome. One of the most dangerous drug combinations known. |
| Tramadol | Dangerous | Potentially fatal combination. MAOIs prevent the breakdown of serotonin while tramadol inhibits its reuptake, leading to rapid serotonin accumulation. Multiple deaths have been reported from this combination. |
| DMT | Caution | MAOIs are actually used intentionally with DMT in ayahuasca. However, this requires careful dosing and carries significant risks. The MAOI dramatically potentiates and extends the DMT experience. Dangerous if dosing is not carefully controlled. |
Toxicity & Safety
No toxicity data available.
Dangerous Interactions
The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.
MAOIs prevent the breakdown of norepinephrine and dopamine. Amphetamine causes their release. The combination can cause fatal hypertensive crisis — a sudden, extreme spike in blood pressure.
Cocaine blocks reuptake of catecholamines while MAOIs prevent their breakdown. This can cause hypertensive crisis and is potentially fatal.
Risk of fatal serotonin syndrome. Must wait at least 2 weeks between fenfluramine and any MAOI.
MAOIs prevent the breakdown of serotonin while MDMA floods the synapse with it. This combination has caused multiple deaths from serotonin syndrome. One of the most dangerous drug combinations known.
Potentially fatal combination. MAOIs prevent the breakdown of serotonin while tramadol inhibits its reuptake, leading to rapid serotonin accumulation. Multiple deaths have been reported from this combination.
Tolerance
| Full | Unknown |
| Half | Unknown |
| Zero | Unknown |
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