In recent years, psychiatry has witnessed a renaissance in the investigation of psychedelic compounds, a broad class of psychoactive substances that induce altered states of consciousness, often characterized by changes in perception, mood, and cognition, which were largely shelved following regulatory crackdowns in the 1970s. The renewed interest is driven by a mounting crisis in mental health...
Background: The discovery of new neurotransmitters is crucial for the in-depth understanding of neural signal transmission, neurological disorders, and relevant treatment strategies. Emerging evidence has indicated that harmine is an important endogenous compound, and its level is closely related to different physiological and disease states. Inspired by this, we propose a hypothesis that...
Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses and a leading cause of disability worldwide. Key symptoms of these conditions include a depressed mood or anhedonia, sleep and psychomotor disturbances, changes in appetite or weight, and fatigue or loss of energy. Prolonged cognitive disturbances further impair the ability to...
The recreational abuse of addictive drugs poses considerable challenges to public health, leading to widespread neurotoxicity and neurological dysfunction. This review comprehensively examines the neurotoxic mechanisms, clinical manifestations, and treatment strategies associated with six commonly abused substances: methamphetamine, cocaine, synthetic cathinones, ketamine, nitrous oxide and...
Alpha-pyrrolidinopentiophenone (α-PVP) is a commonly consumed analogue of pyrovalerone, a synthetic cathinone with psychostimulant properties similar to those of 3,4-Methylenedioxypyrovalerone (MDPV) and cocaine. Since the pharmacology of α-PVP remains scarcely studied, we aimed to evaluate the acute pharmacological effects and its abuse potential in humans after intranasal administration. We...
The combination of remimazolam and esketamine effectively alleviates adverse hemodynamic effects, such as tachycardia and hypertension, during intubation. However, the dosage for achieving optimal intubation conditions when co-administered with remifentanil remains unestablished. Therefore, this study aimed to determine the effective doses of remimazolam and esketamine for endotracheal...
Ketamine and esketamine have demonstrated rapid, short-term antidepressant effects in major depressive disorder (MDD), but their relative safety remains unclear. This review aims to update the evidence on the safety of two agents for MDD and indirectly compare their safety and tolerability. We systematically searched PubMed, PsycINFO, Embase, and Cochrane databases up to 1 May 2025. Eligible...
Frontiers in Pharmacology2025Elizabeth G. Neureiter, M Quincy Erickson-Oberg, Aparna Nigam et al.4 citations
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels present at most excitatory synapses in the brain that play essential roles in cognitive functions including learning and memory consolidation. However, NMDAR dysregulation is implicated in many nervous system disorders. Diseases that involve pathological hyperactivity of NMDARs can be treated clinically through inhibition by...
Beside image vision, light plays a pivotal role in regulating diverse non-visual functions, including affective behaviors. Recently, bright light stimulation (BLS) was revealed to be beneficial for treating non-seasonal depression, although its mechanism of action is not fully understood. We developed a novel mouse model of refractory depression, induced through social isolation and chronic...
Interest in the therapeutic effects of classical psychedelics has risen recently. However, little epidemiological knowledge exists about the use of classical psychedelics in Scandinavian countries. Additionally, there is a limited understanding of what factors drive self-reported improvement in wellbeing. The aim of this study was to investigate the relationship between the use of classical...
Frontiers in Pharmacology2025Denise Elfriede Liesa Lockhofen, Nils Hübner, Ranjan Debnath et al.2 citations
Patients with schizophrenia frequently experience inadequate attribution of motivational salience, possibly related to impaired attentional processing and dysfunctional reward learning. According to the "glutamate hypothesis of schizophrenia", glutamatergic dysregulations can contribute to the emergence of psychotic symptoms and cognitive deficits in patients with schizophrenia. Blocking the...
Ketamir-2 is a new molecular entity, and a novel ketamine analog designed to improve oral bioavailability, and offer a superior safety profile compared to existing ketamine treatments. It was found that Ketamir-2 is a low affinity NMDA receptor antagonist, that selectively binds to the PCP site. Its IC50 on this receptor site is ∼100 µM. Ketamine acts as an NMDA receptor antagonist (0.5-1 µM...
Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases. This methodology is especially relevant in streamlining early drug development stages. Our research utilized a Physiologically Based Pharmacokinetic (PBPK) model and Monte Carlo simulations to examine factors...
Editorial on the Research Topic Incorporating Phase 0 microdosing as a powerful tool into a new vision of drug developmentPhase 0 microdosing, the testing of compounds at subtherapeutic doses in human to enable early decisions in drug discovery and development has been utilized for some years.The uptake was slow even though the concept is attractive and the pre-clinical safety package enabling...
One of the most important developments in psychopharmacology in the past decade has been the emergence of novel treatments for mood disorders, such as psilocybin for treatment-resistant depression. Psilocybin is most commonly found in different species of mushroom; however, the literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just...
Frontiers in PharmacologyMay 24, 2024Norman Nyazema, Jonathan Tinotenda Chanyandura, B. Egan7 citations
Background Most Bantu ethnic groups in southern Africa utilize indigenous herbal medicines, some of which have psychoactive properties. Traditional medical practitioners (TMPs) commonly use them not only for divinatory purposes but to treat and manage mental and other illnesses. Unfortunately, the research on their results, risks, and benefits do not align. Little is known about their potential...
In vivo , psilocybin is rapidly dephosphorylated to psilocin which induces psychedelic effects by interacting with the 5-HT 2A receptor. Psilocin primarily undergoes glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). Herein, we investigated psilocybin’s metabolic pathways in vitro and in vivo , conducting a thorough analysis of the enzymes involved. Metabolism studies were...
Background: Immediate early genes (IEGs) are rapidly activated and initiate diverse cellular processes including neuroplasticity. We report the effect of psilocybin (PSIL), PSIL-containing psychedelic mushroom extract (PME) and 5-hydroxytryptophan (5-HTP) on expression of the IEGs, cfos, egr1 , and egr2 in mouse somatosensory cortex (SSC). Methods: In our initial experiment, male C57Bl/6j mice...
Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT 2A -serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review...
Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with...
The modulation of social cognition is suggested as a possible mechanism contributing to the potential clinical efficacy of psychedelics in disorders involving socio-emotional and reward processing deficits. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) can be used to detect changes in brain connectivity during psychedelic-induced states. Thus, this pharmacoimaging study...
(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting...
Ketamine was developed as an anesthetic. Esketamine is the isolated S-enantiomer of racemic ketamine. They provide new avenues for the treatment of depression, especially treatment-resistant depression. Considering differences in the pharmacokinetics and hormonal status of ketamine in patients of different genders, sex-based differences in esketamine adverse drug events (ADE) may also be...
The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy. Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial...
There have been numerous studies on NMDA receptors as therapeutic targets for depression. However, so far, there has been no comprehensive scientometric analysis of this field. Thus, we conducted a scientometric analysis with the aim of better elucidating the research hotspots and future trends in this field. Publications on NMDAR in Depression between 2004 and 2023 were retrieved from the Web...