New Psilocybin Microdosing Data: How Much is Too Much?

Real-time gathering of physiological data and subjective effects give clues that may help define a microdose of psilocybin.

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Based on news stories and social media activity, the practice of microdosing continues to be a growing trend for those interested in improving their daily lives, work output, and problem-solving skills, to name a few. People also microdose psychedelics like LSD and psilocybin mushrooms (aka magic mushrooms or psychedelic mushrooms) for self-medicating to treat depression, PTSD, and other mental conditions. Women, who are often overlooked when it comes to psychedelic research, are turning to microdosing psychedelics to relieve their symptoms. However, there continues to be confusion regarding what constitutes a microdose.

In July of this year, PSR published an article titled Microdosing Psychedelics: Does it Work? According to psychedelic experts like Dr. David Nutt and Dr. David Nichols, there is not enough scientific evidence right now to conclude that microdosing works. And on top of that, the article discussed how researchers have not even agreed on a definition for microdosing.

A Groundbreaking Psilocybin Study

A 2019 study published in Neuropsychopharmacology provides data for one of the study subjects, giving valuable information on the physiological and subjective effects of a 3 mg dose (0.05 mg/kg) of pure psilocybin.1

This groundbreaking study recruited eight healthy subjects who received baseline blood testing and PET (positron emission tomography) scans. They also completed a questionnaire to evaluate their subjective experiences before, during, after taking psilocybin. While they were still in the PET scanner, the volunteers received a single oral dose of 3 – 30 mg of pure psilocybin. The researchers monitored the serotonin 5-HT2A receptor occupancy in the brains of the volunteers throughout the study. Blood draws were also done to check their amount of psilocin in their blood.

As the title of the paper says, the main findings of the study (the first of its kind) were that the subjective effects of psilocybin correlated with the levels of psilocin the blood and the 5-HT2A receptor occupancy in their brains. The data for Subject 1, who ingested the lowest dose of 3 mg of pure psilocybin, is intriguing. And although this is a small sample size of just one person, the information may be helpful for defining a microdose.

The Data from a 3 mg Dose of Psilocybin

In the study, Subject 1 experienced “noticeable perceptual effects” with the 3 mg dose of psilocybin. At this dose, the 5-HT2A receptor occupancy in their brain was 43%, and the maximum psilocin level in their blood reached 2.3 µg/L.1 Subject 1 rated the intensity of their psychedelic experience as approximately 4.5/10.0, as scored on the Likert scale. From this, the authors suggested,

This indicates that a smaller dose/lower occupancy would be needed for microdosing studies. Based on our data, a dose range of 0.5 – 2.0 mg is a reasonable suggestion for potential psilocybin microdose studies.

So, how does 0.5 – 2.0 mg (0.0005 – 0.002 g) of psilocybin translate into a dose of dried psilocybin mushroom flesh? That depends on a lot of factors, including the species of mushroom, the part of the mushroom (cap, stem), environmental conditions, and soil conditions, to name a few. Mushroom expert Paul Stamets cautions that there can be a difference of tenfold or more between batches of the same species.2 Despite these variables, some rough calculations can be done that may provide some insight for microdosing dried mushrooms.

Magic Mushroom Mathematics

It is unclear exactly how much psilocybin gets converted to psilocin in the human body (i.e., 0.001 g of psilocybin may not chemically convert into 0.001 g of psilocin). There are likely many factors playing a role including the person’s metabolism, health, sex, and the salt form of the compound. Dosage calculations don’t take these variables into consideration. Therefore, calculating the amount of psilocybin in a dose may not be equivalent to the amount that is metabolized to psilocin and delivered to receptors in the brain.

How Much Psilocybin is in These Mushrooms?

Based on the information in discussion boards and experience reports on sites like Erowid and Bluelight, Psilocybe cubensis is one of the most popular species of magic mushrooms. In his book Psilocybin Mushrooms of the World, Paul Stamets calculated the approximate percentage of psilocybin, psilocin, and baeocystin in 12 species of dried magic mushrooms.2 He says these numbers are likely on the high end, and the mushrooms most people collect will be less potent. For P. cubensis:

Psilocybin = 0.63%
Psilocin = 0.60%
Baeocystin = 0.025%

Below is an example calculation showing the amount of psilocybin in a 0.25 g dose of dried P. cubensis. 

(weight of dried mushrooms) x (percentage of psilocybin in dried mushrooms) / 100
= (0.25 g x 0.63) / 100
= 0.0016 g psilocybin

The calculated value of 0.0016 g is within the microdosing range suggested by the study authors (0.0005 – 0.002 g).

But Wait, There’s More – Factoring in the Psilocin Content of Mushrooms

There is another important factor to consider when using this calculation for a microdose. Psilocybin is a prodrug of psilocin. This means that the body metabolizes psilocybin to psilocin, which is the compound that binds to the 5-HT2A receptor, eliciting the psychedelic effect. Perhaps a more accurate calculation of a microdose considers the levels of both psilocybin and psilocin in the dried mushrooms. Keep in mind that similar to what was discussed earlier for psilocybin, ingesting 0.001 g of psilocin doesn’t mean it all ends up bound to 5-HT2A receptors in the brain. These dosage calculations are generalizations.

To do this calculation, add together the percentages of psilocybin and psilocin and do the math, as shown above. For example, running the same 0.25 g dose of dried P. cubensis through the calculation, but this time adding the percentages of psilocybin and psilocin (0.63 + 0.60):

=(0.25 x 1.23) / 100
=0.0031 g psilocybin

A different picture of this microdose emerges when factoring in the psilocin in the dried mushroom. The amount of active compounds in the dose of 0.25 g of dried P. cubensis now falls outside the high end of the microdosing range suggested by the study authors. In his book, Paul Stamets says he believes baeocystin may also be an active compound, although no researchers are investigating this yet. If baeocystin is active, it will change the calculation again, and possibly the overall effects.

The results of this study shed some light on the effects of low doses of psilocybin and may help guide microdosing for some people. It’s important to keep in mind that there are many other variables, besides the levels of psychedelic compounds in magic mushrooms, that are influencing the effects. Not only are the type and amount of compounds in mushrooms important to consider, but people have different physiologies and body chemistries.

The Importance of the Entourage Effect with Dosing

Going beyond the simple calculating shown above, it is likely that the effects of magic mushroom compounds are not just additive. It is feasible that the entourage effects seen with cannabis compounds are also at play with magic mushroom compounds. Scientists don’t know all the compounds in magic mushrooms and how they work together and with receptors to give the overall psychedelic effect for the user. There is a need for standardizing doses of psychedelics to achieve predictable, effective, and optimal results, whether for medical, recreational, or microdosing use. Many questions would be answered with placebo-controlled studies administering precise and accurate amounts of known compounds.

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Bill
5 months ago

So true.

Amelie
4 months ago

Bill is right.

Timothy
2 months ago

Paul Stamets information is not consistent with recent studies and quantitative results are variable based on extraction technique used in a particular study. ie. Identification of ω‑N‑Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product Claudius Lenz, Jonas Wick, and Dirk Hoffmeister.