Therapeutic advances in psychopharmacology
February 1, 2015
Hannah Steeds, Robin L Carhart-Harris, James M Stone
132 citations
Schizophrenia involves positive, negative, and cognitive symptoms, and about one-third of patients do not respond to existing medications. This review evaluates how drugs acting on dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic, and kappa opioid systems model aspects of schizophrenia in animals and humans. Understanding interactions between these neurotransmitter systems and their links to symptoms is crucial for forming a coherent hypothesis of schizophrenia's pathogenesis and developing new therapies.
Nature medicine
July 24, 2025
Luke A Jelen, David J Lythgoe, James M Stone et al.
29 citations
Blocking the opioid system with naltrexone reduced both the brain glutamate response and the antidepressant effect of ketamine in adults with major depressive disorder. In a double-blind crossover study of 26 adults, naltrexone before ketamine infusion attenuated the rise in glutamate+glutamine relative to N-acetylaspartate in the anterior cingulate cortex and lessened the drop in depression scores the next day. The opioid system modulates ketamine's acute brain effects and subsequent mood improvement, suggesting interactions between glutamate and opioid systems may inform new depression treatments.
The American journal of psychiatry
June 1, 2026
Luke A Jelen, Owen O'Daly, Fernando O Zelaya et al.
2 citations
Ketamine increased blood flow in specific brain regions (subgenual, pregenual, and dorsal anterior cingulate cortices) in adults with major depressive disorder, and this effect was not blocked by the opioid blocker naltrexone. However, naltrexone did disrupt the relationships between blood flow changes and both acute subjective effects and antidepressant response. The blood flow changes aligned with patterns of opioid and glutamate receptor distribution, suggesting that ketamine's effects involve interactions among multiple neurotransmitter systems.
Journal of psychoactive drugs
January 1, 2025
Morgan Hadley, Alicia Halliday, James M Stone
1 citation
Hallucinogen Persisting Perception Disorder (HPPD) may be more common than previously thought. Among 415 hallucinogen and other drug users who completed an online questionnaire, 39.7% reported symptoms of Type I HPPD and 4.3% reported symptoms of Type II HPPD. Neuroticism scores did not differ between those with and without HPPD. Individuals with Type II HPPD were more likely to report anxiety, obsessional thoughts, paranoia, hypochondria, and panic attacks, and were also more likely to have used 25I-NBOMe, dextromethorphan, nitrous oxide, and benzodiazepines. Nearly half (47.3%) had never tested their drugs, complicating attribution of HPPD severity to specific substances.