Harmala alkaloids are classed as MAOIs. This means that they inhibit the activity of monoamine oxidase metabolic enzymes, of which two varieties exist: MAO-A and MAO-B. The alkaloids bind reversibly to the active site of the enzyme, inhibiting its endogenous function of destroying amine functions of neurotransmitters and externally administered centrally active drugs. This has the effect of potentiating and prolonging the central and peripheral activity of both neurotransmitters and a variety of drugs. They are reversible MAOIs of the MAO-A isoform of the enzyme, and can stimulate the central nervous system by inhibiting the metabolism of monoamine compounds such as serotonin and norepinephrine.
Harmala alkaloids are selective for MAO-A at reasonable doses and bind to the enzyme temporarily, so they are classed as a reversible inhibitor of monoamine-A (RIMA). At higher doses, they also affect the MAO-B enzyme. Because of the reversible selectivity for MAO-A, harmala alkaloids are considered to be less dangerous when combined with food containing tyramine and other substances with monoamine moieties which are reliant on monoamine oxidase for decomposition.
However, it is important to understand that this does not imply that harmala alkaloids will not cause neurotoxicity. Harmala alkaloids temporarily disable the brain's primary mechanism for breaking down neurotransmitters and drugs which can have negative consequences as material builds up in the synapses, leading to a huge range of downstream central and peripheral effects including sedation, stimulation, anxiety, cognitive dysphoria, euphoria, headaches, eye strain, and muscle convulsions. The harmala alkaloids are not especially psychedelic, even at higher dosages, when hypnagogic visions, alongside vomiting and diarrhea, become the main effect.
Since DMT is broken down by monoamine oxidase A, inhibition of this enzyme allows for the oral activation of DMT and prolongs the experience for the duration of the harmala alkaloid effects. In combination, harmala alkaloids and DMT are known as ayahuasca.
Harmala alkaloids, along with other beta-carbolines, also function as GABA-A receptor (benzodiazepine site) inverse agonists, likely contributing to their anxiogenic and convulsant effects.
Common harmala alkaloids include:
- Harmane
- Harmane** (harman) is a MAO-A inhibitor.
- Harmine
- Harmine** is a reversible inhibitor of MAO-A (RIMA)
Threshold: ~30mg
Light: 30-80mg
Common: 80-130mg
High: 130-180mg
Strong: 180mg+
- Harmaline
- Harmaline** is a reversible inhibitor of MAO-A (RIMA)
Threshold: ~40mg
Light: 40-90mg
Common: 90-140mg
High: 140-190mg
Strong: 190mg+
- Tetrahydroharmine (THH)
- L-Tetrahydroharmine** does not inhibit monoamine oxidase A. Instead, it weakly inhibits reuptake of serotonin.
- D-THH**, on the other hand, has similar potency in terms of inhibiting MAO as harmine.
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors.
Banisteriopsis caapi (also known as ayahuasca, caapi or yajé) is a South American jungle vine of the family Malpighiaceae. It contains harmine, harmaline, and tetrahydroharmine in the following proportions:
- Harmine:** 0.31-8.43%
- Harmaline:** 0.03-0.83%
- Proanthocyanidins** (less known MAOIs)
- (−)-epicatechin**
- (−)-procyanidins**
- Tetrahydroharmine:** 0.05-2.94%
- Peganum harmala (Syrian rue)
Peganum harmala, commonly called esfand (native name), syrian rue, is a plant native to the eastern Iranian region west to India. It has also spread invasively throughout Arizona, California, Montana, Nevada, Oregon, Texas and Washington. The plant itself produces seeds which contain harmala alkaloids and is easily accessible and legal to purchase online through the use of google. Powdered syrian rue seeds act as a reversible inhibitor of MAO-A (RIMA) at doses of 2 - 5g.
Syrian rue seeds contain several different harmala alkaloids at slightly varying percentages. Only some are monoamine oxidase A inhibitors. In one study, total harmala alkaloids were at least 5.9% of dried weight.
Though ground seeds can be consumed raw, this is an unreliable method of accessing the contained harmala alkaloids. The stomach can only soak the seed material in gastric juice for a limited period before it is moved further along the digestive system for absorption of molecules in solution. Because of this, whole seeds are ineffective; ground or pulverized seeds work in some circumstances, but to reliably and predictably achieve psychoactivity, it is most efficient to first extract the alkaloids from the seeds of peganum harmala into a solution by brewing it for at least 30 minutes.
The brewing environment can be enhanced by acidifying the water, using stronger solvents, and increasing the temperature. Using more water will also increase the concentration gradient, allowing more alkaloids to dissolve.
MAOIs have highly dangerous and sometimes fatal interactions with many common drugs. They can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant, stimulant, common migraine medication, certain herbs, most cold medicine (including decongestants, antihistamines, and cough syrup), nicotine, caffeine, etc. Sedatives are likely easier tolerated, but potentiation should be expected.
Acetylcholinesterase inhibitors (AChEIs) combined with cholinergic substances can result in a cholinergic crisis.
Banisteriopsis caapi and Peganum harmala contain harmaline and harmine. Both alkaloids are acetylcholinesterase inhibitors (AChEIs).
When intravenously injected into mice, the LD50 of harmine is 38mg/kg. There is no data for the other harmala alkaloids in humans or animals.
It is strongly recommended that one use harm reduction practices when using this drug.
There is no tolerance built up with harmala alkaloid use. There are no real reports of addiction to harmala alkaloids.
Harmala alkaloids and their natural sources are legal in most parts of the world.
Australia:** Harmala alkaloids are Schedule 9 drugs under POISONS STANDARD of DECEMBER 2019. HARMALA ALKALOIDS except in herbs, or preparations, for therapeutic use:
containing 0.1 per cent or less of harmala alkaloids; or
in divided preparations containing 2 mg or less of harmala alkaloids per recommended daily dose.
Canada:** Harmala alkaloids are Schedule III drugs.
France:** Possession and sale of harmala alkaloids is illegal.
Responsible use
Beta-Carbolines
Psychedelics
Tryptamines
Phenethylamines
Lysergamides
Harmala alkaloids
Harmala alkaloids (Wikipedia)
Harmaline (Wikipedia)
Harmine (Wikipedia)
Tetrahydroharmine (Wikipedia)
Harmala Alkaloids (Erowid Vault)
Harmaline (TiHKAL / Isomer Design)
Harmine (TiHKAL / Isomer Design)
Tetrahydroharmine (TiHKAL / Isomer Design)
Natural sources
Banisteriopsis caapi* (Wikipedia)
Banisteriopsis caapi* (Erowid Vault)
Peganum harmala* (Wikipedia)
Syrian rue (Erowid Vault)
Morales-García, J. A., de la Fuente Revenga, M., Alonso-Gil, S., Rodríguez-Franco, M. I., Feilding, A., Perez-Castillo, A., & Riba, J. (2017). The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific Reports, 7(1), 5309. https://doi.org/10.1038/s41598-017-05407-9