Mood Effects of Serotonin Agonists: Depression

Summary

This study will examine the effect of a low dose of the 5HT2A agonist LSD (26 µg), compared to placebo, on acute and protracted mood states in individuals with depression. The investigators will assess the relationship between mood-related symptoms and EEG as a neurophysiological marker.

Timeline

Start

2025-06-09

Primary completion

2026-06-01

Completion

2026-06-01

Publications

• Background Duan W, Cao D, Wang S, Cheng J. Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chem Rev. 2024 Jan 10;124(1):124-163. doi: 10.1021/acs.chemrev.3c00375. Epub 2023 Nov 30.
• Background Husain MI, Ledwos N, Fellows E, Baer J, Rosenblat JD, Blumberger DM, Mulsant BH, Castle DJ. Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? Front Psychiatry. 2023 Feb 10;13:1076459. doi: 10.3389/fpsyt.2022.1076459. eCollection 2022.
• Background Ling S, Ceban F, Lui LMW, Lee Y, Teopiz KM, Rodrigues NB, Lipsitz O, Gill H, Subramaniapillai M, Mansur RB, Lin K, Ho R, Rosenblat JD, Castle D, McIntyre RS. Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs. 2022 Jan;36(1):17-30. doi: 10.1007/s40263-021-00877-y. Epub 2021 Nov 17.
• Background Murphy RJ, Muthukumaraswamy S, de Wit H. Microdosing Psychedelics: Current Evidence From Controlled Studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):500-511. doi: 10.1016/j.bpsc.2024.01.002. Epub 2024 Jan 26.
• Background Walsh CA, Gorfinkel L, Shmulewitz D, Stohl M, Hasin DS. Use of Lysergic Acid Diethylamide by Major Depression Status. JAMA Psychiatry. 2024 Jan 1;81(1):89-96. doi: 10.1001/jamapsychiatry.2023.3867.
• Background Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018 Jun 12;23(11):3170-3182. doi: 10.1016/j.celrep.2018.05.022.
• Background Moliner R, Girych M, Brunello CA, Kovaleva V, Biojone C, Enkavi G, Antenucci L, Kot EF, Goncharuk SA, Kaurinkoski K, Kuutti M, Fred SM, Elsila LV, Sakson S, Cannarozzo C, Diniz CRAF, Seiffert N, Rubiolo A, Haapaniemi H, Meshi E, Nagaeva E, Ohman T, Rog T, Kankuri E, Vilar M, Varjosalo M, Korpi ER, Permi P, Mineev KS, Saarma M, Vattulainen I, Casarotto PC, Castren E. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci. 2023 Jun;26(6):1032-1041. doi: 10.1038/s41593-023-01316-5. Epub 2023 Jun 5.
• Background Allen N, Jeremiah A, Murphy R, Sumner R, Forsyth A, Hoeh N, Menkes DB, Evans W, Muthukumaraswamy S, Sundram F, Roop P. LSD increases sleep duration the night after microdosing. Transl Psychiatry. 2024 Apr 15;14(1):191. doi: 10.1038/s41398-024-02900-4.
• Background Hutten NRPW, Quaedflieg CWEM, Mason NL, Theunissen EL, Liechti ME, Duthaler U, Kuypers KPC, Bonnelle V, Feilding A, Ramaekers JG. Inter-individual variability in neural response to low doses of LSD. Transl Psychiatry. 2024 Jul 15;14(1):288. doi: 10.1038/s41398-024-03013-8.
• Background Bershad AK, Schepers ST, Bremmer MP, Lee R, de Wit H. Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers. Biol Psychiatry. 2019 Nov 15;86(10):792-800. doi: 10.1016/j.biopsych.2019.05.019. Epub 2019 Jun 3.

Drugs

Indications