General Hospital Psychiatry
July 3, 2025
Kush V. Bhatt, James D Asuncion, Al Alam et al.
4 citations
The resurgence of interest in classical psychedelics brings both promise and challenges to psychiatric care. Increasing evidence supports the therapeutic potential of psychedelics for a range of mental health conditions, and approval for clinical use appears inevitable. The psychedelic-associated acute subjective experience may mediate or enhance therapeutic outcomes, but also presents...
Pharmaceuticals (Basel, Switzerland)
January 24, 2025
John E Donello, Roger S McIntyre, Donald B Pickel et al.
14 citations
Plastogens are a class of therapeutics that function by rapidly promoting changes in neuroplasticity. A notable example, ketamine, is receiving great attention due to its combined rapid and long-term antidepressant effects. Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist, and, in addition to its therapeutic activity, it is associated with psychotomimetic and dissociative side...
The American journal of psychiatry
2025
Roger S McIntyre, Angela T H Kwan, Rodrigo B. Mansur et al.
23 citations
During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder....
CNS Spectrums
2025
Emma O’leary, Seetal Dodd, Stephen M Stahl
Psychoactive substances, known for their acute impact on perception and cognition, are gaining attention for their potential therapeutic applications. Many of these substances are plant-derived with deep-rooted histories of use in non-medical contexts, where they have been viewed as either tools for social cohesion or sources of discord, depending on cultural and societal contexts. This review...
World Psychiatry
September 15, 2023
Roger S McIntyre, Mohammad Alsuwaidan, Bernhard T Baune et al.
712 citations
Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a...
Journal of psychopharmacology (Oxford, England)
March 1, 2023
Takesha Cooper, Michael David Seigler, Stephen M Stahl
18 citations
Numerous new agents with rapid onset antidepressant effects are entering clinical trials and clinical practice. Studies focus on either first-line treatment of major depressive disorder or on patients whose major depressive disorder is resistant to prior antidepressant drugs. Novel agents target three very different central nervous system sites: as antagonists of N-methyl-d-aspartate (NMDA)...
International Journal of Molecular Sciences
October 13, 2022
Stephen M Stahl, Sara de Martin, Andrea Mattarei et al.
This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in...
CNS Spectrums
July 11, 2022
Seetal Dodd, Trevor R. Norman, Harris A. Eyre et al.
61 citations
Abstract Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to...
American Journal of Psychiatry
March 17, 2021
Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al.
694 citations
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
CNS Spectrums
September 30, 2019
Stephen M Stahl
Although currently available antidepressants increase monoamine levels soon after the start of treatment, therapeutic benefits are often delayed by several weeks and the majority of patients with major depressive disorder fail to achieve an adequate response to first- or second-line therapies targeting monoamines. The recent approval of the NMDA (N-methyl-d-aspartate) antagonist esketamine...