Harmaline

Harmaline-containing preparations produce modest diastolic blood pressure elevation (~9 mmHg at high ayahuasca doses). While cardiovascular effects appear modest in healthy volunteers, no data exist for individuals with pre-existing cardiovascular disease. Harmaline possesses vasorelaxant properties that may partially moderate pressor response.

Individuals with seizure disorders should exercise caution. MAO inhibition may lower seizure threshold, though this is an inferred risk without harmaline-specific evidence.

Individuals with personal or family history of psychotic disorders should exercise caution. This is a standard recommendation for all psychoactive substances with serotonergic activity. No harmaline-specific data on psychosis precipitation exist.

Harmaline is primarily cleared via hepatic CYP enzymes. Hepatic impairment would reduce clearance and increase systemic exposure. No hepatotoxicity has been documented — animal studies suggest hepatoprotective properties — but increased exposure in liver disease is a pharmacokinetic certainty.

CYP2D6 poor metabolizers face substantially elevated harmaline exposure because CYP2D6 is the primary metabolic enzyme (~50% contribution, Km = 1.4 µM — among the lowest for any CYP2D6 substrate). Effects will be amplified and prolonged. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) would produce a similar pharmacokinetic effect.

Harmaline should be avoided during pregnancy. Peganum harmala has a well-documented traditional use as an abortifacient across North African and Middle Eastern cultures. No reproductive safety data for isolated harmaline have been published.

dextromethorphan

Concurrent dextromethorphan use (including OTC cough medicines) is contraindicated due to serotonin syndrome risk. Class-level RIMA inference.

lithium

Concurrent lithium use is contraindicated due to serotonin syndrome risk. Class-level RIMA inference.

sumatriptan, zolmitriptan

Concurrent triptan use (sumatriptan, zolmitriptan, etc.) is contraindicated due to serotonin syndrome risk. Class-level RIMA inference.

clomipramine, imipramine, amitriptyline

Concurrent TCA use is contraindicated, particularly clomipramine which has the strongest serotonergic reuptake inhibition among TCAs. Class-level RIMA inference.

Hypericum perforatum

Concurrent use of Hypericum perforatum (St. John's Wort) is contraindicated due to serotonin syndrome risk from combined serotonergic mechanisms and potential CYP interaction increasing harmaline exposure.

Tyramine-rich foods (aged cheeses, cured meats, fermented products, red wine) should be avoided or minimized during harmaline use. As a reversible MAO-A inhibitor, harmaline poses less tyramine risk than irreversible MAOIs (phenelzine, tranylcypromine), but dose-dependent risk persists. The cheese effect is reduced but not eliminated by RIMA reversibility.

tramadol

Concurrent tramadol use is contraindicated due to combined serotonin syndrome and seizure risk. Class-level RIMA inference.

fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine

Concurrent use of any selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine) is contraindicated. Patients must observe a washout period appropriate to the medication's half-life (typically 2 weeks; 5 weeks for fluoxetine due to active metabolite norfluoxetine). Class-level RIMA inference — no harmaline-specific serotonin syndrome case reports exist.

venlafaxine, duloxetine

Concurrent use of SNRIs (venlafaxine, duloxetine) is contraindicated due to serotonin syndrome risk. Standard MAOI washout periods apply. Class-level RIMA inference.

phenelzine, tranylcypromine, selegiline, moclobemide, linezolid, methylene blue

Concurrent use of any monoamine oxidase inhibitor — irreversible (phenelzine, tranylcypromine) or reversible (moclobemide) — is contraindicated. Linezolid and methylene blue (non-psychiatric MAOIs) also apply.

meperidine, pethidine

Concurrent use of meperidine (pethidine) is absolutely contraindicated. This combination has the highest documented fatality risk among opioid-MAOI interactions. Class-level inference from RIMA mechanism.