The Future of Magic Mushrooms is Formulations of Tryptamines

Several organizations in the United States and worldwide are seeking to legalize or decriminalize “magic mushrooms” (the organism) and/or psilocybin (the molecule).  At a high level, these two approaches represent opposite medical philosophies: Eastern medicine v. Western medicine; or Naturopathy v. Pharmaceutical.  As outlined below, each approach has strengths and weaknesses. Not surprisingly, the best solution appears to be a compromise between these two extreme approaches. 

  • Natural Mushrooms: Decriminalizing magic mushrooms seems reasonable based solely on their natural abundance.  (“How can picking this thing in my yard subject me to criminal liability?”) But, using “magic mushrooms” as a means for administering psychoactive drugs causes concerns because of the substantial variability in the chemical composition of magic mushrooms and the potential side effects caused by some magic mushrooms.
  • Pure Molecules: Unlike natural mushrooms, pure psilocybin allows for administering a known amount of a known drug.  However, treatments using only pure psilocybin fail to account for the polypharmacology of magic mushrooms.  In other words, pure psilocybin does not produce the same effects as magic mushrooms because magic mushrooms have multiple active ingredients. Substituting pure psilocybin for the full spectrum of active ingredients in magic mushrooms does not replicate the properties of magic mushrooms.

The disadvantages of using either (A) magic mushrooms or (B) pure psilocybin can be overcome by creating formulated products containing precise amounts of the active ingredients found in magic mushrooms (aka tryptamines, psilocybin derivatives).  Such formulations would provide both (a) the full spectrum of psychoactive ingredients contained in naturally occurring mushrooms and (b) precise dosing of the active ingredients.

Some traditionalists object to formulating magic mushroom products instead of simply using what Nature provides. Arguments for using all-natural, organic foods and medicines certainly have merit.  And, such unmodified products will probably always have benefits over processed ones.  However, for some of the practical reasons discussed below, increasing access to magic mushroom medicines will require products that have consistent amounts of known ingredients.  And those products can be made in a way that preserves (or even improves on) the full spectrum of ingredients contained in natural mushrooms.

Are Magic Mushrooms as Safe as Pure Psilocybin?

Despite clear, undisputed evidence regarding the safety and efficacy of pure psilocybin, very little information is available about “magic mushrooms.”

Most journalists and organizations either (A) use the term “psilocybin” interchangeably with “magic mushrooms” or (B) refer to psilocybin as the only active ingredient in magic mushrooms.  See Tips for Journalists. Accordingly, the mainstream media has inadvertently suggested that research on pure psilocybin applies equally to magic mushrooms. Not true. Psilocybin and magic mushrooms would be most accurately described as different drugs.

The scientific community unanimously agrees that (1) psilocybin has tremendous potential for helping many people and (2) psilocybin is one of the safest drugs available. Last year, John’s Hopkins University scientists recommended re-categorizing psilocybin from a Schedule I drug–one with no known medical potential–to a Schedule IV drug like prescription sleep aids.  But, what scientific studies have been conducted on “magic mushrooms”?  What does science really know about the pharmacology or clinical effects of naturally occurring magic mushrooms?

Here are some facts about “magic mushrooms” that raise concerns about using them as a means for administering psilocybin:

  • Magic mushrooms vary wildly in their chemical composition and concentration. See Chemical Variability in Magic Mushrooms.
  • Magic mushrooms contain multiple active ingredients that have yet to be studied.  See What are Psilocybin Derivatives?
  • For many people, consuming “magic mushrooms” leads to unwanted side effects, such as late-onset temporary paralysis reported by Paul Stamets and Michael Pollan. (Notably, this paralysis does not occur with pure psilocybin, indicating that the paralysis is due to one or more of the other molecules present in magic mushrooms.)  See Wood Lover Paralysis.
  • Distinguishing “magic mushrooms” from deadly lookalikes can present difficulty for inexperienced foragers.  See, e.g., Stamets “Comparing two mushroom species: one magic, one deadly.”

Are Magic Mushrooms a Good Drug Delivery Vehicle?

Whether or not lawmakers decriminalize them, magic mushrooms are unlikely to serve as a mainstream means for administering psilocybin or other psychoactive molecules. Administering psilocybin via magic mushrooms introduces uncertainty regarding both (a) the identity of the drugs administered and (b) the amount of the drugs administered.

This uncertainty regarding the identity and amount of the active ingredient(s) creates a significant barrier for people advocating for increased access to psilocybin therapies. Here are a few illustrative questions that have been raised by critics of the magic mushroom movement:

  • How can medical professionals recommend a medicine without knowing both (a) what it is and (b) how much they are prescribing?
  • How can medical professionals evaluate the efficacy of a medicine without knowing what medicine they administered or how much?

Most medical professionals would insist that they cannot recommend or evaluate a drug treatment without knowing what’s in the drug and how much they are administering.  This seems like a reasonable assessment.  And it can be addressed by making products that have known amounts of known drugs.

Increasing Access to Psilocybin Therapies by Making Formulated Magic Mushroom Products

For the reasons discussed above, efforts to increase access to psilocybin therapies would benefit from methods of administering known amounts of known molecules.  Opponents of his pharmaceutical approach (correctly) point out that a single molecule isolated from a natural medicine does not provide all of the benefits of that medicine.  For those seeking to preserve the full spectrum of active ingredients in magic mushrooms, magic mushroom formulations could be made will multiple active ingredients instead of only psilocybin.

Recent developments in the cannabis industry illustrate that consumers can have both (a) the full spectrum of active ingredients present in a naturally occurring organism and (b) pharmaceutical precision. In the cannabis industry, both consumers and regulators benefited from a better understanding of product composition, i.e., knowing what drugs and how much. Consistent compositions provided consumers with consistent effects. Consumers could then rely on those effects for both medicinal and recreational purposes.

Focussing on the chemical composition also allowed innovators to experiment with Nature’s recipes in pursuit of designer formulations of natural molecules. These formulations leveraged the so-called “Entourage Effect.”

Notably, research and development in the cannabis industry did not restrict access to the cannabis plant. Today, traditionalists are still welcome to “smoke weed.” But, consumers also have other options. And many consumers appear to prefer consistent, reliable products. For example, Rolling Stone recently reported, The Future of Cannabis is Formulations of Cannabinoids.

As discussed above, the chemical uncertainty inherent to magic mushrooms is the strongest argument against their medicinal use. Accordingly, addressing concerns about the chemical variability of magic mushrooms would eliminate this barrier to increasing access to psilocybin therapies.  Precisely dosed formulated products would remove all uncertainty regarding the identity and amount of the drug administered. 

Conclusions

Despite our present understanding regarding the safety and enormous therapeutic potential of psilocybin, “magic mushrooms” will probably not provide a reliable means for bringing this drug to the masses. Natural mushrooms are highly variable in chemical composition.  Most likely, lawmakers will conclude that increasing access to wildly variable amounts of powerful psychedelic drugs creates an unnecessary risk.  Using a pure molecule (synthetic psilocybin) makes it possible to precisely administer a known amount of a known drug.  But, unfortunately, pure synthetic psilocybin does not replicate the effects attained by administering the cocktail of molecules contained in magic mushrooms. Formulated magic mushroom products offer the best of both approaches.  Formulated products would offer both (a) the full spectrum of psychoactive ingredients contained in naturally occurring mushrooms and (b) precise dosing of the active ingredients.

10 thoughts on “The Future of Magic Mushrooms is Formulations of Tryptamines

  1. Anthony Garner Reply

    As ever Government and bureaucracy muddle around while people are left to suffer. The ignorance and prejudice is staggering. Vaccine was only discovered by taking great risk (in that case disgracefully on a third party). In the case of psilocybin there are people out there so desperate they really do not care what happens to them – any chance to alleviate their misery would be welcome.

    Little harm ever seems to have arisen from psychedelics in any event. Happily people are taking the matter into their own hands regardless of the risk.

    Its rather like expecting to discover space travel while remaining safely in bad. It doesn’t happen.

  2. Jim Freire Reply

    Selected strains on a consistent substrate in consistent conditions easily can produce a standardized extract that is fully effective as the fruit body itself while having quantified formulation.
    Synthetic molecules blended will be less effective than the whole plant extract. This is how synergistic plant medicines work. Disassembled and reblended or synthesized products will fall along the same line as cannabis products in which the extract of the whole plant always out performs the attempted artificial synergy of blended single factors

    • Staff Scientist Post authorReply

      Thank you for your comments Jim. Is your idea to homogenize a large batch of mushrooms to arrive at an extract having a standard concentration for that batch?
      Here’s why this seems important: Studies have shown that different samples taken from the same crop/batch of mushroom contain highly variable chemotypes for both cultivated mushrooms and those collected from the wild. See Gartz, J., J. Basic Microbiol. 24 (1994) 1, 17-22 (“We generally found variations from one mushroom to another in every species even within… a single location and also in controlled cultures.”)

      To your point, using a large batch of mushrooms to make a single extract would guarantee that portions of that extract were internally consistent. However, it would not guarantee that other extracts (whether or not prepared in the same manner) would be consistent with one another.

  3. Safe Spaces Amsterdam Reply

    With decriminalisation plant medicines should not follow the pharma-medical journey. Like Ayahuasca and other plant medicines and their use, they have been known to have centuries or even thousands of years of history. Trying to purify, analyse, chemically copying or other “scientific ways”, seem to miss the point; Is it a different medical philosophy and school o thought where intention, emotion and psychological insights and healing go hand in hand with those who administer it and are gifted to do so.

    In the press the “risks” of a mushroom are a little exaggerated on the “safe side”. But every knows already, the science is necessary and will proof psilocybin containing plants have the potential to cure many people from day to day psychological struggles. Including scepticism 😉

    • Bruce Brandy Reply

      Have you people not done your homework? Albert Hofmann 1963 Tryptamines. Come on now people, wtf?

  4. Joanne Oake Reply

    Setting out to deal with psychedelics as drugs is a mistake in understanding the nature of these substances from the beginning. They can’t be reduced to mere drugs with predictable and uniform results.

    • Bruce Brandy Reply

      Joanne….Seriously, woman don’t keep the bullshit rhetoric based on disinformation ALIVE with ignorance like that. Please. Learn….Google Micro-dosing.

  5. Kilindi Iyi Reply

    Bull s–t we have something special in magic mushrooms learn to grow your own.

  6. Greg Reply

    I’m presently taking microdose psilocybin for treatment of C-PTSD. This, in the form of dried mushrooms, 50 – 100 mg of dried mushrooms once per week, roughly equivalent to 500 micrograms to 1 milligram of psilocybin (as compared to a psychedelic dose of 2 grams of mushrooms or 20 mg. psilocybin). The result has been a radical alleviation of C-PTSD flashbacks, from more than 50 per day before treatment, to approx. 3 per day at present, and those are mild and easily overcome with the usual cognitive methods. These benefits persist for the entire week between doses. The only “overt” cognitive effect of the microdose in the hours after taking it, is an increase in task concentration. To say this has been a life-changer, would be an understatement. It’s been utter liberation from a lifelong hellscape.

    I mention the above to make clear that I have serious “skin in the game.”

    The first issue here is to obtain access legally. Legalization of the mushrooms will almost by definition open up the research environment to enable the development of new pharmaceuticals. On the other hand, continued scientific research and peer-reviewed publication, for psilocybin and related compounds (and now, “entourages” of compounds), will lead to FDA approvals of less-restrictively-scheduled medications. To my mind both approaches are valuable, as long as everyone involved takes all due care to ensure they don’t lead to a situation similar to that in the 1960s that led to the prohibition of psychedelics.

    The second issue is to do the kind of extensive clinical research that will establish treatable diagnoses, treatment protocols, dosage levels, and the like. To some extent this is inherent in the FDA-approval approach, though it will need to be repeated for each new compound or entourage, and each new diagnosis being considered for treatment. Between now and then, the plural of anecdote is “testable hypotheses,” in that the anecdotal reports from all the usual sources will suggest new avenues of research.

    Finally to make this point clearly: On one hand, we should recognize that some individuals may prefer to take the mushrooms as such, largely for philosophical reasons, such as in the course of spiritual or religious practices. However when it comes to the treatment of diagnosable illnesses, such as anxiety, depression, PTSD, and C-PTSD: accessibility, affordability, and reliability, are essential. Reliability in turn depends on purity and potency, or as you say in these blogs, precision and accuracy. For this we need prescription medications, properly compounded, supported by peer-reviewed research published in leading journals, and available through Obamacare or equivalent insurance.

    This isn’t an either/or, it’s an and/both, depending on one’s purposes. But to bring it back to the personal level, I would strongly prefer to pick up a prescription once a month for four capsules of microdose psilocybin (or some subsequent “entourage” compound), than to have to grind up and weigh out dried mushrooms and hope they’re consistent from one dose to the next. It’s highly likely that the vast majority of people who could obtain medical benefits from psilocybin and related compounds, would agree.

    Lastly, some of the leading minds advocating for the spiritual and religious value of psychedelics, were fully on-side with the scientific and pharmacological approach. Aldous Huxley, his friend Humphrey Osmond, Albert Hofmann himself, and Sasha Shulgin, to name a few. So there is arguably also a spiritual/religious tradition there, and it’s convergent with the current scientific and medical interests, in seeking out the active compounds and providing them in pharmaceutical form.

    All of these approaches, and all of their advocates, can coexist, and should.

  7. Julie Reply

    I would agree with Greg in that it’s not an either/or situation, it’s an and/both. We need to decriminalize nature (having made it criminal in the first place doesn’t even make sense). And, we need to legalize the cultivation (self included), processing, distribution, and use of all psychedelics. Period. That is the only way to ensure that quality control oversight and standardized processes will be applied to the commercialization of these fungi and plants and their derivatives. Also, I do not categorize plants and fungi as ‘drugs’. They are plants and fungi. Psilocybin is a molecule. Drug is a word with a negative connotation applied to molecules/substances that cause certain molecular effects. I actually detest the word, ‘drug’. In the scientific community, I think we can do better to use less biased language as descriptors. Molecules are molecules, and whole plants and fungi are food. They can be foods that cause experiential effects, but they are foods – that we eat – nevertheless. The amount of refinement is the differentiating factor between food and molecular derivatives.

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