Harmine Guide: Effects, Benefits, Risks, and Legality

• What Is Harmine?
• Natural Sources of Harmine
• Harmine Chemical Structure and Mechanism of Action
• Harmine Effects
• Harmine Benefits
• Harmine Risks
• Harmine in Psilocybin Mushrooms
• Harmine Legality
• Bottom Line

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Harmine is a psychoactive alkaloid (plant chemical). It is well-known as a key psychoactive component found in the ayahuasca vine and in the seed coats of Syrian rue (Peganum harmala), two plants revered by ancient cultures across the Andes Mountains, the Middle East, Central Asia, and South America for religious and medicinal uses. Recently, scientists found harmine also exists in trace amounts in psilocybin mushrooms.  

This article investigates harmine’s effects, benefits, mechanisms of action, and existence in magic mushroom species. 

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What Is Harmine?

Harmine is a harmala alkaloid in the beta-carboline family with significant physiological effects. Beta-carbolines are a large group of indole alkaloids found in various plants, foods, marine creatures, insects, mammals, and human tissue and body fluids. Tryptophan, an amino acid precursor to serotonin, is the source of indole alkaloids like harmine. As such, beta-carbolines are closely related to serotonin in their neural impact. 

Harmine is an essential natural product due to its interesting chemical profile. It offers hallucinogenic properties similar to psilocybin mushrooms, also known as “magic” mushrooms or “shrooms.” 

Similar to psilocybin, harmine also has pharmacological importance and therapeutic potential. In particular, harmine displays many antioxidative, anti-inflammatory, and neuroprotective properties that could help fight brain diseases, cancer, and depression. 

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Natural Sources of Harmine

Harmine is found throughout nature in various plants, mammals, insects, and marine organisms. Sources containing the most harmine include plants and fungi: 

• Peganum harmala (Syrian rue), a plant native to the western United States, Asia, Africa, and Europe.
• Banisteriopsis caapi, a South American jungle vine.
• Ayahuasca, a hallucinogenic drink from the Amazon traditionally used as a spiritual medicine containing Banisteriopsis caapi.

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In a recent study, scientists also isolated harmine from several species of psychedelic mushrooms, notably: 

• P. mexicana
• P. cubensis

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Harmine Chemical Structure and Mechanism of Action

Harmine (7-methoxy-1-methyl-9H-pyridoindole) is a tricyclic beta-carboline alkaloid. 

Tricyclic beta-carboline alkaloids are a type of β-carboline alkaloid with a unique chemical structure consisting of three fused rings. 

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• The first ring is a pyridine ring, a six-membered ring containing five carbon atoms and one nitrogen atom. 
• The second ring is an indole ring, a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. 
• The third ring is a seven-membered ring containing two nitrogen and one oxygen atom. 

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The three rings are fused in a specific way, giving tricyclic beta-carboline alkaloids their unique biological and medicinal properties. 

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Biologically:

• Harmine crosses the blood-brain barrier and binds to serotonin receptors, primarily 5HT2A, followed by 5HT2C, to exhibit its hallucinogenic and mood-altering effects. 

• Harmine also classifies as monoamine oxidase inhibitors (also known as MAOIs). 

Monoamine oxidase inhibitors (MAOIs) are a type of chemical that works by blocking the activity of an enzyme called monoamine oxidase. This enzyme breaks down certain neurotransmitters in the brain, including serotonin, dopamine, and norepinephrine. By inhibiting monoamine oxidase, MAOIs increase the levels of these neurotransmitters in the brain, leading to various physiological effects, like improved mood and energy.

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Harmine Effects

Scientists do not fully understand the exact mechanism by which harmine produces its hallucinogenic effects. Still, they believe harmine’s ability to modulate serotonin and other neurotransmitters (chemical messengers) is a crucial factor. 

Harmine can interact with neurotransmitters and their receptors, causing changes in how the brain processes sensory information. This alteration can lead to visual, auditory, and other sensory distortions. 

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Visual effects:

• Pattern recognition enhancement
• Tracers
• Vibrating vision
• Color enhancement

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Cognitive effects:

• Dream potentiation
• Time distortion
• Creativity
• Conceptual thinking
• Anxiety
• Confusion

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Physical effects:

• Decreased heart rate
• Increased pulse pressure
• Raised peak aortic flow 
• Raised myocardial contractile force
• Appetite suppression

• Changes in gravity

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Harmine Benefits

In addition to its hallucinogenic effects, harmine may display antimicrobial, antifungal, antioxidative, neuroprotective, antitumor, and anti-cancer properties. 

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Harmine for depression

• One study showed harmine has antidepressant effects, possibly due to its interaction with the MAO-A enzyme and the serotonin 5-HT2A receptor. 
• The psychotherapeutic use of indole alkaloids derived from magic mushrooms shows potential as an alternative to the synthetic antidepressant drugs currently on the market. 

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Harmine for brain health

• Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects. Observational investigations of the mental health of long-term ayahuasca users indicate that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. 
• Harmine shows promise as a safe and effective therapeutic agent for treating neuropsychiatric disorders.

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Harmine for cognitive function and memory

• Studies involving hippocampal cell cultures and animal models show harmine associated with neuroprotective effects, such as reducing excitotoxicity, inflammation, and oxidative stress and increasing brain-derived neurotrophic factor (BDNF) levels, helping to improve memory and learning.

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Harmine to fight tumors and cancer

• A study showed harmine possesses anti-tumor potential, inhibiting the metastasis of melanoma cells. 
• Another study reported harmine had cytotoxic activity against human tumor cell lines. 

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Harmine Risks

Like other chemicals in the beta-carboline alkaloid family, harmine can be neurotoxic in large doses. High levels of harmine in the blood can cause uncomfortable symptoms, such as:

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• Visual and auditory hallucinations
• Locomotor ataxia (losing control of body movement)
• Gastrointestinal issues
• Nausea
• Vomiting
• Confusion and agitation
• Tremors

The acute toxicity of harmine is significantly dose-dependent, and the median lethal dose is 26.9 mg/kg in vivo.

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Harmine in Psilocybin Mushrooms

Concentrations of beta-carboline compounds in fungal species are very low compared to their main psychedelic substance, psilocybin. 

Harmine exists in magic mushrooms in trace amounts measured in micrograms.

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• P. mexicana mushrooms reportedly contain less than two micrograms of harmine per gram. One would ingest 5-8 micrograms of harmine with a 2-5] gram dose of dried fruiting bodies. 
• P. cubensis mushrooms contain a beta-carboline concentration 100-fold (or 100,000th) less than P. mexicana. 

The presence of harmine and other beta-carboline compounds is so minimal that it’s unlikely to significantly affect the mushroom experience. However, some researchers speculate that harmine contributes to the overall magic mushroom experience by interacting with other alkaloids in the body to amplify each other’s effects.

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Harmine Legality

Harmine and other harmala alkaloids and their natural sources are legal in most parts of the world. For instance, people can generally buy, possess, and distribute harmine in the U.S. The Controlled Substances Act and the Drug Enforcement Agency (DEA) website do not specifically mention Peganum harmala (aka Syrian rue), a major source of harmine. 

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However, brands that sell harmine as a supplement must conform to U.S. supplement laws. 

• The FDA regulates all products it determines to be food or drugs. As of March 2022, the U.S. Department of Agriculture (USDA) confiscated Peganum harmala in US Customs. 

• In September 2019, the USDA openly restricted Peganum Harmala in Arizona, California, Colorado, Nevada, New Mexico, and Oregon, which regulate Peganum Harmala to prevent it from becoming an invasive species.

Outside the U.S., some countries, including Australia, Canada, and France, list harmala alkaloids like harmine as illegal drugs or limit their preparations. 

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Bottom Line

Harmine is a beta-carboline alkaloid well-known for giving Ayahuasca its hallucinogenic effects. Its main sources are the wild plants Peganum harmala (Syrian rue) and Banisteriopsis caapi, which are noted for their therapeutic value. However, researchers recently isolated harmine from magic mushrooms. Although toxic in large doses, harmine displays smaller amounts of antioxidative, anti-inflammatory, and neuroprotective properties that could improve cognitive function, fight cancer, and boost mood. 

With magic mushroom use increasing in popularity, mycological enthusiasts, medicinal patients, and DEA-licensed clients want to be better informed about mushroom products and their active ingredients. ACS Laboratory has cutting-edge techniques and equipment to ensure the potency and purity of multiple psychedelic compounds, including harmala alkaloids such as harmine. Contact ACS Laboratory about quality mushroom testing.