Psychedelics, as a plant-derived material, have been used for millennia in reli-
gious and medical practices. They produce an altered state of consciousness
characterized by distortions of perception, hallucinations, dissolution of self boun-
daries and the experience of unity with the world. Classic psychedelics, also
known as serotonergic hallucinogens, such as lysergic acid diethylamide (LSD)
and psilocybin were extensively investigated in substance-assisted psychotherapy
during the 1950s–1960s. These early clinical studies reported improvement rates
in patients with various forms of depression, anxiety disorders, alcohol dependen-
ce. The development of modern neuroimaging techniques renewed interest in
the investigation of psychedelics as a class of drugs that may reopen multiple the-
rapeutic benefits. Current behavioral and neurochemical data show that psy-
chedelics induce their psychological effects primarily via 5-hydroxytryptamine
type 2A (5-HT2A) receptor activation and modulate neural circuits involved in mood and affective disorders. Clinical trials examining psilocybin have suggested
that the compound relieves symptoms of depression and anxiety with rapid onset
and longer duration. Serotonergic psychedelics enhance expression of neurotro-
phic factors such as brain-derived neurotrophic factor (BDNF) as well as expres-
sion of genes associated with synaptic plasticity and stimulate synapse formation.
These effects are similar to those produced by fast-acting antidepressant keta-
mine. Basic science research can reveal the neural mechanism of psychedelics
action and how they can be used for treatment.
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