d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders

Prog Brain Res. 2018;242:69-96. doi: 10.1016/bs.pbr.2018.07.008. Epub 2018 Aug 31.


Depression and anxiety are psychiatric diagnoses commonly associated with low quality of life and low percentage of responsiveness by patients treated with currently available drugs. Thus, research into alternative compounds to treat these disorders is essential to guarantee a patient's remission. The last decade has witnessed a revamped interest for the application of psychedelic medicine for the treatment of mental disorders due to anecdotal reports and clinical studies which show that low doses of d-lysergic acid diethylamide (LSD) and psilocybin may have antidepressant effects. LSD and psilocybin have demonstrated mood-modulating properties likely due to their capacity to modulate serotonergic (5-HT), dopaminergic (DA) and glutamatergic systems. LSD, belonging to the category of "classic halluginogens," interacts with the 5-HT system through 5HT1A, and 5HT2A receptors, with the DA system through D2 receptors, and indirectly also the glutamatergic neurotransmission thought the recruitment of N-methyl-d-aspartate (NMDA) receptors. Randomized clinical studies have confirmed its antidepressant and anxiolytic effects in humans. Thus, in this chapter, we will review the pharmacology of psychedelic drugs, report the most striking clinical evidence which substantiate the therapeutic potentials of these fascinating compounds in mood disorders, and look into the horizon of where psychedelic medicine is heading.

Keywords: Anxiety; Depression; Hallucinogens; Psilocybin; d-Lysergic acid diethylamide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Hallucinogens / pharmacology
  • Hallucinogens / therapeutic use*
  • Humans
  • Lysergic Acid Diethylamide / pharmacology
  • Lysergic Acid Diethylamide / therapeutic use*
  • Mood Disorders / drug therapy*
  • Psilocybin / pharmacology
  • Psilocybin / therapeutic use*


  • Hallucinogens
  • Psilocybin
  • Lysergic Acid Diethylamide