After a lengthy period of stagnation, share prices across the space are rising once again. Our bet is that this is in anticipation of COMPASS Pathways’ Phase 2b data readout, expected in the coming weeks. We’re just polishing off a deep dive on that topic, replete with a Shakespeare-inspired pun (Hamlet, Act 3, Scene 1 – no prizes).

This week we spoke to Rick Doblin, Executive Director of MAPS, about a couple of recent drug development announcements in the psychedelics space.

But first, an exciting announcement…

Psilocybin Alpha is Going Beta

We’re excited to announce the next phase in Psilocybin Alpha’s growth, which we’ll be revealing in the coming months.

What started in a coffee shop—and persisted as a side gig between my ‘real job’ in research—has become something much larger; not least due to you: our diverse, accomplished, and loyal readers.

This next phase is an expansion in terms of team, ambition, focus and resources; all dedicated to properly informing and supporting the effort and capital pouring into this space.

We can’t wait to share this journey with you, and encourage each of you to share your thoughts along the way: you can always reach us via reply to this email, or by reaching out directly to me via email to arrange a call (josh@psychedelicalpha.com).

For those of you attending Microdose’s Wonderland conference in Miami, we look forward to seeing you in person. This includes myself, as well as members of the leadership team working on this next phase of growth: look out for David J. Fishman, Ryan Cummins and Alyssa Segula.

–  Josh Hardman

Psychedelic Sector News

We’re bringing you a slightly different format this week. As opposed to our usual laundry-list of company announcements (which you can find below this section), we’re highlighting one development from the past week, and asking a psychedelic pioneer for their thoughts.

In this case, we asked Rick Doblin for his comments on COMPASS Pathways’ Phase II trial of its psilocybin-assisted therapy for PTSD, which it announced earlier this week. As a ‘bonus’, we also asked Doblin for his thoughts on MindMed’s R-MDMA program, which the company announced last week.

COMPASS Pathways Targets PTSD in Phase II Trial

Earlier this week, COMPASS Pathways announced that it will launch a Phase II clinical trial of its COMP360 psilocybin therapy for PTSD.

The Phase II open label “COMP201” study will enrol 20 participants, and will initially take place at King’s College London. The study will follow the COMP360 protocol, including a fixed dose (25mg) administered in conjunction with psychological support.

This news comes ahead of a data readout of the company’s highly-anticipated Phase IIb trial assessing COMP360 for treatment-resistant depression. Data is expected in the coming weeks.

***

Psychedelic-assisted therapies for PTSD have largely, at least in the clinical realm, been firmly in MAPS’ remit. The nonprofit is conducting its second Phase III trial of MDMA-assisted therapy for PTSD, and has already published promising results from its first Phase III.

As such, we spoke to MAPS Executive Director Rick Doblin about this latest development.

Doblin began by explaining that MAPS (and its wholly-owned Public Benefit Corporation) is “committed to maximizing patient outcomes,” and as such, “welcome COMPASS’ research into psilocybin-assisted therapy for PTSD as well as research into ketamine, ibogaine and other treatments for PTSD.”

This commitment to a variety of drug-based approaches to treating PTSD is seen in MAPS’ own work. For example, the nonprofit is researching marijuana for PTSD via a study involving over 300 veterans backed by a $12.9m grant from the State of Michigan. If the Phase 2 trial is a success, MAPS hopes to carry the inhaled cannabis medication through to approval and insurance coverage for PTSD.

Doblin also expresses a genuine interest in obtaining “a better sense of the differences between the therapeutic use of MDMA and psilocybin to treat PTSD,” noting that he had encouraged other researchers in the field to carry out this work with the backing of organisations like COMPASS.

On the topic of such comparative work he reminded us that the Texas Legislature has allocated around $1.5m for a study of psilocybin-assisted therapy for PTSD. Doblin hopes that Texas will now allocate funds for an MDMA arm of the study, comparing it to both the psilocybin arm and treatment as usual.

If the funds don’t come from the Legislature, Doblin said, “we are going to try raise the funds from philanthropists.” It would be the first study directly comparing psilocybin-assisted therapy to MDMA-assisted therapy, “which is why we think it’s critical that an MDMA arm be added to this study at the Houston VA,” he commented.

Commenting on the differences he expects to be observed between MDMA- and psilocybin-assisted therapies for PTSD, he explained:

“It’s our view that MDMA-assisted therapy is likely to be psychologically safer  and more effective than psilocybin or LSD-assisted therapy for PTSD due to MDMA’s fear-reduction properties. However, this is an empirical question that needs to be resolved through research which is why we welcome  Compass’ study.”

Doblin went on to tell Psilocybin Alpha that he believes there is no correlation between the depth of the mystical experience and therapeutic outcomes in the case of MDMA, a correlation which has been observed in studies involving psilocybin (see Yaden and Griffiths, 2021, for more on this).

“Furthermore, based on our Phase 2 data, we’ve found that there is no correlation between the depth of the mystical experience from MDMA and therapeutic outcomes. While MDMA subjects don’t score as high on the mystical experience questionnaire as subjects who receive psilocybin, the average mystical experience scores in the MDMA group are larger than initially anticipated. We therefore don’t consider the increased ability of psilocybin over MDMA to produce mystical experiences to be a significant therapeutic advantage in treating PTSD.”

In the type of big-picture thinking that Doblin is renowned for, he went on to explain how both modalities, and others such as LSD-assisted therapy, might be used as part of a treatment arc; or even simultaneously (candy-hippy flipping?):

“It’s also possible that for some PTSD patients, a course of treatment that starts with MDMA and then at a later time involves a psilocybin or LSD session could be ideal, or even  the simultaneous administration of MDMA and psilocybin or LSD.”

Doblin also told us that MAPS is “in discussions with a for-profit psychedelic company,” the name of which we won’t divulge, to possibly conduct “a PTSD study that would initially administer a session of MDMA-assisted therapy and then a month or so later a psilocybin-assisted therapy session.”

Rick Doblin’s perspective is perhaps best captured in this simple conviction:

No one treatment works best for everybody so the more therapies that become available for PTSD, the better.

***

While we had Rick Doblin’s ear, we asked him for his thoughts on MindMed’s recently-announced R-MDMA for social anxiety program…

Among his comments, Doblin responded to MindMed’s announcement of the program by picking up on their framing of R-MDMA as potentially safer than racemic MDMA.

“The MindMed press release makes some claims about the enhanced safety of R-MDMA over racemic MDMA in terms of neurotoxicity, hyperthermia, abuse liability and stimulant properties,” Doblin notes.

“There is no significant risk from racemic MDMA of neurotoxicity or hyperthermia and its stimulant properties are also not problematic,” he argued. “We also see no evidence of abuse liability in terms of subjects seeking out illicit Ecstasy after treatment.” He did concede that “R-MDMA is significantly less desirable of a drug than racemic MDMA.”

Perhaps the most interesting comment that Rick Doblin told Psilocybin Alpha is around the more naturalistic use of the individual isomers of MDMA in the mid-80s:

“around 1985, a bunch of MDMA therapists and activists, including me, experimented personally with each isomer of MDMA. We found them to be subjectively inferior to racemic MDMA and likely to be less therapeutic.”

Further details of MindMed’s latest program can be found in last week’s bulletin.

Other Announcements & News

🍄 Filament Health Shares Clinical Trial Update  |  Vancouver-based Filament Health announced FDA authorization of a Phase 1 clinical trial taking place at UCSF. The “exclusively all-natural psychedelic drug discovery company” claims to be launching the first clinical trial using naturally-sourced psychedelic substances, as well as the first trial of the direct administration of psilocin as opposed to its prodrug, psilocybin. Three of the company’s botanical drug candidates will be examined.

🏦 Bright Minds Biosciences to Become Latest Nasdaq-listed Psychedelics Company  |  Next Monday (8^th November), Vancouver-based Bright Minds Biosciences will become the latest psychedelics company to trade on the Nasdaq, under ticker symbol DRUG.

🥼 Cybin Secures Schedule I Manufacturing License from DEA  |  Cybin has been granted a Schedule I manufacturing license from the U.S. Drug Enforcement Agency, allowing the company to work with such controlled substances. The license pertains to the company’s research lab in the Boston area, through which it hopes to in-house much of its formerly-outsourced drug discovery and delivery work.

🧾 COMPASS’ 5^th U.S. Patent   |  Our editor-at-large Graham Pechenik broke the news that COMPASS Pathways has received notice that its fifth U.S. patent now has a patent number and issuance date, November 23. Certain claims cover administering psilocybin that “compromises a crystalline Polymorph A,” but the crucial question now will be: “how much?” Might trace amounts of crystalline Polymorph A constitute an infringement, Pechenik asks?

And the rest…

• Algernon Pharmaceuticals established 6 hours as optimum treatment period for DMT in neuron study;
• atai Life Sciences announces supportive interim data from first cohort of Phase 2a trial for novel treatment of cognitive impairment associated with schizophrenia;
• Cybin hosting R&D briefing on November 8 at Wonderland Miami;
• Field Trip Q2 2022 results call scheduled for November 16;
• Mydecine files patent application covering new formulations that bring nanoemulsion technology to traditional medicine ingredients;
• Mindcure provides update on studies and clinical trials;
• MindMed appoints Dr. Maria Oquendo to Scientific Advisory Board;
• Nova Mentis secures orphan drug status from FDA;
• PharmaDrug expands product offering to prepare for potential adult use market in Germany;
• Red Light Holland appoints new CFO;
• Revive Therapeutics enters into research collaboration agreement with PharmaTher for development of psilocybin microneedle patch.

Read more on our News page.

Weekend Reading

Detroit becomes second largest city in the U.S. to decriminalize psychedelics

In Tuesday’s elections, Detroit joined a growing number of U.S. cities and states passing initiatives effectively decriminalizing psychedelics.

Here’s the update, pulled from our Psychedelic Legalization & Decriminalization Tracker that’s maintained by Calyx Law and Emerge Law Group:

On November 2, 2021 the voters of the City of Detroit accepted Proposal E to enact a city ordinance decriminalizing “the personal possession and therapeutic use of Entheogenic Plants by adults and make the personal possession and therapeutic use of Entheogenic Plants by adults the city’s lowest law-enforcement priority.”  Entheogenic plants include “the full spectrum of plants, fungi, and natural materials and/or their extracted compounds, limited to those containing the following types of compounds: indole amines, tryptamines, and phenethylamines.”

Prop E does not decriminalize sales or distribution but requires the Detroit Police Department to cease directing resources to investigating and prosecuting Detroit residents for personal possession and therapeutic use of those substances.

Odds and Ends

🎙️ Hamilton Morris appeared on Psychedelics Today’s podcast to discuss PCP, 5-MeO-DMT, and the synthesis of new psychedelics. We particularly enjoyed what we understand to be the first public discussion of Hamilton’s work with COMPASS Pathways, toward the end of the episode.

📰 Shayla Love’s latest piece in VICE is an important read for those of us prone to getting caught-up in the exuberance of this exciting space.

💊 Writing in the New York Times, David Dodge takes a look at the ketamine ‘industry’ which may be getting ahead of itself. For those with a shorter attention span, take a look at his short Twitter thread for the key takeaways.

👐 Consider supporting a new initiative, Psychedelic Survivors, which is dedicated to supporting survivors of sexual abuse, assault and other harms within the context of psychedelic therapy (donate here).

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