Pharmacological Reports
September 25, 2026
Paweł Śliwa, Karina Pakosz, Aleksandra Banach
Abstract Background The 5-HT 2 receptor subfamily (5-HT 2A , 5-HT 2B , and 5-HT 2C ) is a cornerstone of neuropsychiatric drug design, yet the precise molecular determinants of their activation and biased signaling remain only partially elucidated. This study aimed to investigate the conformational transitions and energetic landscapes across diverse functional states to provide a refined...
Pharmacological Reports
June 22, 2026
Magdalena Zaniewska
Serotonin (5-hydroxytryptamine; 5-HT) is a key neuromodulator involved in the regulation of mood, appetite, aggression, and impulse control. Dysregulation of central 5-HT function has been implicated in alcohol use disorder (AUD) and comorbid depression. This review summarizes clinical and preclinical evidence on the role of 5-HT in AUD development, heterogeneity, and treatment response....
Pharmacological Reports
June 12, 2026
Wojciech Ziemichód, Natalia Kajka, Klaudia Kister et al.
The glutamatergic system, particularly N-methyl-D-aspartate (NMDA) receptors, has long been a significant focus of research into new strategies for treating depression, and the clinical success of ketamine, an NMDA receptor antagonist, has been a significant breakthrough. In parallel, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, another key component of the...
Pharmacological Reports
May 20, 2026
Aleksander Kwaśny, Alina Wilkowska, Michał Pastuszak et al.
Background: Treatment-resistant depression (TRD) poses a significant therapeutic challenge, with remission often unattainable. Recognition and detection of treatment-emergent adverse events (TEAEs) are essential, as these events may significantly influence the quality of treatment response. This knowledge aids in personalizing care and selecting the best treatment strategy. Methods: In a...
Pharmacological Reports
April 1, 2026
Elmira Zolali, Mallory Burns, Sebastiano Intagliata et al.
BACKGROUND: Mu opioid receptor (MOR) agonists are the primary medication class used to treat moderate to severe pain; however, the ongoing opioid overdose crisis underscores the need for alternatives to MOR agonists for pain treatment. Delta9-tetrahydrocannabinol (THC), a cannabinoid CB1 receptor (CB1R) agonist, and sigma1 receptor (σ1R) antagonists elicit antinociceptive effects albeit less...
Pharmacological Reports
March 11, 2026
Benjamin D. Brody, Dora Kanellopoulos
1 citation
Recent retrospective analyses have shown that individuals with comorbid Substance Use Disorders (SUDs) are overrepresented among responders to ketamine for Treatment Resistant Depression (TRD). Ketamine is an effective treatment for depression and also a potential substance of misuse. The authors contrast a mechanistic pathway with a possible expectancy effect to account for these findings, and...
Pharmacological Reports
February 1, 2026
Zuzanna Kościuk, Izabela Szpręgiel, Agnieszka Bysiek et al.
2 citations
The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmission remains unexplored. This study aimed to...
Pharmacological Reports
January 22, 2026
Taichi Goto, Joy D Kreskow, Alexander L R Ross et al.
Fatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed the anti-fatigue effects of ketamine (0.5 mg/kg) versus midazolam (0.045 mg/kg), the active comparator. Ten participants, who were cancer survivors, with fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, or systemic lupus...
Pharmacological Reports
January 20, 2026
Piotr Olejnik, Katarzyna Kamińska, Krystyna Gołembiowska et al.
INTRODUCTION: Psilocybin, a classic serotonergic psychedelic, has antidepressant, anxiolytic, anti-inflammatory, and analgesic properties. However, the immunomodulatory effects of psilocybin within the central nervous system, particularly on microglial activation, remain poorly understood. Therefore, this study aimed to investigate the effects of psilocybin on microglial activation markers and...
Pharmacological Reports
June 16, 2025
Tereza Klučková, Marek Nikolič, Filip Tylš et al.
4 citations
Recent studies intensively explore psilocybin's antidepressant potential, but variables like previous experience, repeated use, setting, and sex remain underexplored. This study examines acute and long-term effects of psilocybin in healthy individuals. A double-blind, placebo-controlled, cross-over study included 40 healthy participants (20 females, mean age 38). Each received two doses of...
Pharmacological Reports
April 30, 2025
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.
3 citations
Ketamine is currently gaining attention as a rapid-acting antidepressant for treatment-resistant depression (TRD). However, many patients fail to respond, and limited data exist on predictors of non-response. This study aims to characterize the sociodemographic and clinical features associated with non-response to ketamine among TRD patients. This is a post-hoc analysis of a naturalistic...
Pharmacological Reports
December 1, 2024
Izabela Szpręgiel, Agnieszka Bysiek
18 citations
In recent decades, psilocybin has gained attention as a potential drug for several mental disorders. Clinical and preclinical studies have provided evidence that psilocybin can be used as a fast-acting antidepressant. However, the exact mechanisms of action of psilocybin have not been clearly defined. Data show that psilocybin as an agonist of 5-HT2A receptors located in cortical pyramidal...
Pharmacological Reports
December 1, 2024
Adrian Andrzej Chrobak, Marcin Siwek
11 citations
Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of...
Pharmacological Reports
December 1, 2024
Julia Kwaśna, Wiesław Jerzy Cubała, Aleksander Kwaśny et al.
4 citations
Emerging evidence indicates that intravenous ketamine is effective in managing treatment-resistant unipolar and bipolar depression. Clinical studies highlight its favorable efficacy, safety, and tolerability profile within a dosage range of 0.5-1.0 mg/kg based on actual body weight. However, data on alternative dosage calculation methods, particularly in relation to body mass index (BMI) and...
Pharmacological Reports
December 1, 2024
Aleksander Kwaśny, Wiesław Jerzy Cubała, Adam Włodarczyk et al.
2 citations
This study examines self-reported sleep alterations in treatment-resistant depression (TRD) inpatients following intravenous ketamine administration. This is a post-hoc analysis of a naturalistic observational study, which enrolled 28 inpatients with treatment-resistant major depressive disorder and analyzed self-reported sleep changes (items 1-4; 'insomnia', 'nighttime restlessness', 'early...
Pharmacological Reports
November 27, 2024
Ewelina Cyrano, Piotr Popik
Serotonergic psychedelics, which display a high affinity and specificity for 5-HT2A receptors like 2,5-dimethoxy-4-iodoamphetamine (DOI), reliably induce a head-twitch response in rodents characterized by paroxysmal, high-frequency head rotations. Traditionally, this behavior is manually counted by a trained observer. Although automation could simplify and facilitate data collection, current...
Pharmacological Reports
October 1, 2024
Elena Hernández-Hernández, Sandra Ledesma-Corvi, Jordi Jornet-Plaza et al.
8 citations
The aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces the efficacy of classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates to be explored in the context of aging, especially given the lack of previous research on its efficacy for this age period. Thus, the aim of...
Pharmacological Reports
August 1, 2024
Maja Owe-Larsson, Katarzyna Kamińska, Barbara Buchalska et al.
11 citations
Abstract Obsessive-compulsive disorder (OCD) is a chronic mental disease that affects approximately 2% of the population. Obsessions and compulsions are troublesome for patients and may disturb their everyday activities. The pathogenesis of this disease is still not fully elucidated, but dysfunctions of serotonin-, dopamine- and glutamate-mediated neurotransmission together with early...
Pharmacological Reports
June 1, 2024
Agnieszka Pałucha-Poniewiera, Anna Rafało-Ulińska, Michal Santocki et al.
8 citations
Partial negative allosteric modulators (NAM) of the metabotropic glutamate 5 (mGlu5) receptor are an excellent alternative to full antagonists and NAMs because they retain therapeutic effects and have a much broader therapeutic window. Here, we investigated whether partial mGlu5 NAM, 2-(2-(3-methoxyphenyl)ethynyl)-5-methylpyridine (M-5MPEP), induced a fast and sustained antidepressant-like...
Pharmacological Reports
June 1, 2024
Katarzyna Kuczyńska, Katarzyna Bartkowska, Ruzanna Djavadian et al.
3 citations
Synthetic cathinones (SC) constitute the second most frequently abused class of new psychoactive substances. They serve as an alternative to classic psychostimulatory drugs of abuse, such as methamphetamine, cocaine, or 3,4-methylenedioxymethamphetamine (MDMA). Despite the worldwide prevalence of SC, little is known about their long-term impact on the central nervous system. Here, we examined...
Pharmacological Reports
December 1, 2023
Magdalena Kolasa, Agata Faron-Górecka
18 citations
Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least...
Pharmacological Reports
December 1, 2023
Adam Wojtas
10 citations
Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions of patients. While crucial in the history of drug development, recent studies undermine the effectiveness of currently used antidepressant drugs in comparison to placebo, emphasizing the long time it takes to initiate the...
Pharmacological Reports
December 1, 2023
Justyna Holka-Pokorska
5 citations
In recent years, scientific research into the therapeutic potential of psychedelic compounds has experienced a resurgence of interest. New studies have shown promising results, supporting the use of psychedelic drugs in treating various psychiatric disorders, including treatment-resistant depression, post-traumatic stress disorder, and even alcohol addiction. The FDA has recognized...
Pharmacological Reports
December 1, 2023
Barbara Chruścicka-Smaga, Agata Machaczka, Bernadeta Szewczyk et al.
2 citations
The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high complexity and variety of symptoms. Over the last decades, the understanding of the mechanism of pathophysiology of depression and its key consequences for brain functioning have undergone significant changes, referring to the...
Pharmacological Reports
November 6, 2023
Paweł Holas, Justyna Kamińska
39 citations
Abstract There has been increasing scientific and clinical interest in studying psychedelic and meditation-based interventions in recent years, both in the context of improving mental health and as tools for understanding the mind. Several authors suggest neurophysiological and phenomenological parallels and overlaps between psychedelic and meditative states and suggest synergistic effects of...