Pharmacopsychiatry
April 17, 2025
Aleksander Kwaśny, Zuzanna Gaca, Damian Swieczkowski et al.
2 citations
Regulatory compliance in clinical trials of psilocybin for major depressive disorder and treatment-resistant depression shows gaps. A review of four trial protocols from ClinicalTrials.gov found that while they superficially met regulatory requirements, they inadequately addressed drug interactions, concurrent antidepressant use, and prohibited medications. Functional unblinding and expectancy bias were not fully accounted for. Risk mitigation relied on external criteria. Patients with bipolar or schizoaffective disorders were excluded. The most common psilocybin dose studied was 25 mg. Two trials were double-blind. The findings underscore the need for stricter adherence to regulatory standards in psychedelic clinical research and for exploring efficacy in broader populations.
Pharmacopsychiatry
September 1, 2005
Euphrosyne Gouzoulis‐mayfrank, Anna Neukirch, Karsten Heekeren
2 citations
Two classes of hallucinogens—serotonergic agonists like DMT and NMDA antagonists like S-ketamine—produce distinct patterns of psychosis-like symptoms, rather than one being a universally better model of schizophrenia. In a double-blind crossover study with 15 healthy volunteers, DMT more strongly induced positive symptoms such as thought disorder and inappropriate affect, while S-ketamine more strongly induced negative symptoms, attention deficits, body perception disturbances, and catatonia-like motor phenomena. The findings suggest that each drug class models different aspects or subtypes of schizophrenia, not that the NMDA antagonist model is overall superior to the 5-HT2A agonist model.
Pharmacopsychiatry
June 2, 2025
Ludovic C Dormegny-Jeanjean, Suzie Lenoir, Ilia Humbert et al.
1 citation
Ketamine and esketamine, when used alongside non-selective monoamine oxidase inhibitors, do not cause clinically significant increases in blood pressure or heart rate. In 193 esketamine sessions with 13 patients, systolic pressure rose by 8.68 mmHg, diastolic by 6.57 mmHg, and heart rate by 3.5 beats per minute—changes not considered clinically meaningful. The combination of esketamine with monoamine oxidase inhibitors was not linked to elevated blood pressure. These results suggest minimal risk of sympathomimetic synergy with this drug combination, supporting its safe use in treatment-resistant depression.
Pharmacopsychiatry
December 20, 2024
Mu-Hong Chen, Tung-Ping Su, Wei-Chen Lin et al.
1 citation
Low-grade inflammation (LGI) is linked to poor response to standard antidepressants, but its role in ketamine treatment for treatment-resistant depression (TRD) was unclear. In 167 patients with TRD, 46 had LGI (C-reactive protein ≥3 mg/L) and 121 did not. A single low-dose ketamine infusion improved depressive symptoms only in patients without LGI, showing no significant antidepressant effect in those with LGI. However, ketamine reduced suicidal thoughts in both groups. The placebo response was notably greater in patients with LGI, which may explain the lack of observed ketamine effect in that group. Further research is needed to confirm these findings.
Pharmacopsychiatry
July 7, 2026
Kie Nomoto, Yohei Ohtani, Taisuke Yatomi et al.
In a double-blind, randomized, placebo-controlled trial, 34 Japanese patients with treatment-resistant depression received four intravenous doses of either ketamine (0.5 mg/kg) or saline. No significant differences emerged between the groups on objective or subjective cognitive function measures. Among ketamine-treated patients, those who responded to treatment (at least 50% reduction on the Montgomery-Åsberg Depression Rating Scale) showed greater improvement in subjective cognitive function than non-responders. Participants with weaker inhibitory control at baseline experienced larger reductions in depressive symptoms after ketamine. Repeated ketamine administration did not worsen cognitive function compared to placebo, suggesting cognitive safety, and baseline cognitive control deficits may predict better treatment response.
Pharmacopsychiatry
February 26, 2026
Ping-Chung Wu, Wei-Chen Lin, Tung-Ping Su et al.
A combination of clinical markers better predicts which patients with treatment-resistant depression and suicidal thoughts will respond rapidly and durably to a single low-dose ketamine infusion than any single marker alone. The markers include mild or moderate depression severity, a shorter current episode, no more than four prior antidepressant failures, low or moderate current suicide risk, and a history of suicide attempts. The analysis of 67 patients from previous trials used a decision-tree model to identify these predictors. Clinicians can use these findings to select patients most likely to benefit, though further confirmation is needed.
Pharmacopsychiatry
February 5, 2026
Tianyi Xu, Sabrina Wong, Gia Han Le et al.
Lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine activate the 5-hydroxytryptamine 2B receptor, a pathway known to cause drug-induced valvular heart disease. This systematic review of 17 studies found no research on psilocybin, dimethyltryptamine, or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine show high or moderate affinity for this receptor and promote signaling linked to fibrotic changes in heart valve tissue. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valve abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data suggest potential for fibrotic signaling under sustained exposure. Preliminary evidence supports the need for cardiac safety monitoring in psychedelic research.
Pharmacopsychiatry
September 1, 2011
Simone Grimm, Milan Scheidegger, A Henning et al.
Ketamine, a glutamatergic NMDA receptor antagonist with rapid antidepressant properties, was used to investigate the neurobiology of major depressive disorder. In a multimodal imaging study of 23 healthy subjects, a single ketamine infusion increased negative BOLD responses in brain regions involved in emotional processing, particularly limbic areas linked to emotional information and higher-order mental functions. During cognitive processing, ketamine affected negative BOLD responses in anterior but not posterior regions of the default-mode network. Strong correlations were found between glutamate, glutamine, GABA, and glutamine/glutamate ratios and these brain responses after ketamine administration, suggesting a link to glutamatergic neurotransmission.
Pharmacopsychiatry
September 1, 2011
Milan Scheidegger, A Henning, Martin Walter et al.
A subanaesthetic dose of ketamine alters brain activity during emotional processing and increases glutamate-glutamine cycling in the pregenual anterior cingulate cortex, a region linked to mood regulation. In 23 healthy subjects, ketamine infusion changed fMRI responses to emotional pictures, and these changes correlated with shifts in glutamine-to-glutamate ratios measured by spectroscopy. The findings suggest ketamine's rapid antidepressant effect may stem from enhanced glutamatergic neurotransmission.
Pharmacopsychiatry
August 31, 2009
Torsten Passie
A new classification of psychoactive substances is proposed, based on the idea that specific psychophysical activation and deactivation patterns are preformed in normal neurophysiological states such as hypnagogic states, postorgasmic states, and dreaming. These patterns can be activated by various means of altering consciousness, including different psychoactive substances. The classification draws on the author's experimental studies of altered states induced by hallucinogens and other methods, along with a comprehensive literature review. The model may have implications for psychophysiology, psychopharmacology, and addiction research.
Pharmacopsychiatry
November 1, 2004
G Skuza, K Wedzony
Sigma receptors are unique brain binding sites distinct from opioid and PCP receptors, classified into sigma-1 and sigma-2 subtypes, with sigma-1 recently cloned. They modulate neurotransmitter systems including noradrenergic, glutamatergic, and dopaminergic pathways. Initially linked to psychotic disorders, they are now implicated in motor disorders, psychotic disorders, and neuroprotective mechanisms. Recent development of high-affinity, selective sigma ligands has enabled investigation of their therapeutic potential. This review summarizes behavioral effects of sigma receptor ligands in animal models related to schizophrenia and affective disorders.
Pharmacopsychiatry
July 1, 1998
W M Abi-Saab, D C D'Souza, B Moghaddam et al.
Drug models help researchers understand schizophrenia's neurobiology but have limitations that affect how results are interpreted. The N-methyl D-aspartate antagonist model, using drugs like phencyclidine and ketamine, has gained attention because these drugs produce symptoms beyond psychosis, including thought disorder, negative symptoms, cognitive deficits, and abnormal electrophysiologic test results similar to those in schizophrenia. Subanesthetic doses of ketamine in healthy individuals induce paranoia, perceptual alterations, and these other schizophrenia-like symptoms. This paper discusses the shortcomings of drug models generally and focuses on the NMDA antagonist model, emphasizing what ketamine's effects reveal about schizophrenia's pathophysiology and potential treatments.