Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr;68(2):264-355.
doi: 10.1124/pr.115.011478.

Psychedelics

David E Nichols  1
Affiliations
Review

Psychedelics

David E Nichols. Pharmacol Rev. 2016 Apr.

Erratum in

  • Correction to: "Psychedelics".
    [No authors listed] [No authors listed] Pharmacol Rev. 2016 Apr;68(2):356. doi: 10.1124/pr.114.011478err. Pharmacol Rev. 2016. PMID: 26931125 Free PMC article. No abstract available.

Abstract

Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Chemical structures of serotonin and LSD.
Fig. 2.
Fig. 2.
Chemical structures of classic psychadelics mescaline, psilocybin, and DMT.
Fig. 3.
Fig. 3.
NBOMe compounds.
Fig. 4.
Fig. 4.
Chemical structures of DOM, DOB, and DOI.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abi-Saab WM, Bubser M, Roth RH, Deutch AY. (1999) 5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex. Neuropsychopharmacology 20:92–96. - PubMed
    1. Abuzzahab FS, Sr, Anderson BJ. (1971) A review of LSD treatment in alcoholism. Int Pharmacopsychiatry 6:223–235. - PubMed
    1. Adams KH, Hansen ES, Pinborg LH, Hasselbalch SG, Svarer C, Holm S, Bolwig TG, Knudsen GM. (2005) Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei. Int J Neuropsychopharmacol 8:391–401. - PubMed
    1. Aghajanian GK. (1980) Mescaline and LSD facilitate the activation of locus coeruleus neurons by peripheral stimuli. Brain Res 186:492–498. - PubMed
    1. Aghajanian GK, Foote WE, Sheard MH. (1968) Lysergic acid diethylamide: sensitive neuronal units in the midbrain raphe. Science 161:706–708. - PubMed

Publication types