Trial Design; Policy Design; Healthcare Groups Pressure DEA for Online Prescribing
If the emphasis of last week’s dispatch was the current state of the psychedelic space, today we are considering its future by looking at:
The status of the Public Health Emergency waiver that enables Direct-to-Consumer Ketamine
A novel Phase I clinical trial design meant to scale future treatments
A two-pronged state policy design in Colorado: Decrim + Regulated Access
I hope you enjoy this week’s analysis; please reach out with suggestions, feedback, comments, and ideas.
Let’s get to it.
📲💊 Stop the Haight Act
Several Direct-to-Patient Ketamine startups are possible because of covid-era changes to legislation that previously prevented online prescribing of controlled substances.
Until the Covid pandemic, doctors had to conduct in-person evaluations to prescribe scheduled substances like Buprenorphine for opioid use disorder and ketamine for depression.
In March 2020, this restriction was temporarily lifted under an emergency authorization—now, stakeholders are trying to make these changes permanent.
The in-person requirement was part of The Ryan Haight Online Pharmacy Consumer Protection Act of 2008. It was meant to regulate the then-nascent practice of prescribing controlled substances through telemedicine, specifically to prevent the diversion to illegal markets.
However, lockdowns in the early days of the pandemic prompted the DEA to waive the requirement for an initial in-person visit, thereby allowing patients to receive controlled substances through telemedicine (emphasis added):
"for the duration of the public health emergency, a practitioner may prescribe a controlled substance to a new patient via telemedicine—using a real-time, two-way, interactive audio-visual communication—without first conducting an in-person examination."
As the National Law Review noted at the time, the Public Health Emergency “not only necessitated the shift from in-person to virtual care, but also continued to drive interest, adoption, investment and transactions in digital health in 20211.”
As a result, several companies, including Mindbloom, Journey Clinical, and Nue Life, began virtual evaluation, prescription, and delivery of ketamine which enables patients to self administer in their homes or with their therapists.
Lasting Change?
Despite the intention to waive the in-person requirement for “the duration of the public health emergency,” several groups are calling on the DEA and HHS to make the change permanent, citing that the loosened regulations actually improve public health:
In a letter to the DEA and HHS, the stakeholder group, including The American Psychiatric Association, American Telemedicine Association, American Medical Association, wrote:
Specifically, we believe that the in-person evaluation prior to prescribing controlled substances via telemedicine only results in reduced access to care and does not enhance the DEA’s ability to do its job of limiting drug diversion or pursuing illegal actors.
…the experience during the pandemic which has shown increased access to necessary care when the patient is able to use telemedicine in their home or other location. While the Ryan Haight Act was intended to enhance DEA’s ability to pursue illegal online drug sellers, this limitation only results in less access to legitimate health care providers and does not give DEA additional tools to go after bad actors.
Furthermore, as far back as 2018, telemedicine advocates had made progress in wiping out the in-person visit requirement as evidenced by draft discussion bills to amend the federal Ryan Haight Act (emphasis added):
“Congress simultaneously released a companion discussion bill titled the “Special Registration for Telemedicine Clarification Act”… This special registration would allow practitioners to use telemedicine to prescribe controlled substances without the per se in-person exam.”
With this organized opposition of the in-person requirement by large healthcare incumbents, signs that congress is open to such a change, and a history of emergency measures outlasting the emergencies that prompted them, my hunch is virtual prescribing of scheduled substances is here to stay.
⚕️🧠 Unbundling PAT: Eleusis' Phase I of LSD
Researchers from Eleusis and the University of Alabama at Birmingham published two papers (here and here) this week describing the results of LSD in healthy volunteers.
Most notable about this trial design is that it is “conceptualized as more scalable than traditional approaches to administering classic psychedelics.”
Using abbreviated preparation and integration protocols, “the current study was conceptualized as a valuable first step in refining the novel intervention paradigm and generating hypotheses for future clinical trials.”
As I noted in Psychedelic ‘Procedures’ & Regulatory Leakage, we should expect to see an ‘unbundling’ of the psychedelic experience and the psychotherapeutic process. I hypothesized:
“the clinical workflow of psychedelic experiences within healthcare settings would increasingly look like surgical workflows (standardized, long duration, altered consciousness, recovery period, etc.)"
Preparation and integration will be to the psychedelic experience what physical therapy is to orthopedic surgery— a necessary but less glamorized component of the complete treatment.
So what makes this trial more scalable?
To date, clinical trials of psychedelic substances have used a framework that combines dosing sessions with psychotherapy sessions before and after, commonly referred to as preparation and integration, respectively. For example, the current MAPS Phase III trial includes three preparation sessions and nine integration sessions.
In this trial, rather than several individual psychotherapy sessions as preparation, the study participants arrived a day before the dosing session for a day of
communal meals (with other participants, study administrators, and attendants)
education and guidance about the potential for challenging experiences
breathing exercises
an individual session with their attendant
Keep in mind, this was a Phase I trial emphasizing participants’ perception of safety and feasibility. Nevertheless, the authors acknowledge the limitation by saying:
"Results of the current research should be interpreted in light of some important limitations. Most notably, participants were healthy and did not meet criteria for any mental health conditions…
It is possible, therefore, that individuals suffering from anxiety, mood, substance use, or other disorders might require more intensive pre-drug preparation, support during the acute period of drug action, and post-drug integration so as to mitigate these outcomes."
We should expect to see more experimentation in trial design like this as the field evolves.
Formats like group administration and alterations to the set and setting, specifically the use of technology to stimulate audio, visual, haptic, and olfactory effects that could influence the psychedelic experience, are examples of how these trials may evolve.
I imagine we’ll eventually see trials that exclude guided support or facilitation altogether, but perhaps not for some time.
🌄Colorado=Oregon 2.0
Two psychedelic policy reform strategies have gained traction in the US: Decriminalization and Regulated Access/Supported Adult Use.
Decriminalization prohibits local government funds from being used to arrest or prosecute the possession of naturally occurring psychedelics. They allow for the cultivation, possession, and gifting to others. These measures do not authorize commercial sales.
Regulated Access/Supported Adult Use Oregon voters approved a ballot measure in the 2020 election that would implement a legalization framework that would allow for the consumption of psychedelic mushroom products in licensed facilities with “support” from trained and specially certified facilitators. The aim is to enable safe and facilitated psychedelic-assisted healing outside of the medical setting but avoid a cannabis-style retail market.
If approved a ballot initiative in Colorado, the Natural Medicine Health Act (NMHA) would see both models rolled out simultaneously.
In an explanatory post from David Bronner, a prominent proponent (emphasis added):
“I see what the NMHA does as one seamless policy: making natural medicines—psychedelic plant and fungal medicines containing psilocybin, DMT, ibogaine or mescaline (excepting peyote)—available to all adult Coloradans in two powerful healing modalities: via a regulated access model in a therapeutic context; and the self-regulating community healing model in a decriminalized context.”
Further Reading
Former Moderna Executive Joins MAPS
“Mullette most recently served as the Vice President and Managing Director of North America for Moderna, where he oversaw commercialization of the company’s COVID-19 vaccine during the height of the pandemic.”
The challenges ahead for psychedelic ‘medicine’
“While there are numerous works on the potential benefits and applications of psychedelics as medicines, relatively little has been written about the challenges this field will face when incorporated into modern medical practice. Indeed, as a new or at least revived area of investigation, psychedelic medicine has a particular set of challenges which need to be addressed. In this viewpoint, we identify a number of these challenges.”
Stat News: ‘It’s not medical’: Oregon wrestles with how to offer psychedelics outside the health care system
“Everything around the bill, though, is unavoidably focused on mental health. It was widely promoted as a way to treat depression and trauma and, even among those figuring out regulations, there is confusion and debate around how medical Oregon’s psychedelics will be.”
Frontiers in Psychology: Virtual Reality as a Moderator of Psychedelic-Assisted Psychotherapy
“We suggest virtual reality (VR) as a full-spectrum tool able to capitalize on and catalyze the innately therapeutic aspects of the psychedelic experience, such as detachment from familiar reality, alteration of self-experience, augmentation of sensory perception and induction of mystical-type experiences.”
Thanks for reading, and have a great weekend.
Zach
According to Rock Health, digital health funding doubled from 2020 to 2021.
