lysergide tartrate (DT120) / Definium Therapeutics, University Hospital Basel, Maastricht University Medical Centre - LARVOL DELTA

Definium Therapeutics…announced positive topline results from Panorama, the Company’s second Phase 3 study of DT120 (lysergide) Orally Disintegrating Tablet (ODT) in adults with generalized anxiety disorder (GAD) (Businesswire) - "Panorama met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement from baseline compared with placebo, as measured by the change in Hamilton Anxiety Rating Scale (HAM-A) total score at Week 12. The Least Squares (LS) mean change from baseline in HAM-A total score at Week 12 in participants who received DT120 ODT 100 µg was -9.8 compared with -4.7 for participants who received placebo, an LS mean difference of -5.1 points (p<0.0001), corresponding to a standardized effect size of d=0.64. Efficacy was rapid, with changes seen as early as Day 2 and sustained at all post-baseline timepoints in Part A....'We are advancing toward an NDA submission and look forward to aligning with the FDA at our upcoming pre-NDA meeting'."

FDA event • P3 data: top line • General Anxiety Disorder

Definium Therapeutics has received a second Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for DT120 (lysergide) orally disintegrating tablet (ODT), this time for major depressive disorder (MDD)… (HCPLive) - "The Breakthrough Therapy designation is supported by data from the phase 3 Emerge study evaluating a single 100 µg dose of DT120 ODT in adults with MDD."

Breakthrough therapy • Major Depressive Disorder

Low-dose lysergic acid diethylamide alters subjective visual perception but not visual contrast surround suppression. (PubMed, Neurosci Conscious) - "Our findings indicate a dissociation between subjective experience and early visual contextual processing, suggesting that subjective visual effects of low-dose LSD may arise through mechanisms distinct from those mediating contrast surround suppression. Future research should test whether higher doses of LSD affect contrast surround suppression."

Clinical • Journal

Predictors of Therapeutic Response to LSD in Anxiety: Short- and Long-Term Outcomes (CINP 2026) - "Psychedelics, such as lysergic acid diethylamide (LSD) that act via agonism on serotonin 2A receptors, have recently been shown to be effective in the treatment of anxiety symptoms... Summarized, these findings indicate that acute positive drug effects and mystical-type experiences predict short and long-term therapeutic outcomes, while acute negative drug effects remain neutral."

CNS Disorders • Mood Disorders • Psychiatry

Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment. (PubMed, Cell Rep Med) - P2 | "In this group, post-intervention FA values correlate with improvements in depressive symptoms at 2, 6, and 12 weeks, measured using the Inventory of Depressive Symptomatology (IDS-clinician rated [C] and IDS- self report [SR]). These findings suggest that LSD-induced WM microstructural changes are associated with antidepressant effects in MDD."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Evaluating the evidence for repressed memory recovery in psychedelic contexts. (PubMed, Psychopharmacology (Berl)) - "The included literature did not offer a coherent explanation on how psychedelics could recover repressed memories, nor consistent evidence that they did so reliably. Future work should provide clear definitions of repressed memory in the context of psychedelics, test proposed effects of psychedelics on memory and executive control across multiple psychedelic substances, include placebo-controlled designs, and account for the potential occurrence of false memories."

Journal • Review • CNS Disorders • Cognitive Disorders

An international mega-analysis of psychedelic drug effects on brain circuit function. (PubMed, Nat Med) - "Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research."

Journal

Psychological Therapy Quantity and Depressive Symptom Reduction in Psychedelic-Assisted Therapy: A Systematic Review and Meta-Analysis. (PubMed, JAMA Netw Open) - "The analysis included controlled clinical trials involving adults with depressive symptoms who received PAT using classic serotonergic psychedelics (eg, psilocybin or lysergic acid diethylamide)...The observed association primarily reflects quantitative aspects of therapy exposure rather than qualitative or process-related dimensions of the therapeutic interaction. Additional systematic research is needed to clarify this association and optimize all therapeutic components within psychedelic interventions."

Clinical • Journal • Retrospective data • Review • CNS Disorders

The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research. (PubMed, J Psychopharmacol) - "The 3D-ASCr is an updated version of the ASC and is recommended for use with classic serotonergic psychedelics in both clinical practice and research."

Journal • Mood Disorders • Psychiatry

A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness. (PubMed, Adv Sci (Weinh)) - "Here, individualized whole-brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion-weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated...In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine."

Journal • Anesthesia

Acute effects of mescaline on emotional and cognitive empathy (ECNP 2025) - "Introduction: Mescaline is a classic psychedelic inducing similar acute effects like lysergic acid diethylamide (LSD) and psilocybin [1]... The findings indicate that mescaline acutely increases emotional empathy, especially for positive stimuli and at higher doses. These findings further support the evidence that classic psychedelics enhance prosocial effects and emotional empathy, which might be relevant to psychedelic's therapeutic use. Similar to LSD and psilocybin mescaline increased oxytocin plasma concentrations but only after higher doses."

CNS Disorders

LSD increases working memory-related brain function in patients with major depressive disorder (ECNP 2025) - "Background: Classic psychedelics including lysergic acid diethylamide (LSD) show promise as treatment for major depressive disorder (MDD), yet the underlying neural mechanisms remain poorly understood... Compared to low-dose, high-dose LSD significantly decreased depressive symptoms and increased WM-related activity in frontoparietal and subcortical regions in patients with MDD, diverging from the typical normalisation pattern seen with standard treatments. The lack of any significant associations between neural activity and depression symptoms raises the possibility that LSD's effects on cognitive brain function may be mechanistically distinct from its antidepressant effects. These findings indicate that psychedelics modulate cognitive brain function in clinical cohorts and warrant further investigation."

Clinical • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Behavioral effects of psychedelic and non-psychedelic serotonin 2A receptor agonist drugs in pigs (ECNP 2025) - "Here, we have determined the relationship between plasma concentration and cerebral 5-HT2AR occupancy of N,N-dimethyltryptamine (DMT), psilocybin, lysergic acid diethylamide (LSD) and lisuride in pigs, and measured psychedelic-induced behavior (headshakes) at doses generating 60-70% occupancy...The behavioral study was done in 8 awake female pigs each receiving IV DMT, 0.4 mg/kg (injected 30 min after monoamine oxidase inhibitor, moclobemide, 0.85 mg/kg), psilocybin, 30 µg/kg, LSD, 0.6 µg/kg, and lisuride, 5.8 µg/kg, in a randomized order, with 3-4 days separating each drug... We have for the first time established relationships between cerebral 5-HT2AR occupancy, drug plasma concentrations and drug dose for 5-HT2AR agonists in vivo in pigs, and subsequently compared psychedelic-induced behavior in awake pigs on the basis of the cerebral 5-HT2AR occupancy."

CNS Disorders

A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers. (PubMed, Br J Pain) - "The dose used in this study may be below the threshold dose that is needed to produce a solid and consistent analgesic effect. Future research with larger, appropriately selected samples and higher doses is recommended to further elucidate LSD's analgesic effects and its application in clinical settings."

Journal • Pain

Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial. (PubMed, JAMA) - P2 | "These results support the dose-dependent efficacy of MM120 and inform the dose selection for phase 3 pivotal trials. ClinicalTrials.gov Identifier: NCT05407064."

Clinical • Journal • CNS Disorders • Depression • General Anxiety Disorder • Mental Retardation • Mood Disorders • Pain • Psychiatry

Implementing psychedelic-assisted therapy: History and characteristics of the Swiss limited medical use program. (PubMed, Neurosci Appl) - "In 2024, there were approximately 100 physicians who held authorizations to treat 723 patients with MDMA (245 patients), lysergic acid diethylamide (130 patients), or psilocybin (348 patients)...Various aspects of the program, including its history, provider characteristics and setting, legal requirements, treatment cost, the role of professional societies, education and continuous formation, personal experience, patient characteristics, outcome, and adverse effects, are described and discussed relative to other recently established programs in Canada and Australia. Such information could be of interest to psychedelic-assisted therapy stakeholders, including professionals, patients, and regulatory bodies that are considering setting up similar restricted access programs."

Journal • Review

Motivation and retrospective appraisal of psychedelic study participation: a qualitative study in healthy volunteers. (PubMed, Psychopharmacology (Berl)) - "This paper identified four pivotal factors to be considered for psychedelic study experiences: (1) a secure interpersonal relationship, (2) an aesthetically pleasing environment, (3) access to nature, and (4) the use of music. This analysis reveals subjective views of volunteers in psychedelic Phase-I trials and may improve research standards."

Clinical • Journal • Retrospective data • CNS Disorders

Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry? (PubMed, Int Rev Neurobiol) - "The chapter also discusses the influence of extra-pharmacological factors, such as the baseline subjective state, expectations, and individual differences in drug metabolism, on treatment outcomes. Overall, controlled microdosing studies suggest the potential therapeutic applications of small psychedelic doses, warranting further exploration through large-scale trials in clinical populations."

Journal • CNS Disorders • Depression • Pain • Psychiatry

Clinical pharmacology. (PubMed, Int Rev Neurobiol) - "This chapter summarizes pharmacological characteristics of the serotonergic psychedelics psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), and MDMA. Thus, MDMA, but not the psychedelics, exhibits marked acute pharmacological tolerance. A good understanding of the pharmacology of classic psychedelics and MDMA forms the basis for their clinical use and the design of clinical therapeutic trials."

Journal

Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial. (PubMed, Med) - P2 | "The findings of this exploratory study support further investigation of LSD-assisted therapy in depression in a larger phase 3 trial."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study. (PubMed, Clin Pharmacol Ther) - "Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders...Intravenous LSD administration produced higher "any drug effect," "good drug effect," and "ego dissolution" compared with oral LSD tartrate, more "anxiety" compared with all oral formulations, and more "nausea" and "bad drug effect" compared with oral LSD base and tartrate. In conclusion, dosing with LSD base and tartrate can be considered bioequivalent with high and similar oral bioavailability."

Clinical • Journal • CNS Disorders • Mood Disorders • Psychiatry

Clinical Trial Participant and Clinician Experience in a Phase 2 (US-only) Trial of MM120 for Generalized Anxiety Disorder (ISPOR 2025) - "This research outlines a successful strategy for soliciting input regarding clinical trial participant experiences. Projective techniques and visual stimuli worked well to gain a holistic picture of the participant’s experience, including difficult-to-quantify emotional experiences. These insights may provide practical solutions to improving psychedelic clinical trials."

Clinical • P2 data • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

Program Updates and Anticipated Milestones (Businesswire) - "Enrollment is on track in the Phase 3 Voyage study of MM120 ODT for the treatment of GAD. Voyage is expected to enroll approximately 200 participants in the U.S. who will be randomized 1:1 to receive MM120 ODT 100 µg or placebo. Topline data from the 12-week double-blind period (Part A) is anticipated in the first half of 2026; Enrollment is on track in the second Phase 3 Panorama study of MM120 ODT for the treatment of GAD. Panorama is expected to enroll approximately 250 participants (randomized 2:1:2 to receive MM120 ODT 100 µg, MM120 ODT 50 µg or placebo) in the U.S. and Europe. Topline data from the 12-week double-blind period (Part A) is anticipated in the second half of 2026....Topline data from the 12-week double-blinded period (Part A) is anticipated in the second half of 2026. The Company expects to conduct a second Phase 3 registrational study in MDD, with the study design and timing to be informed by the progress of Emerge..."

Enrollment status • New P3 trial • P3 data: top line • General Anxiety Disorder • Major Depressive Disorder

Contextual and experiential aspects of the psychedelic experience predicting improvement in subjective wellbeing: results from a Norwegian internet convenience sample. (PubMed, Front Pharmacol) - "This relationship seems dependent upon various experiential aspects of acute subjective drug effects. These findings should be viewed as hypothesis-generating rather than confirmatory due to the study's limitations."

Journal

A Phase 3 Trial of MM120 for Major Depressive Disorder (Emerge) (clinicaltrials.gov) - P3 | N=140 | Recruiting | Sponsor: Mind Medicine, Inc.

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry