Translational Psychiatry
November 18, 2025
Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al.
2 citations
In neurons derived from induced pluripotent stem cells of five women with treatment-resistant depression (average age 40.2 years), both the glycoprotein reelin and the ketamine metabolite (2R,6R)-hydroxynorketamine increased expression of several synaptic proteins (GluA1, PSD-95, Dab1, Synapsin I, and p-ERK) within one hour, with effects declining by 24 hours. Gene expression changes were similar for both compounds, though only reelin upregulated mTORC1 signaling. The findings suggest that iPSC-derived neurons may serve as a useful in vitro model for studying treatment-resistant depression and testing potential therapeutics.
General Hospital Psychiatry
February 25, 2026
Alan C. Courtes, Blake Myers, Noah Daly et al.
1 citation
Psychological stress worsens cancer outcomes by activating adrenergic signaling between nerves and tumors, a process called tumor-neuron crosstalk. Preclinical models show stress triggers sympathetic pathways that promote cancer progression and treatment resistance. Conventional antidepressants are often less effective for cancer patients, but psilocybin has achieved 60-80% long-term remission of cancer-related depression and anxiety in limited samples, while ketamine provides rapid but short-lived symptom control. These agents may normalize HPA axis function and upregulate neurotrophic factors, reducing sustained adrenergic tone and interrupting stress-driven tumor-neuron signaling. Integrating these drugs into oncology could improve survival, and hospital-based psychiatrists are positioned to lead interdisciplinary research with biomarker-rich trials.
February 28, 2026
Burton J. Tabaac, Kenneth Shinozuka, Fadel et al.
preprint
Mescaline, a classic serotonergic psychedelic used ceremonially by Indigenous peoples, shows preliminary safety in healthy humans under controlled conditions, producing dose-dependent subjective effects with moderate, transient autonomic stimulation and no serious medical complications. Adverse effects are generally self-limited, and pooled safety analyses and observational data support an overall favorable safety profile in screened populations. However, there is a lack of controlled clinical trials evaluating mescaline in patient populations, so its safety in individuals with cardiovascular, metabolic, or psychiatric comorbidities remains unclear. Controlled clinical trials are needed to establish its safety and therapeutic potential.
Research Square
February 12, 2026
Jenessa N Johnston, Greg Jones, Shiyong Peng et al.
Rapid-acting antidepressants such as ketamine and psychedelics share common downstream effects on gene expression in human cortical neurons, despite targeting different initial receptors. Using stem cells from people with treatment-resistant depression and healthy volunteers, neurons were treated with several compounds. After 6 and 24 hours, gene activity was highly correlated across all drugs, converging on pathways related to inflammation, mTORC1 signaling, and cell growth. One compound, HNK, increased gene activity in excitatory neurons and decreased it in inhibitory neurons. These gene changes matched protein changes in spinal fluid from people given ketamine, supporting the model's relevance for studying antidepressant mechanisms.
American Journal of Therapeutics
Burton J. Tabaac, Kenneth Shinozuka, Mahdi Fadel et al.
Mescaline, a classic psychedelic with a history of indigenous ceremonial use, is being reexamined for psychiatric therapy. It works primarily by activating serotonin-2A receptors. Most modern safety data come from healthy volunteers, leaving its effects in patients with cardiovascular, metabolic, or psychiatric conditions unclear. Randomized, placebo-controlled studies show mescaline produces dose-dependent subjective effects with moderate, temporary autonomic stimulation and no serious complications under controlled conditions. Adverse effects are generally self-limiting, and pooled analyses indicate a favorable safety profile in screened populations. Controlled clinical trials are needed to establish its safety and therapeutic potential in patient groups.