Home Supplements That Start With H Harmine: What It Is, Research-Backed Benefits, Dosage Ranges, and Contraindications

Harmine: What It Is, Research-Backed Benefits, Dosage Ranges, and Contraindications

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Harmine is a naturally occurring β-carboline alkaloid best known from two plants: the Syrian rue (Peganum harmala) and the ayahuasca vine (Banisteriopsis caapi). In the body, harmine acts primarily as a reversible, selective inhibitor of monoamine oxidase-A (MAO-A), the enzyme that breaks down serotonin, norepinephrine, and dopamine. Because of this, it has strong effects on neurotransmitters and can dangerously interact with many medicines and certain foods. Outside of its psychoactive context, researchers are exploring harmine for potential roles in mood support, neuroplasticity, and even pancreatic beta-cell regeneration—areas that need larger and longer studies before clinical recommendations. If you’re curious about harmine as a supplement, it’s essential to know that human data are limited, doses in research vary, and safety hinges on avoiding drug interactions. This guide organizes what’s known today so you can make informed, cautious decisions.

Quick Overview

  • May acutely elevate monoamines by reversibly inhibiting MAO-A, with possible short-term mood and focus effects.
  • Early studies suggest harmine can influence neuroplasticity pathways (e.g., BDNF/DYRK1A), but evidence is preliminary.
  • Research doses of oral harmine have been tolerated below about 2.7 mg/kg; higher doses increased nausea and vomiting.
  • Avoid if taking SSRIs/SNRIs, other MAO inhibitors, linezolid, dextromethorphan, many opioids, stimulants, or if you have uncontrolled hypertension.

Table of Contents

What is harmine and how it works

Harmine is a β-carboline alkaloid found in several plants, most prominently Peganum harmala seeds and Banisteriopsis caapi vine. Traditional preparations that contain harmine (alone or with related alkaloids harmaline and tetrahydroharmine) have been used ceremonially and medicinally in different cultures. In modern biomedical language, harmine is best described as a reversible inhibitor of monoamine oxidase-A (often abbreviated RIMA). MAO-A’s job is to oxidatively deaminate monoamines—serotonin, norepinephrine, dopamine, and others—so transiently blocking MAO-A increases their availability. This mechanism underlies harmine’s ability to “activate” or potentiate serotonin signaling and to boost oral bioavailability of tryptamine compounds by preventing their breakdown in the gut and liver.

Importantly, harmine’s selectivity and reversibility do not make it benign. Even reversible MAO-A inhibition can interact seriously with serotonergic drugs (like SSRIs/SNRIs), with linezolid and methylene blue, with certain cough suppressants (dextromethorphan), and with some opioids that also raise serotonin tone. In addition, MAO-A is a gatekeeper for dietary tyramine; inhibiting it may increase the risk of hypertensive reactions after high-tyramine meals, though the risk is lower and shorter-lived with reversible inhibitors than with older irreversible MAOIs. In short: “reversible” is not the same as “safe to mix.”

Beyond MAO-A, harmine shows other intriguing biological actions. It binds to and inhibits DYRK1A (dual-specificity tyrosine-regulated kinase 1A), a brain-expressed kinase involved in neuronal development, learning pathways, and cell-cycle regulation. This has sparked research into whether harmine analogs might modulate neuroplasticity or even encourage pancreatic beta-cell proliferation in preclinical models. These findings are early and do not translate into medical use yet, but they explain why you may see harmine mentioned in contexts far from psychedelics.

Chemically, harmine is lipophilic enough to cross the blood–brain barrier. Pharmacokinetically, oral effects are influenced by gastric acidity, hepatic first-pass metabolism, and co-ingested substances. When taken with other β-carbolines, the cocktail can alter onset and duration; tetrahydroharmine, for instance, is a weak serotonin reuptake inhibitor that may add its own profile to the overall experience. All of this means that “harmine” can behave differently depending on the preparation (pure compound vs. plant extract vs. multi-alkaloid brew) and on what else is on board.

The take-home: harmine’s best-characterized action is short-term inhibition of MAO-A, which can raise monoamine levels. That same mechanism creates a long list of medically significant interactions. Any potential upside should be weighed against those predictable, mechanism-based risks.

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Evidence-backed benefits

When people ask about harmine benefits, they often mean one of three things: (1) mood-related effects in the context of ayahuasca-like formulations, (2) cognitive or neuroplasticity-oriented effects discussed in preclinical work, and (3) metabolic ideas (like beta-cell regeneration) that remain experimental. Here is where evidence stands:

1) Antidepressant effects within multi-compound formulations. Randomized human studies using ayahuasca (which combines harmala alkaloids with N,N-DMT) have shown rapid, short-term antidepressant effects in treatment-resistant depression. In these trials, harmine is not administered alone, and the overall effect reflects a synergy: MAO-A inhibition by harmine/harmaline increases DMT’s oral activity, and the psychological experience, context, and integration likely contribute. Still, the findings establish a plausible role for harmine as an enabler of acute antidepressant responses in controlled settings. Whether harmine by itself has antidepressant efficacy in people remains insufficiently tested.

2) Potential contributions to neuroplasticity. Harmine interacts with targets relevant to neuroplasticity, including DYRK1A and downstream pathways linked to BDNF expression. Preclinical studies show changes consistent with enhanced synaptic remodeling or neurogenesis signaling in cell and animal models. This line of research has sparked interest in whether carefully designed harmine-like molecules might one day support recovery from neuropsychiatric conditions. Human trials isolating harmine’s effect on neuroplasticity endpoints (cognition, learning, brain-derived biomarkers) are still sparse.

3) Metabolic and beta-cell hypotheses. In animals and ex vivo human islets, harmine has been studied for promoting beta-cell proliferation, which—if translated safely—could be meaningful for diabetes research. However, cell-cycle modulation in the pancreas raises obvious safety and specificity questions. No approved therapy uses harmine for diabetes, and the distance from lab bench to clinic here is large.

4) Anti-inflammatory and antioxidant signals. Extracts containing harmine exhibit antioxidant activity and changes in inflammatory markers in preclinical models. These effects may be secondary to monoamine changes or to kinase interactions. Translating them to human health outcomes will require controlled trials that isolate harmine from confounding plant constituents.

5) Secondary outcomes in mental-health studies. In standardized psychedelic protocols that include harmine plus other actives, participants sometimes show improvements in measures like rumination, emotional processing, and psychological flexibility. Harmine’s MAO-A action is necessary but not sufficient for these outcomes; expectancy, set and setting, and the presence of DMT matter.

Practical takeaway: the most credible human signal tied to harmine so far is its role in enabling rapid antidepressant effects as part of a broader formulation under supervision. For standalone supplementation, evidence remains preliminary. If you’re evaluating harmine for mood or cognition, it is more accurate to think of it as a pharmacological tool that modifies monoamine dynamics—with substantial interaction risks—than as a conventional “mood supplement.”

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How to use harmine safely

Safety with harmine is mostly about what you avoid. Because harmine inhibits MAO-A, it can dangerously amplify the effects of common medications and certain dietary amines.

1) Screen your medications thoroughly. The highest-risk combinations include:

  • Antidepressants: SSRIs (e.g., sertraline, fluoxetine), SNRIs (e.g., venlafaxine, duloxetine), tricyclics with strong serotonin effects (e.g., clomipramine), and other MAO inhibitors. Combining these with harmine can precipitate serotonin syndrome.
  • Antibiotics that inhibit MAO-A: linezolid is a notable example; it can cause serotonin toxicity when mixed with serotonergic agents or MAO inhibitors.
  • Dyes/agents with MAOI properties: methylene blue can behave as a potent reversible MAOI.
  • Cough and cold medicines: dextromethorphan is serotonergic and risky in this context; decongestants (pseudoephedrine, phenylephrine) raise blood pressure and can compound hypertensive reactions.
  • Opioids with serotonergic activity: tramadol, meperidine, and tapentadol are of special concern. Safer choices (still requiring medical oversight) include morphine, codeine, and oxycodone when MAO-A is inhibited, but any opioid co-use requires prescriber guidance.
  • Stimulants and sympathomimetics: amphetamines, ADHD meds, and certain weight-loss agents heighten the risk of hypertensive events.

2) Respect washout periods. If you are on an SSRI/SNRI or similar agent, you must not add harmine. Medical sources recommend stopping serotonergic antidepressants well in advance of any MAOI exposure; washout lengths range from two weeks for most SSRIs/SNRIs to five weeks for fluoxetine due to its long half-life. Only a clinician should plan and supervise any such transition.

3) Mind dietary tyramine—especially within 24 hours of dosing. Reversible MAO-A inhibition increases sensitivity to tyramine-rich foods (aged cheeses, cured meats, certain fermented products, some draft beers). While the risk window is typically shorter with reversible inhibitors, it’s prudent to keep tyramine intake low on the day of harmine and through the following day.

4) Start low, avoid stacking, and never combine with unknown plant blends. Plant extracts can vary widely in harmine content; adding harmaline or tetrahydroharmine changes the profile and can prolong effects. Stacking with other psychoactives (even botanical ones) makes adverse outcomes more likely.

5) Choose contexts with medical oversight. If harmine is used in a clinical research setting, teams typically review medications, check blood pressure, and have a plan for hypertensive spikes or serotonin toxicity. Recreating that vigilance at home is not feasible.

6) Know the red flags. Seek urgent care for severe headache with chest pain or neck stiffness (possible hypertensive crisis), high fever with agitation and clonus (possible serotonin syndrome), fainting, uncontrolled vomiting, or persistent confusion. Bring a full list of everything taken.

Bottom line: the safest approach is to avoid self-administering harmine if you take any serotonergic or sympathomimetic medication, or if you have cardiovascular, hepatic, or psychiatric conditions. A careful medication review is mandatory.

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Dosage forms and typical ranges

There is no medically established, over-the-counter “supplement dose” of harmine. What exists are: (a) standardized clinical-research products with defined purity and dosing schedules, and (b) plant extracts with highly variable alkaloid content. Understanding the landscape helps set expectations.

Clinical-research dosing (pure harmine). A recent Phase 1, single-ascending-dose study in healthy adults administered oral harmine hydrochloride and found that doses below ~2.7 mg/kg were generally tolerated with minimal adverse events, while higher doses produced more frequent nausea, vomiting, and drowsiness. This human-tolerance threshold offers a reference point, not a self-medication recommendation. In a separate pharmacology program, buccal/orodispersible formulations in the 150–200 mg total range have been explored to characterize absorption and onset. These formulations and protocols are designed for controlled labs, with monitoring that’s not available to consumers.

Traditional/plant preparations. The concentration of harmine in B. caapi can span single-digits mg per gram of dried material and varies by vine, region, and extraction. A given brew may deliver tens to hundreds of milligrams of total harmala alkaloids (harmine + harmaline + THH) per serving, but batch-to-batch variability is large. Because other β-carbolines alter both pharmacology and side-effect profiles, translating plant-brew volumes (e.g., milliliters of tea) into predictable harmine dosages is unreliable.

Extracts and capsules. Commercial “Syrian rue” or mixed harmala products may not state—and often do not precisely control—harmine content. Certificates of analysis (when available) may refer to “total harmala alkaloids,” not pure harmine. Variation in extraction solvents, seed sourcing, and storage further widens the dosage window.

Practical guidance for readers evaluating harmine in any context:

  • Treat 2.7 mg/kg oral as a research-context tolerance ceiling, not a target. Many people will experience adverse effects at far lower doses, especially with co-factors like dehydration, low body weight, or concurrent substances.
  • If exposure is unavoidable (e.g., supervised clinical participation), empty stomach or standardized meals are typically used to reduce variability. Alcohol and cannabis are avoided.
  • Do not combine with serotonergic or sympathomimetic drugs (see safety section). Even small amounts can change the risk calculus.
  • Do not use daily or chronically without medical oversight; MAO-A inhibition can create cumulative interaction risks with ordinary life events (like taking a cold medicine).

Finally, recognize that many claimed “microdosing” regimens circulating online are not grounded in peer-reviewed human data. The wisest policy for self-care seekers is to defer harmine until better dose-finding and safety studies exist for the specific goal you have in mind.

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Side effects and interactions

Common short-term effects at research-scale doses include nausea, vomiting (especially above the tolerated range), drowsiness, dizziness, lightheadedness, and changes in blood pressure or heart rate. Some individuals report transient anxiety or a feeling of overstimulation—consistent with rising monoamine levels—followed by fatigue. With plant preparations that include other β-carbolines, gastrointestinal upset is more frequent.

Serious risks to understand:

  • Serotonin syndrome. This is a potentially life-threatening toxicity characterized by agitation/confusion, fever, sweating, shivering, tremor, clonus, and diarrhea. It most often appears when an MAOI is combined with another serotonergic agent—for example, mixing harmine with an SSRI/SNRI, certain opioids (like tramadol), or dextromethorphan. Prompt medical treatment is essential.
  • Hypertensive reactions. MAO-A inhibition lowers your threshold for a tyramine “cheese reaction.” Within hours of dosing—and sometimes into the next day—high-tyramine foods (aged cheeses, cured meats, soy ferments), and OTC decongestants can trigger severe headache, chest pain, neck stiffness, or dangerously high blood pressure.
  • Drug–drug interactions beyond serotonin. Linezolid (an antibiotic) and methylene blue can behave like MAO inhibitors and additively increase risk. Sympathomimetics and stimulants (including some ADHD medications) may precipitate hypertensive crises. Polypharmacy magnifies uncertainty.
  • Medical conditions that add risk. Uncontrolled hypertension, cardiovascular disease, arrhythmias, hepatic impairment, bipolar disorder with manic risk, and seizure disorders warrant strict avoidance outside of clinical trials. Pregnancy and breastfeeding are no-use zones; safety is unestablished and theoretical risks are significant.
  • Overdose/toxicity. Very high exposures to harmala alkaloids (as with concentrated Peganum harmala extracts) have been linked to agitation, tremor, ataxia, visual disturbances, profound nausea/vomiting, and altered consciousness. Emergency care should be sought for persistent vomiting, confusion, severe headache, chest pain, or collapse.

Who should avoid harmine entirely (non-exhaustive):

  • Anyone taking SSRIs, SNRIs, TCAs with strong serotonergic action, buspirone, MAOIs, linezolid, methylene blue, tramadol/meperidine/tapentadol, dextromethorphan, or stimulant medications.
  • Individuals with uncontrolled hypertension or significant cardiovascular disease.
  • People with liver disease, current substance misuse, or a history of serotonin syndrome.
  • Those who are pregnant, trying to conceive, or breastfeeding.
  • Adolescents and children (safety data are lacking).

If adverse effects occur:

  • Stop further exposure.
  • For worrisome symptoms (e.g., high fever, severe headache, chest pain, confusion), seek urgent care and tell clinicians you took an MAO-A inhibitor.

The guiding principle is simple: treat harmine with the same respect you would give any prescription-strength MAOI. The mechanism is predictable, the interaction list is long, and most harms are preventable by avoiding risky combinations.

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What the research says today

Harmine research now spans three major domains: human tolerance and acute effects, psychiatric applications within multi-ingredient protocols, and molecular targets relevant to neurobiology and metabolism.

Human tolerance and pharmacology. A recent single-ascending-dose study in healthy adults established a practical tolerance threshold for pure oral harmine hydrochloride: doses below about 2.7 mg/kg were generally tolerated, while higher exposures frequently caused vomiting, drowsiness, and limited psychoactivity. This quantifies what clinicians have long observed in plant-based settings and gives researchers a map for designing safe dose-finding protocols. Parallel formulation work (e.g., buccal/orodispersible tablets) is characterizing ways to manage onset and reduce GI upset, still at an experimental stage.

Psychiatry within controlled protocols. Randomized, placebo-controlled trials using ayahuasca in treatment-resistant depression have shown rapid—often within hours—antidepressant effects that can persist for days to weeks in some participants. Harmine is essential in these protocols because it transiently disables MAO-A in the gut and liver, allowing oral DMT to reach systemic circulation and the brain. Ongoing studies are probing moderators of response (set and setting, prior experience, expectancy), the relative contribution of psychological processing vs. direct pharmacology, and the durability of benefit with or without psychotherapy integration.

Mechanisms beyond MAO-A. At the molecular level, harmine is a potent, ATP-competitive inhibitor of DYRK1A, a kinase implicated in neuronal development and synaptic plasticity. This has inspired efforts to design harmine analogs that retain neuroplasticity benefits while reducing MAO-A interaction risks. In parallel, preclinical teams are evaluating whether harmine-like compounds can safely encourage beta-cell proliferation to support diabetes treatment. These are early-stage programs; specificity, off-target effects, and long-term safety must be solved before human therapies are realistic.

Open questions for the next five years:

  • Can low-dose, intermittent harmine yield measurable cognitive or affective benefits without unacceptable interaction risks in everyday life?
  • Will selective DYRK1A inhibitors derived from harmine demonstrate meaningful clinical effects in neurodegenerative or developmental conditions?
  • Can researchers separate the psychological and pharmacological drivers of rapid antidepressant effects in ayahuasca-style protocols—and translate that into standardized, scalable treatments?
  • What are the long-term cardiovascular or hepatic consequences of repeated, intermittent MAO-A inhibition in otherwise healthy adults?
  • Where is the therapeutic index—if any—for metabolic targets like beta-cell support, and can off-target proliferation be avoided?

In summary, harmine is moving from ethnobotanical interest to carefully measured clinical pharmacology. The clearest near-term value is as a controllable MAO-A tool compound in supervised psychiatric protocols and as a scaffold for medicinal chemistry aimed at neuroplasticity targets. For general supplementation, evidence is not yet strong enough to recommend routine use, and safety depends on strict avoidance of interactions.

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References

Disclaimer

This information is educational and is not a substitute for professional medical advice, diagnosis, or treatment. Harmine is a monoamine oxidase-A inhibitor with significant interaction risks. Do not start, stop, or combine it with any medication or supplement without guidance from a qualified clinician who knows your full medical history and current prescriptions. If you experience severe headache, chest pain, agitation with fever, muscle jerks, or persistent vomiting after exposure, seek urgent medical care.

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