N, N-dimethyltryptamine (DMT IV) / Definium Therapeutics - LARVOL DELTA

Predicting disease progression in multiple sclerosis with clinically accessible information and technology. (PubMed, J Neurol) - "We developed two well-calibrated machine-learning-based tools for individualized 5-year prediction of clinically- and objectively-defined MS progression, each with distinct strengths in usability, bias handling, and treatment modeling. These findings support future tool use in personalized risk stratification and secondary prevention."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis

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

DPS: Acute Analgesic Effects of DMT on Experimentally Induced Pain in Healthy Participants (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: University Hospital, Basel, Switzerland | Recruiting ➔ Completed

Trial completion • Pain

Dose-dependent pharmacokinetics and acute effects of intravenous bolus N,N-dimethyltryptamine: double-blind, randomized versus open-label dose-escalation administration study in healthy participants. (PubMed, Transl Psychiatry) - "The tolerability markedly improved with open-label dose-escalation compared with double-blinded, randomized administration, and at equivalent dose levels, subjective effects were rated as less intense. These findings highlight the impact of blinding and expectancy on the subjective experience and suggest that individual dose-escalation may improve tolerability and help with dose selection for future DMT studies."

Journal • PK/PD data • CNS Disorders • Depression • Mood Disorders • Psychiatry

MEOS: Acute Effects of Intravenous 5-MeO-DMT in Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: University Hospital, Basel, Switzerland

New P1 trial

Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A Multicenter Cohort Study. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "This study provides valuable insights into the management of iatrogenic PML in patients with MS. The findings may guide clinicians in making informed decisions, particularly regarding the use of PlEx, corticosteroids, and the management of PML-IRIS."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis • Rare Diseases

Safety and efficacy of opicinumab in participants with relapsing multiple sclerosis (AFFINITY Part 1): A randomized, controlled, phase 2 trial. (PubMed, Mult Scler) - P2 | "Although the AFFINITY study did not show significant difference in mean ODRS between opicinumab and placebo groups, data from AFFINITY interpreted with the previous SYNERGY study may inform the design of future remyelination trials."

Journal • P2 data • CNS Disorders • Inflammation • Multiple Sclerosis • Solid Tumor

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

From diagnosis to treatment: patterns in disease-modifying therapy initiation in multiple sclerosis. (PubMed, Ther Adv Neurol Disord) - "In Switzerland, the first DMT use has evolved, with patients starting DMTs earlier and more frequently with higher-efficacy DMTs. While moderate and high-efficacy DMTs were associated with fewer sADRs, they may also carry a higher risk of severe sADRs, underscoring the need to balance personal preferences, efficacy, and safety in first-line MS treatment."

Journal • CNS Disorders • Multiple Sclerosis

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

Treatment strategies after cell-trafficking agents in MS patients older than 50 years (ECTRIMS 2025) - "Introduction: Discontinuation of cell-trafficking therapies (e.g., natalizumab, fingolimod) carries a risk of disease reactivation or rebound... We analyzed MS patients from MSBase, the Italian MS Register, and the Swiss MS Cohort, who had ⩾3 visits, complete datasets, and ⩾6 months of treatment with a cell-trafficking disease-modifying therapy (DMT)... After 50th year of age, switching to anti-CD20 or cladribine after discontinuing a cell-trafficking agent is associated with a relapse risk similar to continued therapy. In contrast, de-escalation to lower-efficacy agents offers no apparent advantage over treatment cessation. Disclousure of interest: Jannis Müller received ad personam funding from the Swiss National Science Foundation (Grant No P500PM_214230 and P5R5PM_225288]) Pascal Benkert has nothing to disclose."

Clinical • Late-breaking abstract • CNS Disorders • Hodgkin Lymphoma • Multiple Sclerosis

Disease-Modifying Therapy Initiation Patterns: Insights from the Swiss Multiple Sclerosis Registry (ECTRIMS 2025) - "In Switzerland, the landscape of first-line DMT use in MS has evolved, with patients starting treatment more promptly and shifting toward higher efficacy therapies. While moderate and high efficacy DMTs appear to be associated with fewer side effects, weighing their potential benefits and risks remains an important consideration in treatment decisions."

CNS Disorders • Multiple Sclerosis

Two-year outcomes in MultipleMS, a prospective observational study in new onset Multiple Sclerosis across 7 European countries (ECTRIMS 2025) - "DMT groups were defined as: (1) injectable, (2) oral platform, (3) highly effective therapies (fingolimod, cladribine, natalizumab, alemtuzumab), (4) B cell-depleting (BCDT), and (5) untreated. Substantial differences between DMT classes were observed with respect to relapse rates and treatment persistence, but not sNfL z-scores. Findings suggest that structured monitoring in real-world practice may facilitate earlier treatment escalation, if needed. Longer follow-up is required to assess potential differences in disability outcomes."

Clinical • Observational data • CNS Disorders • Multiple Sclerosis • NEFL

Cladribine as an exit strategy in people with MS over the age of 50 (ECTRIMS 2025) - "Introduction: Cladribine (CLD), a purine nucleoside analogue, is a highly effective immune reconstitution therapy for relapsing multiple sclerosis (MS). In patients over 50, starting treatment with CLD offers superior relapse control compared to DMT discontinuation. Disease outcomes are comparable between patients initiating CLD and those continuing their existing DMT. These findings support the use of CLD as a viable treatment exit strategy in people with MS over the age of 50."

CNS Disorders • Multiple Sclerosis

Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated with Multiple Sclerosis Treatments: A Multicenter Cohort Study (ECTRIMS 2025) - "While natalizumab is most frequently associated with this risk, PML also occurs less commonly with sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab. Objectives/Aims: This study aimed to identify factors predicting worse outcomes, focusing on the impact of PML-IRIS, plasma exchange, corticosteroids, and DMT reintroduction... This study provides valuable insights into the management of iatrogenic PML in MS patients. The findings may guide clinicians in making informed decisions, particularly regarding plasma exchange, corticosteroids, and PML-IRIS management."

Clinical • CNS Disorders • Multiple Sclerosis • Rare Diseases

Cytomegalovirus is linked to T cell senescence and to disease course in multiple sclerosis (ECTRIMS 2025) - "Patients were undergoing the following treatments: 39 untreated, 88 B cell depletion therapy (BCDT), 36 dimethyl fumarate (DMF) and 66 fingolimod... CMV is a main driver of T cell senescence in pwMS, independent of DMT. CMV modulates the relationships between blood T cell immunosenescence and MS disease course."

CNS Disorders • Cytomegalovirus Infection • Infectious Disease • Multiple Sclerosis • GDF15 • MMP1 • NEFL

Ever-smoking and hypercholesterolemia are associated with a more active course of myelin oligodendrocyte glycoprotein antibody-associated disease (ECTRIMS 2025) - "Multifactorial analysis included age/phenotype at onset, sex, smoking (ever/never), obesity at disease onset (Body Mass Index >30 kg/m2 ), hypercholesterolemia, diabetes mellitus, hypertension and disease-modifying therapy (DMT; ever/never)... Ever-smoking and hypercholesterolemia are modifiable factors linked to increased attack risk in MOGAD. Smoking may also influence disability progression in non-ON attacks. Further studies should explore the benefits of smoking cessation and lipid control in MOGAD."

Cardiovascular • CNS Disorders • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Immunology • Metabolic Disorders • Neuromyelitis Optica Spectrum Disorder • Obesity • Ocular Inflammation • Ophthalmology • Optic Neuritis • Rare Diseases • Solid Tumor • Tobacco Cessation

Real-world use of disease-modifying therapy in persons with multiple sclerosis aged 55 and over. (PubMed, BMJ Neurol Open) - "Despite unclear efficacy and safety, many older pwMS continue DMT use. Use is primarily associated with relapsing-remitting MS, while age and disease duration show only modest or no association."

Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

DMT4D: Antidepressant Response of DMT Masked With Propofol (clinicaltrials.gov) - P=N/A | N=112 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Treatment Strategies and Disease Activity During Pregnancy and Postpartum: Real-World Data From the Swiss Multiple Sclerosis Cohort. (PubMed, Neurol Clin Pract) - "We compared pregnancies continuously exposed to high-efficacy disease-modifying therapies (cHET: anti-CD20 monoclonal antibodies (aCD20) and natalizumab [NTZ]) with those where other therapeutic regimens (OTRs) were used...The last disease-modifying therapy (DMT) before birth was NTZ in 29 (23.5%) and aCD20 in 25 (20.3%) pregnancies; of those, 3 and 24 were exposed until birth, respectively (cHET). Fingolimod was the last treatment before birth in 25 pregnancies (20.3%), stopped in all before or after confirmation of pregnancy...Treatment strategies for pregnant patients with MS were heterogeneous, and continuous exposure to HET showed superior efficacy against acute disease activity compared with other DMTs or no treatment. Further studies are needed to confirm these results and assess maternal and fetal longer term outcomes."

Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis • NEFL

DMT4D: Antidepressant Response of DMT Masked With Propofol (clinicaltrials.gov) - P=N/A | N=112 | Not yet recruiting | Sponsor: University Hospital, Basel, Switzerland | Initiation date: Apr 2025 ➔ Jul 2025

Trial initiation date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • 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

Editorial: Beyond psilocybin: exploring the clinical potential of alternative and novel psychedelics. (PubMed, Front Psychiatry) - No abstract available

Journal

Personalized treatment decision algorithms for the clinical application of serum neurofilament light chain in multiple sclerosis: A modified Delphi Study. (PubMed, Mult Scler) - "The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice."

Journal • CNS Disorders • Multiple Sclerosis • NEFL

Early cardiovascular autonomic failure in ATTRv predicts poor prognosis and may respond to disease-modifying therapy. (PubMed, Amyloid) - "Autonomic testing is a valuable biomarker to capture disease progression. Prospective studies need to confirm the benefit of DMT on autonomic dysfunction."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hypotension