Enhancing Psilocybin: MAOI’s & the Entourage Effect

Key takeaways.

Just as cannabis has an entourage effect, so do magic mushrooms. In fact, every consumable plant out there has an entourage effect because plants and fungi typically contain a variety of biologically active compounds. Because of a 50-year moratorium on the research of psychedelic substances, we’re still only just beginning to understand what’s in magic mushrooms. And early in 2020, researchers made a discovery that multiple species of Psilocybe magic mushrooms contain β‐carbolines — an MAOI (monoamine oxidase inhibitor).

For the avid psychonaut, MAOI will be a familiar term. It’s a class of compounds present in a number of psychoactive plants. For example, the Ayahuasca vine contains MAOI’s, and it’s these MAOI’s that allow the psychedelic effects of DMT to take place. Essentially, without the MAOI, the brew wouldn’t work.

The first antidepressant ever made was an MAOI — and its antidepressant effects were well documented. However, because of safety, they were replaced with other forms of antidepressants (SSRI’s). To understand these safety concerns, we first have to look at the pharmacokinetics of MAOI’s. 

Β‐carbolines, which have now been isolated from magic mushrooms, contribute to the entourage effect of magic mushrooms, potentiating and enhancing the effects of psilocybin. Like we just mentioned, they might also contribute their own pharmacological effects (antidepressant). 

What is a monoamine oxidase inhibitor (MAOI)?

MAOI’s are a class of compounds often found in plants but they can also be synthesized. As their name suggests, MAOI’s inhibit the monoamine oxidase enzyme in our body tissues. Monoamine oxidase enzymes are present in almost all body tissues and are responsible for the breakdown of certain neurotransmitters such as serotonin, dopamine, norepinephrine and tyramine. 

When a person consumes an MAOI, the monoamine oxidase enzyme is inhibited — that is, it doesn’t carry out any of its activities. This leads to slower degradation of the aforementioned neurotransmitters, therefore increasing their serum levels. This is essentially the foundation of why MAOI’s are therapeutic.

At the same time, with an inhibited enzyme all throughout the body, there is the potential for accumulation of compounds — tyramine is the main culprit. Certain foods contain high levels of tyramine and if a strict diet isn’t observed during MAOI consumption, tyramine can reach toxic levels and might even be life-threatening.

On top of this, MAOI’s have interactions with a number of pharmaceutical drugs that range from mild to life-threatening. For example, MAOI’s, when consumed with SSRI’s (another form of antidepressant), can cause life-threatening side effects.

Β‐carbolines are a magic mushroom’s MAOI.

In a study published in Chemistry early in 2020,  researchers uncovered a biochemical pathway through which magic mushrooms make β‐carbolines. They isolated β‐carbolines from a number of different species of magic mushrooms including Psilocybe mexicana and Psilocybe cubensis. 

The MAOI is produced by the mushroom pretty much simultaneously with its production of psilocybin, psilocin and baeocystin. 

Thanks to previous studies, we know that psilocybin is active even if an MAOI is not present. However, we also know that pure psilocybin is less effective than a whole mushroom extract. This doesn’t strictly mean that the MAOI potentiates mushrooms or makes them more effective, but it’s thought that the interplay between all the compounds in magic mushrooms are responsible for this result.

What does this mean for magic mushroom users?

There’s a few things to consider here. Firstly, now that we know that magic mushrooms contain MAOI’s, it starts to raise questions about the concurrent use of magic mushrooms with other medications. At the same time, there’s virtually no research on drug interactions with magic mushrooms.

Some people think that because magic mushrooms are natural, they can be used however and whenever. But that’s not true. The ayahuasca brew is natural but it can actually kill people if it’s not taken in the correct context (diet, abstinence from drugs, etc.) With that in mind, those who take antidepressants (especially SSRI’s) should seriously consider whether or not they want to mix magic mushrooms with their antidepressant drugs. It also means that those on antidepressants should consult their mental health professional before taking magic mushrooms.

It’s an especially important topic to talk about because lots of people who take magic mushrooms do so to alleviate symptoms of depression and anxiety — which means it’s entirely possible that they are already on some kind of antidepressant or anxiolytic medication.

Knowing that magic mushrooms contain MAOI’s also means that users can optimize their experience by optimizing their diet in the days leading up to it. It’s also recommended that those who are microdosing observe a low tyramine diet to optimize effects. Examples of high tyramine foods that should be avoided:

• Strong or aged cheese
• Processed and cured meats
• Soybeans and soy products
• Alcohol
• Onions
• Overripe avocados and bananas
• Chocolate

Avoiding these foods reduces the amount of tyramine in your body and therefore less of a reaction with the MAOI present in magic mushrooms. In turn, this should optimise your experience, making it more pleasant and smoother.

Our diets and choices are part of the entourage effect.

What this teaches us is that how we approach the magic mushroom experience is part and parcel of the entourage effect. After all, you are a fundamental part of what happens, aren’t you! Once you understand the fact that compounds you consume are constantly interacting with compounds in your body, you start to understand that your dietary choices are part of the entourage effect.

Knowing that magic mushrooms contain MAOI’s means that you can avoid certain foods and include others to create a smoother experience for yourself. Sounds a lot like the entourage effect, doesn’t it?

We are learning more and more every day about how magic mushrooms produce their therapeutic effects. And naturally, the more we learn, the better we’re all going to get at taking them.