Naturalistic Research & Behavioral Psychedelics
Naturalistic Research & Behavioral Psychedelics
Two things caught my attention this week that I want to explore.
Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Wellbeing
Two editorials in scientific journals about Psychedelic Therapy as a tool for Health Behavior Change (HBC)
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🌍 Naturalistic Research: Insights from the Psychedelics and Wellness Study (PAWS)
This week, a group of researchers published results of the Psychedelic and Wellness Study (PAWS) in Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States.
Results from this survey-based study that included 2,510 respondents found (emphasis added):
“Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit.”
Unlike most drug candidates undergoing trials for FDA approval, psychedelics are already in wide use in various contexts, making their study in naturalistic or Real-World settings possible.
Usually, such research methodologies are deployed after a drug has been approved and is in clinical use and referred to as Phase IV or Pragmatic Clinical Trials. These post-approval studies fill knowledge gaps around safety and effectiveness in broader patient populations and additional indications.
With the surge of psychedelic initiatives, including clinics, digital infrastructure, and policy reform efforts, we could see a surplus of this ‘post-approval research’ even before many of these drugs get FDA approval and are used in conventional clinical settings.
For further treatment of this idea, see The Middle Way: Tech-Enabled Psychedelic Pragmatic Clinical Trials.
The obvious limitations of this study include the fact that it was a retrospective online survey and thus unable to confirm the validity of responses. Still, it sheds light on what we might find when researchers can capture data in real-time from naturalistic settings.
But the three primary takeaways from this study are consistent with other research and anecdotal evidence.
Apositive correlation with psychedelic use and improvements in depression and anxiety
A dose-response of “improvement increasing in magnitude with increasing psychedelic exposure” up to a point
A worrisome percentage (13%) were harmed by psychedelic use
As a result of increasing interest and drug policy liberalization, the opportunity to conduct Pragmatic Clinical Trials at a larger scale in controlled, real-world settings should expand. I think this basic pattern (dose-dependent improvement with a ceiling for most and a smaller group for whom psychedelics are harmful) will persist.
Eventually, we will see attempts to establish predictive frameworks for who will have positive outcomes and who will have adverse consequences. This strikes me as the first order of business of such research.
👀 Psychedelic Assisted Behavior Change
Two recently published opinion articles point to psychedelic therapy’s potential as a treatment for extinguishing unhealthy behaviors like smoking, alcohol use, and poor diet and promoting healthy ones like exercise and healthy eating:
These are undoubtedly compelling use cases and lend themselves to the potential for broader application of psychedelic therapy to address major public health concerns. But, I think the real significance is that these reviews point to how mental health conditions will be defined, quantified, and treated in the near future.
I say this because while we are seeing a rising interest in psychedelics as therapeutics, there are also two coinciding trends:
The advent of digital therapeutics, including Remote Patient Monitoring, Patient Reported Outcomes via smartphone, and Digital Phenotyping.
A shift in mental health research away from the traditional DSM-based diagnoses and towards the Research Domain Criteria (RDoc) with the goal of understanding mental health and illness in terms of varying degrees of dysfunction in general psychological/biological systems, which includes an emphasis on health-related behaviors.
These developments allow the tracking of day-to-day behavior—such as sleep, activity, food choices, social engagement, etc.—and for these measures to be considered in diagnosis and disease progression.
For a more extensive treatment of these themes, see:
What if the ‘Psilocybin vs. Escitalopram’ trial used Digital Biomarkers to measure results?
Atai's Enabling Technologies; Trends in Digital Health & Neurotech: Part 1
Behavioral Psychedelics
This week, Edmund C. Neuhaus (Harvard & atai) and George M. Slavich (UCLA) published an opinion piece in Frontiers in Psychiatry titled Behavioral Psychedelics: Integrating Mind and Behavior to Improve Health and Resilience in which they coin the phrase “Behavioral Psychedelics.”
They note:
“Changing human behavior may sound simple but is exceedingly difficult, especially for behaviors that arise from years of thinking and acting in relatively rigid, routinized ways. One emerging strategy for accomplishing behavior change involves using psychedelic compounds to make the mind more malleable and open…
We discuss these timely issues here through the lens of behavioral psychedelics, which we define as the study of psychedelics to foster intentional changes in habits and behaviors to improve health and resilience.”
Psychedelics and health behavior change
This echoes the sentiment from another recent publication by prominent psychedelic researchers at Johns Hopkins and Imperial College London published in January titled Psychedelics and health behaviour change:
“if psychedelic-assisted therapy is found to work through general processes, such as relaxed beliefs, psychological flexibility and self-determined motivation, this might be used to enhance behaviour change across a number of disorders and lifestyle challenges, and enhance the effects of multiple psychotherapeutic approaches.”
While these papers suggest that health-related behaviors (which are a major causative factor in chronic diseases) may be more easily changed by using psychedelics, again, I think the broader takeaway is that the ability to track health behaviors with connected sensors via wearables and smartphones will increasingly feature as a strategy that therapists and clinicians use to treat mental health.
As we observed in What if the ‘Psilocybin vs. Escitalopram’ trial used Digital Biomarkers to measure results?:
“The ‘Godfather’ of digital phenotyping, JP Onnela, and colleagues note in the journal Translational Psychiatry:
“Combining the RDoC framework with digital phenotyping offered from smartphones and other connected devices presents a unique opportunity for psychiatric research. Through incorporating the potential of these new digital technologies into RDoC framed clinical questions, psychiatry can now explore new dimensions of pathology largely inaccessible only a few years before.”
So, the future looks like this: sleep, activity, situation avoidance, energy, mood, attention, focus, lethargy, emotional valence (positive affect, negative affect), and other data points will be passively collected and analyzed.
The result of this process is information that can then inform diagnosis, treatment and personal health practices.
The optimistic take is that in the future we will be evaluating the effect of psilocybin and escitalopram on discrete dimensions objectively captured in order to understand the organism-wide response, not rely on self report surveys.
In other words the term depresion and the current way it is defined and diagnosed is under intense evolutionary pressure.
Further Reading
Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences
“Here, we have explored word usage in 6850 free-form testimonials about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to three-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies…
Coanalyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.”
Related:: See our quick synopsis of Mindstate Design Labs from a few weeks ago.
Connecticut Lawmakers Discuss Bill to Fund Psilocybin and MDMA Therapy
“Psychedelic therapy would be specifically provided and funded for military veterans, retired first responders, health care workers and any person from a “historically underserved community, and who has a serious or life-threatening mental or behavioral health disorder and without access to effective mental or behavioral health medication…
The new legislation would require the state Department of Mental Health and Addiction Services to launch a “psychedelic-assisted therapy pilot program to provide qualified patients with the funding” to receive MDMA- or psilocybin-assisted therapy as part of FDA’s expanded access program, the text of the bill states.”
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Zach