Co-Written with graphical support and insight from
Science Communicator and Researcher Dr. Claire Malone
TL;DR
The burgeoning entheogenic movement, emboldened by the promising results of psychedelic research, faces a myriad of questions and challenges as it strides towards mainstream acceptance. Central to these challenges is the conversation around dosing, especially concerning psilocybin-containing mushrooms. This post endeavors to delve into potential trajectories this conversation might take, underpinned by three hot takes that beckon a shift from conventional paradigms to more precise and scientifically grounded narratives. Seeing as the history of the conversation has always been around "grams of fruit" consumed, I believe the next best step forward in that conversation is "milligrams of Psilocybin (PCB) per gram of fruit" as people will still be able to measure the amount of fruit consumed and be able to readily understand dosage ranges (between 1.0mg-30.0mg of PCB) and thus better be able to dose according to their set intentions. Furthermore we expand upon on what calculating equivalencies of active compounds will likely look like as inspiration for possible follow-up conversations as well!
Brief Conversion Basics
Before delving into the hot takes, a brief discussion on unit conversions is warranted. The conversion between milligrams (mg) and micrograms (µg or mcg) is straightforward: 1 milligram equals 1,000 micrograms, and the conversion from milligrams to micrograms is achieved by multiplying the milligram value by 1,000 as depicted in Figure 1. Conversely, to convert micrograms to milligrams, one would divide the microgram value by 1,000 [1][2].
Hot Take #1: Milligram, Micrograms, and Percents
The following table strives to elucidate the inadequacy of representing analytical data for dosing in terms of potency percentage and micrograms. It highlights how the same sample data can be depicted as at least three different percent numbers, yet only the percent dry weight proves technically useful.
The following figure takes a similar approach to understanding the deceptive aspects of percent values, which, by omitting other compounds present, distort the true picture of sample potency. By using a 'focused' view on just the compounds of interest shows skewed values (i.e. 72.50% of compounds analyzed), this numberignores other compounds in the mushroom. Even if the perspective is expanded to compounds extracted and observed (i.e. 65.40% of compounds observed), again still ignores compounds that were not observed or extracted. Now percent dry weight (i.e. 1.25%DW) is the first of the arguably usable percentage values; it gives a more accurate representation of the relative amount of compound in the dried mushroom itself. However, not without its shortcomings. The percent dry weight number depends on doing extra work determining the amount of moisture present in the sample and then using that dry mass to calculate the percentage; thus if this work is not appropriately or consistently performed, numbers can become skewed and incomparable between data-sets. Lastly, are the two more definitive descriptors: milligrams of compound per gram of fruit (i.e. 12.5m/g) and micrograms of compound per gram of fruit (i.e. 12500.00µg/g); of which I see more social and scientific push towards the former rather than the later.
Furthermore, the pitfalls of using micrograms are manifold, chiefly clerical errors, as exemplified by the common error of writing µg/mcg incorrectly as mg, followed promptly by missing trailing zeros (10000 accidentally becomes 1000 due to missing a trailing zero). Currently, the leading research, chiefly conducted with pure psilocybin dosed in milligrams, heralds a shift towards a standardized metric (as observed in studies by Johns Hopkins Medicine), underscoring milligrams as the favorable starting point [3].
Review of Atomic Mass Units and Molecular Weights
Before we dive into the calculations and conversion factors, molecular weights need to be discussed. When discussing the weight of individual atoms, we use the term "atomic mass unit," abbreviated as "u" or "amu." It's a standard unit to describe how much atoms or molecules weigh compared to a defined standard, which is one twelfth the mass of a carbon-12 atom. The amu is conceptually a unit of mass used for individual atoms and molecules, when you scale it up to a mole of those atoms or molecules, that mass is given in grams. So, for substances in bulk quantities, we often use the term "gram per mole" (g/mol). For example, if an atom has a mass of 12amu, then one mole of those atoms would have a mass of 12g/mol. The amu and g/mol are numerically equivalent, but they describe different contexts: amu is for individual atoms or molecules, while g/mol is for a mole of those entities.
For Psilocybin, with chemical formula C12H17N2O4P, we can break down each atomic mass and then add them together:
Carbon (C):
Each carbon atom weighs about 12.01 g/mol
Psilocybin has twelve (12) carbon atoms: 144.12g/mol
Hydrogen (H):
Each hydrogen atom weighs about 1.008g/mol
It has seventeen (17) hydrogens: 17.14g/mol
Nitrogen (N):
Each nitrogen atom weighs about 14.01g/mol
It has two (2) nitrogen atoms: 28.02g/mol
Oxygen (O):
Each oxygen atom weighs about 16.00g/mol
It has four (4) oxygen atoms: 64.00g/mol
Phosphorus (P):
Each phosphorus atom weighs about 30.97g/mol
It has one (1) phosphorus atoms: 30.97g/mol
So, the total weight (or molecular weight) of Psilocybin is approximately 284.25g/mol.
Hot Take #2: Psilocybin, Psilocin, and Equivalence Calculations
The deliberation between Psilocybin and Psilocin as focal points for dosage discussions continues, albeit the current research momentum seems to favor Psilocybin equivalency (PCBeq). The following discussion strives to elucidate the process of calculating PCBeq by converting Psilocin concentration to its Psilocybin equivalent. This transition towards a common standard compound mirrors practices in determining active dosages in other medical fields [4]. While Psilocin stands as the active component, its relative instability compared to Psilocybin nudges the conversation towards more stable compounds Psilocybin or its less stable synthetic, Psilacetin (4-ACO-DMT) as the initial conversation point; however inclusion of Psilacetin does hint at a future transition towards Psilocin equivalency (PCNeq) instead. Granted, the jury is still out on which to focus on Psilocybin or Psilocin for dosage discussions; based on the above mentioned research being conducted, the Psilocybin equivalent is where the conversation will likely start.
To calculate the Psilocybin equivalent (PCBeq) concentration from a known Psilocin concentration it requires the following formula, where the ratio of molecular weights is used as a conversion factor.
For example, if there was a Psilocin concentration of 0.45 mg/g (mg of active compound/dry weight in g) the PCBeq would be:
A similar conversion can also be done to obtain the Psilocin equivalent (PCNeq).
Therefore if there was Psilocybin concentration of 12.50 mg/g then the PCNeq would be:
Calculating equivalencies is a very common practice when trying to determine active dosages for individuals [4]. It is important to note that Psilocin is the active component between the two compounds, however it is also described as relatively unstable compared to Psilocybin. In the future compounds like Psilacetin (4-ACO-DMT); which readily converts to Psilocin will be utilized more, thus a transition towards PCNeq from Psilacetin will likely happen (with its own conversion factors and calculations).
An example of this would be if there was 10.00 mg/g Psilacetin concentration, it would correspond to a Psilocin concentration of:
As a quick reference, conversion factors can be understood as the ratio between the compound desired and the original compound. The following table depicts conversion factors for the above calculations.
Hot Take #3: Expanding Monoamine Interests
The psychedelic tapestry is rich, with synthetic tryptamines, like those documented in Sasha and Anne Shulgins' TIHKaL, offering a plethora of psychedelic experiences from only slight variations in masses and compositions. As our understanding of serotonergic systems these compounds interact with deepens, the discourse may evolve towards Serotonin equivalency (5-HTeq) in binding affinity based on concentration, transcending the confines of individual compound concentrations and unifying a single conversation-space for better dosing.
Furthermore this could even expand into β-carboline discussions as well, and start to note a compound's capacity to act as a monoamine-oxidase inhibitor (MAOI) relative to both natural and pharmaceutical compounds.
Trying not to get too deep into the weeds; the last thing to observe is that there can be multiple values of interest a compound might have, Psilocin can have a PCBeq, 5-HTeq, βCBeq, and arguably countless more; it will depend upon the context to determine which becomes the more pertinent data point. A therapist discussing with their patient about weaning off MAOIs to a microdosing regime is very likely interested in at least the three equivalencies just mentioned, while a person just trying to figure out what to take for a recreational dose will likely only care about PCB/PCBeq.
Psilocybin Dosing Conversation Take-Aways
The narrative around psilocybin-containing mushroom dosing is in flux, poised at the cusp of a more scientifically rigorous and standardized dialogue. The shifts proposed in this discourse not only pave the way for more precise dosing guidelines but also foster a broader understanding of the serotonergic and social at play. As the entheogenic community marches towards a future where psychedelics play a pivotal role in mental health and consciousness exploration, anchoring dosing discussions in solid scientific grounds becomes imperative. As long as we have a common language, any of the points discussed here can hold merit, but we must strive to understand the language and intention we are coming into the space with. I feel consumers should have the easiest dosage information to understand and relate to as many discussions as possible. Seeing as the history of the conversation has always been around "grams of fruit" consumed, I believe the next best step forward in that conversation is "milligrams of PCB/PCBeq per gram of fruit" as people will still be able to measure the amount of fruit consumed and be able to readily understand dosage ranges (between 1.0mg-30.0mg of PCB/PCBeq) and thus better be able to dose according to their set intentions.
References
The Calculator Site. (n.d.). Micrograms and Milligrams Converter (mcg to mg). Retrieved 10/10/2023 from https://www.thecalculatorsite.com/conversions/common/mcg-mg.php
Unit Converter. (n.d.). Convert Microgram to Milligram. Retrieved 10/10/2023 from https://www.unitconverters.net/weight/microgram-to-milligram.htm
Johns Hopkins Medicine. (n.d.). Psychedelic Research. Retrieved 8/5/2023 from https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research
Critical Care. (2023). Equivalence Calculations in Active Dosages. Retrieved 10/10/2023 from https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04322-y
Dargan, P., & Wood, D. (2013). Novel Psychoactive Substances: Classification, Pharmacology and Toxicology. Academic Press. Retrieved 10/15/2023.
Berlowitz, I., Egger, K., & Cumming, P. (2022). Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca. Frontiers in Pharmacology, 13. Retrieved 10/15/2023 from https://doi.org/10.3389/fphar.2022.886408​