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2016 ; 68
(2
): 264-355
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English Wikipedia
Psychedelics
#MMPMID26841800
Nichols DE
Pharmacol Rev
2016[Apr]; 68
(2
): 264-355
PMID26841800
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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.
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