MAO inhibitors have many uses in medicine — they’ve been used as antidepressants, nootropics, and for neurodegenerative disorders like Parkinson’s disease.
There are quite a few plant sources of MAO inhibiting compounds as well, which is what we’ll be discussing in this article.
What is an MAO Inhibitor?
MAO stands for monoamine oxidase — it's an enzyme that breaks down neurotransmitters in the brain like dopamine, serotonin, and dimethyltryptamine (DMT) after they’ve been used. All of which are critically important to brain function.
MAO inhibitory compounds block the effects of this enzyme, allowing monoamine-based neurotransmitters to exert their effects longer.
There are actually 2 types of MAO in the body (MAO-A, and MAO-B). Although the two are similar, each of them have different roles for the monoamines they break down (deaminate).
Inhibiting this enzyme slows the breakdown of neurotransmitters, allowing their numbers to increase.
This can offer many benefits to both cognitive function, as well as psychological disorders like depression and anxiety.
List of Monoamine Neurotransmitters:
Dopamine
Serotonin
Adrenalin
Dimethyltryptamine (DMT)
Melatonin
Noradrenalin
B-phenylethylamine (PEA)
Benzylamine
MAO & Neurological Disorders
An increase in monoamine oxidase has been shown to have a correlation with age-related cognitive disorders [2].
Increased levels of MAO-B, for example, has been closely associated with the development of Alzheimer’s disease, Huntington’s disease, some forms of Parkinson’s disease and normal aging [3], while increased MAO-A has been associated closely with depression, anxiety and psychiatric disorders [4].
The reason MAO tends to increase with age is not yet well understood.
Why We Need New MAO Inhibitors
The use of MAO inhibitors has been found to alleviate many of the symptoms of neurological disorders and is becoming a more valuable method of prevention and treatment as time goes on [6].
The downside to MAO inhibition is the adverse side effects that often come along with their long term use [9].
This has lead us to a point where it is clear that we need new, safer MOA inhibitors.
Fortunately, in recent years, there have been several plant-based MAO inhibitors that have so far shown low side effects, despite therapeutic doses of MAO inhibition.
MAO Inhibition And Nootropics
There is a growing trend of MAO inhibitors (generally plant-based)finding there way into nootropic formulas. The idea is that with a reduction in MAO, neurotransmitters and other monoamines found in the nootropic formulas will have a more prolonged effect.
Additionally, over more extended periods, the MAO intake will improve the overall effect of the nootropic on monoamine neurotransmitters in the brain.
A common mechanism for nootropics is to improve the production of various neurotransmitters. Therefore, inhibition of the enzymes that destroy them is likely to have a synergistic action on the overall effect.
Featured Herbal MAO Inhibitors
Bioprospecting Plant-Based MAO Inhibitors
Bioprospecting is the act of seeking out new medicines and commercial compounds from plant and animal species.
Here we highlight a few plants that have been found to have marked MAO inhibiting properties [7].
1. Phellodendron amurense
AKA: Amur Cork Tree
MAO-B Inhibition Very High (IC50 <.07 mg/ml)
Amur cork tree is one of the 50 fundamental Chinese herbs. It's commonly used for its sedative, muscle relaxant, anti-arrhythmic, positive inotropic, hypotensive, and antibacterial actions.
2. Glycyrrhiza uralensis
AKA: Gan Cao
MAO-B Inhibition Very High (IC50 <.07 mg/ml)
Gan Cao is a type of liquorice (same genus), and is used in much the same way. Its traditional uses involves female disorders, digestive disorders, ulcers, and heart arrhythmias. One of the most interesting sue of this plant, is as a "harmonizer" of other medicinal plants. In Chinese traditional medicine this is one of the main herbs used in formulas for its ability to improve the outcomes of other plants.
3. Psoralea corylifolia
AKA: Psorlea Fruit, Babchi, or Bakuchi
MAO-B Inhibition Very High (IC50 <.07 mg/ml)
Psorlea fruit (aka Babchi or Bakuchi) is a lesser known Ayurvedic and Traditional Chinese medicinal plant species. It was used in the past for conditions like vitiligo and other skin related conditions. Recently it has received a lot of attention for its MAO inhibiting properties and is suggested to be a norepinephrine, re-uptake inhibitor.
4. Glycyrrhiza Glabra
AKA: Licorice Root
MAO-B Inhibition Very High (IC50 <0.07 mg/ml)
Licorice and Gan Cao are very similar and have virtually the same uses. Licorice was often added to Chinese formulas for its ability to improve the actions of the other herbs in the formula.
5. Cyamopsis psoralioides
AKA: Guar, Bakuchi, or Lond bean
MAO-B Inhibition Very High (IC50 <0.07 mg/ml)
The seed oil of guar is mainly used for treating skin and muscle damage. It's an old Ayurvedic herb with a long history of use and a long list of traditional uses in the body.
6. Piper nigrum
AKA: Black Pepper
MAO-B Inhibition High (IC50 <0.2 mg/mL)
The black pepper extract piperine is a common addition to herbal and pharmaceutical medicines for its ability to dramatically improve intestinal absorption. Interestingly, piperine is also at least one of the components of black pepper shown to inhibit MAO-B. [7].
7. Green Tea (Camellia sinensis)
MAO-B Inhibition High (IC50 <.2 mg/ml)
Green tea (Camellia sinensis) is by far one of the most popular health beverages on the planet.
The health benefits of green tea are long and highly dependant on the way the harvested plant has been harvested and processed. In the study quotes for this MAO inhibitor data, the chosen product was Chinese Gunpowder Green Tea.
8. Piper methysticum
AKA: Kava Kava
MAO-B Inhibition High (IC50 <.2 mg/ml)
Kava (Piper methysticum) is most popular for its use as an anxiolytic.
It’s a common trick among public speakers to take a shot of kava kava extract before entering the stage.
This herb is better for anxiety disorders than depression, and is popular for helping users get to sleep and remain in a deep sleep for the entire night.
9. Lady's Mantle (Alchemilla vulgaris)
MAO-B Inhibition High (IC50 <.2 mg/ml)
Lady's Mantle (Alchemilla vulgaris) is most commonly used to slow or stop bleeding (both externally and internally). The herb has also been used as a muscle relaxant and anticonvulsant.
10. Turmeric (Curcuma Longa)
MAO-B Inhibition High (IC50 <.2 mg/ml)
Turmeric is one of the most popular herbs in the world. It's one of the main ingredients in curry and a popular anti-inflammatory supplement. It has a long list of uses, including antidepressant, hypotensive, cardiac tonic, antibacterial, and anti-arthritic.
Conditions That May Benefit From MAO Inhibitors
1. Parkinson's Disease
Parkinson's disease is a condition related to low levels of dopamine. Much of this originates from the actual production of dopamine, and its release from the hypothalamus, but can also be affected by the enzymatic breakdown.
The modern treatment of Parkinson's disease usually involves an MAO-B inhibitor, along with L-Dopa in an attempt to increase dopamine levels in the brain [1]. Due to the common side effects of synthetic MAO inhibitors, the therapeutic use of naturally derived MAO inhibitors should be considered for closer examination with long-term randomized clinical trials.
2. Depression
Depression is another condition brought on by reduced neurotransmitter levels, particularly serotonin. Pharmaceutical medications like serotonin reuptake inhibitors (SSRIs) are most commonly used to prevent the reuptake of serotonin into the neuron.
By preventing this from happening, serotonin has a better chance of being reused, thus maximizing its effectiveness.
This is beneficial in conditions of depression where serotonin is the main causative factor of the condition. With MAOs, this can be further optimized by inhibiting the extracellular breakdown of serotonin as well as its re-uptake.
3. Cognitive Enhancement
One of the main uses for MAO inhibitors is in nootropic formulas or nootropic stacks that work off dopamine or serotonin receptors. They allow some synergy to prevent the breakdown of the improved serotonin or dopamine production nudged by other aspects in the nootropic stack.
Piperine, commonly found in the product Bioperine, is a highly beneficial addition to nootropic supplements for both its MAO inhibition activity, as well as its ability to improve the bioavailability through the intestinal tract directly.
MAO inhibitors are used mainly to optimise the effectiveness of the nootropic formula, rather than cause nootropic action on their own. After reviewing the evidence put forth in this article however, it's likely that MAO inhibition on it's own has nootropic potential.
Monoamine Inhibition & Ayahuasca
Ayahuasca is another interesting use of MAO inhibition. The ayahuasca brew, which is a psychedelic plant decoction used by Amazonian shamans, is a combination of dimethyltryptamine (DMT), and an MAO inhibitor.
The combination of MAO inhibitor (from Banisteriopsis capi) and a plant high in DMT allows for maximum effects of the DMT to take place.
DMT is a monoamine neurotransmitter and is quickly broken down by enzymes in the intestinal tract.
Interestingly enough, DMT is also the same molecule that is thought to cause dreaming while we sleep. By inhibiting the breakdown of this molecule, it can persist and cause the desired effects.
Featured Herbal MAOI’s
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References:
Mazzio, E., Deiab, S., Park, K., & Soliman, K. F. A. (2013). High throughput screening to identify natural human monoamine oxidase B inhibitors. Phytotherapy Research, 27(6), 818-828.
Gal, S., Zheng, H., Fridkin, M., & Youdim, M. B. (2005). Novel multifunctional neuroprotective iron chelator‐monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP‐induced striatal dopamine depletion. Journal of neurochemistry, 95(1), 79-88.
Rehman, H. U., & Masson, E. A. (2001). Neuroendocrinology of ageing. Age and ageing, 30(4), 279-287.Chicago
Shih, J. C. (2004). Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology, 25(1-2), 21-30.Chicago
Guang, H., & Du, G. (2006). High-throughput screening for monoamine oxidase-A and monoamine oxidase-B inhibitors using one-step fluorescence assay. Acta Pharmacologica Sinica, 27(6), 760-6.
Yamada, M., & Yasuhara, H. (2004). Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology, 25(1-2), 215-221.
Kong, L. D., Cheng, C. H., & Tan, R. X. (2004). Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones. Journal of Ethnopharmacology, 91(2), 351-355.
Symposium on Monoamine Oxidase and its Inhibition, & Bernheim, M. (1976). Monoamine oxidase and its inhibition : In honour of Mary L.C. Bernheim (Ciba Foundation symposium, 39 (new ser.); Ciba Foundation, new ser., 39). Amsterdam: Elsevier/Excerpta Medica/North-Holland. http://site.ebrary.com/id/10575452
Riederer, P., Lachenmayer, L., & Laux, G. (2004). Clinical applications of MAO-inhibitors. Current medicinal chemistry, 11(15), 2033-2043.
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