Synthesized Versus Natural Psilocybin

Why is Synthetic Psilocybin Important?

“For thousands of years, humans have used psilocybin from mushrooms growing naturally. If we can get psilocybin naturally from the Earth, why do we need synthetic psilocybin?”

I’m glad you asked! There are several reasons why pursuing synthetic psilocybin is important.

Let’s first talk about scalability. Natural psilocybin exists in sufficient quantities to sustainably supply traditional and indigenous psilocybin mushroom practices. This has been the case for thousands of years. But if we are going to use psilocybin for modern uses (such as treating PTSD and depression) and want to meet modern demand (treat millions and millions of people across the world), the scalability and feasibility of using natural psilocybin begins to fall apart. Psilocybin doesn’t grow overnight.

Further, to be used at scale as a modern pharmaceutical, psilocybin yields must be consistently free of potential environmental allergens or toxins – in the same manner we expect blood pressure medications to be manufactured free of contaminants that may cause harm. (And when we find contaminants in medications, the FDA can step in and request that they be removed from the market, which occurred with ranitidine in 2020.)

As we’ve discussed in past articles, not everyone can safely consume natural psilocybin. Synthetic psilocybin may bemodified to lower the risk for heart-related side effects, or to reduce or fully eliminate hallucinations which could allow for at-home dosing and better safety in people with psychiatric conditions.

Penicillin was discovered by accident when mold inadvertently grew on an agar plate in the London lab of bacteriologist Alexander Fleming. Notice how nowadays, no one is asking, “But if penicillin naturally grows in mold, why do we need to synthetically manufacture it?” See, we didn’t immediately begin distributing this mold to treat infection. It took over a decade for scientists to figure out how to isolate and purify penicillin from mold, so that it could be safely used in humans and manufactured at scale.

There is a common fallacy that “natural” always equals “better”, usually paired with the twin thought that “synthetic” always equals “worse”. Just because a molecule or compound exists naturally does not mean there’s no room for modification and improvement.

What Did This Study Analyze and Find?

Researchers analyzed the effects of ingesting PME and PSIL on the following measures in mice:

• Head Twitch Response (HTR): HTR is a side-to-side head movement that happens in mice when the 5-HT2A receptor is activated. In this study, both PME and PSIL outperformed placebo with respect to an increase in HTR, and no significant difference between PME and PSIL was noted.

• Neuroplasticity-Related Synaptic Proteins: assessing brain specimens for synaptic proteins may serve to show the potential for inducing synaptic plasticity – your brain’s ability to require itself in response to stimuli.

  • Three days after treatment, researchers noted minimal increase in synaptic proteins in either group. But at 11 days post-treatment, both PME and PSIL increased synaptic proteins in the hippocampus, amygdala, striatum, and frontal cortex. There were differences in which specific proteins were increased by PME or PSIL in differing brain regions.

  • An ANOVA analysis showed PME increased all four synaptic proteins of interest across all brain areas analyzed, while PSIL only increased two synaptic proteins and these effects were only noted in the amygdala and hippocampus.

• Frontal Cortex Metabolomic Profiles: as defined in the study, “Metabolomics is an emerging field that seeks to systematically characterize the unique chemical fingerprint that low-molecular-weight molecules leave behind after a given stimulus in a biological specimen”. According to their findings, PME may have a stronger and prolonged effect on synaptic plasticity compared to PSIL.

What Comes Next?

As usual, we need further studies to confirm these findings, and to continue exploring questions raised – such as, what molecules are responsible for the noted enhanced effects of PME compared to PSIL and psilocybin alone? This and similar future research will help development of synthetic pharmaceutical psilocybin, as we discover which specific molecules are responsible for triggering synaptic plasticity – and how psilocybin triggers these molecules.

While in theory it’d be ideal to simply treat everyone in need with natural psilocybin, this simply isn’t feasible given a global population of 8 billion people, 280 million of whom have depression – and with an estimate that at least 30% of persons diagnosed with major depressive disorder have treatment-resistant depression, the math shakes out to at least 84 million people globally who could potentially benefit from psilocybin. And this is for ONE indication – not accounting for PTSD or other possible conditions that psilocybin may treat.

Like or not, we’re going to need synthetic psilocybin molecules if we want to utilize this medication to its full potential.