COMPASS Pathways – Access to Synthetic Psilocybin

COMPASS Pathways Targeting “Patient Access” to Synthetic Psilocybin

COMPASS Pathways is a life sciences company, founded in 2016, to “accelerate patient access to evidence-based innovation in mental health.”

According to their Chairman and Co-Founder, George Goldsmith, COMPASS Pathway’s goal is “to speed up evidence-based innovation for mental health treatments by researching, and potentially be the first to market the psychedelic substance psilocybin to combat treatment-resistant depression [TRD].”  Mr. Goldsmith further explains: “Our principles right now are simply to make it as accessible to as many people who have treatment-resistant depression as possible.”

In his interview with WIkiTribuneMr. Goldsmith repeatedly emphasized COMPASS Pathway’s commitment to improving “access to mental healthcare.”  “[O]ur goal, as I said, is ubiquitous, make sure the patients have access to this technology….”  “We’re not about psychedelics, were about accelerating patient access to evidence-based innovation and mental health.”

Mr. Goldsmith pointed out that improving patient access to psilocybin does not happen overnight.  Rather, he explains, “There are multiple steps in bringing a medicine to patient access. The step that we’re in right now is called dose finding.”

COMPASS Pathways has raised about $30 million dollars for purposes of improving patient access to psilocybin.  This sounds like advancing the common good, doesn’t it?

Balancing (A) Access to Psilocybin with (B) Maximizing Profits

Critics of corporate psilocybin research fear that pressure to maximize profits for investors will harm access to psilocybin therapies. Notably, COMPASS Pathways has earned a lot of attention for raising outside money from investors like Peter Thiel.  Regardless of COMPASS Pathway’s stated objectives of improving access and serving the common good, the company will ultimately answer to its investors, who will expect to see a return on their investment.

The pharmaceutical industry has long recognized the tension between (A) Maximizing Profits and (B) Improving Access to Medicines.  Traditionally, pharmaceutical companies develop patented products and then leveraged the resulting monopoly to maximize profits by controlling the price of the product. Some critics have expressed concern about these incentives for “patenting everything possible—from the drugs themselves to the tools used to administer those drugs—so that the company could charge whatever they want for their products.”

On the bright side, COMPASS Pathways unquestionably states that the company is 100% focused on improving access while remaining cognizant of pricing concerns.  Mr. Goldsmith explains, “Access is really important to us, and pricing is really connected….

On the other hand, COMPASS Pathways does not appear to have a plan for maximizing access within a pharmaceutical business model traditionally accustomed to leveraging a monopoly on therapeutic products in order to maximize profits.  Mr. Goldsmith explains that he has “Absolutely no idea how to accurately say how much it will cost…There’s a lot of uncertainty.”

Bottom Line: Hopefully COMPASS Pathways will develop a plan for maintaining its focus on “improving patient access” amidst the economic realities arising from answering to shareholders.

Determining the best Psilocybin Dosing Regimen

COMPASS Pathways is partnering with Worldwide Clinical Trials in conducting the first clinical trials for treating TRD with psilocybin-assisted psychotherapy.  See Financial Times, September 20, 2017.

The first round of clinical trials is focused on “Dose Finding” which means determining the correct dosing regimen for treating TRD. The clinical trial participants “will be given synthetic psilocybin” in trials designed to determine the best dose of psilocybin–whether 1 mg, 10 mg, or 25 mg – is most effective.

Here, it’s encouraging to see that the study is measuring the effects of a known amount of a known drug.  In terms of dosing, the COMPASS studies represent a significant improvement over other microdosing methods which rely on eating magic mushrooms.   See State of the Art Microdosing. Accordingly, at the very least, the formulations created by COMPASS Pathways satisfy an unmet need for microdosing formulations.

COMPASS Pathways – Focused on Synthetic Psilocybin

Magic mushrooms contain many different molecules. Several of those molecules, including psilocybin, are psychoactive. Each of them can either be isolated from naturally occurring mushrooms or synthesized in a lab. COMPASS Pathways is studying formulations containing pure, synthetic psilocybin as the only active ingredient.

The COMPASS Pathways clinical trials use precise amounts of pure synthetic psilocybin.  As discussed above, using known amounts represents a significant advantage over eating mushrooms. (Mushrooms are notorious for having highly variable chemical compositions).

COMPASS Pathways has filed a patent application in Great Britain for “Preparation of Psilocybin, different polymorphic forms, intermediates, formulations and their use.”  Presumably, this patent application covers some novel process for making the “synthetic psilocybin” used in their trials.  According to their web page, COMPASS is also providing synthetic psilocybin to academic researchers free of charge to foster research in the area of psychoactive care.

Precise Doses of Inferior Formulations?

Although COMPASS Pathway’s psilocybin formulations provide precisely dosed psilocybin, those formulations may not provide all of the benefits of magic mushrooms.

Magic mushrooms contain many active ingredients, including several different psilocybin derivatives.  All of those ingredients contribute to the effects of magic mushrooms.  Because different mushrooms have different chemical compositions, they provide different effects.

By analogy, the cannabis industry has recognized the importance of combining multiple active ingredients–just like the naturally occurring plants. Although THC was once heralded as the only important molecule, later studies have unquestionably uncovered advantages of combining multiple active ingredients in order to capitalize on synergistic effects.


The effects provided by “magic mushrooms” arise from combining multiple different active ingredients to arrive at an “entourage effect.”
Focusing on a single active ingredient potentially fails to take advantage of the synergistic relationships of active molecules present in magic mushrooms.

Certain combinations of multiple cannabinoids and terpenes provide users with effects superior to pure, isolated THC.  When properly formulated, these synergistic combinations increase the benefits and lessen the side effects experienced by the cannabis user.

Pharmaceutical products consisting of pure synthetic THC (e.g., Dronabinol, aka Marinol or Syndros) are often considered substantially inferior to analogous natural cannabis products, which have multiple active ingredients.  Mark Kleiman, director of the Drug Policy Analysis Program at UCLA’s School of Public Affairs described the pharmaceutical Marinol product as follow: “It wasn’t any fun and made the user feel bad, so it could be approved without any fear that it would penetrate the recreational market….”

Much like cannabis, magic mushrooms contain synergistic combinations of active ingredients.  This can be demonstrated by comparing cellular binding assays of (A) psilocybin formulations containing multiple psilocybin derivatives with (B) cellular binding assays containing only a single active ingredient.  Here, the best comparator is psilocin, which is the active ingredient–not psilocybin, which is best referred to as a prodrug of psilocin.  The activity of psilocin at serotonin receptors (for example 5HT-2a) can be dramatically modified by co-administering other naturally occurring molecules– much the same way mother nature serves up psilocybin along with other active ingredients.

Bottom line: Making and studying formulations consisting of pure synthetic psilocybin may not be the best goal.  The approach fails to account for the benefits of combining multiple actives and lend itself to the possibility of determining the best dose of an inferior formulation.

A better approach would be as follows:

  • First, figure out which combination of psilocybin derivatives provides the most advantageous properties for the patient.  Use that combination for future study.
  • Then, conduct “Dose Finding” studies aimed at determining the best dose of that formulation.


1. COMPASS – Navigating Mental Health Pathways. Accessed August 23, 2018.
2. Q&A: COMPASS Pathways’ Goldsmith on fighting depression with psilocybin. WikiTribune. Published June 27, 2018. Accessed October 1, 2018.
3. Kopytoff V. Peter Thiel’s Unusual Bet on Magic Mushrooms For Treating Depression Is About to Be Tested. Fortune. Accessed October 1, 2018.

2 thoughts on “COMPASS Pathways – Access to Synthetic Psilocybin

  1. Bernadette Nouel Reply

    Thank you for informing me of trial sites in France, Brittany in the Morbihan department for treatment for depression

  2. Richard Tyll Reply

    Balancing (A) Access to Psilocybin with (B) Maximizing Profits
    This is always the downfall of Pharmaceutical Companies trying to provide drugs that come from a naturally-growing plant. People will always revert back to obtaining a natural plant rather than paying for High-priced Pills. Especially when it is far easier to grow your own plants for far less cost. While it would be of benefit to have precise dosing for particular ailments, I believe people will opt for finding the correct dosage for themselves over being held hostage to the Pharmaceutical Industries quest to Maximize Profits.

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