Atai's Enabling Technologies; Digital Health & Neurotech Trends: Part 2

A look under the hood of atai's tech platform

👋 Hi, I’m Zach Haigney; I write The Trip Report to help us understand what the intersection of psychedelic therapies and exponential technologies might look like in the not-so-distant future.

Psychedelic therapy combined with neurotechnologies and digital health tools will be the most powerful tools for leveraging the brain’s capacity to change—and thus the most powerful1 tools for addressing mental health, brain health, and personal transformation.

If you’re interested in these topics or working at the intersection of technology and psychedelics, I would love to connect.


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Atai's Enabling Technologies; Digital Health & Neurotech Trends: Part 2

In Part I, I argued that three trends are maturing at the same time as the psychedelic renaissance2, and this coincidence makes for compelling overlaps and synergies. These trends are:

  1. The study of neuroplasticity has matured from the lab to the clinic. Validated techniques that modulate the structure and function of neural pathways are here and will only get better.

  2. The adoption of digital technology in healthcare has reached an inflection point. The FDA and other regulatory bodies are adopting frameworks for validating software as medicine, virtual reality, & immersive experiences as medicine and drug + software combination products.

  3. The advancement of personalized medicine and precision psychiatry

We also noted two challenges that technology is poised to address:

  • The challenges of time and personnel requirements in psychedelic therapy

  • The challenge of patenting psychedelic medicines.

These trends and challenges are (among others) the “set & setting” for the rollout of psychedelic therapy.

Part I was a preamble for the context in which companies like Atai, MindMed, Compass Pathways, and others are developing supportive technologies alongside drug development.

Here in Part II, we look at technology programs in Atai’s portfolio.

Let’s dive in.


Clinically Oriented Enabling Technologies

From the Atai S-1 (emphasis added):

“Currently, we have 10 therapeutic programs, including five psychedelic compounds in our pipeline, complemented by six enabling technologies in development.

We believe our enabling technologies have the potential to support the development of our pipeline and be used as patient-support tools. The FDA has also recently expressed support for digital health initiatives through its Digital Health Innovation Action Plan.”

We are going to focus on the three clinically oriented enabling technologies that could ultimately enable:

  1. Diagnosis & symptom measurement

  2. Care delivery (the administration and observation, not route of delivery, i.e., oral, nasal delivery, etc.)

  3. Preparation and integration

  4. Neurostimulation before, during, or after psychedelic experiences

Atai currently has three clinical technology products:

  • IntroSpect Digital Therapeutics— “a digital therapeutics platform dedicated to improving patient outcomes through personalized care.”

  • Psyber— “developing an electroencephalography, or EEG, -based brain-computer interface technology for psychiatric use.”

  • PsyProtix— “developing metabolomics-based biomarkers that stratify patients with treatment-resistant depression.”

Introspect Digital Therapeutics

The adoption of digital technologies, including Telemedicine and Remote Patient Monitoring (RPM), will increasingly make web and mobile applications the primary point of contact between patients and providers.

These applications will also serve as the primary data collection vehicle and include the capacity to track symptoms, collect surveys and questionnaires, and connect to wearables and sensors to capture health data like heart rate, heart rate variability, blood pressure, activity levels, computer use, and other behavioral measures.

Such applications can also deliver educational content that can help patients prepare and integrate their psychedelic experiences.

Introspect is Atai’s version of this technology layer.

From the S-1 (emphasis added):

“IntroSpect Digital Therapeutics is a wholly owned digital therapeutics platform dedicated to improving patient outcomes through personalized care. We believe capabilities such as symptom tracking, mobile application-based therapy (e.g., cognitive behavioral therapy) and remote monitoring, have the potential to improve patient outcomes as has been observed with other, similar therapies, such as Pear Therapeutics’ reSET-O.”

Last summer, Atai announced Introspect and the leadership of CEO David Keene (former CTO of Dthera, an early pioneer in the Digital Therapeutic’s space) with the goal of “creating a tightly integrated Digital Therapeutics on a shared architecture across all of Atai’s platform.”

We covered the Introspect announcement in last year's Software-Assisted Psychedelic-Assisted Psychotherapy: Part 1 and the intention of developing a digital platform to accomplish three goals:

Magnifies the effect

“IntroSpect will create digital tools and devices that will “magnify” the effects of drugs in development at ATAI’s companies, David Keene, CEO of IntroSpect, told Fierce MedTech.”

Allows for Remote Monitoring

“Another use case is remote monitoring, which could make psychedelic treatments available for patients who live far away from treatment centers. The technology could come in handy at Compass Pathways, for example, which is working on a psilocybin therapy for people with treatment-resistant depression.”

Digital Aftercare

“What separates apart a recreational psychedelic experience versus a clinical one is the clinical setting and aftercare therapy,” Keene said. “This type of aftercare can help patients take advantage of the neuroplasticity—the brain’s ability to change itself—that comes with a psychedelic experience and use it to make life changes”

Such a platform, in conjunction with a drug, is, according to the FDA, a combination product.

As we noted in Part I, Pear Therapeutics’ ReSET-O is the archetypal drug-software combination product that combines a smartphone-based app with buprenorphine to treat Opioid Use Disorder (OUD) with greater efficacy than buprenorphine alone.

In practice, it looks like this:

In the context of psychedelic-assisted therapy, a reSET-like application serves as a portal for patients to access their providers, track their progress, and learn about their conditions and the treatment.

It could also serve as the foundation upon which other tools like Digital Phenotyping, Contingency Management, and neuromodulation protocols could be built.

In Part I, we noted that, broadly speaking, there are two primary technologies we are interested in, Remote Patient Monitoring (RPM) and Neurotechnology (neurotech).

If Introspect is the RPM, Psyber is the neurotech.

Psyber

From the S-1 (emphasis added):

Psyber is developing an EEG-based brain computer interface, or BCI, technology for psychiatric use. Beneficial effects of BCI-based approaches have been observed on stress reduction, attention and emotional modulation in humans. Our initial application of this technology platform is to enhance both “(mind)set and setting” prior to and during psychedelic dosing. We intend to co-develop this technology with our psychedelic therapies and IntroSpect Digital Therapeutics’ mobile application.

Electroencephalography (EEG) captures the electrical activity of the brain through non-invasive electrodes placed on the scalp.

Clinically, the primary use case for EEG has been neurofeedback which “uses real-time displays of brain activity in an attempt to teach self-regulation of brain function…with feedback presented using video displays or sound3.”

Neurofeedback is an adaptive stimulus that, in theory, modulates a person's neurophysiology by visualizing brain activity so that patients can see it in real-time and learn to control their ability to focus, emotional regulation, and other cognitive traits.

Neither EEG nor neurofeedback is new or cutting edge. The first human EEG was recorded in 1924, and the first study of neurofeedback was in 1962.

There is evidence that neurofeedback is an effective treatment for several conditions, but at least three things have prevented neurofeedback from more mainstream adoption.

  1. It’s not a pill

  2. Clunky hardware, poor user interfaces, and labor-intensive setup and operation

  3. Heterogeneity in the research methods has, according to some,4 lead to an inconclusive evidence base

As an off-patent, non-invasive, time-consuming treatment5, neurofeedback hasn’t been as readily adopted as pharmaceuticals6 and other devices. However, with the increased scrutiny of pharmaceutical approaches to mental health, neurofeedback has gained momentum as a treatment option.

A handful of consumer-focused mobile neurofeedback companies, including Muse and Myndlift, have made the hardware and user interfaces more elegant and engaging on the hardware and design side. And companies like TrippVR and Healium are incorporating neurofeedback into virtual reality.

On the evidence base front, as we move more towards N=1/personalized frameworks and mental health biomarkers become more objective, we should expect that practices like neurofeedback, which can be tailored to the individual, would become more effective.

Since neurofeedback leverages experience-dependent neuroplasticity, the thinking is that psychedelics could create increased ‘malleability’ and thus make neurofeedback more effective.

As clinical neuropsychologist Michael Thaut, Ph.D. notes:

"I think the next frontier may be to combine neurofeedback with biologically-based psychotherapies such as CBT or ECT and, ultimately, psychoactive drugs."

This is where Psyber appears to be heading.

From April 7th  announcement article in the Daily Mail:

The device will record electrical activity in the brain for real-time interpretation of emotional, behavioural, and mental states, providing the patient with live feedback.

The timing of the Psyber announcement is also noteworthy.

A week before, Robin Carhart-Harris announced he would join UCSF’s Neuroscape lab, the very group that developed the first FDA-cleared video game that uses closed-loop algorithms that can be thought of as AI/ML mediated neurofeedback.

The developments we can expect from Neuroscape and the proposed product from Psyber share a lot of features.

Again from the Daily Mail piece:

The bulk of the data from their BCI is EEG, but also pulse, eye tracking, heart rate, and other elements currently being explored by the Atai. 'The idea isn't to take one signal and create a metric, but to look at many different elements including facial expressions to inform of the next steps,' Keene said, adding it would help the patient and improve safety of the treatment.

In the case of Psyber, EEG-based BCI development will be enabled through a tailored software platform that includes machine learning elements.  

Atai is not alone in developing EEG-based tools for use in psychedelic therapy.

Heather Hargraves has been researching psilocybin informed neurofeedback for at least a few years and is a co-founder of Divergence Neuro, a neurofeedback platform operating in the psychedelic arena.

Plus, there is major DIY/open source energy in EEG-based neurotech since the hardware is cheap and the software open source, which leads to a lot of cool tinkering like this.

PsyProtix

From the S-1 (emphasis added):

“PsyProtix is a joint venture with Chymia, a spinout of Duke University, with Atai owning 75% as of March 31, 2021. PsyProtix intends to develop metabolomics-based biomarkers that stratify TRD patients, for a currently undisclosed class of compounds, with the aim to improve patient outcomes through a precision psychiatry approach. Currently, this program is in the preclinical phase with an initial focus on mitochondrial energetics. Targeting this metabolic pathway may provide a new treatment approach for subsets of TRD cases.”

Along with digital biomarkers, metabolomics-based biomarkers are a frontier technology aimed at quantifying human suffering.

From the paper titled Metabolomics Biomarkers for Precision Psychiatry:

“metabolomics studies measure our metabolic state, determined not only by genomic factors but also modified by diet, environmental factors, and host factors such as the childhood experiences and gut microbiome. The metabolic profile serves as a quantifiable, dynamic readout of biochemical state that can inform underlying molecular mechanisms of the disorder or phenotype. As such, metabolomics data have higher relevance to the “disordered state” and may serve well as predictive, prognostic, diagnostic biomarkers [25] for psychiatric disorders.”

Measurement and Intervention: Towards a Thermostat for the Mind

So we have these simultaneous emerging paradigms of applied neuroplasticity, increased technology adoption, and a march towards personalized medicine coinciding with the advent of psychedelic science and therapy7.

These trends coalesce to:

  • Drive targeted, measured, and efficient changes to the brain and neural tissue8

  • Help us understand ourselves, our environment, make changes and track our progress

  • Allow us to go from numbing emotional pain to uncovering, addressing, and confronting the source

  • Help us move from episodic, subjective, one-dimensional measurement to objective, continuous and wholistic measurement9 enabling a ‘thermostat for the mind’

And even though this series was focused on Atai, their technology, and the context of bringing these products to market in regulated healthcare systems, all of the components are (basically) freely available:

  • The Active Pharmaceutical Ingredient (API) grows out of the ground for free

  • Software to create EMR, Telemedicine and RPM is open source and free

  • The Software and Hardware needed to build EEG based measurement and feedback is open source and cheap10

  • The software and hardware needed to monitor one’s activity, mood, symptoms, and behavior are in our pockets.

The resurgence of interest in psychedelics as tools for healing and transformation will not be limited to the halls of medicine.

And neither will the technology.

1

I mean powerful in the most literal sense, P=W/t, where the work (W) is the structural/function modulation of neural connections/pathways.

2

Whatever you want to call it

3

https://en.wikipedia.org/wiki/Neurofeedback

4

“The greatest complication preventing certain protocols from reaching higher evidence levels is a relatively high number of uncontrolled studies and an absence of accurate replications arising from the heterogeneity in protocol details, course lengths, measures of improvement, control conditions, and sample characteristics.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878101/

5

Sound familiar?

6

“As we address these Big Pharma issues, we must examine the fact that as a profession, we have allowed the biopsychosocial model to become the bio-bio-bio model. In a time of economic constraint, a “pill and an appointment” has dominated treatment. We must work hard to end this situation and get involved in advocacy to reform our health care system from the bottom up.” —Steven S. Sharfstein, MD in Big Pharma and American Psychiatry: The Good, the Bad, and the Ugly.

7

I mean, come on, how is this not the most interesting thing in the world!

8

This statement is probably premature, according to the literature, because the trials that would confirm it from places like Neuroscape and Atai are yet to be done. But I think you can see where I am going.

9

Shout out to Aware Healthcare for this framing:

10

There is even a precedent for this type of DIY digital health, most notably from the diabetes community. https://loopkit.github.io/loopdocs/

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