East meets Tech: Digital Shamanism & Closed-Loop Psychedelic Therapy

Hello!

On the occasion of my recent appearance on the Business Trip Podcast, where I spoke with Greg Kubin of the Psychedelic Medicine Syndicate, I wanted to say hello, and update you on future plans.

I also want to share some thoughts on my current fascination—the interface between technology and psychedelics, specifically what Adam Gazzaley calls Closed-Loop Psychedelic Therapy.

For new readers, this is a good place to start to get a sense of what The Trip Report is all about.

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The Trip Report Update

The last few months have been wonderful and challenging. As any parent will know, a new baby in the family wreaks havoc on routine, sleep, plans, sanity, etc. So I decided to hit pause on writing 3 times a week, rest up and think about the future.

And change diapers.

Fortunately, I have met some wonderful people, and we have exciting plans that I look forward to sharing with you in the coming weeks.

East meets Tech: Digital Shamanism & Closed-Loop Psychedelic Therapy

TL;DR

  • Robin Carhart Harris Joins UCSF’s Neurscape Lab

  • Neuroscape, headed up by Adam Gazzaley, develops Closed-Loop Human-Computer systems that target cognitive and neurological conditions and brain optimization.

  • Closed-Loop systems work by driving neuroplastic changes by applying adaptive loads on targetted neural circuits. Psychedelics “soften” these circuits making them malleable. combine the two and….

  • Closed-Loop systems create the possibility for effective and scalable tech-enabled psychedelic therapy.

Robin Carhart-Harris Joins UCSF & Adam Gazzaley Officially Steps into Psychedelic Science

OK, this is exciting:

Psychedelics research in support of brain health is getting a major boost this month with the formation of the Neuroscape Psychedelics Division at the University of California, San Francisco (UCSF). Through $6.4M in private funding, the new division will take a unique translational research approach to integrate cutting-edge neuroscience technology with psychedelics treatment...

"Heading up the new Neuroscape division as Founding Director will be Robin Carhart-Harris, one of the most cited researchers in the world in psychedelic science and the founder of the first center for psychedelic research at Imperial College London. "The founding of this new division is a hugely exciting development in the story of the psychedelic renaissance," says Carhart-Harris, who is the newly endowed Ralph Metzner Distinguished Professor of Neurology and Psychiatry at UCSF. "I'm delighted to be joining UCSF and the Neuroscape team and hope to steer this new division to great success." (emphasis added)

This is big.

Why?

The world’s foremost psychedelic researcher is joining the world’s foremost translational neuroscience lab at one of the world’s foremost biomedical research institutions.

If you’re reading this, you probably know who Robin Carhart-Harris is, but you may not know about Neuroscape or its founder, Adam Gazzaley.

Neuroscape is “a translational neuroscience center at UCSF engaged in technology creation and scientific research to better assess and optimize brain function of both healthy and impaired individuals1.”

Founded and led by neuroscientist and neurologist Adam Gazzaley, Neuroscape developed the core technology that underpins the first FDA-approved video game to treat ADHD. Gazzaley is a co-founder and chief scientific officer of Akili Interactive, which developed EndeavorRx, the video game approved for ADHD, last summer.

I didn't realize it at the time, but we touched on Neuroscape’s technology in June of last year in Software-Assisted Psychedelic-Assisted Psychotherapy: Part 1 when discussing the first FDA approval of a video game as a treatment for ADHD:

This announcement from ATAI comes days after a watershed moment for the field of Digital Therapeutics.

The FDA approved the first video game for the treatment of ADHD developed by Boston based Akili Interactive.

“The U.S. Food and Drug Administration (FDA) has granted clearance for EndeavorRx as a prescription treatment for children with attention-deficit/hyperactivity disorder (ADHD). Delivered through a captivating video game experience, EndeavorRx is indicated to improve attention function as measured by computer-based testing in children ages 8-12 years old with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue”

The FDA's approval of Akili's EndeavorRX was significant, not merely for the irony of the headline "FDA Approves Video Game for ADHD" but because it marked an inflection point in the field of digital therapeutics.

Again from June's dispatch:

“This is significant because digital therapeutics (DTx), as a field, has been limited in its ability to create a therapeutic effect directly.

The term has referred to the use of digital and Internet-based health technologies to make behavioral and lifestyle changes that indirectly affect clinical endpoints through behavior modification, this is what we mean by DTx 1.0.

However, Nikhil Krishnan, healthcare analyst and author of the Out of Pocket newsletter, made the case that Akili’s EndeavorRX marks the leap from Digital Therapeutics 1.0 to 2.0 on yesterday’s A16Z podcast.

“One really cool thing about this is Akili is a therapeutic through and through. It is not trying to incentivize a behavior change to induce the therapeutic effect. The goal of the video game is to actually induce the therapeutic effect directly which brings a lot of the promises of true scaleability.””

Closed-Loop Human-Computer Systems

The technology that enabled this leap from Dtx 1.0 to 2.0 is called Closed-Loop Human-Computer System or what the creator, Adam Gazzaley, calls “Closed-Loop algorithms for experiential treatments.”

From the Neuroscape website (emphasis added):

“Our goals to improve quality of life for both healthy and impaired individuals are focused at creating and validating new approaches to better assess and optimize brain function. We propose that the most effective approach to accomplish this is via dynamic interactions with a closed-loop system.

In this context, a ‘closed-loop system’ is one where: (1) an individual is challenged by an intervention, (2) the influence the challenge has on the individual is recorded in real-time, (3) these data then immediately update the challenge to be more effective in eliciting the desired response. The cycle then begins again with the updated challenge being reapplied, and real-time data being again collected and used to update the challenge. This closed-loop cycles over and over again – targeting and personalizing the challenge to the individual at every pass.

The closed-loop allows for high precision, personalized data to be collected so we can rapidly assess where an individual begins, and how to keep him/her at the edge of their ability for optimal learning.

In Neuroscape’s Technology division, we create closed-loops between an individual and custom-designed video games. Video games are an ideal platform to create closed-loop systems, as they are interactive and fun, leading to deep engagement.”

Challenge, Stressors, and Neuroplasticity

I want to acknowledge the risks of overselling technology, especially in healthcare, that creates outsized power dynamics between tech operators and users2. But the techniques discussed here make so much intuitive and conceptual sense to me based on the ups and downs of my own mental/emotional wellbeing and the science of biological tissue remodeling (aka neuroplasticity)3.

Here’s how I think about it:

The word ‘challenge’ was mentioned six times in one paragraph in Neuroscape’s description of closed-loop technology.

Why?

When I hear Adam Gazzaley explain the premise of closed-loop systems he often begins with exercise.

Lifting heavy things causes muscles to grow in size and strength. If muscles aren’t stressed enough, they don’t grow. If they are stressed too much, they get injured.

It turns out that all biological tissues, including neural circuits, operate according to this same principle. This dose-response relationship is generalizable across systems. It goes by many terms, but the basic framework is called hormesis.

Challenges come in a few flavors. There are cognitive challenges like learning a new language. Physical challenges like weightlifting and endurance exercise. Metabolic challenges like fasting and thermal conditioning. There are also psychological and emotional challenges like confronting fear and reliving traumatic events.

Such biological stressors and challenges cause structural and functional changes in biological systems according to predictable dose-response relationships, and we can leverage them for health-promoting and healing.

In closed-loop digital therapeutics, the challenge imposed by the increasing difficulty of a sensory-motor experience (video game) applies an adaptive pressure to the neural circuits involved. In the case of the EndeavoRX game for ADHD, the adaptive pressure is on the neural circuitry that governs attention and working memory.

This challenge changes the structure and function of the circuits that are “loaded” by the sensory, motor, and cognitive demand of the video game through a process called experience-dependent neural plasticity.

Dr. Gazzaley from his recent appearance on The Tim Ferriss Podcast:

“Probably what makes EndeavorRx so unique, as well as the dozen other video game technologies that we have at Neuroscape… they’re all closed-loop. What that means is that real-time data about your state, and it may be very simple data like your performance data, how fast or accurate you are, feeds into a processor, a computer, that records that data, makes a decision about it and then updates your environment. The challenges that you’re experiencing, the stimuli, the rewards that you’re being exposed to, and it goes on and on constantly adapting.

That’s why I made the analogy to a personal trainer. Imagine going to a gym and having a trainer that has access to every aspect about you in the moment. And also this ability to change things so subtly, to just push you to the next level. That is what this closed-loop system does.”

But, what does this have to do with psychedelics?

I’ve become convinced that:

  • Closed-loop systems will enable safe, scalable, and effective psychedelic medicine.

  • Closed-loop systems will empower human therapists, not replace them.

  • Rather than usurp traditional wisdom systems, closed-loop technology has the potential to breathe life into millennia-old healing practices like shamanism, contemplative traditions, and other lineage-based practices under intense extinction pressure.

Again, Dr. Gazzaley from Tim Ferriss’s Podcast:

“I think that what we’re doing here is building a set of tools, really sophisticated, informed, data-driven tools that will allow a therapist or any practitioner in the space to be more effective at helping their patient. That is what I hope and believe will come from this long journey. And that technology will be what it always should be, is just another human tool…

“Now, let’s talk about psychedelics. I described to you a system where technology enables multimodal biosensing, so we can understand your state in real time. And I described us having the ability to change what you see, hear, smell, and feel. So we have the two sides. We have the ability to know what’s going on with you, and we have the ability to shape your environment. What we didn’t talk about is what you just said: creating a closed-loop psychedelic experience. That is the goal here.”

The closed-loop systems apply adaptive pressure (challenges) to targeted neural systems, thus provoking selective neuroplastic changes.

Psychedelics, molecularly speaking, create an environment in which these neural circuits become more malleable and changeable.

Combine them, and the implications are incredibly compelling.

1

https://neuroscape.ucsf.edu/

3

Really should be bioplasticity since changes in immune, endocrine, even soft tissue are implicated.