June 16, 2026

Top News
Spironolactone Repurposed for Schizophrenia: RCT Targets NRG1-ERBB4 Pathway
Drug Development
Researchers receive funding to launch USC’s first clinical study of psilocybin for mental health - Keck School of Medicine of USC

USC has secured funding to initiate its first clinical trial evaluating psilocybin for mental health conditions, marking a step in the ongoing research into psychedelic pharmacotherapy.

Drug Development
Antagonizing NRG1-ERBB4 signaling pathway with spironolactone for the treatment of schizophrenia: results of a randomized controlled drug repositioning clinical trial - Nature

A randomized controlled trial published in Nature demonstrates that spironolactone, repurposed to antagonize the NRG1-ERBB4 signaling pathway, is a viable treatment for schizophrenia.

Podcast Summary
The Art of Deprescribing: A Framework for Ending Medication with Joseph Goldberg, MD

This podcast episode outlines the American Society of Clinical Psychopharmacology's consensus framework on deprescribing psychotropics, offering practical guidance on managing polypharmacy, addressing pseudotreatment resistance via long-acting injectables, and navigating the psychological aspects of medication discontinuation.

Drug Development
Psilocybin to target persistent concussion symptoms in Australia's first clinical trial

Monash University has launched Australia's first randomized clinical trial to evaluate psilocybin-assisted therapy for persistent post-concussion symptoms, targeting neuroinflammation and neural plasticity.

Clinical Pearl
Antagonizing NRG1-ERBB4 signaling pathway with spironolactone for the treatment of schizophrenia: results of a randomized controlled drug repositioning clinical trial

A proof-of-concept trial found that spironolactone did not significantly improve working memory in schizophrenia compared to placebo, though post-hoc analyses suggest potential benefit warranting further study.

Clinical Pearls

Bite-sized clinical takeaways from today's literature (sources from Jun 14 – Jun 16)

  • Consider repurposing prucalopride for patients with depression who present with prominent cognitive fog, given early-phase evidence of cognitive improvement via 5-HT4 agonism.
  • Utilize subcutaneous extended-release risperidone (Uzedy) for patients requiring long-acting injectable coverage, as it maintains therapeutic plasma levels for up to 56 days without new safety signals.
  • Counsel patients on cannabis use that psychiatric adverse events are the most common serious side effects and include risks of hospitalization or death.
  • Apply the ASCP consensus framework to identify pseudotreatment resistance in polypharmacy cases, potentially resolving it by switching to long-acting injectables rather than adding more oral agents.
  • Monitor for significant psychiatric adverse reactions when prescribing spironolactone off-label for schizophrenia, as recent proof-of-concept trials showed no significant benefit on working memory compared to placebo.
  • Exercise caution with high-dose dextromethorphan (300-400 mg) due to dose-dependent hallucinatory effects, as current evidence is insufficient to define safe therapeutic parameters for psychiatric use.
  • Refer patients with opioid use disorder to hospital-based addiction consultation services like START, which have been shown to improve clinical outcomes at low cost.
  • Anticipate that spironolactone may still hold potential for specific schizophrenia subtypes based on post-hoc analyses suggesting benefit in working memory, warranting further targeted study.

Drug Development 2

HMNC Brain Health raises $50M Series B to advance two depression drugs

HMNC Brain Health raised $50M in Series B funding to advance its two depression drug candidates into mid-stage clinical trials.

A Phase 1 Open-Label Study Assessing the Safety and Pharmacokinetics of TV-46000, an Extended-Release Injectable Suspension of Risperidone for Subcutaneous Use

A Phase 1 study confirms the safety and pharmacokinetic profile of TV-46000 (Uzedy), a subcutaneous extended-release risperidone formulation, demonstrating therapeutic plasma levels maintained for up to 56 days with no new safety signals.

Substance Use 2

Hospital addiction consultation service may improve outcomes at low cost

A hospital-based addiction consultation service (START) for opioid use disorder improves clinical outcomes at low cost.

Cannabis and Cannabinoid-Related Suspected Adverse Drug Reactions: Global Patterns and Cross-National Analysis Based on VigiBase® Data

A global pharmacovigilance analysis of nearly 10,000 cannabis-related adverse drug reaction reports reveals that psychiatric and nervous system disorders are the most frequent suspected side effects, with a high proportion of serious outcomes including hospitalization and death.

Diagnosis & Treatment 1

UNM Researchers to Study the Use of Psilocybin in Group Therapy Treatment for PTSD - UNM HSC Newsroom

A clinical trial is being conducted to evaluate the efficacy of psilocybin administered within a group therapy setting for the treatment of PTSD.

Mechanism of Action 1

Dextromethorphan Beyond the Cough: Exploring Its Psychedelic Potential: A Systematic Review

This systematic review characterizes the dose-dependent psychedelic effects of dextromethorphan, noting hallucinatory phenomena at 300-400 mg, but concludes evidence is insufficient to define therapeutic parameters for psychiatric use.