Discover more from The Trip Report by Beckley Waves
The Mindful Metaverse; Intravenous Psilocin; MindState Design
Today, we’re exploring recent announcements from:
Mindstate Design Labs
The common theme is innovation—innovation in community, drug delivery, and drug discovery, respectively.
Thanks for reading 🙏 I hope you enjoy it.
🧘 A Tech Company Acquires a Meditation Community
EvolVR, founded by a Unitarian Universalist minister and meditation instructor, claims to be the world’s first — and the largest — live meditation community in VR, claiming more than 40,000 people don a VR mask to tap into the powers of meditation.”
This announcement struck me as significant for the following reasons.
First, suppose you break it down into its constituent parts. In that case, it combines several early technology-driven trends—Virtual Reality, The Creator Economy, and Digital Communities—which I am interested in exploring, but more importantly, are already intertwining with the emerging psychedelic landscape.
Second, it occurred to me that the founder of EvolVR, Jeremy Nickel, is a Creator Economy success story—that is, he took a passion/interest and started something.
It did not start as a venture-backed, built-for-scale project with unicorn ambitions. Instead, according to the website, “EvolVR is an incubated project of the Center for Progressive Renewal, a registered 501c3.”
It is the kind of project from which therapists, meditation teachers, spiritual teachers, and other potential “creators” can find inspiration.
Third, psychedelic experiences are the start of a healing journey, not the conclusion. Thus, a recurring theme in conversations with psychedelic stakeholders is “What do we do for people after the journey and integration work? After the week-long retreat? After the study is over?”
“Community” is always one of the first responses to these questions.
These niche, digital-first communities and others like them may prove invaluable as the cultural adoption of psychedelics for healing and spiritual inquiry continues to grow.
This acquisition marks a ‘fish crawling out of the water’ moment that points to future “exit opportunities” for creators, teachers, and leaders who have formed communities but want to collaborate or want operational and financial resources and support.
“2021’s investors shelled out $198M in funding for U.S. digital health startups integrating VR or AR technologies across 11 deals, more than double the $93M raised across eight deals in 2020.”
🥼Psychedelic Procedures: Eleusis' Intravenous Psilocin
In Psychedelic ‘Procedures’ & Regulatory Leakage, I posited:
“I have begun to think the clinical workflow of psychedelic experiences within healthcare settings would increasingly look like surgical workflows (standardized, long duration, altered consciousness, recovery period, etc.).”
A recent announcement from Eleusis points to a more procedure-like intervention using intravenous psilocin, the active metabolite of psilocybin.
From the Eleusis blog:
"Eleusis is developing ELE-Psilo an investigational psychedelic drug candidate designed to deliver the prodrug psilocybin’s active metabolite, psilocin, by infusion. Unlike orally administered psilocybin product candidates that must be metabolized by the body to be converted to psilocin, ELE-Psilo is designed to deliver psilocin directly. As part of the development of ELE-Psilo, we devised a method of stabilizing psilocin in a drug formulation.
By using IV administration of psilocin, we believe it may ultimately be possible to personalize potential therapy to the individual patient’s needs based on that patient’s response. We also believe psilocin delivered via infusion could significantly reduce the variability in response that has been observed in clinical studies using oral administration of psilocybin, by facilitating control of dosing and duration of administration in real-time."
The article goes on to cite some practical challenges of orally administered psilocybin, including:
delayed time to onset
variability of absorption and metabolism
variability of response
inability to increase or decrease the intensity of the experience
Last Mile challenges for psychedelic medicine are formidable.
Creating shorter trips is a common strategy among developers. However, a less considered factor is addressing the issue of absorption and metabolism with orally administered psilocybin that leads to a high variation in responses.
One approach is to increase the baseline dosage, 25mg of synthetic psilocybin has become the standard, but I believe we will see higher doses in trials soon.
However, a route of administration, such as IV infusion, that allows for ‘in flight’ adjustments is more representative of precision practices we should expect as the field evolves.
Furthermore, the rationale and metrics by which the intensity of an experience is increased or decreased will be interesting to see—what clinical markers prove useful in whether an experience necessitates additional dosage?
Will they use biomarkers of arousal or anxiety, like Heart Rate Variability, blood concentration levels, or good old-fashioned patient self-report?
With the advent of AI, we can probably assume all of the above.
🧠 Mindstate Design Labs
Mindstate Design Labs announced an $11.5 million seed round this week.
It is a compelling project for a few reasons:
the unique scientific work of cofounder Tom Ray
the inversion of the drug discovery process
the investors they have been able to attract.
I want to touch on these quickly and hopefully follow up with a longer piece soon.
Scientific Co-Founder Tom Ray
Add Tom Ray to the candidates for Most Interesting Man in the World.
To say Ray has an interdisciplinary background would be an understatement.
An evolutionary biologist by training, he is a professor of zoology at the University of Oklahoma, a chemist, self-taught computer scientist, friend of Alexander Shulgin, and has a long-held interest in psychedelics as tools of scientific inquiry.
In recounting a significant psychedelic experience on the Business Trip Podcast, Ray said it:
“caused a light bulb to go on, and I realized that the qualitative diversity of psychedelic drugs would be a powerful toolkit for probing the chemical architecture of the human mind.”
This insight from decades ago that the idea of Mindstate Design Labs was conceived.
Psychedelics are pharmacological agents that act on these receptors and deform neural activity, leading to their signature hallucinogenic effects. As it turns out, many psychedelics are actually very safe in humans… This creates a promise of precision interrogation of neural processing along the dimensions of these receptor systems, potentially allowing us to dissect cognition and study it far more deeply than we have previously without an implant.
Drug Mindstate Discovery Platform
The Mindstate approach to developing drugs appears straightforward at first glance—they are combining known psychedelics with known, non-psychedelic compounds to produce New Chemical Entities (NCEs).
However, it is the method of uncovering clues for which drug combinations might produce calibrated mindstates where things get interesting.
Half of the process comes from Ray’s previous work that he lays out in Psychedelics and the Human Receptorome, a fascinating look into the map of psychedelic interactions across different receptors.
This paper and accompanying datasets (image below) include the binding affinity for thirty-five psychoactive drugs at forty-two neuronal receptors.
The second component is a database of thousands of first-person accounts of psychedelic experiences from Reddit, Erowid, clinical trials, and elsewhere which have been processed by machine learning techniques to identify the shared semantics people use to describe their experiences.
From this processing, the various mindstates can theoretically be ‘quantified.’
By comparing these two datasets, the goal is to identify specific combinations of psychedelics with non-psychedelic compounds to precisely activate some receptors, but not others, to reliably create specific mindstates.
Hence the ‘mindstate first’ approach to drug discovery.
Finally, this round of funding is notable for including several well-known silicon valley investors, including Gerry Tan, Naval Ravikant, and Fred Ehrsam.
I read this as a nod to the goal of precision that the project aims for compared to first-generation psychedelics.
With few exceptions, most psychedelic drug development projects have focused on reducing the duration of the trip, eliminating the trip, modifying the route of administration, or replacing a hydrogen atom with deuterium for patentability.
The Mindstate project strikes me as ambitious in a way that we haven’t seen yet, and these illustrious investors recognize this ambition.
Now it’s time to find out if it will work.
Right to Try
Last week we looked at the progress of the Right to Try route to access psilocybin for terminally ill patients.
On Friday, Marijuana Moment covered the developing plot as plaintiffs filed a formal petition with the DEA:
"The petition, dated Tuesday, requests the agency to reschedule psilocybin as a less-restricted Schedule II drug, pointing to its relatively low potential for abuse and “exceptional promise in relieving debilitating symptoms in those with intractable and otherwise untreatable illness,” including the severe anxiety and depression that can result from a terminal illness."
Oregon: Natural Cubensis Only
“…under the draft rules, manufacturers can only cultivate one mushroom species: Psilocybe cubensis…
The draft rules also show the state is taking the significant step of prohibiting the chemical synthesis of psilocybin. In practical terms, that means it may be harder for large pharmaceutical companies to come into Oregon with a cheap pill and potentially dominate the market.”
Our friends as Psilocybin Alpha published a tome of a document. Get up to speed with the events of 2021 in psychedelics in their Year in Review.
Psychedelic Group Therapy
In it, he offers suggestions for moving from an individual treatment paradigm that has been the typical format in most trials to date (emphasis added):
"For psychedelic therapy however, individual treatment guided by one or sometimes even two therapists is the most common and widespread treatment model for clinical research and therapy thus far. Since the foundation of the Swiss Medical Society for Psycholytic Therapy (Schweizerische Ärztegesellschaft für psycholytische Therapie, SÄPT) in 1985 in Switzerland, we however had the opportunity to conduct psychedelic group treatment in specific settings, which the following article describes."
The Psychedelic Origins of Alcoholics Anonymous
“By the time the man millions affectionately call “Bill W.” dropped acid, he’d been sober for more than two decades. His experience would fundamentally transform his outlook on recovery, horrify A.A. leadership, and disappoint hundreds of thousands who had credited him with saving their lives.”
Interested readers will also want to consult the academic version of the Bill W story—Classic psychedelics in the treatment of substance use disorder: Potential synergies with twelve-step programs.
“Accordingly, religious communities who operate under M109 should have the option to provide their own peer-support assistance through community members that have been certified by their community as being qualified and capable to provide that assistance.”
This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches…24 healthy volunteers received 50 μg of LSD or inactive placebo. Near drug peak, a creativity task battery was applied…
Results: LSD, compared to placebo, changed several creativity measurements pointing to three overall LSD-induced phenomena: (1) 'pattern break', reflected by increased novelty, surprise, originality and semantic distances; (2) decreased 'organization', reflected by decreased utility, convergent thinking and, marginally, elaboration; and (3) 'meaning', reflected by increased symbolic thinking and ambiguity in the data-driven results.
“In fact, it increasingly seems that pain – one of the most universal experiences in the human condition – is now the next frontier for psychedelics after mental health.”
That’s all for this week; thanks for reading, and see you next time.