2-bromo-D-lysergic acid diethylamide (NYPRG-101) / Ceruvia Lifesci, Yale University - LARVOL DELTA

Molecular and cellular mechanisms of the long-lasting effects of psychedelics and their non-hallucinogenic derivatives. (CINP-AsCNP 2025) - "Aims & Objectives: This study aims to determine how 2-Bromo-LSD, a non-hallucinogenic compound, regulates neuronal morphology, myelination and gene expression and how these effects compare to classic serotonergic psychedelic drugs... Our results indicate that 2-Br-LSD has effects comparable to those of classical psychedelic drugs, which have been shown to produce lasting antidepressant-like effects. This suggests that 2-Br-LSD has the potential to be an effective treatment for MDD."

CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Solid Tumor

Symposium 8: From Molecular Mechanisms to Brain Circuitries: How Psychedelics are Reshaping Our Understanding of Neuropsychiatric and Behavioral Disorder Treatments (CINP-AsCNP 2025) - "Argel Aguilar-Valles (Male, CINP Member) will discuss the effects of the non-hallucinogenic LSD derivative, 2-bromo-LSD (2-Br-LSD) on the brain, focusing on the mechanisms underlying its impact on stress-coping behaviours and its ability to reverse the mal-adaptive behavioural changes produced by chronic stress exposure...The speakers represent diverse geographical regions and are all experts in the field. The session includes contributions from early career investigators and female researchers."

Addiction (Opioid and Alcohol) • Anorexia • Behavior Disorders • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry

Theoretical Framework for the Abuse Potential Assessment and Scheduling of Psychedelic Drugs (CPDD 2025) - "Hallucinogenic psychedelics induce head-twitches [2,3], but non-hallucinogenic compounds (e.g. 2-bromo-LSD) do not [4]... These pharmacological and safety criteria are sufficient to determine the abuse potential of all psychedelic drug-candidates. Classical/novel psychedelic drug-candidates meeting these criteria would be placed in the same controlled drug schedule. Those falling outside with greater (hybrid psychedelic/entactogens) or lesser risks of abuse (non-hallucinogenic 5-HT2A agonists) would be assessed/scheduled on an individual basis."

A highly sensitive UHPLC-MS/MS method for determining 15 designer LSD analogs in biological samples with application to stability studies. (PubMed, Analyst) - "In the presented paper, an UHPLC-QqQ-MS/MS method was developed for trace determination (fg mL-1) of LSD, its designer analogs (ALD-52, AL-LAD, LAMPA, LSM-775, LSZ, MiPLA, 1B-LSD, 1cP-LSD, 1cP-MiPLA, 1P-LSD, 1P-MiPLA, 1V-LSD and 2-Bromo-LSD) and its metabolite (2-oxo-3-OH-LSD) with simultaneous separation of structural isomers...The presented method is the most sensitive to date for analyzing designer LSD analogs in biological samples, with potential for routine clinical and forensic use, enhancing detection of emerging illicit compounds. By examining the mass spectra (QTOF-MS/MS) obtained in this study and reviewing the literature on analytical characterization of LSD analogs, we proposed fragmentation patterns to aid in future identification of new designer LSD analogs (NPS)."

Journal

2-Bromo-LSD: A Non-Hallucinogenic LSD analogue with therapeutic potential in mood disorders (Neuroscience 2023) - "This symposium will discuss the drugs' receptor targets, downstream pathways, and implicated brain regions. These data will help in the fields of clinical application and targeted drug discovery."

CNS Disorders • Mood Disorders • Psychiatry

A non-hallucinogenic LSD analogue with therapeutic potential in mood disorders (CAN-ACN 2023) - "2-Bromo-LSD (2-Br-LSD/BETR-001) is an LSD derivative with 5-HT2A partial agonist activity that lacks hallucinogenic effects...Our findings demonstrate that 2-Br-LSD induces cortical plasticity in vitro and in vivo, promotes active stress-coping behaviours, and reveres the behavioural effects of chronic stress. These results show that 2-Br-LSD possesses therapeutic potential and represents a promising alternative to classic psychedelics in treating depression."

CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

A Non-Hallucinogenic LSD Analogue With Therapeutic Potential in Mood Disorders (SOBP 2023) - "2-Bromo-LSD (2-Br-LSD/BETR-001) is an LSD derivative with 5-HT2A partial agonist activity that lacks hallucinogenic effects...Conclusions Our findings demonstrate that 2-Br-LSD induces cortical plasticity in vitro and in vivo, promotes active stress-coping behaviours, and reveres the behavioural effects of chronic stress. These results show that 2-Br-LSD possesses therapeutic potential and represents a promising alternative to classic psychedelics in treating depression."

CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. (PubMed, Cell Rep) - "Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD also reverses the behavioral effects of chronic stress. Overall, 2-Br-LSD has an improved pharmacological profile compared with LSD and may have profound therapeutic value for mood disorders and other indications."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Ceruvia Lifesciences Announces First Participant Dosed in BOL-148 Phase 1 Clinical Trial (PRNewswire) - “Ceruvia Lifesciences…announced the first participant has been dosed in their Phase 1 clinical trial of NYPRG-101 (2-bromo-d-lysergic acid diethylamide) in healthy adult participants….‘We believe that NYPRG-101 offers great promise to provide meaningful relief from the disability and psychosocial burdens that impact the lives of several patient populations, including those suffering from migraine and cluster headaches’….Ceruvia's Phase 1 clinical trial is a single ascending dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NYPRG-101 in healthy adult participants. Up to 40 participants will be enrolled and randomized into ascending dose cohorts, each receiving a single dose of NYPRG-101.”

Trial status • CNS Disorders • Migraine • Psychiatry

A Non-Hallucinogenic LSD Analog With Therapeutic Potential for Mood Disorders (ACNP 2022) - "2-Bromo-LSD (2-Br-LSD, BETR-001) is an LSD derivative with 5-HT2A partial agonist activity that lacks hallucinogenic effects and has been safely used for cluster headache treatment...The maximal effect was achieved with the 1 uM dose comparable to the 10 uM ketamine treatment... Our findings demonstrate that 2-Br-LSD induces structural plasticity in cortical neurons in vitro and in vivo, promotes active stress-coping behaviours and reverses the behavioural effects of CVS. These results show that 2-Br-LSD may possess a therapeutic potential and represents a promising alternative to psychedelics in treating MDD."

CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Pain • Psychiatry

Investigation of the Pharmacological Properties of 2-Br-LSD, a Non-Hallucinogenic LSD Analog (ACNP 2022) - "Similar to LSD, the closely related derivative 2-bromo-LSD (2-Br-LSD, TD-0418A) is also being investigated as a potential treatment for depression and headache. Overall, 2-Br-LSD has an improved pharmacological profile compared to LSD. 2-Br-LSD appears to act as a non-hallucinogenic 5-HT2A agonist, similar to the isolysergic acid derivative lisuride. Our studies provide insight into the non-hallucinogenic activity of 2-Br-LSD, which is probably a consequence of its weak partial agonist activity at the 5-HT2A receptor."

CNS Disorders • Depression • Mental Retardation • Mood Disorders • Pain • Psychiatry • Substance Abuse • ARRB1

Ceruvia Lifesciences Submits FDA Investigational New Drug Application for NYPRG-101 Migraine Prevention Program (PRNewswire) - "Ceruvia Lifesciences...announced the submission of an IND application to begin a Phase 1, single center, randomized, double blind, placebo controlled, single ascending dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NYPRG-101 (2-bromo-D-lysergic acid diethylamide) in healthy adult participants....This Phase 1 single ascending dose (SAD) trial, to be held at a single clinical research site in the United States, will evaluate the safety, tolerability, pharmacokinetics and effects on neurocognitive functioning of healthy adult participants."

IND • New P1 trial • CNS Disorders • Migraine • Pain