The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Abstract

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism

“…This pattern of action is similar to that observed in recent human neuroimaging studies with ketamine (Vollenweider and Kometer, 2010). Given the top-down control exerted by PFC on most cortical and subcortical areas (Miller and Cohen, 2001), the disruption of PFC and thalamic function by PCP may have a profound impact on a large number of brain functions, which may account for the perceptual, cognitive, affective, and motor actions of PCP (Krystal et al, 1994(Krystal et al, , 2003.…”

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

“…In particular, LSD produced 30% higher ratings for both oceanic boundlessness (mostly blissful state), 30% higher ratings for anxious ego dissolution, and 63% higher ratings for visionary restructuralization (mostly greater audio-visual synesthesia) compared with a high dose of psilocybin (54,56 with DMT and ketamine, LSD produced 50% higher ratings for both oceanic boundlessness, 50% higher ratings for visionary restructuralization, and comparably high ratings for anxious ego dissolution (21,28). LSD produced similar ratings on the AMRS for emotional excitation, inactivation, and dreaminess compared with high-dose psilocybin (54).…”

Animal models for predicting the efficacy and side effects of antipsychotic drugs

“…30 In rodents, acute or chronic treatment with these drugs induces behavioral abnormalities such as scratching, forepaw treading, head twitches, and lower lip retraction. 30,31 Some of these effects may depend on functional interplay between dopamine and serotonin pathways.…”

“…30 In rodents, acute or chronic treatment with these drugs induces behavioral abnormalities such as scratching, forepaw treading, head twitches, and lower lip retraction. 30,31 Some of these effects may depend on functional interplay between dopamine and serotonin pathways. 27,[31][32][33] Indeed, some studies report that there is a decrease in the density of 5-HT2A receptors in the prefrontal cortex of patients, while there was a significant increase in the density of dopamine D2 receptors in the caudate nucleus, suggesting that dysfunction in serotoninergic activity could contribute to the alteration of dopaminergic function seen in schizophrenia.…”