Pharmacological reports : PR
January 1, 2011
Joanna Listos, Alicja Merska, Sylwia Fidecka
52 citations
Salvinorin A, the active compound in the hallucinogenic plant Salvia divinorum (magic mint), produces hallucinogenic, antinociceptive (pain-relieving), and antidepressant-like behavioral effects in animals. The compound also shows addictive properties. Its mechanisms of action remain unclear or not well recognized. The paper reviews these behavioral effects and the legal status of the plant and its derivatives. Given the rising recreational use of Salvia divinorum, compiling pharmacological data on salvinorin A is important.
Pharmacological reports : PR
December 1, 2020
Monika Herian, Adam Wojtas, Małgorzata Katarzyna Sobocińska et al.
19 citations
The hallucinogenic compound 25I-NBOMe acts through specific serotonin receptors to produce its effects. In rats, blocking the 5-HT2A or 5-HT2C receptors with selective antagonists reduced both the hallucinogenic-like behavior (wet dog shakes) and the release of glutamate, dopamine, and serotonin in the frontal cortex caused by 25I-NBOMe. Blocking the 5-HT1A receptor did not affect the behavior or glutamate release but did decrease dopamine and serotonin release, likely by disinhibiting GABA neurons. These findings indicate that 5-HT2A and 5-HT2C receptors are key mediators of 25I-NBOMe's hallucinogenic activity and its effects on neurotransmitter release in the frontal cortex.
Pharmacological reports : PR
December 1, 2024
Izabela Szpręgiel, Agnieszka Bysiek
18 citations
Psilocybin, a 5-HT2A receptor agonist on cortical pyramidal cells, increases glutamate release in the frontal cortex and hippocampus. This elevated glutamate boosts activity of GABAergic interneurons, raising GABA levels, which appears to promote antidepressant effects. Psilocybin also interacts with glutamatergic pathways to support neuroplasticity. This mini-review discusses how psilocybin affects glutamatergic neurotransmission and its therapeutic potential for depression and other nervous system disorders.
Pharmacological reports : PR
December 1, 2023
Magdalena Kolasa, Agata Faron-Górecka
18 citations
Treatment-resistant depression (TRD) is a subset of major depressive disorder where standard antidepressants fail. No universal criteria exist for TRD, but it commonly involves non-response to at least two medication trials. Up to 60% of TRD patients may be pseudo-TRD, where factors like gender, age, and hormonal disturbances contribute to drug resistance. The complexity of TRD makes diagnosis and treatment challenging. This review discusses animal models that meet validity criteria for TRD, including chronic mild stress and the Wistar Kyoto rat strain. It also examines preclinical studies of novel therapies such as ketamine, deep brain stimulation, and psychedelic drugs.
Pharmacological reports : PR
June 1, 2016
Xi-Ling Jiang, Hong-Wu Shen, Ai-Ming Yu
13 citations
Co-administering the monoamine oxidase inhibitor harmaline with a low dose of 5-MeO-DMT triggers excessive late-phase hyperactivity in mice, an effect that requires activation of both 5-HT1A and 5-HT2A serotonin receptors. High doses of either drug alone produce biphasic effects: early-phase hypoactivity mediated by 5-HT1A receptors and late-phase hyperactivity mediated by 5-HT2A receptors. Harmaline alone at 15 mg/kg causes early hypoactivity blocked by a 5-HT1A antagonist and late hyperactivity reduced by a 5-HT2A antagonist. The findings indicate that combining these drugs, as often done recreationally, can provoke prolonged overactivity through dual serotonin receptor mechanisms.
Pharmacological reports : PR
December 1, 2024
Adrian Andrzej Chrobak, Marcin Siwek
11 citations
Standard psychiatric medications work by altering serotonin, dopamine, or norepinephrine, but they often act slowly and lose effectiveness over time, leading to treatment resistance. A growing body of evidence suggests that drugs targeting glutamate receptors can produce rapid, robust, and lasting therapeutic effects, potentially overcoming these limitations. This review covers glutamate-modulating drugs, their mechanisms, and preclinical and clinical studies. Ketamine shows rapid and long-lasting effects. Memantine and minocycline are supported for major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts may improve depressive symptoms. Glutamate-based drugs are promising for treatment-resistant mental disorders, but more research is needed on safety, dosage, and interactions.
Pharmacological reports : PR
December 1, 2023
Adam Wojtas
10 citations
The serotonergic theory of depression, which emerged in the 1960s, led to many antidepressant drugs that have helped millions, but recent studies question their effectiveness compared to placebo, noting slow onset and side effects. Research now focuses on rapid-acting antidepressants like ketamine, an NMDA receptor antagonist that quickly alleviates depression symptoms, though its effects last only about two weeks and it has severe side effects. A safer, more efficient approach may involve hallucinogenic 5-HT2A receptor agonists—psychedelics—which are being reconsidered in clinical practice after their 1970s stigma. This review examines current literature and recent clinical studies on the antidepressant potential of LSD, psilocybin, DMT, and 5-MeO-DMT, along with other applications.
Pharmacological reports : PR
October 1, 2024
Elena Hernández-Hernández, Sandra Ledesma-Corvi, Jordi Jornet-Plaza et al.
8 citations
A single dose of ketamine produced a fast-acting antidepressant-like effect in 14-month-old male rats, reducing immobility in the forced-swim test within 30 minutes, accompanied by increased levels of mature brain-derived neurotrophic factor (mBDNF) in the prefrontal cortex. However, repeated daily ketamine for 7 days did not sustain antidepressant-like effects and instead decreased mBDNF in the same brain region. Neither acute nor repeated ketamine altered hippocampal cell proliferation or other neurotrophic markers. The findings extend evidence for ketamine's rapid antidepressant potential to older age, but the loss of efficacy with repeated dosing and possible adverse effects in aging require further investigation.
Pharmacological reports : PR
June 1, 2024
Agnieszka Pałucha-Poniewiera, Anna Rafało-Ulińska, Michal Santocki et al.
8 citations
A partial negative allosteric modulator of the mGlu5 receptor, M-5MPEP, produced rapid and sustained antidepressant-like effects in mice, similar to the rapid-acting antidepressant ketamine. These effects depended on brain-derived neurotrophic factor (BDNF). M-5MPEP also enhanced the action of (R)-ketamine, suggesting their mechanisms converge. The findings indicate potential for M-5MPEP as a rapid-acting antidepressant with a broader therapeutic window than full antagonists.
Pharmacological reports : PR
December 1, 2023
Justyna Holka-Pokorska
5 citations
Entactogens like MDMA may recreate the subjective experience of emotional intimacy, initiation of intimate relationships, or feelings of 'falling in love' with previously neutral individuals. MDMA-induced sexual arousal-like effects are observed through subjective behavioral perceptions of desire and arousal and specific physiological markers such as oxytocin and prolactin. Although modern MDMA-assisted psychotherapy protocols follow strict ethical guidelines, little consideration has been given to the potential neurobehavioral effects of entactogens on participants' sexuality, including the potential experience of sexualized pharmacotransference. The psychophysiological and sexual effects of entactogens should be discussed more openly in current protocols.
Pharmacological reports : PR
October 1, 2018
Karolina Noworyta-Sokołowska, Anna Maria Górska, Krystyna Gołembiowska
5 citations
Repeated intermittent exposure to the hallucinogenic novel psychoactive substance 5-MeO-DIPT during adolescence impaired adult rats' exploratory activity in the open field test, reducing the number of crossings, and impaired learning in the serial pattern learning test, suggesting deficits in long-term memory and cognitive flexibility. No change was observed in the novel object recognition test. The findings indicate that adolescent exposure to 5-MeO-DIPT can cause long-lasting behavioral changes that persist into adulthood.
Pharmacological reports : PR
June 16, 2025
Tereza Klučková, Marek Nikolič, Filip Tylš et al.
4 citations
In healthy individuals, psilocybin produces lasting positive effects regardless of previous psychedelic experience, repeated use, setting, sex, or occupation. In a double-blind, placebo-controlled crossover study with 40 participants (20 females, mean age 38), each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart. Acute effects were moderate on the Altered States of Consciousness Scales, with mostly pleasant or fluctuating experiences and only one unpleasant session; all sessions ended positively or neutrally. Long-term effects, assessed by the Persisting Effects Questionnaire, were positive across all domains with negligible negative effects. Peak experiences ending in a positive mood strongly predicted favorable long-term outcomes, while challenging experiences did not cause adverse outcomes. These findings support psilocybin's psychological safety and repeated use in clinical trials.
Pharmacological reports : PR
December 1, 2024
Julia Kwaśna, Wiesław Jerzy Cubała, Aleksander Kwaśny et al.
4 citations
Intravenous ketamine at 0.5-1.0 mg/kg based on actual body weight is effective for treatment-resistant depression. In a retrospective analysis of 28 inpatients with treatment-resistant major depressive disorder, alternative dosing formulas using lean body mass, ideal body weight, or body surface area generally led to underdosing compared to the standard 0.5 mg/kg dose. Only two participants received higher doses when using the Devine formula. The findings suggest that alternative dosing methods may reduce treatment response and complicate outcome interpretation. Future studies should incorporate direct body composition measures like bioimpedance and waist-to-hip ratio.
Pharmacological reports : PR
April 30, 2025
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.
3 citations
Among inpatients with treatment-resistant depression receiving ketamine over four weeks, 75% did not respond. Non-responders had lower rates of prior substance use disorder (53.3% vs. 100%) and fewer psychiatric comorbidities. The findings suggest that a higher burden of traditional risk factors for treatment-resistant depression may not limit ketamine's effectiveness and could even enhance response compared to 'pure' major depressive disorder. Early identification of potential non-responders could optimize treatment decisions and reduce ineffective exposure.
Pharmacological reports : PR
June 1, 2024
Katarzyna Kuczyńska, Katarzyna Bartkowska, Ruzanna Djavadian et al.
3 citations
Repeated exposure to the synthetic cathinone MDPV during infancy in mice impairs spatial working memory and object recognition memory in young adulthood, but does not affect hippocampus-dependent spatial learning and memory as measured by the Morris water maze. Hippocampal neurogenesis and synaptogenesis remain intact, and the memory deficits are not linked to disrupted hippocampal development. The effects are the same in both male and female mice.
Pharmacological reports : PR
February 1, 2026
Zuzanna Kościuk, Izabela Szpręgiel, Agnieszka Bysiek et al.
2 citations
Psilocin and 25I-NBOMe, two serotonergic psychedelics, both altered neurotransmitter levels in the rat claustrum but produced distinct neurochemical profiles. Psilocin elevated noradrenaline and acetylcholine, yielding a balanced excitatory–inhibitory pattern, while 25I-NBOMe induced a stronger excitatory shift with the largest increase in serotonin release. These differences reflect psilocin's engagement of both 5-HT2A and 5-HT1A receptors versus 25I-NBOMe's selective, high-affinity 5-HT2A agonism. The claustrum is highlighted as a convergence point for psychedelic action, and the contrasting profiles suggest fundamentally different therapeutic and toxicological potentials.
Pharmacological reports : PR
December 1, 2024
Aleksander Kwaśny, Wiesław Jerzy Cubała, Adam Włodarczyk et al.
2 citations
In a small observational study of 28 inpatients with treatment-resistant major depressive disorder, neither those who responded to ketamine treatment nor those who did not reported significant changes in self-reported sleep problems—including insomnia, nighttime restlessness, early morning waking, or hypersomnia—after eight intravenous ketamine infusions over seven days. These results contrast with previous research that had suggested modest sleep improvements with ketamine. The authors caution that the small sample size limits the reliability of the findings.
Pharmacological reports : PR
December 1, 2023
Barbara Chruścicka-Smaga, Agata Machaczka, Bernadeta Szewczyk et al.
2 citations
Developing a universal pharmacotherapy for depression is challenging due to symptom complexity. Understanding of depression's pathophysiology has shifted from the monoaminergic theory after ketamine's discovery, focusing on glutamatergic transmission as a new target. Glutamate plays a key role in rapid-acting antidepressants (RAAs) like ketamine, scopolamine, and psilocybin. These hallucinogens provide fast, robust, and sustained antidepressant action but have significant undesired effects that limit clinical use. This review explores combining lower doses of RAAs with mGlu2/3 receptor antagonists to reduce adverse effects and improve outcomes, examining behavioral, synaptic, and molecular actions.
Pharmacological reports : PR
January 22, 2026
Taichi Goto, Joy D Kreskow, Alexander L R Ross et al.
A small pilot trial tested whether a single low dose of ketamine (0.5 mg/kg) can reduce fatigue in people with chronic illnesses such as cancer, fibromyalgia, chronic fatigue syndrome, or lupus. Ten participants received both ketamine and the active placebo midazolam in random order, with a washout period between treatments. Because fatigue levels differed between the two study periods, results were analyzed separately. In the first period, fatigue scores dropped 21.0% after ketamine and 17.7% after midazolam; in the second period, the drops were 10.9% and 12.6%, respectively. The differences were not statistically significant, but the ketamine group showed a peak 38.7% reduction one day after infusion. The authors suggest future studies avoid crossover designs and find a better active placebo.
Pharmacological reports : PR
April 1, 2026
Elmira Zolali, Mallory Burns, Sebastiano Intagliata et al.
Combining the sigma1 receptor antagonist CM304 with delta9-tetrahydrocannabinol (THC) enhances pain relief without worsening THC's side effects. In mice, CM304 increased the pain-blocking effect of THC and caused greater body temperature drops when combined. A high dose of CM304 alone reduced movement. In rats, CM304 made THC's pain relief more potent. CM304 did not produce THC-like effects in rats trained to recognize THC, nor did it amplify THC's subjective effects. The findings suggest sigma1 receptor antagonists could be safer adjuncts to cannabinoid-based pain treatments, offering pain relief without increasing adverse effects like sedation or abuse potential.