Psychedelics Promote Structural and Functional Neural Plasticity

Calvin Ly, Alexandra C. Greb, Lindsay P. Cameron, Jonathan M. Wong, Eden V. Barragan, Paige C. Wilson, Kyle F. Burbach, Sina Soltanzadeh Zarandi, Alexander Sood, Michael R. Paddy, Whitney C. Duim, Megan Dennis, A Kimberley Usrey, Kassandra M. Ori-McKenney, John Gray, David Olson

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders.

Original languageEnglish (US)
Pages (from-to)3170-3182
Number of pages13
JournalCell Reports
Volume23
Issue number11
DOIs
StatePublished - Jun 12 2018

Fingerprint

Hallucinogens
Neuronal Plasticity
Plasticity
Ketamine
Prefrontal Cortex
Synapses
Antidepressive Agents
Dissociative Anesthetics
Electrophysiology
Lysergic Acid Diethylamide
Dendritic Spines
Pharmaceutical Chemistry
Fluorescence microscopy
Fluorescence Microscopy
Scaffolds
Neurons
Atrophy
Growth

Keywords

  • depression
  • DMT
  • ketamine
  • LSD
  • MDMA
  • neural plasticity
  • noribogaine
  • psychedelic
  • spinogenesis
  • synaptogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., ... Olson, D. (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell Reports, 23(11), 3170-3182. https://doi.org/10.1016/j.celrep.2018.05.022

Psychedelics Promote Structural and Functional Neural Plasticity. / Ly, Calvin; Greb, Alexandra C.; Cameron, Lindsay P.; Wong, Jonathan M.; Barragan, Eden V.; Wilson, Paige C.; Burbach, Kyle F.; Soltanzadeh Zarandi, Sina; Sood, Alexander; Paddy, Michael R.; Duim, Whitney C.; Dennis, Megan; Usrey, A Kimberley; Ori-McKenney, Kassandra M.; Gray, John; Olson, David.

In: Cell Reports, Vol. 23, No. 11, 12.06.2018, p. 3170-3182.

Research output: Contribution to journalArticle

Ly, C, Greb, AC, Cameron, LP, Wong, JM, Barragan, EV, Wilson, PC, Burbach, KF, Soltanzadeh Zarandi, S, Sood, A, Paddy, MR, Duim, WC, Dennis, M, Usrey, AK, Ori-McKenney, KM, Gray, J & Olson, D 2018, 'Psychedelics Promote Structural and Functional Neural Plasticity', Cell Reports, vol. 23, no. 11, pp. 3170-3182. https://doi.org/10.1016/j.celrep.2018.05.022
Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC et al. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Reports. 2018 Jun 12;23(11):3170-3182. https://doi.org/10.1016/j.celrep.2018.05.022
Ly, Calvin ; Greb, Alexandra C. ; Cameron, Lindsay P. ; Wong, Jonathan M. ; Barragan, Eden V. ; Wilson, Paige C. ; Burbach, Kyle F. ; Soltanzadeh Zarandi, Sina ; Sood, Alexander ; Paddy, Michael R. ; Duim, Whitney C. ; Dennis, Megan ; Usrey, A Kimberley ; Ori-McKenney, Kassandra M. ; Gray, John ; Olson, David. / Psychedelics Promote Structural and Functional Neural Plasticity. In: Cell Reports. 2018 ; Vol. 23, No. 11. pp. 3170-3182.
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