Plus Homecoming's $4M Seed; Policy updates from Canada, Oregon, and Michigan; and other industry news
Today we’re looking at the following developments:
A new paper highlights the challenges to psychedelic research. These challenges are an important consideration even for non-scientists, especially those building the “infrastructure and operational layer,” which includes clinics, retreats, guides, therapists, and technology providers.
Homecoming, the Psychedelic Therapy companion platform, announced a $4M seed round
Oregon Health Association (OHA) has opened a public comment period on the proposed rules for manufacturing, product testing, and facilitator training programs.
Health Canada approved the first patient requests for access to psilocybin through the Special Access Program (SAP)
Michigan organizers are canvassing for 340,000 signatures to get a psychedelic ballot initiative on the November ballot
Onto this week’s dispatch.
In a recent paper titled Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials, UCSF’s Jacob Aday and colleagues highlight the unique challenges the psychedelic experience poses to rigorous scientific research:
“psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants’ expectations for treatment benefit…”
This is an important concept for the broader stakeholder community (not just researchers) to understand because:
“participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects.”
‘Great Expectations’ is the second recent “Premortem” style paper that addresses the unique challenges to the rigorous study of psychedelics and offers potential solutions.
The other is from Suresh Muthukumaraswamy of the University of Auckland and colleagues who published The challenges ahead for psychedelic ‘medicine’ which highlighted similar hurtles.
Both papers wrestle with the main problem that the gold standard of clinical research is the Double-Blinded Randomized Placebo-Controlled Trial. Participants either receive the study drug or a placebo, and neither they nor researchers know which one. This works for medicines that don’t have intense psychoactive effects, but studying psychedelics under these constraints seems impossible since it is pretty apparent for both participants and study administrators to know who got the active drug and who got the placebo.
This ‘unmasking’ affects study results. As Muthukumaraswamy and colleagues describe:
“When a participant correctly believes they have received the treatment, they may show greater treatment response due to expectancy effects and, conversely, the disappointment of those who know they have received a placebo may decrease the placebo response.”
In other words, the placebo response is increased in the active arm and decreased in the placebo arm. The placebo response is supposed to be constant across both groups, thus making the effects of the active drug discernable.
Therefore, the large effect sizes reported in many psychedelic trials may be overstated.
With this in mind, ‘Great Expectations’ offers an excellent summary image with some ideas to address this and other issues.
The authors make two suggestions worth highlighting for operators of clinics, retreats, technology companies, therapists, guides, and other facilitators.
“Consider pragmatic clinical trials and natural experiments as alternatives to RCTs.”
Focus on treatment optimization research
Pragmatic Clinical Trials & Real-World Research
In ‘Challenges’ Muthukumaraswamy and colleagues offer a similar idea:
“If psychedelic RCTs cannot be conducted satisfactorily given the limitations described above, then additional real-world evidence might be needed. This might include epidemiological evidence, use of surrogate and digital biomarkers, case and n=1 studies (Carhart-Harris et al., 2022).
Regular Trip Report readers may be rolling their eyes at yet another invocation of real-world research and the role of technology in psychedelic science and clinical practice, but here we are. It’s in my nature.
The proliferation of psychedelic use, the advent of Regulated Use frameworks (i.e., Oregon), the rise of retreats and clinics, and the adoption of digital health technology are aligning to make naturalistic/real-world research an increasingly compelling research format. Therefore, our understanding can come from real-world clinics, retreats, and even personal use scenarios, not just laboratories.
Head-to-Head Comparison: Treatment Optimization Research
The other idea worth highlighting is that of head-to-head trials seeking to identify practices that lead to minimal risk and maximum benefit compared to other treatments—effectiveness, not efficacy.
In “Great Expectations” Aday and colleagues note (emphasis added):
“One notion to consider is embracing expectancy and placebo effects. The important role of expectancies in psychedelic therapy blurs the line between treatment-specific and treatment-nonspecific effects and raises the broader question: rather than eliminating treatment-nonspecific effects, should trialists be looking for ways to optimize and synergize them with treatment interventions to enhance clinical outcomes?
Instead of trying to reduce placebo and expectancy—which all good clinicians want to leverage in clinical practice anyway—why not compare different modes of set and setting or therapeutic modalities (Transpersonal vs. Non-Directive vs. IFS, etc.), shamanic vs. clinical, group vs. solo, etc.—to find optimal strategies for the different contexts, intentions, and settings?
As the authors note:
“…it may be the case that the “therapeutic window” opened by psychedelics is an emergent property of a complex system comprising expectations, drug effects,
setting, and therapeutic alliance. It may be impossible to isolate an individual component of this complex package in an RCT.”
In closing, both papers acknowledge that the gold standard is still the gold standard but that it will only get us so far.
To maximize benefit, reduce harm, and understand how to use psychedelics most effectively, the evidence base will be established in novel ways in coordination with the emerging infrastructure and operational layer.
Homecoming Closes $4M Seed Round
My sense of the current mental health technology landscape is that many venture-backed companies sought to create the “Uber for therapy.”
The touted benefits are reduced cost and near 24/7 support through text or smartphone apps.
However, this two-sided marketplace approach to providing a highly skilled service like psychotherapy extracts value from both therapists and patients. As a result, therapists are underpaid and overworked while patients do not get consistent, quality care as they are assigned a revolving cast of providers.
This is where Homecoming seeks to offer therapists and patients a technology solution that fosters the therapeutic alliance rather than disintermediate it.
From the press release:
“Homecoming has closed an over-subscribed $4 million seed funding round led by Evolve Ventures and Integrated, with participation of SV Angel, Bridge Builders Collaborative, Amanda Feilding, Lionheart Ventures, Ocama LP, JLS Fund, Michael Cotton, Seth Feuerstein, Talia Eisenberg, Jesse Hudson, and David Fraga.
Founded by Yuriy Blokhin, Toronto and Los Angeles, California based Homecoming is a patient care platform for psychedelic therapy that partners with psychedelic clinics, therapists, and retreats to support clients before, between, and after sessions. Homecoming helps clinics reach more patients and fulfill operational goals using modern therapy tools, precision data, and enhanced management of the entire patient experience.”
Given the consensus that psychedelics as healing tools are only as good as the set, setting, and support accompanying the experience, educational and therapeutic support through human-centered technology will play a significant role in the education, preparation, and integration of these journeys.
Rather than a marketplace, Homecoming works with clinics, therapists, and retreat centers to develop therapeutic and educational content that supports the therapeutic alliance, not replace it.
Over the next few years, we will see a Cambrian explosion of modalities, frameworks, and methodologies for Psychedelic Assisted Therapy. Each with its own educational content supporting the therapeutic alliance and patient journey. Delivering this supportive content according to the phase of treatment—preparation, between sessions, and integration—will require a human-centered technology platform—Homecoming hopes to build it.
Psychedelic Policy Updates
Oregon Enters Public Comment Period
From KDRV News 12 Oregon:
“The Oregon Psilocybin Services (OPS) Section at Oregon Health Authority (OHA) released a new set of proposed rules April 1 related to psilocybin products, testing and training programs.
It is inviting public comment about the proposed rules during a public comment period from April 1 to April 22, 2022, when the comment period closes at 5pm.”
From the Notice of Proposed Rulemaking:
“The Oregon Health Authority, Oregon Psilocybin Services (OPS) section is proposing to adopt administrative rules in chapter 333, division 333. The rules are needed to implement ORS chapter 475A, the Oregon Psilocybin Services Act. The products rules set forth standards for the types of psilocybin products that may be sold and how psilocybin products must be produced. The products rules protect the health and safety of workers who manufacture psilocybin products and clients who consume these products. The act requires Oregon Health Authority to approve training program curriculum for psilocybin facilitators. The training curriculum rules set forth requirements for approval. The act requires Oregon Health Authority to adopt rules establishing standards for testing psilocybin products. The testing rules specify requirements for testing psilocybin products. The rules protect consumer health and safety by ensuring that psilocybin products are properly tested for psilocybin content and do not contain contaminants.”
Cost of Regulated Access
“The statute creates the first regulatory framework for licensed manufacture of psilocybin products. Less restrictive rules could carry a lower cost of compliance for manufacturers. However, this lower cost would be coupled with higher risks of negative outcomes for clients, including health and safety concerns, leading to fiscal and economic impact to individuals.”
This is interesting, but the real show will be in the Fall when the second rulemaking process will consider the remainder of the rules, which I presume will deal more specifically with the set-and-setting, consumer education, the role of facilitators,, and monitoring of the experiences.
Michigan Initiative for Community Healing
From Alexander Lekhtman at Filter Magazine:
“Michigan state officials certified the “Michigan Initiative for Community Healing” on March 28. Activists must now gather 340,000 valid signatures by June 1. If they succeed, the initiative will be put on the ballot for voters to decide on election day, November 8.
The initiative would amend Michigan’s health code to decriminalize use, possession, cultivation, production, and sharing of naturally-occurring psychedelics—including psilocybin, ibogaine, mescaline, and dimethyltryptamine (DMT). It would also allow doctors to recommend psychedelics to their patients, and medical and religious entities could produce, sell or administer the substances for therapeutic or spiritual use. Those who provide support for psychedelic users—including “trip sitters” and guides—could charge for their services.”
Health Canada Authorizes Special Access Program
From Therapsil’s Press Release:
“On March 21st, 2022, Dr. Valorie Masuda MD received authorization under the Special Access Program (SAP) to treat six patients experiencing end-of-life distress with psilocybin and psychotherapy. GMP synthetic psilocybin was donated by Psygen Labs Inc., and Apex Labs Ltd. provided access to its psilocybin investigators’ brochure, in support of the SAP application. This is the first known case of psilocybin being accessed through Canada’s SAP since the Food and Drug Regulations were amended on January 5th, 2022 to allow access to psilocybin and other restricted drugs through the SAP. The six patients were treated in early April of 2022 by Roots to Thrive, co-led by Dr. Masuda.”
MAPS Places cGMP MDMA Synthesis Method in the Public Domain
“The manufacture methods of MDMA at a laboratory scale were originally placed in the public domain by Alexander Theodore Shulgin, Ph.D., Ann Shulgin, and David E. Nichols, Ph.D., in 1991 with the publication of PiHKAL: A Chemical Love Story (1st Edition). With this peer-reviewed scientific publication, the manufacture methods for MDMA at industrial scale are also placed in the public domain. The chemical purity of the final product exceeded 99.9% in each of the four validation trials with an acceptable yield, which is a noteworthy accomplishment.”
Beckley Psytech Starts Phase I Intranasal 5-MeO-DMT
From the Press Release:
“the first healthy volunteers have been dosed in a Phase 1 clinical trial exploring the safety and pharmacokinetics of BPL-003, Beckley Psytech's second innovative formulation of 5-Methoxy-N, N-Dimethyltryptamine (5-MeO-DMT)…
The trial will also look to characterise the psychedelic experience of the subjects, with several scales and micro-phenomenology interviews carried out by a specialist to fully understand the experience of each individual.
The data from both Phase 1 studies will then be analysed to determine which formulation will be used in the upcoming Phase 2 studies, aimed at evaluating the use of 5-MeO-DMT in combination with assisted psychotherapy in the treatment of treatment resistant depression (TRD) and other indications.”
Field Trip Health Granted Patent
From the Press Release:
“Claims in the patent application titled, “Tryptamine Prodrugs,” grant exclusive rights to Field Trip for the composition of matter, use and manufacturing of a family of hemi-ester compounds of hydroxytryptamines, including FT-104. The patent will provide protection until 2040.”
Plant Medicine Week from Malta
Our friends at Blossom are keeping us up to speed on conversations from the Mediterranean.
UC San Diego Begins Trial of Psilocybin for Phantom Limb Pain
Endpoints News: The New Psychedelic Age in Biotech
History of Psychedelic Research: Banned or ‘Dropped’?
Integration in Psychedelic-Assisted Treatments
“In the present project, semi-structured interviews with 30 integration therapists focused on definitions of integration as well as challenges and concerns that they associated with the practice…Interviewees viewed integration as a process that begins prior to the administration of substances, never ends, makes sense of the psychoactive experience, creates behavioral change, is personalized, and makes the individual whole.”
Government Policy Makes Psychedelics Research ‘Extremely Hard,’ Top Federal Drug Official Says
“The scheduling process makes it extremely hard to do research and it has slowed down the process enormously,” Volkow said at last week’s event. “We need to work together both with the FDA and the DEA to ensure ways that we can carry on research on Schedule I substances without having to go through the procedures that are entailed for someone that is actually using these drugs for other purposes.”
The official also talked about how changing federal rules can help scientists get access to a broader the pool of substances to research, from more sources.
“By being able to change the current laws for Schedule I substances for research, we can hopefully expand access to drugs that come from multiple sources, and not just as has been the case for marijuana, coming from NIDA,” she said. “It has taken a very long time to change these rules related to Schedule I, and we need to address it for accelerating research.”
Thanks for reading and have a great weekend!
Also, this week, a presentation by Johns Hopkins’ David Yaden at the University of Zurich titled “Psychedelic Hype Bubble” sought to inspire sobermindedness