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Otsuka Eyes Psychedelic Future in Japan with New Infrastructure Drive
Yesterday, Japanese pharmaceutical giant Otsuka announced a joint research agreement with Keio University aimed at building infrastructure for “the social implementation of psychedelics in Japan.”
The non-clinical research agreement will see the pair focus on four key areas:
- “Optimal clinical trials designed to maximize the therapeutic potential of psychedelics
- Establishment of a system for the professional development of psychiatrists and psychologists and the development of a system for implementing medical institutions
- Addressing legal and ethical issues and regulatory compliance related to the use of psychedelics
- Public awareness campaigns to correct social prejudices and misconceptions about psychedelics”
Otsuka emphasised Japan’s unmet mental health needs and highlighted international momentum, noting U.S. breakthrough therapy designations and ongoing Phase 2 and 3 trials in the U.S. and Europe. In contrast, Japan has seen only limited, small-scale psychedelic research, mainly through Professor Hiroyuki Uchida’s government-funded work at Keio.
It appears, then, that Otsuka is aiming to shape the environment for the potential launch of psychedelics-based treatments in its HQ country, from clinical trial designs through to addressing the stigma attached to the class of drugs.
That stigma could be a substantial barrier. Japan is known for its strict drug laws rooted in a fraught history with substances like methamphetamine, with stimulants banned in the island nation.
Cannabis enforcement has intensified as of late, too: over 6,000 cannabis-related criminal investigations took place in 2023, surpassing meth-related cases for the first time. What’s more, a recent amendment to the country’s drug laws criminalised THC consumption (previously, only possession was criminalised), with prison sentences of up to seven years for those who run afoul. But that same Act, which came into force this March, legalised medical cannabis, suggesting at least some openness to medical forms of banned drugs.
On the psychedelics front, there’s little of note, though authorities have grappled with LSD prodrugs and new psychoactive substances that attempt to get around the hawkish laws.
All this to say: while some in Japan—particularly young people—are skirting laws to consume LSD-like drugs, cannabis, and other psychoactives, the country is very strict, with plenty of deep-seated stigma.
So, Otsuka and Keio’s “public relations and public awareness campaigns”, as well as “professional development of psychiatrists and psychologists”, will be important work to set the stage for any launch.
Even outside of stigma, however, it’s not exactly an easy country to launch in. J&J’s esketamine nasal spray (Spravato) has experienced back-to-back trial failures in Japan and China, ‘raising questions’ about its utility in non-Western patient populations, according to Korea Biomedical Review.
Historically, the country has largely expected drug developers to conduct studies in-country, or at least include Japanese sites in multi-site studies. It is unclear whether that would be an expectation for psychedelics studies, and that might be a topic for exploration under the research agreement.
While Otsuka has an in-house psychedelics program, including candidates it acquired through its purchase of Mindset Pharma in 2023, one might wonder whether it is also positioning itself to be a launch partner for other psychedelic drug developers, like Compass Pathways.
Yesterday’s press release specifically highlights studies of psilocybin, citing Compass’ Phase 2b study in treatment-resistant depression, for example. What’s more, there are strong linkages between the company—Otsuka’s McQuade Center for Strategic Research and Development participated in Compass’ $80M Series B financing back in 2020, and since then a number of Otsuka execs have joined the team (most notably Kabir Nath, CEO, but as recently as two months ago another long-time Otsuka exec, Dana Sultan-Rothman, joined the psilocybin drug developer as VP Comms).
Whether it’s getting a head-start on shaping the landscape for its own pipeline or preparing to support others’ launches in the region, Otsuka’s Thursday announcement is an interesting development.
ASCP 2025 Preview: Psychedelic Therapies Dominate Clinical Psychopharmacology Agenda
Later this month, the American Society of Clinical Psychopharmacology (ASCP) hosts its annual meeting in Scottsdale, Arizona. Psychedelics (and neuro/psychoplastogens) feature heavily on the agenda, so we are providing a round-up of some of the abstracts. (All links from here on out lead to PDFs.)
Poster sessions on Wednesday and Thursday feature a range of psychedelics-related projects, including (but not limited to, if you can believe it!):
- Compass Pathways’ Matt Young will share a post-hoc analysis of the company’s Phase 2b study of psilocybin in TRD focusing on anhedonia-related items of the MADRS and PANAS scales; while Chief Medical Officer Guy Goodwin has a poster on the candidate in PTSD, summarising the company’s Phase 2 open-label results; and, Senior MSL Caroline Hostetler will present a poster on some of the clinical trial design considerations for psilocybin studies with reference to the company’s Phase 3 program;
- Reunion Neuroscience Chief Medical Officer Mark Pollack will report on a Phase 1 study of the company’s 4-OH-DiPT prodrug, and provide an update on the ongoing Phase 2 study in women with moderate to severe postpartum depression;
- The surreptitiously-named Julie Tripp of MindMed presents on the TrkB receptor as a target for neuroplasticity, sharing data suggesting that LSD, 25B-NBOMe and fluoxetine—but not psilocin, DMT, mescaline, DOI, MDA, or 2C-B—activate TrkB as partial agonists; the company’s Director of Clinical Development, Todd Solomon, meanwhile, will present a poster on the correlation between the efficacy of the company’s LSD candidate in generalised anxiety disorder (GAD) and self-reported mystical experience (spoiler alert: “Results suggest MEQ30 does not strongly predict reductions in HAM-A after a single MM120 treatment”, but for the placebo and 25 µg groups, “MEQ30 demonstrated some predictive value for reduction in HAM-A at week 4, suggesting that the degree of mystical experience in these groups may have contributed to a placebo response”, though there were no statistically significant associations at week 12); Solomon will present another poster that shows a single LSD treatment demonstrated efficacy in reducing depressive symptoms in patients with moderate to severe GAD; the company’s VP of Research and Development Strategy Javier Muniz is set to present an analysis of whether central raters remain blinded in the company’s Phase 2b study of LSD in GAD (spoiler alert: the analysis “indicates most [central raters] were unable to distinguish active drug from placebo at the primary endpoint and throughout the trial”); Director of Global Clinical Development Sarah Karas will present PK and safety comparisons of LSD capsules and orally disintegrating tablets; and, Chief Medical Officer Daniel Karlin will deliver a poster providing a look at quality of life and depressive symptoms in the Phase 2b study;
- Emma Lehmann of Intra-Cellular Therapies (recently bought by J&J for $14.6 billion) will present preclinical research findings on the company’s neuroplastogen candidate, ITI-1549;
- Cybin Chief Medical Officer Amir Inamdar will report on the company’s development of deuterated analogues of psilocin and DMT;
- Wiesław Cubała of the Medical University of Gdańsk in Poland will present on the safety and tolerability of GH Research’s 5-MeO-DMT candidate, as reported in the company’s Phase 2b study in TRD; the company’s own Claus Bo Svendsen, meanwhile, will present on Phase 2a results in a trial of the candidate in patients with postpartum depression; while Kelly Doolin, a Director in Clinical Science at the company, presents on data from three early studies of the drug;
- Audrey Shoultz of Sheppard Pratt will present a poster that looks at two small open-label psilocybin studies by Scott Aaronson and co. to demonstrate improvement in depression and quality of life, examining whether improvements in one domain mediated the other (spoiler alert: there was no bidirectional relationship found).
- Erica Kaczmarek of the University of Toronto will present a poster on an fMRI-assisted pilot study investigating the neurobiological effects of psilocybin in treatment-resistant bipolar depression, in which she hopes neuroimaging will provide hints at the pathobiology of BD as well as the neurobiological effects of psilocybin; Diana Orsini, also of the University of Toronto, will share a poster outlining the protocol for a randomised, double-blind, midazolam-controlled Phase 2 trial investigating repeated ketamine infusions for treatment-resistant depression (TRD) and an individual research report presenting interim blinding integrity analysis from that study (with results suggesting that “midazolam is a suitable active control for ketamine); in a hat-trick for the University, Danica Johnson will present an examination of the impact of childhood trauma on ketamine’s real-world effectiveness in TRD, which suggests that it does not impact outcomes; and
- Samantha Lim from Our Lady of Fatima University in Manila will present a meta-analysis of psilocybin-assisted therapy for cancer-related existential distress, which “revealed themes of existential relief and deeper life meaning”.
A two-hour session on Tuesday afternoon sees a rapid-fire review of the pharmaceutical pipeline, including five psychedelics-related presentations (each 10 minutes). With ten sessions scheduled thus far, that means that a full half of the pipeline on show this year is psychedelics-related1.
Specifically, those showcased are:
- Jennifer Warner-Schmidt of Transcend Therapeutics will present results from a Phase 2 study of methylone for PTSD;
- Jason Tucciarone of Stanford University School of Medicine will discuss a double-blind trial of open-label IV ketamine followed by either dose-escalated buprenorphine or placebo in TRD patients (the buprenorphine treatment group will be completed ahead of the meeting, meaning there may be a readout, which the authors hypothesise will demonstrate that buprenorphine prolongs the therapeutic benefits of ketamine);
- atai Life Sciences’ Sarah McEwen will present on EmpathBio’s EMP-01, their empathogen candidate for social anxiety disorder (SAD), which has been through a Phase 1 study and is currently in Phase 2a;
- Michael Thase of the Perelman School of Medicine will deliver a presentation on results from GH Research’s Phase 2b study of its 5-MeO-DMT candidate in TRD; and
- Gerard Marek, Gilgamesh Pharmaceuticals’ Chief Medical Officer, is set to present Phase 2a data from a study of GM-2505…
First Look at Gilgamesh’s Phase 2a Data: Psychedelic Candidate Yields Effect Size of ~1.0, But Sparse Details
That’s right: Gilgamesh Pharmaceuticals is slated to share data from a Phase 2a study (NCT06236880) of its lead candidate during both poster sessions and the pharmaceutical pipeline session. While thin on details, the abstract provides a first look at the data.
It suggests that the trial of GM-2505—a substituted tryptamine derivative also known as bretisilocin, a serotonergic psychedelic—was successful, in that it appeared efficacious in treating major depressive disorder (MDD).
The study evaluated the drug, which the company describes as a “short acting 5-HT2A agonist and serotonin releaser”, in 40 patients, initially randomised to receive either a ‘low’ or ‘moderate’ dose of GM-2505, followed by both arms receiving a ‘high’ dose of GM-2505 two weeks later. The drug was administered intravenously.
Participants had not taken antidepressant medications for at least six weeks prior to screening and remained antidepressant-free throughout the study.
The low dose, which the company describes as an active control, “produced measurable, but minimal, psychotropic effects in healthy volunteers”, the abstract discloses, while the ‘moderate’ first dose “exerted robust psychedelic effects” in the healthy volunteers.
The company reports statistically significant drops in MADRS scores across both study arms, but notes that those decreases were “always greater for Arm 2, which received two robustly psychedelic doses.”
At day 14, the company further discloses, “there was an effect size of ~1.0 for a between-subjects comparison of the least square mean change from baseline in MADRS scores for Arm 2 treated with the moderate dose compared to Arm 1 treated with the active control low dose.”
At the day 29 timepoint, two weeks after both arms had taken the high dose, “MADRS scores further significantly decreased in both arms based on a within-subject comparison of Day 29 to Day 14 and the MADRS change from baseline in Arm 2 was significantly greater than in Arm 1 based on a between-subjects comparison.”
What’s more, Gilgamesh reports that “there were robust categorical MADRS response and remission rates indicating that both the moderate and high doses were efficacious.”
“The superior response in Arm 2 also suggests that a regimen of two robustly psychedelic doses, administered two weeks apart, produces greater efficacy than a single robust psychedelic dose”, the abstract continues, suggesting that there may be an additive benefit of repeat dosing.
Gilgamesh is presumably hoping that the use of an active comparator, the ‘low’ dose of GM-2505, will alay certain methodological concerns from the FDA, such as functional unblinding. It is not clear, however, whether the company directly measured expectancy or blinding in the trial.
On the safety front, the company reports no serious adverse events, no patients exhibiting suicidal ideation and a plan/intent, and treatment-emergent adverse events are reported to be “similar to that in [healthy volunteers].”
It’s undoubtedly an enticing first look at the study, with an impressive effect size—for context, conventional antidepressants tend to have an effect size in the region of 0.3. Given that the drug is relatively short-acting, Gilgamesh will presumably hope it might fit into the paradigm carved out by Spravato, but with potentially greater efficacy and/or durability.
But, the paucity of details makes it very difficult to say much more. For example, there is little understanding of the non-pharmacological support employed in the trial, both in terms of quantity and intensity. What’s more, the doses have not been publicly disclosed, though a Phase 1 study tested the drug in doses up to 15 and 20mg. We also await details on future development plans.
Nonetheless, at a moment when psychedelic drug developers and investors alike are feeling antsy ahead of Compass Pathways’ first Phase 3 readout, expected next month, this might be seen, at least prima facie, as a win for developers of subjective psychedelics. (Note that Gilgamesh is collaborating with AbbVie to develop its non-hallucinogenic candidates, too.)
Gilgamesh declined to comment.
VA Secretary Pressed for Details on Psychedelics Plans
Some lawmakers have pressed VA Secretary Doug Collins to provide more colour on just how he plans to promote psychedelic research and implementation in his agency, after a string of comments to that effect.
This week, during a Senate Veterans’ Affairs Committee hearing, Senator John Boozman—a long-time Republican politician who has played a prominent role in anti-drug efforts such as the Speaker’s Task Force for a Drug-Free America—asked Collins to elaborate.
“During your remarks at President Trump’s April 30th Cabinet meeting”, he started “you mentioned that you and Secretary Kennedy have discussed the potential of researching psychedelics as an effective tool to combat PSTD, TBI, and other mental issues.” “Can you provide further details on how your team plans to take action on this? The Committee is very interested”, he added.
Collins responded by saying that he is, “committed to doing whatever we can to provide veterans and those who have maybe not responded to traditional care and others, especially in the area of PTS, also TBI…that lead to a lot of what we’re seeing in suicide.”
“I think right now there’s elevent studies going on”, Collins continued, “most are performed outside of the VA with our help.” “MDMA is another one, I just saw a program at Emory University in which they’re seeing some really good results—a single treatment followed up by two weeks of intensive counselling that has lowered the score number on the PTS scale.”
“I want to make sure that we’re not closing off any outlet for a veteran that could be helped by these programs”, he said, adding: “We will definitely be working with Congress on that if there seems to be something else that needs to happen.”
Other Stories
Rythmia Launches Affiliate Program. Rythmia Life Advancement Center, an ayahuasca retreat in Costa Rica, has announced the launch of an affiliate program offering “healthy commissions for every qualified guest referral”, which includes “second-tier affiliate earnings”. “Promote a life-changing experience with a 95.12% guest-reported miracle rate”, the company press release reads (though, the affiliate landing page suggests a 98% rate!). The affiliate rate, meanwhile, is a cool $1,500 for each new guest who “fully pays for their first retreat”. In February, we covered how Mindbloom, the at-home ketamine company, pays affiliates $100 for each new client they draw in.
EXCLUSIVE: Heroic Hearts and Healing Breakthrough Merge to Expand Stateside Psychedelic Access for Veterans (May 6) ↗ Psychedelic Alpha
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- One presentation is not quite psychedelic, but interesting nonetheless: Venkat Bhat from the University of Toronto will present findings from a trial of nitrous oxide—laughing gas—for TRD. Given its potential as a rapid-acting antidepressant, might the psychedelics field start claiming it as its own?
