MM120 (Lysergide) May Enhance Neuroplasticity by Post-Dose Upregulation of TrkB
G. Smagin, J. Tripp
European Psychiatry June 1, 2026 DOI: 10.1192/j.eurpsy.2026.11607 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | NIH/3T3 cells stably expressing human TrkB |
| Interventions | LSD psilocin DMT mescaline DOI 25B-NBOMe 2C-B MDA fluoxetine |
| Measures | inositol monophosphate 1 (IP1) accumulation, Homogeneous Time-Resolved Fluorescence (HTRF) |
| Topics | LSD Neuroplasticity |
| Key points | LSD, 25B-NBOMe, and fluoxetine activated TrkB as partial agonists with EC50 values of 811, 26370, and 6040 pM, and maximal efficacies of 40%, 57%, and 60%, respectively. Psilocin, DMT, DOI, MDA, and 2C-B did not activate TrkB at concentrations <1 mM. Cotreatment with LSD increased BDNF-induced TrkB activation potency (EC50 0.06 pM) but reduced efficacy to 60%. |
Abstract
Introduction: MM120 (lysergide D-tartrate, a formulation of LSD) is under development as a potential treatment for generalized anxiety and major depressive disorders. How psychedelic drugs interact at the TrkB receptor, a key target of neuroplasticity, is not reported.
Objectives: The study evaluated binding and functional activity of known serotonergic psychedelic compounds and SRI fluoxetine at the TrkB receptor.
Methods: Activation of TrkB by brain-derived neurotrophic factor (BDNF) was assessed by measuring inositol monophosphate 1 (IP1) accumulation. NIH/3T3 cells stably expressing human TrkB were used. BDNF was added, followed by incubation with Anti-IP1-Cryptate and IP1-d2. IP1 formation was determined by Homogeneous Time-Resolved Fluorescence (HTRF). We tested LSD, psilocin, N,N-dimethyltryptamine (DMT), mescaline, 2,5-dimethoxy-4-iodoamphetamine (DOI),N-2-methoxybenzyl- phenethylamine (25B-NBOMe), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), methylenedioxyamphetamine (MDA), and the selective serotonin reuptake inhibitor fluoxetine. Activation potencies (EC 50 ) were derived from the concentration-response curves using nonlinear regression.
Results: BDNF was highly potent at the TrkB receptor, activating it in the sub-picomolar range (EC 50 0.2 pM). LSD, 25B-NBOMe, and fluoxetine activated TrkB (EC 50 of 811, 26370, and 6040 pM respectively) with low maximal efficacies (40, 57, and 60% respectively). All remaining drugs did not activate the TrkB at concentrations <1 mM. Cotreatment with BDNF and a fixed concentration of LSD increased the BDNF-induced TrkB activation potency (EC 50 0.06 pM) and reduced the activation efficacy to 60%. Other drugs reduced the activation potency, as well as the maximal receptor activation. Image 1: Image 1: Long description.
Conclusions: LSD, 25B-NBOMe, and fluoxetine activated TrkB at pharmacologically relevant concentrations as partial agonists, while psilocin, DMT, DOI, MDA, and 2C-B did not. Induced TrkB upregulation may underly and provide evidence for the neuroplastic effects of LSD. Disclosure of Interest G. Smagin Shareolder of: 100%, Employee of: 100%, J. Tripp Shareolder of: 100%, Employee of: 100%
Comparable studies
Other experimental studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics Promote Structural and Functional Neural Plasticity Neurons in vitro and in vivo | 2018 | Laboratory study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Focused attention meditation changes the boundary and configuration of functional networks in the brain One human participant | 2020 | Single-case experimental design with intensive longitudinal data | n = 1 |
| Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation. Rat brain models | 2002 | Review with experimental data |