Is Psilocybin a Nootropic?

 

Psilocybin...

                    ... for those who don't know is the active ingredient in psycadelic mushrooms or "magic" mushrooms. It's a very interesting molecule, that can be found in various mushroom species all over the world, mainly the Psilocybe genus. 

This isn't a new drug, as people have been taking it to receive visions and clarity since at least 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 has come to light that the psilocybin molecule may actually be a potent natural antidepressant agent. Other sources (non-peer reviewed) have suggested that the effects of low-dose psilocybin may classify it as a nootropic.

We are always looking for new and effective nootropic agents to add to our stacks, and psilocybin is a particularily interesting one. It has a long history of use, and contains some of the most psychoactive substances in the world. Interesting as it may be, lets have a look at whether or not these claims have any standing in the real world. 

This article aims to investigate some of the recent claims made at psilocybin as a possible nootropic agent. This is for educational purposes only, and seeks to fuel future research on the subject in places open to honest scientific discovery. At no time do I suggest you break your local laws. 

psilocybin nootropic or antidepressant

What Is The Theory?

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 to simple to take at face value.

 

mushroom nootropics

At What Dose Is Psilocybin Used At?

Microdosing is the process whereby only a very small amount of something is taken, generally far below the normal dosage. When it comes to magic mushrooms, these powerful little mushrooms need only a few grams to take some serious action. 

At over 5 grams of dried mushroom, the result can include high-level hallucinations, spiritual transcendence, out of body experiences, mania, euphoria, emesis, anxiety, uncontrollable laughter, a sense of impending doom, and a distorted sense of time.

The medicinal actions of a dose like this are similar to ayahuasca. They are 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 highly potent psychedelic substances (yes they do exist). 

Coming down to about 2 grams, we reach 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 0.3 grams (300 mg) is what we would consider a microdose. This is what we are talking about 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 is very little chance of any psychoactive effects taking place to hinder the clear cognitive thought process we are trying to reach. 

 

hallucinogenic mushrooms

How Might 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 a 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 (5HT 2a) as well as some of the other serotonin receptors (5HT-1A, 5HT-2C, and 5HT-1D) [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 agonism (stimulation) on the serotonin receptors that creates the visual, auditory, and imaginative distortions.

One of the main side effects of psilocybin is a distortion in 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 (less than 3 mg), 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. 

 

When we consider how this may be applied as a nootropic, we may find some disappointment. 

 

This pathway is not a common mechanism for nootropics at all. 5HT agonism is most commonly found in SSRI (serotonin reuptake inhibitor) medications. These act on the same 5HT receptor sites (mostly 5HT-1A and 5HT-2A) that psilocin acts on, but work instead to prevent the removal and reuptake of serotonin into the neuron. Thus making 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. 

 
magic mushrooms

To Answer The Question...

...Is Psilocybin a nootropic?

A photo posted by @thesunlightexperiment on

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 great alternative or adjuvant antidepressant medication. The similarity in mechanism, 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. 

 

Synergy With Psilocybin

Psilocin 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 Baanisteriopsis caapi (Ayahuasca vine) and passionflower are commonly used in nootropic formulas to stop this enzyme from breaking down neurotransmitters. If MAO is inhibited, serotonin and dopamine will be able to exert their effects for a longer duration before being broken down. This is a common tactic in nootropic formulas aiming at neurotransmitter levels as well as treating depression.

Taking a MAOI will mean the psilocin will be more efficient, and a smaller dose will be needed. It also helps with the duration of action. Passionflower extract is a great place to start. 

Other synergistic substances for psilocybins nootropic effect would be 5HT upregulators or precursors. This can include the infamous Bacopa monieri. [7]. 

By upregulating 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.

 

is psilocybin dangerous

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 be much much higher. In reality, this is far too high a number to be realistically consumed. 

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.

Currently, medical scientific research is in jeoapardy in the United States. It's important to support the growth of scientific discovery, and remain open (and skeptical) towards the claims or theories made therein.


Author:

Justin Cooke

The Sunlight Experiment


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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.
  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.
  3. Harrington, D. L., & Haaland, K. Y. (1999). Neural underpinnings of temporal processing: Α review of focal lesion, pharmacological, and functional imaging research. Reviews in the Neurosciences, 10(2), 91-116.
  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): 202–7. doi:10.1159/000317249. PMID 20606445.
  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.
  6. Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002). The pharmacology of psilocybin. Addiction biology, 7(4), 357-364.
  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.