For those who don’t know, psilocybin is the active ingredient in psychedelic mushrooms.

There are some reports going around that small doses (0.1–0.3 g of dried mushroom, roughly a few milligrams of psilocybin) have nootropic benefits over time.

In this article we’re going to explore this in more detail by looking at how it works, and how this relates to common nootropic mechanisms.

Psilocybin can be found in mushroom species all over the world within the Psilocybe genus.

Psilocybin isn’t a new drug, as people have been taking it to receive visions and clarity since at least the time of the Mayans. In modern times, this fungus is generally taken to “trip” and not aimed to improve normal cognitive function.

Interestingly, in recent years it’s come to light that the psilocybin molecule may actually be a potent antidepressant.

Other sources (non-peer reviewed) have suggested that the effects of low-dose psilocybin may classify it as a nootropic.

We’re always looking for new and effective nootropic agents to add to our stacks, and psilocybin is a particularly interesting one.

Interesting as it may be, let’s have a look at whether or not these claims have any merit in the real world.

This is for educational purposes only, and seeks to fuel future research on the subject in places open to honest scientific discovery.

What is Microdosing?

The idea is that since psilocybin is a hallucinogenic at high doses, and tends to promote a significant increase in things like creativity and out-of-the-box type thinking, it must be a nootropic in smaller, less psychoactive doses.

We call this “microdosing”.

While this is an interesting idea, it’s far too simple to take at face value.

Let me explain.

At What Dose Is Psilocybin Used At?

Microdosing is the process whereby a small amount of something is consumed, generally far below the normal dosage.

When it comes to magic mushrooms, these powerful organisms need only a few grams to produce some serious psychoactive effects.

At over 5 grams of dried mushroom, the result can include:

• Hallucinations
• Feelings of spiritual transcendence
• Out of body experiences
• Mania
• Euphoria
• Emesis
• Anxiety
• Uncontrollable laughter
• Sense of impending doom
• Distorted sense of time

The medicinal actions of a dose like this are similar to ayahuasca.

They’re more aligned with spiritual healing and have been reported by users to act as a sort of “reset button” on deep psychological conditions like depression, PTSD, and drug addiction.

This type of dose is not recommended by anybody except in the presence of professionals who have spent years training to work with these potent psychedelic substances (yes they do exist).

At a dose of about 2 grams, we start to reach more modern-day dosages.

2-3 grams are often taken to experience hallucinations without going over the top. This dose doesn’t appear to have much effect medicinally as it’s far too high for regular consumption.

Comment below if you disagree.

Less than about 0.3 grams of dried mushroom is what we would consider a microdose.

A quick unit note, since this gets confusing fast: microdoses are described two different ways in the literature and online — as a fraction of a gram of dried mushroom (typically 0.1–0.3 g), or in milligrams of psilocybin content. The two describe the same thing from different angles. Dried Psilocybe cubensis runs roughly 0.5–1% psilocybin by weight, so a 0.1–0.3 g mushroom microdose works out to somewhere around 1–3 mg of actual psilocybin — the low end of what most clinical microdosing studies use as a dose. Because potency varies a lot between species, batches, and even individual mushrooms, the milligram figure is the more precise of the two, but the gram figure is what most people are actually measuring at home with a kitchen scale. Both refer to the same low-dose range discussed throughout this article.

This is what we are talking about here in this article.

These doses are not hallucinogenic for the majority of people. There may be some slight fuzziness or mild euphoria for the first day or two until the body develops a tolerance, though.

In fact, we develop a tolerance very quickly with psilocybin. This is beneficial for this application because with regular consumption there’s very little chance of any psychoactive effects taking place to hinder the clear cognitive thought process we’re trying to reach.

Does Psilocybin Have Nootropic Potential?

The real question of this article is whether or not psilocybin has nootropic benefit or not. Let’s begin by following the path it takes within the body…

Upon ingestion, the psilocybin molecule is quickly converted to a metabolite known as psilocin.

Mushrooms will also contain varying amounts of this dephosphorylated version of psilocybin, and will simply enter circulation as is.

The conversion of psilocybin to psilocin takes place in the liver almost immediately after absorption into the body.

Psilocin then attaches to the serotonin receptors in the brain (5HT2a) as well as some of the other serotonin receptors (5HT1A, 5HT2C, and 5HT1D) [6].

This leads to an indirect increase in dopamine production but has no direct affinity to the dopamine system itself (which is the main difference between psilocybin and LSD which binds to dopamine D2 receptors).

These serotonin receptors are found all over the brain, especially in the cerebral cortex which is associated with higher thought and imagination.

It’s this activation of the serotonin receptors that creates the visual, auditory, and imaginative distortions.

One of the main side effects of psilocybin is a distortion of the sensation of time.

Interestingly, this is a characteristic of the prefrontal cortex [3], where psilocin has been shown to have particularly strong action [2].

In smaller doses, such as with a microdose (roughly 1–3 mg of psilocybin, or about 0.1–0.3 g of dried mushroom), these effects would not be felt to nearly the same degree, but these areas of the brain would see an increase in stimulation all the same.

Psilocybin Isn’t (Technically) A Nootropic

The mechanisms of psilocybin are not shared by most other nootropics.

Instead, 5HT agonism is most commonly found in SSRI (serotonin reuptake inhibitor) medications.

These act on the same 5HT receptor sites (mostly 5HT1A and 5HT2A) that psilocin acts on, but work instead to prevent the removal and reuptake of serotonin into the neuron.

This makes the actions of the serotonin last longer.

Psilocin accomplishes the same thing by binding to these receptors itself by mimicking serotonin.

This is why euphoria is one of the most reliable, and immediate effects of psilocybin intake.

SSRI’s are potent antidepressants with plenty of evidence to back up their efficacy.

Due to the similar actions of medicinal mushrooms like Psilocybe spp. it’s not such a stretch to suggest them as a possible alternative to these controversial medications.

To Answer The Question…

…Is Psilocybin a nootropic?

Based on this short but enlightening research, I don’t believe psilocybin to be a particularly good nootropic.

Rather, it appears psilocybin may be a good alternative or adjuvant antidepressant medication.

The similarity in mechanisms, and specific targeting of 5HT-2A receptors (and mild 5HT-1A), suggests psilocybin and subsequent psilocin to be a likely candidate as an antidepressant instead.

Nootropics and antidepressants alike tend to work best if taken over long periods of time.

Most of the medical research on psilocybin was conducted in the 1960’s (see The Harvard Psilocybin Project) which mainly focused on larger, more “heroic” doses.

These doses are not realistic to consume on a daily basis over the long term.

Microdosing, however, allows the user to consume a non-psychoactive dose over longer periods of time.

An important, honest update since this article was first written: most of the enthusiasm for microdosing comes from open-label, self-selected, and observational reports — and when researchers have actually run rigorous double-blind, placebo-controlled trials, the results have been far less impressive. A 2021 preregistered self-blinding citizen-science study and a 2022 clinical double-blind trial both found that microdosed psilocybin failed to outperform placebo on mood, cognition, and well-being measures once expectancy effects were properly controlled for ^{8Reference 8Szigeti et al. · 2021Self-blinding citizen science to explore psychedelic microdosing. eLife, 10, e628789Reference 9Cavanna et al. · 2022RCTMicrodosing with psilocybin mushrooms: a double-blind placebo-controlled study}. Several people in these studies who received placebo but believed they’d taken psilocybin reported the same subjective improvements as those who actually had. That doesn’t mean microdosing does nothing — but it’s a real caution against taking the anecdotal case for it at face value, and it undercuts the idea that microdosing is a straightforwardly proven nootropic strategy.

Psilocybin Synergy

Psilocin is the first stage.

It’s the pro drug compound in the psilocybe mushrooms.

This compound is broken down by an enzyme known as monoamine oxidase. This is the same enzyme that breaks down serotonin, dopamine, and all other monoamines in the body, including DMT.

Monoamine oxidase inhibitors (MAOI’s) such as via the infamous Banisteriopsis caapi (Ayahuasca vine) and passionflower are commonly used in nootropic formulas to stop this enzyme from breaking down neurotransmitters.

If the enzyme is inhibited, serotonin and dopamine are able to exert their effects for a longer period of time before being broken down.

This is a common tactic in nootropic formulas aiming at neurotransmitter levels and treating depression.

Taking a MAOI will mean the psilocin will be more efficient, and a smaller dose becomes necessary. It also helps with the duration of action.

Other synergistic substances for psilocybin’s nootropic effect would be 5-HT up-regulators or precursors — compounds that increase the density or sensitivity of serotonin receptors rather than acting on the receptors directly. Bacopa monnieri is one example studied for this kind of receptor up-regulation, though the evidence is animal-only ^{7Reference 7Krishnakumar et al. · 2009AnimalUpregulation of 5-HT 2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri}.

By up-regulating the receptors of 5HT in the brain, the psilocin (and serotonin) will have more places to “latch-on” to, and as such, exert a stronger effect.

A caveat that matters more than anything else in this section: combining an MAOI with a serotonergic compound like psilocybin is not a casual stacking decision — it carries a real risk of serotonin syndrome, a potentially dangerous overaccumulation of serotonin. This is discussed in more depth in our natural MAO inhibitors article, but the short version is: don’t combine MAO-inhibiting herbs with psilocybin, SSRIs/SNRIs, or other serotonergic drugs without understanding the interaction risk first.

Is Psilocybin Dangerous?

Psilocybin is in fact very safe.

The LD50 (lethal dose for 50% of the population) is a whopping 280 mg/kg [1].

That would mean that for an average person of 70kg (~150 pounds), nearly 20 g of psilocybin is needed to kill them 50% of the time.

This number is for pure psilocybin NOT dried mushrooms.

If the average mushroom has about 1% psilocybin (and psilocin) when dried, that would mean roughly 2kg of dried mushrooms would need to be eaten to reach a deadly dose.

Since the psilocybin content of various fungi can vary greatly, this number can even be much, much higher.

In reality, this is far too high a number to be realistic.

In 2010, a Dutch study investigated the safety of tobacco, alcohol, and illicit drugs and ranked them according to safety.

Psilocybin containing mushrooms were ranked as the illicit drug with the lowest harm [4]. Other studies have also confirmed this [5].

The biggest danger with psilocybin isn’t with the chemistry of the fungi it’s contained in, rather the look alikes found in nature.

Psilocybe cubensis can be described as an “LBM”. This stands for little brown mushroom which is in reference to their plain but very common appearance.

Many other species that look strikingly similar to the untrained eye are mistaken as Psilocybe species. Many of these other species are highly toxic and can result in severe gastrointestinal discomfort or worse.

Supporting Future Research

I would love to see more high-quality research done on this, which will only be possible if we allow scientific research to thrive.

It’s important to support the growth of scientific discovery, and remain open (and skeptical) towards the claims or theories made therein.

---

---

References:

1. van Amsterdam, J., Opperhuizen, A., & van den Brink, W. (2011). Harm potential of magic mushroom use: a review. Regulatory Toxicology and Pharmacology, 59(3), 423-429. Link
2. Carter, O. L., Burr, D. C., Pettigrew, J. D., Wallis, G. M., Hasler, F., & Vollenweider, F. X. (2005). Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. Journal of Cognitive Neuroscience, 17(10), 1497-1508. Link
3. Harrington, D. L., & Haaland, K. Y. (1999). Neural underpinnings of temporal processing: a review of focal lesion, pharmacological, and functional imaging research. Reviews in the Neurosciences, 10(2), 91-116. Link
4. van Amsterdam, J., Opperhuizen, A., Koeter, M., & van den Brink, W. (2010). Ranking the harm of alcohol, tobacco, and illicit drugs for the individual and the population. European Addiction Research, 16(4), 202-207. Link
5. Nutt, D. J., King, L. A., & Phillips, L. D. (2010). Drug harms in the UK: a multicriteria decision analysis. The Lancet, 376(9752), 1558-1565. Link
6. Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002). The pharmacology of psilocybin. Addiction Biology, 7(4), 357-364. Link
7. Krishnakumar, A., Nandhu, M. S., & Paulose, C. S. (2009). Upregulation of 5-HT 2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri. Epilepsy & Behavior, 16(2), 225-230. Link
8. Szigeti, B., et al. (2021). Self-blinding citizen science to explore psychedelic microdosing. eLife, 10, e62878. Link
9. Cavanna, F., et al. (2022). Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study. Translational Psychiatry, 12, 307. Link