May 22, 2026

Top News
Intranasal Clozapine Cuts Dose by 97% in Preclinical Study
Mechanism of Action
Gut-lung microbe shifts may explain clozapine's severe bowel and lung side effects - Medical Xpress

Research suggests gut-lung microbiome shifts may underlie clozapine's severe gastrointestinal and pulmonary adverse effects, offering potential mechanistic insights for managing this high-risk antipsychotic.

Diagnosis & Treatment
A single dose of psilocybin eased depression symptoms for months, our study found - The Conversation

A single dose of psilocybin produced sustained depression symptom relief for months, highlighting its potential as a novel treatment for depression.

Diagnosis & Treatment
Using Bilateral Stimulation (A Pre-existing Trauma Technique) After Eating to Reduce Anxiety in People Recovering From Eating Disorders

A completed study from San Francisco State University investigated using bilateral stimulation after meals to reduce anxiety in individuals recovering from eating disorders.

Substance Use
Multi-Site Trial of Tirzepatide for Smoking Cessation

A multi-site clinical trial is evaluating tirzepatide for smoking cessation, representing a potential off-label or repurposing application of a GLP-1/GIP agonist in substance use disorder treatment.

Policy & Regulation
Attorney Urges DEA to Expedite Psilocybin Rescheduling Following Trump's Psychedelics Order - Hemp Gazette

An attorney is urging the DEA to expedite the rescheduling of psilocybin following a presidential order, highlighting regulatory shifts that may impact future clinical access to psychedelics.

Clinical Pearls

Bite-sized clinical takeaways from today's literature (sources from May 17 – May 22)

  • Consider repurposing tocilizumab for treatment-resistant depression in patients with elevated inflammatory markers, pending further clinical efficacy data.
  • Monitor for severe gastrointestinal and pulmonary adverse effects in patients on clozapine, as gut-lung microbiome shifts may be a contributing mechanism.
  • Evaluate centanafadine as a novel non-stimulant option for adult ADHD, noting its promising profile in recent RCTs.
  • Utilize baseline default mode network functional connectivity as a potential biomarker to predict escitalopram response in adolescents with major depressive disorder.
  • Explore low-dose lithium as an off-label therapeutic strategy for managing behavioral symptoms in patients with mild cognitive impairment.
  • Assess the potential of intranasal clozapine sol-gel formulations to reduce peripheral metabolic side effects while maintaining antipsychotic efficacy.
  • Recognize that among currently studied psychedelics, only psilocybin has demonstrated robust efficacy for depression, distinguishing it from other agents in this class.
  • Consider the potential off-label use of tirzepatide for smoking cessation, given ongoing multi-site clinical trial evaluations for this GLP-1/GIP agonist.
  • Review expert guidelines on the recognition and treatment of bipolar disorder with mixed features to optimize management strategies for this complex presentation.

Mechanism of Action 2

Single psilocybin dose may relieve depression within days - Earth.com

Research indicates that a single dose of psilocybin may provide rapid relief from depression symptoms within days, highlighting its potential as a fast-acting therapeutic agent for major depressive disorder.

Xanomeline-trospium reverses phencyclidine-induced cognitive deficits through modulation of the gut microbiota-brain axis in mice

Preclinical data suggest KarXT (xanomeline-trospium) reverses cognitive deficits in a schizophrenia mouse model via gut microbiota modulation, offering potential insights into its mechanism and gastrointestinal side effects.

Diagnosis & Treatment 3

Study authors suggest optimal dosing for different ADHD medications - The Pharmaceutical Journal

Study authors suggest optimal dosing for different ADHD medications

Low-Dose Lithium Shows Promise for Mild Cognitive Impairment - Pharmacy Times

Low-dose lithium demonstrates potential therapeutic benefit for mild cognitive impairment, suggesting a possible off-label or repurposing opportunity for dementia-related behavioral symptoms.

Targeting inflammation in depression: a proof-of-concept worth following

A proof-of-concept RCT shows that a single dose of the anti-inflammatory agent tocilizumab cleared inflammation in depressed patients, though its clinical efficacy on depressive symptoms requires further investigation.

Drug Development 4

Dementia drug may help treat alcohol withdrawal

Research suggests repurposing a dementia drug targeting neuroinflammation as a potential treatment for alcohol withdrawal, offering a new pathway for alcohol use disorder management.

Compass Pathways Eyes Q4 FDA Filing for Psilocybin Depression Drug After Phase 3 Wins - Yahoo Finance

Compass Pathways plans to file for FDA approval of a psilocybin-based treatment for depression following successful Phase 3 trial results, representing a significant development in psychedelic psychiatry.

“Intranasal clozapine sol-gel formulation induces an antipsychotic effect at a fraction of a comparable oral therapeutic dose”

Preclinical rat data demonstrate that an intranasal clozapine sol-gel formulation achieves antipsychotic efficacy at 3.5% of the oral dose with reduced peripheral exposure and metabolic side effects, suggesting a promising delivery method for further clinical investigation.

The Evolving Pharmacological Landscape for Paediatric and Adult ADHD

This review of 53 RCTs identifies centanafadine as a promising novel non-stimulant treatment for adult ADHD, while noting that dasotraline showed promise in children before development was halted.

Podcast Summary 1

Bipolar Disorder With Mixed Features: Recognition and Treatment, With Roger McIntyre, MD, at APA - Psychiatric Times

This podcast summary covers the recognition and treatment of bipolar disorder with mixed features, featuring expert commentary from Roger McIntyre, MD.

Clinical Pearl 1

Pilot trial suggests anti-inflammatory drug could help difficult-to-treat depression

A pilot randomized controlled trial published in JAMA Psychiatry suggests that an anti-inflammatory immunotherapy may be a promising treatment option for difficult-to-treat depression.