Psychedelics.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms, neuroimaging, and early clinical trials
PubMed 26841800 · doi:10.1124/pr.115.011478
What was done
This review synthesized pharmacological, neurobiological, and clinical literature on classical serotonergic psychedelics, focusing on substances such as LSD and psilocybin. The authors reviewed receptor mechanisms (specifically 5-HT2A receptors on neocortical layer V pyramidal cells), rodent models, human neuroimaging modalities (functional magnetic resonance imaging and magnetoencephalography), and preliminary clinical applications including double-blind placebo-controlled phase 2 trials in cancer-related psychosocial distress and pilot trials in addiction.
What was found
Serotonergic psychedelics act as agonists or partial agonists at brain 5-HT2A receptors. In vivo human neuroimaging (fMRI and MEG) demonstrated that intravenously administered psilocybin and LSD decrease oscillatory power in default mode network regions. Clinical summaries noted relief of anxiety and depression in phase 2 trials of psilocybin-assisted psychotherapy for cancer-related distress, as well as positive signals in two pilot studies for alcohol and nicotine addiction. The abstract provides no specific quantitative effect sizes, sample sizes, or numerical statistics.
Why it matters
This review consolidates the neurobiological mechanism of action and early clinical evidence supporting the therapeutic resurgence of psychedelics for psychiatric conditions and addiction.
Limits
As a broad narrative review, it lacks systematic search methodology, formal study quality appraisal, or meta-analytic quantification. The referenced clinical evidence is drawn from early-phase trials and small pilot studies, and the abstract omits specific sample sizes, adverse event rates, and precise numerical outcomes.
Cited by
- supports MDMA is pharmacologically categorized as an empathogen rather than a classic psychedelic, and ketamine is categorized as a dissociative anesthetic.