Public awareness of mental disorders has increased over the past decade. Post-traumatic stress disorder (PTSD), anxiety and depression are both debilitating and complex to approach therapeutically. Recent research has begun exploring monoamine oxidase (MAO) enzymes as potential treatment options. MAO enzymes are responsible for the metabolism of monoamine neurotransmitters in the central nervous system, such as serotonin and dopamine (Jones & Raghanti, 2021). Abnormal levels of these neurotransmitters within the nervous system are a key characteristic of several neurological conditions. Thus, exploring MAO regulation may help our understanding of these complex clinical conditions.
Despite current knowledge of MAO enzymes, their role within treatment paradigms for neurological well-being is still relatively unknown. The past few decades have seen a greater push for treatment of neurological conditions with psychedelics, such as psilocybin from ‘magic mushrooms’ or with N,N-Dimethyltryptamine (DMT). These therapeutic agents appear to have strong potential in the treatment of these disorders (Raison et al, 2023). At the core of these therapeutics rests questions surrounding the role of monoamine oxidase enzymes. Uncovering this regulation in the central nervous system has exciting potential. Therefor this blog will highlight several studies connecting MAO enzymes and our understanding of treatment of neurological wellbeing.
Recent work by Good and colleagues identified the importance of MAO enzymes in DMT treatment (Good et al, 2023). DMT is a potential treatment option for individuals with major depressive disorder (MDD), however, little is known regarding how MAO enzymes directly affect treatment administration. In this randomized, double-blind, placebo-controlled study, MAO-A and MAO-B were selectively inhibited (clorgyline at 100nM and deprenyl/selegiline at 100nM, respectively) within individuals treated with a single dose of DMT fumarate via two-phase intravenous infusion. They found that MAO-A enzymes are required for appropriate metabolism kinetics of DMT treatment. This group also identified the cytochrome P450 enzyme as necessary for normal metabolism of DMT. P450 enzymes perform cellular metabolism and thus regulate general homeostasis. This work highlights how these enzymes are important factors when it comes to infusion regiments within treatment parameters. This work is vitally important in the identification and standardization of dosing and treatment timelines.
Stepping aside from psychedelics, separate work has focused on MAO enzymes regulation of general mental wellbeing. Recent work explored the association of mediterranean diets high in fruits and vegetables with improved psychological wellbeing. Utilizing the MAO-Glo Assay from Promega, Marzo identified that D-(-)-quinic acid, a metabolite from kiwifruit, selectively inhibited MAO-B activity (Marzo et al., 2022). This is an interesting finding as Kiwifruit is one of the few edible fruits with high levels of free quinic acid found in its flesh. This sheds light on fruits and vegetables containing metabolites that inhibit activity of MAO enzymes and indicates they may be sufficient as treatment options. The authors point out that the hallucinogenic brew Ayahuasca contains Banisteriopsis cappi, a medical plant that also inhibited MAO-A. Work at this level is vital to understand how factors such as diet modifications may lead to changes in neurological conditions.
Alltogether, studies such as these provide exciting evidence of the regulatory role that MAO and cytochrome P450 have on overall neurological health. Certainly, these studies highlight the possible therapeutic potential between MAO enzymes and various kinds of natural remedies. Here at Promega we provide many different assays to quantify levels of previously mentioned enzymes. These include an MAO-Glo assay to detect both MAO-A and MAO-B levels, as well as multiple P450 assays, including a P450-Glo CYP3A4 Assay. Hopefully future work will continue to expand our understanding of how MAO enzymes regulate neurological wellbeing.
Articles Cited
Good, M., Joel, Z., Benway, T., Routledge, C., Timmermann, C., Erritzoe, D., Weaver, R., Allen, G., Hughes, C., Topping, H., Bowman, A., & James, E. (2023). Pharmacokinetics of N,N-dimethyltryptamine in Humans. European Journal of Drug Metabolism and Pharmacokinetics, 48(3), 311–327. https://doi.org/10.1007/s13318-023-00822-y
Jones, D. N., & Raghanti, M. A. (2021). The role of monoamine oxidase enzymes in the pathophysiology of neurological disorders. In Journal of Chemical Neuroanatomy (Vol. 114). Elsevier B.V. https://doi.org/10.1016/j.jchemneu.2021.101957
Marzo, C. M., Gambini, S., Poletti, S., Munari, F., Assfalg, M., & Guzzo, F. (2022). Inhibition of Human Monoamine Oxidases A and B by Specialized Metabolites Present in Fresh Common Fruits and Vegetables. Plants, 11(3). https://doi.org/10.3390/plants11030346
Raison, C. L., Sanacora, G., Woolley, J., Heinzerling, K., Dunlop, B. W., Brown, R. T., Kakar, R., Hassman, M., Trivedi, R. P., Robison, R., Gukasyan, N., Nayak, S. M., Hu, X., O’Donnell, K. C., Kelmendi, B., Sloshower, J., Penn, A. D., Bradley, E., Kelly, D. F., … Griffiths, R. R. (2023). Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial. JAMA, 330(9), 843–853. https://doi.org/10.1001/jama.2023.14530
