Get to Know the Beta Carbolines – Newcomers to the Science of Magic Mushrooms

Understanding the pharmacology of magic mushrooms is not just about tryptamines anymore.

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In 2019, Blei et al. announced that they had isolated new compounds from four species of magic mushrooms, including Psilocybe cubensis.1 Of course, the better-known compounds like psilocybin, psilocin, and baeocystin were present in the mushrooms, but also were some compounds called beta carbolines (ß-carbolines). This groundbreaking discovery has changed the magic mushroom paradigm for psychedelic researchers.

ß-Carboline Basics

ß-carbolines are naturally occurring alkaloids.2 They are most commonly known as components in the psychotropic beverage ayahuasca. Examples of the ß-carbolines in ayahuasca include harmine, harmane, and harmaline (note: ß-carboline is also another name for the compound norharmane).

Much of the effect of ayahuasca is due to the ability of ß-carbolines to inhibit MAO (monoamine oxidase) enzymes.2,3 This inhibition makes it possible for the psychedelic compound DMT (dimethyltryptamine, another compound in ayahuasca) to move out of the digestive system and enter the circulation.

The ß-Carbolines in Magic Mushrooms

Blei et al. analyzed extracts from P. cubensis, P. mexicana, P. cyanescens, and P. semilanceata. In the extracts, they identified the ß-carbolines cordysinin C, cordysinin D, harmane, harmol, norharmane, and perlolyrine. These compounds were previously isolated from fungi and plants in genera such as Cordyceps, Peganum, and Banisteriopsis,4 but this was a eureka moment in Psilocybe research history.

The Importance of Discovering ß-Carbolines in Magic Mushrooms

When it comes to understanding the effects and potential therapeutic applications of magic mushroom compounds, it’s not just about tryptamines anymore. Now scientists have a new path for further discovery. Consider some of what is already known about ß-carbolines. It deepens the complexity of the already challenging magic mushroom chemical landscape.

ß-carbolines are known to play a role in the development of essential tremor (uncontrolled shaking) and have been implicated in Parkinson’s disease.5 In contrast, a systematic review of the literature conducted by Ferraz et al. in 2019, indicated that ß-carbolines (harmane and harmine, in particular) might have antidepressant effects.6 The authors summarized their findings by saying,

In general, β-carbolines modulate 5-HT and GABA systems, promote neurogenesis, induce neuroendocrine response and restore astrocytic function, being effective when administrated acutely or chronically in different animal models, including chronic mild stress protocols.

Some of these effects of ß-carbolines come from their ability to inhibit the uptake of serotonin, dopamine, epinephrine, and norepinephrine via competitive inhibition of the receptors7,8

In 2018, a review article by Dai et al. focused on the occurrence, structural diversity, and biological activity of ß-carboline monomers and dimers.9 Their review found that some ß-carboline monomers have many effects, including antitumor, antiparasitic, and antiviral, as well as antioxidant, antidiabetic, and aphrodisiac activity. Interestingly, some ß-carboline dimers have a significantly higher level of bioactivity than their monomeric counterparts.

Further Research on ß-Carbolines From Magic Mushrooms

It’s unknown how ß-carbolines function in magic mushrooms and the ways they may contribute to the overall psychedelic effect. The discovery of these compounds in magic mushrooms will alter the path of psychedelic drug research, perhaps leading to the discovery of even more beneficial effects.

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A
22 days ago

Hmm these inhibition of Monoamine oxidase A and SRI properties (dont surely know if uptake = reputake) , it may explain why antidepressant effect are more likely to occure after psylocibin mushrooms then after pure tryptamines available. Afterglow after shrooms is much more perceptible then after 4-HO-xxx (But still – it depends

Andrew Chadeayne
15 days ago
Reply to  A

A – Could you please point me to a reference showing how the antidepressant effect is more likely to occur after psilocybin mushrooms than after pure tryptamines? Same question regarding what you’re calling the “afterglow.” Is there a study comparing the mushrooms to a pure tryptamine in a controlled manner– presumably comparing pure psilocybin or an equivalent, like psilacetin to naturally occurring mushrooms? Regarding the beta-carbolines, I think that the authors of the paper were pretty clear that the concentrations found in their samples would not be expected to result in appreciable changes in the pharmacology. Nevertheless, there’s still an… Read more »

    References
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  2. McKenna D, Callaway J, Grob C. The scientific investigation of ayahuasca. A review of past and current research. The Heffter Review of Psychedelic Research. 1998;1:65-77.
  3. Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol. 2010;48(3):839-845. doi:10.1016/j.fct.2009.12.019
  4. Callaway JC, Brito G de S, Neves ES. Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. Journal of psychoactive drugs. 2005;37(2):145-150. doi:10.1080/02791072.2005.10399795
  5. Louis ED, Zheng W, Jurewicz EC, et al. Elevation of blood β-carboline alkaloids in essential tremor. Neurology. 2002;59(12):1940-1944. Accessed November 20, 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992345/
  6. Ferraz CAA, de Oliveira Júnior RG, Picot L, da Silva Almeida JRG, Nunes XP. Pre-clinical investigations of β-carboline alkaloids as antidepressant agents: A systematic review. Fitoterapia. 2019;137:104196. doi:10.1016/j.fitote.2019.104196
  7. Buckholtz NS, Boggan WO. Monoamine oxidase inhibition in brain and liver produced by β-carbolines: structure-activity relationships and substrate specificity. Biochemical Pharmacology. 1977;26(21):1991-1996. doi:10.1016/0006-2952(77)90007-7
  8. Pähkla R, Rägo L, Callaway JJ, Airaksinen MM. Binding of Pinoline on the 5-Hydroxytryptamine Transporter: Competitive Interaction with [3H] Citalopram. Pharmacology & Toxicology. 1997;80(3):122-126. doi:10.1111/j.1600-0773.1997.tb00384.x
  9. Dai J, Dan W, Schneider U, Wang J. β-Carboline alkaloid monomers and dimers: Occurrence, structural diversity, and biological activities. European Journal of Medicinal Chemistry. 2018;157:622-656. doi:10.1016/j.ejmech.2018.08.027