Psychedelics Inc; Compass; Oregon; Gilgamesh; Connecticut; Cybin & Kernel;

It was a busy week, with quite a few developments worth mentioning, so today’s round-up consists mainly of links and highlights from these stories and less commentary and analysis.

Keep an eye out for a long-form piece I’ll publish early next week about the recent paper Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences.

Here’s a preview:

The study is captivating because the intended result—a “map” of the brain regions responsible for specific subjective experience—feels like it should require the most cutting-edge brain imaging technology or invasive Brain-Computer Interface (BCI) to monitor neural activity while subjects are actively under the influence of psychedelics in real-time.

But it doesn’t.

Instead, researchers used Natural Language Processing (NLP) techniques to process almost 7,000 written trip reports from Erowid Experience Vault of psychedelic experiences and cross-referenced this dataset with previously established receptor binding affinity data to generate a “Drug-Experience-Receptor Map”.

There are two limitations to this study,

1. The reliability of the trip reports

2. The suitability of the pharmacological dataset for the intended goal

My thesis is that the first limitation could be significantly improved as the clinical and technological infrastructure for psychedelic therapy is developed and real-world data is captured with greater fidelity.

More to come.

Onto the update.

---

Compass Pathways Developments

Compass Pathways had three notable developments this week.

First, the company had two patent applications announced. One points to MDMA-like molecules, while the second expands upon the use of psilocybin.

Patent attorney Graham Pechenik offers helpful explanations on Twitter (links to Graham’s commentary).

• “Novel Safrylamine Derivatives Having Prodrug Properties”

• “Method for Treating Anxiety Disorders, Headache Disorders, & Eating Disorders with Psilocybin”

Also, the company announced a collaboration with King’s College London and South London and Maudsley NHS Foundation Trust to launch The Centre for Mental Health Research.

From the King’s College London press release:

“The Centre will accelerate research of emerging psychedelic therapies, support therapist training and certification, evaluate real-world evidence, and prototype digital technologies to enable personalised, predictive and preventative care models…

Research will initially focus on COMPASS’s investigational COMP360 psilocybin therapy and supportive technologies, and will also cover other novel therapeutic approaches being researched and developed by COMPASS, in areas of significant unmet mental health need including treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD) and anorexia nervosa…

The Centre will accelerate the integration of innovative psychedelic therapies into the NHS following regulatory approval and reimbursement.

The Centre will initially be located at Maudsley Hospital, London, while state-of-the-art facilities are built within a 200 acre woodland at Bethlem Royal Hospital, London. This dedicated and purpose-built space for late-stage clinical trials will be managed by leading clinical investigators with extensive experience in conducting psychedelic clinical trials, and will provide access to COMP360 psilocybin therapy to an estimated 650-700 patients over a five-year term.”

We have seen the proliferation of psychedelic research centers at universities around the US and Europe. Still, as far as I am aware, this is the first academic-governmental-commercial hybrid center focused on psychedelics—with ambitious goals that touch on each sector, including insurance reimbursement, integration into the NHS, therapist training, and the development of technology-enabled applications.

Oregon Update

Depending on who you ask, the progress towards the rollout of Oregon’s Psilocybin Services Initiative is either right on track or faces some significant challenges.

Of course, these are not mutually exclusive since developing any novel framework via a democratic process would be challenging.

In an email from Sam Chapman of the Healing Advocacy Fund:

"the text of Measure 109 sets the goal for OHA is to begin to receive applications for licensing of service centers, manufacturing centers, and facilitators in January 2023. I expect this goal to be met based on the work from all partners committed to implementing a program that is safe, accessible and equitable.

An update on the licensing subcommittee from the law firm Harris Bricken (an excellent resource) highlights a few challenges.

• Integrating spiritual and religious use:

“Measure 109 has language that may infringe on spiritual and religious practices unrelated to psilocybin. Churches such as the Sacred Garden Community use other plants and fungi for ceremonies, not just psilocybin. Yet, 109 only allows for service centers to have psilocybin on the premises. Thus, if a church like the Sacred Garden Community wishes to operate as a service center under 109, it would have to abandon these other practices or risk penalization.”

• Affordable facilitator training programs:

“If OHA only approves comprehensive training programs, wealthy established training programs outside of Oregon would populate the market. Meanwhile, Oregonians who wish to start their own training programs would have the cards stacked against them.

Hence, the Subcommittee voted to recommend the OHA approve partial training programs, as well as comprehensive training programs.”

• Catering to persons with disabilities:

“First, some prospective clients may not be able to consume psilocybin as an edible. The Subcommittee will recommend there be several options for consuming psilocybin, such as sublingual strips or beverages. Access to psilocybin should not be limited by consumption abilities.”

This is complex stuff, with challenging tradeoffs no matter how you slice it.

In contrast, a legislative proposal in Connecticut appears to be a much simpler approach.

Connecticut’s Approach

Advocates in Connecticut have had a bill pass preliminary gatekeeping in the state legislative process last week.

Unlike Oregon, Connecticut’s HB 5396—AN ACT INCREASING ACCESS TO MENTAL HEALTH MEDICATION—would use state funds to roll out FDA-sanctioned Expanded Access Programs (EAP) rather than develop an entirely novel framework from scratch.

Each of the front runners of psychedelic drug development, MAPS, Compass Pathways, and Usona, have EAPs in which patients, under certain circumstances, can access study drugs before FDA approval.

This program is also called Compassionate Use.

HB 5396 aims to use state funds along with supporting grants to create Expanded Access Programs for MDMA and Psilocybin for a limited patient population—including veterans, first responders, front line healthcare workers, and members of underserved communities—thereby getting a head start on building the infrastructure for a rollout upon FDA approval.

I first saw this from Victor Cabral on Linkedin:

“on Friday (3/18), the Connecticut Public Health Committee unanimously voted to advance HB 5396, an Act Improving Access to Psychedelic Medicine. HB 5396 funds qualified patients (including Veterans, first responders, health care workers, and those from historically underserved communities) who were failed by traditional treatments to receive MDMA-assisted or psilocybin-assisted therapy at a site with an FDA approved expanded access protocol.”

I connected with Brett Waters from Reason for Hope, the policy and advocacy group behind HB 5396. In an email follow up, he sent me the bill’s main provisions:

1) providing $1.5 million for qualified patients (including Veterans, retired first responders, health care workers, and those from underserved communities) to receive MDMA-assisted or psilocybin-assisted therapy at an approved treatment site with an FDA approved expanded access protocol;

2) providing an additional $1.5 million for qualified patients upon proof of a matching grant from a private foundation to an approved treatment site;

3) adopting published federal guidelines from HHS regarding the practice of psychedelic-assisted therapy;

4) establishing an Advisory Board within the Department of Mental Health and Addiction Services to provide ongoing policy support; and

5) automatically rescheduling MDMA and psilocybin to be consistent with federal law.

I sense that in the future, state lawmakers will look at Oregon’s challenges and see something like HB 5396 as easier to understand and implement.

Psychedelics Inc. from The Nation

The Nation, the oldest progressive political and cultural publication in the US, dedicates the April issue to Psychedelics and drug policy issues.

The feature story by Zoe Cormier, titled The Brave New World of Legalized Psychedelics Is Already Here, is worth the read for the comprehensive overview of the field and some of the emerging challenges.

“…despite the fact that all of these “classic psychedelics” are still ranked as Schedule I drugs under the federal Controlled Substances Act. Manufacturing any of these drugs without a license can still land you a long prison sentence. But marketing one, even though they all remain illegal and none have passed all the clinical trials required for approval? That can make you a millionaire…

“Thankfully, some of the eccentric characters from the last psychedelic wave are still around. One of the most noteworthy is Amanda Feilding, Countess of Wemyss and March. Nearly 80 years old, Feilding lives in a Tudor manor in Oxfordshire featuring three moats. Years before most VCs, tech bros, and financiers expressed any interest in psychedelics, Feilding supported research into the compounds with her charity the Beckley Foundation.

Effusive young millionaires hoping to cash in on the psychedelic boom might get more airtime with noisy press conferences about patent portfolios or stock market valuations, but none of those joiners can come close to matching Feilding’s contributions. She may have a hole in her head, but she deserves enormous credit for pouring large volumes of energy, blind faith, and—above all—raw cash into psychedelic research in an age when few others would fund or pursue it.

Feilding’s not the only one to see their contributions overshadowed now.”

While the recent entrants may be getting the lion’s share of the press, I wouldn’t count Feilding out just yet…

The promises and perils of psychedelic pharmacology for psychiatry

A perspective article in Nature Reviews Drug Discovery by UNC professor Bryan Roth and DARPA’s Tristan McClure-Begley seems to be the first publication from Roth’s $27 DARPA grant to develop novel psychedelic inspired drugs, but more importantly

“Here, we discuss this emerging area of therapeutics, covering both controversies and areas of consensus related to the opportunities and perils of psychedelic and psychedelic-inspired therapeutics. We highlight how basic science breakthroughs can guide the discovery and development of psychedelic-inspired medications with the potential for improved efficacy without hallucinogenic or rewarding actions.”

Despite the fanfare around psychedelics-as-medicines, the scientific literature is still sparse compared to other areas. Roth’s project aims to fill in many of the unanswered molecular questions.

In a conversation on the Mind and Matter Podcast, Roth laid out what this grant aims to deliver:

“Roth: And so, in terms of the basic biology of psychedelics, we're actually looking at hundreds of known psychedelic drugs. And we're in the process of putting together basically paper that will serve as, as the database for our understanding of psychedelics. So every psychedelic drug that is known to be psychedelic, we're looking at right now. And at many different levels, so the receptor pharmacology, signaling, transcriptomics, proteomics.”

Gilgamesh Announces Two Development Candidates

From the company press release (emphasis added):

“The first clinical candidate, GM1020, is an orally bioavailable non-competitive N-Methyl-D-aspartate receptor antagonist with the potential for rapid and sustained antidepressant activity.  GM1020 is expected to have a favorable side effect profile allowing for potential at-home use.

The second clinical candidate, GM2505, is a novel rapid short-acting 5HT2A agonist and 5HT releaser that is expected to have a rapid therapeutic effect in a wide spectrum of psychiatric disorders that includes properties of both the classic psychedelic DMT and the empathogen MDMA. GM2505's optimized pharmacokinetic profile allows for convenient and cost-effective treatment. GM1020 and GM2505 will soon complete IND enabling toxicology studies with Phase 1 trials expected to begin in the second half of 2022.”

Cybin x Kernel

I am interested in this trial because Kernel is developing a noninvasive wearable brain imaging ‘helmet’ that may offer a more flexible method than fMRI. I think the jury is still out on how useful the current model is but such a product, you would think, is inevitable given technological trends like Moore’s law.

From the press release:

“Participants will receive either a low dose of ketamine or placebo while wearing the Kernel Flow headset, which is equipped with hi-tech sensors to record brain activity and will report their experience using structured questionnaires and validated assessments during study visits and a follow-up. The study will also evaluate brain activity before and after the administration of the study agents – low-dosed ketamine or placebo.

“The feasibility study using Kernel Flow offers an opportunity for researchers and our study participants to quantifiably gather information on a psychedelic experience,” said Doug Drysdale, Cybin’s Chief Executive Officer. “Until now, our understanding of the psychedelic experience has been fairly subjective. This study may lead to larger studies that have the potential to bridge the gap between bringing psychedelics to therapeutics as we learn more about the advantages of these important molecules on brain activity and overall mental wellbeing.””

---

That’s it for this week! Thanks for reading, and look out for a forthcoming article next week!

Zach