PMID- 33328244
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1521-0081 (Electronic)
IS  - 0031-6997 (Linking)
VI  - 73
IP  - 1
DP  - 2021 Jan
TI  - Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter 
      Mechanisms.
PG  - 202-277
LID - 10.1124/pharmrev.120.000056 [doi]
AB  - Mounting evidence suggests safety and efficacy of psychedelic compounds as 
      potential novel therapeutics in psychiatry. Ketamine has been approved by the 
      Food and Drug Administration in a new class of antidepressants, and 
      3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials 
      for post-traumatic stress disorder. Psilocybin and lysergic acid diethylamide 
      (LSD) are being investigated in several phase II and phase I clinical trials. 
      Hence, the concept of psychedelics as therapeutics may be incorporated into 
      modern society. Here, we discuss the main known neurobiological therapeutic 
      mechanisms of psychedelics, which are thought to be mediated by the effects of 
      these compounds on the serotonergic (via 5-HT(2A) and 5-HT(1A) receptors) and 
      glutamatergic [via N-methyl-d-aspartate (NMDA) and 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors] systems. 
      We focus on 1) neuroplasticity mediated by the modulation of mammalian target of 
      rapamycin-, brain-derived neurotrophic factor-, and early growth response-related 
      pathways; 2) immunomodulation via effects on the hypothalamic-pituitary-adrenal 
      axis, nuclear factor kB, and cytokines such as tumor necrosis factor-alpha and 
      interleukin 1, 6, and 10 production and release; and 3) modulation of 
      serotonergic, dopaminergic, glutamatergic, GABAergic, and norepinephrinergic 
      receptors, transporters, and turnover systems. We discuss arising concerns and 
      ways to assess potential neurobiological changes, dependence, and 
      immunosuppression. Although larger cohorts are required to corroborate 
      preliminary findings, the results obtained so far are promising and represent a 
      critical opportunity for improvement of pharmacotherapies in psychiatry, an area 
      that has seen limited therapeutic advancement in the last 20 years. Studies are 
      underway that are trying to decouple the psychedelic effects from the therapeutic 
      effects of these compounds. SIGNIFICANCE STATEMENT: Psychedelic compounds are 
      emerging as potential novel therapeutics in psychiatry. However, understanding of 
      molecular mechanisms mediating improvement remains limited. This paper reviews 
      the available evidence concerning the effects of psychedelic compounds on 
      pathways that modulate neuroplasticity, immunity, and neurotransmitter systems. 
      This work aims to be a reference for psychiatrists who may soon be faced with the 
      possibility of prescribing psychedelic compounds as medications, helping them 
      assess which compound(s) and regimen could be most useful for decreasing specific 
      psychiatric symptoms.
CI  - Copyright (c) 2020 by The Author(s).
FAU - Inserra, Antonio
AU  - Inserra A
AD  - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 
      Montreal, Quebec, Canada.
FAU - De Gregorio, Danilo
AU  - De Gregorio D
AD  - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 
      Montreal, Quebec, Canada.
FAU - Gobbi, Gabriella
AU  - Gobbi G
AD  - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 
      Montreal, Quebec, Canada gabriella.gobbi@mcgill.ca.
LA  - eng
GR  - 436986/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Pharmacol Rev
JT  - Pharmacological reviews
JID - 0421737
RN  - 0 (Hallucinogens)
RN  - 0 (Neurotransmitter Agents)
SB  - IM
MH  - *Hallucinogens/pharmacology
MH  - Humans
MH  - Hypothalamo-Hypophyseal System
MH  - Immunomodulation
MH  - Neuronal Plasticity
MH  - Neurotransmitter Agents
MH  - Pituitary-Adrenal System
MH  - *Psychiatry
MH  - United States
COIS- G.G. is a consultant for Diamond Therapeutic Inc. The other authors declare no 
      potential conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/12/18 06:00
MHDA- 2021/10/29 06:00
CRDT- 2020/12/17 05:38
PHST- 2020/12/17 05:38 [entrez]
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
AID - 73/1/202 [pii]
AID - 10.1124/pharmrev.120.000056 [doi]
PST - ppublish
SO  - Pharmacol Rev. 2021 Jan;73(1):202-277. doi: 10.1124/pharmrev.120.000056.