Do Different Psilocybe Mushrooms Produce Different Effects? — Part 1

Alkaloid profiles of Psilocybe and related mushrooms

The idea that different species (or even strains and cultivars of the same species) of Psilocybe mushroom elicit their own distinct effects is fairly pervasive amongst even educated aficionados, and often defended vigorously. It’s not uncommon for online vendors to describe certain strains as “euphoric, visual” and others as “introspective, creative”. I shouldn’t need to tell you that this is almost entirely a marketing ploy.

Typical online presentation of alleged distinct effects of different P. cubensis cultivars.

However, those that subscribe to the “strain matters” philosophy will often refer to the so-called entourage effect coined to explain the different effects of cannabis strains: the idea that the particular cannabinoid profile determines whether a strain is energising and euphoric or is more likely to put you to sleep, for example. I’ll talk more about the pharmacology of this idea applied to mushrooms in Part 2 but, for this post, I’ll focus on the measured alkaloid contents of various commonly-used psilocybin-containing mushrooms and how they differ.

A selection of popular Psilocybe cubensis cultivars.

Firstly, there’s no clear evidence that any particular species or strain of Psilocybe mushroom can induce any particular flavour of trip experience beyond certain species being generally more potent — containing more psychoactive alkaloids — than others. Furthermore, we’ve known since the 1960s that set and setting is of central importance in determining the content and emotional colour of a psychedelic trip, so it’s completely unsurprising that last month’s harvest of Psilocybe cubensis ‘Penis Envy’ was a euphoric and visual experience, whilst this latest batch of Liberty Caps plucked from a nearby golf course had a much more introspective and somewhat darker tone.

Every trip is different, even if the mushrooms and their alkaloid content are the same.

Having said that, the idea that certain mushroom species/strains/cultivars might elicit distinct types of experience isn’t entirely unreasonable, since a handful of different potentially psychoactive tryptophan-derived tryptamines have been detected in Psilocybe and related mushroom genera.

Psilocybin is the signature alkaloid, which acts a pro-drug for psilocin — the phosphate group is readily cleaved in vivo — which is itself present at varying levels in different mushroom species. Let’s look at how these and the other major alkaloids are constructed inside the mushroom.

The biosynthesis of psilocybin proceeds — as do all tryptamines — from the amino acid tryptophan, which is decarboxylated (a carbon dioxide molecule is removed, catalysed by an decarboxylase enzyme, PsiD) to yield tryptamine. From here, a number of different tryptamine alkaloids can be generated. Hydroxylation at the 4-position on the indole ring (using molecular oxygen, catalysed by a hydroxylase enzyme, PsiH) yields 4-OH-tryptamine, which is then phosphorylated (by a kinase enzyme, PsiK) to yield norbaeocystin (4-phosphoryloxy-tryptamine), the first plausibly psychoactive alkaloid present in certain mushroom species. Sequential methylation (addition of a CH3 group) of norbaeocystin’s side-chain amine nitrogen then yields baeocystin (4-phosphoryloxy-N-methyltryptamine), psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptamine) (Please don’t ask me how to pronounce aeruginascin — your guess is as good as mine). Psilocybin can also be dephosphorylated to yield psilocin and aeruginascin can be dephosphorylated to yield 4-OH-TMT.

Cyclisation of the tryptamine side chain can also, in principle, occur to generate the MAO inhibitory beta-carbolines more commonly associated with the ayahuasca vine, Banisteriopsis caapi. We’ll return to the beta-carbolines in Part 2.

Variations in precursors and activity of the key biosynthetic enzymes can certainly lead to variations in both the overall level of alkaloids in the harvested mushroom, as well as the representation of specific alkaloids. A new analysis published last month (See here!) analysed the concentration of the five major tryptamine alkaloids found in Psilocybe mushrooms — aeruginascin, norbaeocystin, baeocystin, psilocin, and psilocybin — in 30 species from seven genera, including the usual suspects, as well as a handful of lesser known mushroom types.

What’s immediately striking about the analysed tryptamine concentrations is not just the dramatic variation between species but also between samples of the same species. Psilocybin levels in P. cubensis, for example, varied from as low as 0.65mg/g dried weight up to 3.5mg/g. This is somewhat lower than reported elsewhere: a recent analysis of dried cubensis showed levels at 10-20mg/g ( See here!). It’s known that alkaloids, even in dried mushrooms, degrade slowly over time, so this might account for the relatively low levels in these sample. Decades old dried specimens will sometimes show no traces of psychedelic alkaloids whatsoever.

Tryptamine alkaloid levels in Psilocybe mushrooms over time (from https://doi.org/10.1128/aem.01498-22)

The Wavy Cap mushroom — Psilocybe cyanescens — widely regarded as the most potent of the Psilocybians, contained psilocybin at concentrations between 2.3 and 13.8 mg/g, which is similar to that reported by Kuyper (See here!)

The Liberty Cap — Psilocybe semilanceata — the most commonly harvested wild mushroom in Europe, was also relatively potent, with psilocybin levels measured at between 1.3 to 11.4 mg/g.

It should be pointed out that, even in 2022, there remains some doubt as to the validity of many published analyses: poor storage conditions leading to degradation of alkaloids, misidentification of species/strain, as well as inconsistencies in analytical techniques, all make for a rather messy and unreliable literature on mushroom alkaloids — use all data as a guide only.

Total alkaloid content of Psilocybe species and Inocybe aeruginascens (from https://www.mdpi.com/1422-0067/23/22/14068)

For context, a 30mg dose of psilocybin is fully psychedelic and considered somewhat of a heavy dose. Assuming a 10mg/g psilocybin concentration (often quoted as the average), this amounts to around 3g of dried mushrooms, which is probably about right. However, as this latest study shows, 3g could just as well be a very mild dose (3mg) or, using Terence McKenna’s parlance, something of a heroic one (60mg). As always with psychedelics, caution is advised. Since the levels of alkaloids have also been shown to vary between flushes, the most sensible approach would be to quickly dry and then grind an entire mushroom harvest/purchase to homogenise the mushrooms and thus alkaloid content. As long as they’re stored properly (preferably in gel caps, kept dry and away from light and extreme heat), they should then maintain the same consistent potency over some years.

Whilst we need to take the absolute measured concentrations of alkaloids with a large pinch of Porcini Salt, it’s clear from this recent study and others that alkaloids can vary significantly between species and by as much as 6-fold or more within samples of the same species. But what about the relative concentrations of different alkaloids within a species?

Staying with the most commonly used species, Psilocybe cubensis, psilocybin and, to a lesser extent, psilocin, were most strongly represented, with much lower concentrations of the three other major alkaloids. In contrast, Inocybe aeruginascens, first identified in Hungary in 1965 and widely distributed across Europe and western North America, contains primarily aeruginascin (named after this species), with somewhat lower levels of psilocybin. P. semilanceata contained baeocystin at similar levels to psilocybin, and P. cyanescens boasted high concentrations of psilocybin, psilocin, and baeocystin. Other species also exhibited their own particular alkaloid profile.

Psilocybe mushroom alkaloid profiles (from https://www.mdpi.com/1422-0067/23/22/14068) AE: aeruginascin; BA: baeocystin; NB: norbaeocystin; PS: psilocin; PSB: psilocybin

Psilocybe mushrooms alkaloid profiles showing absolute concentrations of 5 major alkaloids. (Key as above)

Psilocybe mushroom alkaloid profiles showing each alkaloid as a % of total alkaloids.

So, given that different species possess different alkaloid fingerprints, is it plausible that different mushrooms might reliably produce distinct psychedelic effects beyond that which can be explained by differing overall alkaloid concentrations? Perhaps, but we’ll need to think more deeply about the psychoactive effects of the individual alkaloids to really answer this question. And for that you’ll have to wait until next week for Part 2…