Pharmaceuticals (Basel, Switzerland)
April 10, 2023
Bianca-Eugenia Ősz, George Jîtcă, Andreea Sălcudean et al.
29 citations
Benzydamine is a non-steroidal anti-inflammatory drug that differs structurally and pharmacologically from other drugs in its class; its anti-inflammatory mechanism is not fully explained by prostaglandin synthesis inhibition. It is used clinically for local inflammation of the oral and vaginal mucosa. However, in high oral doses it is used as a psychotropic substance with effects similar to LSD. Because it is available over the counter, recreational use raises concerns about its pharmacodynamic and toxicological properties, as the mechanism of action and side effects of systemic high-dose consumption are not fully understood. This review analyzes benzydamine's pharmacodynamics by comparing its chemical structure to similar compounds used therapeutically or recreationally.
Pharmaceuticals (Basel, Switzerland)
June 10, 2025
Layla Bleibel, Paulina Sokołowska, Gabriela Henrykowska et al.
18 citations
Antidepressants like SSRIs, SNRIs, esketamine, and ketamine reduce inflammation in people with depression by lowering pro-inflammatory cytokines or boosting anti-inflammatory cytokines in the blood and brain regions such as the hippocampus and prefrontal cortex. These effects occur through multiple pathways, including NF-κB, the NLRP3 inflammasome, the glutamatergic system, the gut-brain axis, the hypothalamic-pituitary axis, impaired neuroplasticity, and the kynurenine pathway. The findings suggest that anti-inflammatory actions contribute to the therapeutic benefits of these treatments, supporting the link between depression and inflammation.
Pharmaceuticals (Basel, Switzerland)
June 20, 2024
He Zhu, Bei Wen, Jijun Xu et al.
15 citations
A systematic review and meta-analysis of 23 randomized controlled trials involving 1029 patients with complex regional pain syndrome found that bisphosphonates and ketamine each provide long-term (beyond one month) pain relief, though neither showed statistically significant short-term benefit. Both treatments caused mild adverse events that required no special intervention. Ketamine and bisphosphonates appeared to be the best pharmacological strategies for pain relief in CRPS.
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 rapidly promote changes in neuroplasticity. Ketamine, a notable example, is an N-methyl-D-aspartate receptor (NMDAR) antagonist with rapid and long-term antidepressant effects but also psychotomimetic and dissociative side effects. Stinels—rapastinel, apimostinel, and zelquistinel—are plastogens with improved safety and tolerability profiles. This review clarifies the mechanism of stinels, defining them as positive allosteric modulators of NMDAR activity with a novel regulatory binding site, contrasting with earlier descriptions of glycine-like partial agonists. The review presents the rationale for targeting NMDARs in treatment-resistant depression and other psychiatric conditions.
Pharmaceuticals (Basel, Switzerland)
December 28, 2022
Raphaël Serreau, Ammar Amirouche, Amine Benyamina et al.
13 citations
Psychedelic compounds found in Psilocybe mushrooms are being studied for treating central nervous system disorders, but obtaining enough pure material from fungi for research is challenging. This review examines synthetic chemistry methods to produce these molecules, covering classic historical syntheses, modern metal-catalyzed coupling reactions, and biocatalytic approaches. The authors note that alternative synthetic routes will likely be needed as therapeutic interest in these compounds grows.
Pharmaceuticals (Basel, Switzerland)
May 18, 2025
Przemyslaw M Waszak, Jan Opalko, Natalia Olszańska et al.
9 citations
A systematic review of 49 studies found that lithium, ketamine, and clozapine each reduce suicidality in specific psychiatric populations. Lithium shows significant anti-suicidal effects in bipolar disorder, outperforming valproate and other mood stabilizers. Ketamine rapidly reduces suicidal ideation within hours, with effects lasting up to a week, though evidence for long-term benefit and repeated dosing is inconsistent. Clozapine consistently lowers suicide risk in schizophrenia, with large cohort studies showing fewer suicide attempts and deaths compared to other antipsychotics. The review notes limitations including adherence challenges and methodological differences, calling for more robust experimental research.
Pharmaceuticals (Basel, Switzerland)
August 30, 2024
Junhyung Kim, Seung-Hoon Lee, Cheolmin Shin et al.
8 citations
In adults with treatment-resistant depression, esketamine nasal spray combined with daily self-monitoring through a mobile app produced significant reductions in depressive and anxiety symptoms as early as one day after the first dose. The open-label study enrolled 18-65 year olds who had failed at least two prior antidepressant therapies. Participants used the EsCARe app to track mood, sleep, and somatic symptoms alongside standard clinical assessments. By week 2, scores on the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale had notably decreased; the Hamilton Depression Rating Scale showed improvement by week 4. The mobile app reliably and validly tracked depressive symptoms, offering patients and clinicians immediate feedback on treatment effectiveness.
Pharmaceuticals (Basel, Switzerland)
June 27, 2024
Haron Avgana, Roni Shira Toledano, Irit Akirav
8 citations
MDMA treatment facilitated fear extinction and reduced shock-induced freezing and social deficits in a rat model of PTSD. Shock exposure altered oxytocin receptor gene expression and caused neuroinflammation in the medial prefrontal cortex and basolateral amygdala, which MDMA restored. An oxytocin receptor antagonist blocked MDMA's effects on extinction and freezing, indicating that oxytocinergic signaling mediates these therapeutic actions.
Pharmaceuticals (Basel, Switzerland)
August 29, 2025
Gustavo N Silva, Virna G A Brandão, Kenneth Blum et al.
7 citations
Ketamine, an anesthetic, may protect the brain and reduce inflammation by blocking NMDA receptors, decreasing microglial activation, and lowering cytokines TNF and IL-6. A narrative review of existing literature suggests ketamine reduces excitotoxicity and inflammation, potentially contributing to neuroprotection in acute neurological injuries. The review underscores ketamine's potential as an adjunctive neuroprotective agent, warranting further clinical investigation to optimize its therapeutic use across neurological and psychiatric conditions.
Pharmaceuticals (Basel, Switzerland)
December 4, 2024
Andrea Macejova, Veronika Kovacova, Ingrid Tonhajzerova et al.
7 citations
In a sample of 55 adolescent females with treatment-resistant depression, intravenous ketamine reduced depressive and anxiety symptoms over a short-term period, with particular efficacy in alleviating inner tension compared to midazolam. At 2 hours after the initial infusion, 33% of the ketamine group and 14% of the midazolam group responded on the Montgomery-Åsberg Depression Rating Scale; at 24 hours after treatment ended, 59% and 46% responded, respectively. Both groups showed significant reductions in symptoms from baseline at both time points. The findings suggest ketamine may offer specific advantages for symptom relief in this rarely studied population.
Pharmaceuticals (Basel, Switzerland)
February 1, 2024
Dóra Pothorszki, Szabolcs Koncz, Dóra Török et al.
7 citations
In rats, (R)-ketamine, but not (S)-ketamine, dose-dependently increases EEG theta power during wakefulness and REM sleep for 23 hours. Theta rhythm originates in the hippocampus and is linked to cognitive functions, attention, and decreased anxiety. This effect on a hippocampal function not affected by (S)-ketamine may relate to neural plasticity and memory encoding.
Pharmaceuticals (Basel, Switzerland)
April 30, 2025
Paola Bozzatello, Roberta Novelli, Rebecca Schisano et al.
6 citations
Many patients with psychiatric disorders do not respond to existing treatments. About one-third of schizophrenia patients are treatment-resistant, and antidepressants work for only about half of patients with depression. This narrative review covers new drugs, new indications, and new formulations approved by the FDA and EMA from 2018 onward for schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive-compulsive disorder. New approvals include lumateperone, olanzapine/samidorphan, and xanomeline/trospium for schizophrenia; esketamine for treatment-resistant depression and acute suicidal ideation; and brexanolone and zuranolone for postpartum depression. No new drugs were approved for anxiety disorders or OCD. The review highlights efforts to improve outcomes for resistant patients and reduce side effects.
Pharmaceuticals (Basel, Switzerland)
March 31, 2024
Maria Pepe, Marco Di Nicola, Fabrizio Cocciolillo et al.
6 citations
The psychoactive substance 3-MeO-PCP, a type of NMDA receptor antagonist, can cause persistent psychotic symptoms and cognitive impairment. A literature review and case report describe a 29-year-old man who developed substance-induced psychotic disorder after small oral intakes over two weeks, culminating in a high dose. Psychometric tests, neuropsychological assessment, and brain PET-CT imaging revealed lasting effects. Identifying the clinical features and neural substrates of NPS-induced psychoses may help distinguish them from other psychotic disorders and guide tailored treatments.
Pharmaceuticals (Basel, Switzerland)
June 2, 2023
Ahmed Al-Imam, Marek A Motyka, Beata Hoffmann et al.
6 citations
Online searches for DMT, 5-MeO-DMT, and the Colorado River toad increased significantly from 2012 to 2022, with the strongest upward trend for 5-MeO-DMT. Geographic interest in DMT was highest in Eastern Europe, the Middle East, and Far East Asia; 5-MeO-DMT searches prevailed in Western Europe, Indo-China, and Australasia; and toad-related searches originated from the Americas, Australia, India, the Philippines, and Europe. The literature review covers DMT's shamanic history, present-day illicit use, and experimental trials for neurotic disorders, suggesting potential medical uses if legal status changes.
Pharmaceuticals (Basel, Switzerland)
March 29, 2025
Hossein Omidian, Alborz Omidian
5 citations
LSD is being studied as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials showing significant symptom reductions and lasting effects. It works by modulating serotonin 5-HT2A receptors, which affects brain networks involved in emotion and cognition. In psychedelic-assisted psychotherapy, mystical-type experiences during LSD use are linked to improved well-being. This review covers LSD's pharmacokinetics, mechanisms, and safety concerns, including cardiovascular risks, emotional vulnerability, and the risk of hallucinogen-persisting perception disorder (HPPD). Challenges include small sample sizes, variable dosing, and regulatory restrictions. Future research should focus on standardization, pharmacogenetics, and personalized treatment.
Pharmaceuticals (Basel, Switzerland)
January 27, 2025
Matildes de Freitas Menezes Sobreiro, Paulo Sergio Panse Silveira, Vitor Breseghello Cavenaghi et al.
5 citations
In a small group of eight patients with treatment-resistant depression, six months of adjunctive esketamine nasal spray was associated with improvements in attention, memory, and several executive functions, including working memory, set-shifting, and inhibitory control. Most cognitive gains appeared by three months, though working memory and set-shifting improvements were significant only at six months. Depression severity also decreased over the six-month period, and most cognitive improvements correlated with reduced depression severity. No cognitive decline was observed. The authors note that confirmatory studies are needed.
Pharmaceuticals (Basel, Switzerland)
May 22, 2024
Emilija Glavonic, Milorad Dragic, Milos Mitic et al.
5 citations
A single dose of ketamine (10 mg/kg) improved fear extinction in adolescent male mice, likely by enhancing the consolidation or recall of extinction memory. Ketamine increased activity of Akt and mTOR signaling and raised levels of GluA1 and GluN2A proteins in the hippocampus, and upregulated BDNF exon IV mRNA in both the hippocampus and prefrontal cortex. It also increased c-Fos expression in the ventral hippocampus and left infralimbic ventromedial prefrontal cortex. These findings suggest that ketamine's effects on adolescent fear extinction involve activation of hippocampal Akt-mTOR-GluA1 signaling, with the ventral hippocampus and left infralimbic prefrontal cortex as neural correlates.
Pharmaceuticals (Basel, Switzerland)
November 5, 2024
Tamara Valdez, Valbhi Patel, Nattaphone Senesombath et al.
4 citations
Psychedelics are reemerging as potential treatments for substance use disorders (SUDs), including alcohol and opioid use disorders. Early mid-20th century anecdotal reports and pilot studies suggested these compounds could be effective, but legal restrictions and stigma halted research. With rising rates of SUDs and other mental health conditions, researchers are again investigating psychedelics for their unique pharmacological targets and holistic treatment potential. This review examines emerging evidence for treating SUDs with psilocybin, ketamine, LSD, MDMA, ayahuasca, ibogaine, and peyote.
Pharmaceuticals (Basel, Switzerland)
September 3, 2024
Alejandro Bruna-Mejias, Vicente Baeza, Javiera Gamboa et al.
4 citations
A systematic review examined evidence for low doses of ketamine in treating neuropathic pain, a condition marked by burning, stabbing sensations, and heightened sensitivity. The review, which searched multiple databases, found that low-dose ketamine did not produce statistically significant improvements in pain reduction or functionality compared to placebo. Specific measures such as the total symptom score showed a difference, but the neuropathy impairment score and symptom checklist indicated no significant benefit. No specific dosages were identified that support the use of low-dose ketamine for neuropathic pain.
Pharmaceuticals (Basel, Switzerland)
March 10, 2024
Veronika Kovacova, Andrea Macejova, Ingrid Tonhajzerova et al.
4 citations
A single intravenous infusion of ketamine reduced depressive symptoms in hospitalized adolescent girls with major depressive disorder, as measured by the MADRS and CDI scales, without significantly altering electrodermal activity (EDA) parameters such as skin conductance level or nonspecific electrodermal responses. The study involved 20 girls with an average age of 15.0 years. Before treatment, lower skin conductance level correlated with higher scores on certain CDI subscales, and fewer nonspecific electrodermal responses correlated with higher scores on one MADRS item. The findings suggest ketamine may be a safe and effective acute antidepressant for adolescents, as it improved mood without disrupting sympathetic regulation.
Pharmaceuticals (Basel, Switzerland)
May 9, 2025
Ilaria Ammendolia, Carmen Mannucci, Emanuela Esposito et al.
2 citations
Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported suspected adverse reactions to esketamine in European pharmacovigilance data. Women accounted for most reports, except for increased blood pressure and completed suicide, which were more common in men. Adults aged 18–64 and elders aged 65–85 had the largest number of reported adverse reactions. Compared with fluoxetine and venlafaxine, esketamine showed a potential increase in suicide risk among depressed patients. The authors recommend closer monitoring of patients with a history of suicide-related events or significant suicidal ideation before starting esketamine treatment.
Pharmaceuticals (Basel, Switzerland)
April 25, 2025
Jolien K E Veraart, Cornelis F Vos, Nieko C Punt et al.
2 citations
In patients with treatment-resistant depression receiving oral esketamine for six weeks, plasma concentrations of esketamine and noresketamine on day 39 were 59% and 35% lower than predicted by a pharmacokinetic model. This suggests that auto-induction of drug-metabolizing enzymes CYP3A4 and CYP2B6 occurs, which may explain the diminished therapeutic effects and side effects observed with long-term use. Identifying auto-induction as a mechanism of tolerance could have important clinical implications for maintaining efficacy.
Pharmaceuticals (Basel, Switzerland)
July 19, 2025
Daniel Szawarnoga, Joanna Fojcik, Michał Górski et al.
1 citation
Insomnia is common among people with drug-resistant depression and can undermine treatment and quality of life. In a comparison of 50 patients, those taking esketamine combined with other antidepressants had less insomnia than those taking other antidepressants alone. Longer use and higher doses of esketamine were associated with further reductions in insomnia. Esketamine produces a rapid improvement in sleep quality, offering an advantage over standard antidepressants for this population.
Pharmaceuticals (Basel, Switzerland)
May 31, 2026
Wenting Zhang, Xin Guo, Jiping Zhang et al.
Combining the herbal formula Dajianzhong Decoction (DJZT) with ketamine produces synergistic antidepressant effects in a mouse model of depression. The combination restores levels of short-chain fatty acids (SCFAs), particularly acetic acid and isobutyric acid, in the gut. These SCFAs activate the FFAR2 receptor in the brain's medial prefrontal cortex, which suppresses NLRP3-IL-1β-driven neuroinflammation and reverses synaptic deficits. Blocking FFAR2 with the inhibitor GLPG0974 eliminates these benefits. The findings suggest that the SCFA-FFAR2-NLRP3-IL-1β axis mediates the prolonged antidepressant action of the combined treatment, pointing to microbiota-modulating strategies for improving ketamine therapy.
Pharmaceuticals (Basel, Switzerland)
April 24, 2026
Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli et al.
Depression likely arises from a mix of two interacting biological problems: imbalances in monoamine neurotransmitters (like serotonin) and disruptions in glutamate signaling that impair the brain's ability to adapt and form new connections. These two systems can combine in different ways across individuals, helping explain why some people respond to standard antidepressants while others do not. Rapid-acting treatments such as ketamine work by directly targeting the glutamate system to boost synaptic plasticity, offering faster relief, especially for treatment-resistant depression. A framework called the 'monoamine-glutamate continuum' may guide future precision psychiatry by matching treatments to each person's specific neurobiological profile.