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Case Reports in Psychiatry 2023Venlafaxine is an antidepressant belonging to the class of serotonin-norepinephrine reuptake inhibitors that are US Food and Drug Administration-approved to treat and...
Venlafaxine is an antidepressant belonging to the class of serotonin-norepinephrine reuptake inhibitors that are US Food and Drug Administration-approved to treat and manage symptoms of depression, anxiety, and other mood disorders in adults. We describe an adolescent patient who likely had a false-positive phencyclidine result detected with an 11-panel urine drug screen in an outpatient setting of long-term use of therapeutic venlafaxine extended release for the treatment of recurrent major depressive disorder and generalized anxiety disorder. We believe that this may be the first published case report to characterize this phenomenon in a young patient in the absence of an acute overdose.
PubMed: 37404674
DOI: 10.1155/2023/6666197 -
Brain Sciences May 2023Schizophrenia is a debilitating psychiatric disorder comprising positive, negative, and cognitive impairments. Most of the animal models developed to understand the... (Review)
Review
Investigating the Robustness of a Rodent "Double Hit" (Post-Weaning Social Isolation and NMDA Receptor Antagonist) Model as an Animal Model for Schizophrenia: A Systematic Review.
Schizophrenia is a debilitating psychiatric disorder comprising positive, negative, and cognitive impairments. Most of the animal models developed to understand the neurobiology and mechanism of schizophrenia do not produce all the symptoms of the disease. Therefore, researchers need to develop new animal models with greater translational reliability, and the ability to produce most if not all symptoms of schizophrenia. This review aimed to evaluate the effectiveness of the rodent "double hit" (post-weaning social isolation and N-methyl-D-aspartate (NMDA) receptor antagonist) model to produce symptoms of schizophrenia. This systematic review was developed according to the 2020 PRISMA guidelines and checklist. The MEDLINE (PubMed) and Ebscohost databases were used to search for studies. The systematic review is based on quantitative animal studies. Studies in languages other than English that could be translated sufficiently using Google translate were also included. Data extraction was performed individually by two independent reviewers and discrepancies between them were resolved by a third reviewer. SYRCLE's risk-of-bias tool was used to test the quality and biases of included studies. Our primary search yielded a total of 47 articles, through different study selection processes. Seventeen articles met the inclusion criteria for this systematic review. Ten of the seventeen studies found that the "double hit" model was more effective in developing various symptoms of schizophrenia. Most studies showed that the "double hit" model is robust and capable of inducing cognitive impairments and positive symptoms of schizophrenia.
PubMed: 37371328
DOI: 10.3390/brainsci13060848 -
Forensic Science International Aug 2023Due to the diversity and fast evolution of new psychoactive substances (NPS), both public health and safety are threatened around the world. Attenuated total...
Due to the diversity and fast evolution of new psychoactive substances (NPS), both public health and safety are threatened around the world. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), which serves as a simple and rapid technique for targeted NPS screening, is challenging with the rapid structural modifications of NPS. To achieve the fast non-targeted screening of NPS, six machine learning (ML) models were constructed to classify eight categories of NPS, including synthetic cannabinoids, synthetic cathinones, phenethylamines, fentanyl analogues, tryptamines, phencyclidine types, benzodiazepines, and "other substances" based on the 1099 IR spectra data items of 362 types of NPS collected by one desktop ATR-FTIR and two portable FTIR spectrometers. All these six ML classification models, including k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), extra trees (ET), voting, and artificial neural networks (ANNs) were trained through cross validation, and f1-scores of 0.87-1.00 were achieved. In addition, hierarchical cluster analysis (HCA) was performed on 100 synthetic cannabinoids with the most complex structural variation to investigate the structure-spectral property relationship, which leads to a summary of eight synthetic cannabinoid sub-categories with different "linked groups". ML models were also constructed to classify eight synthetic cannabinoid sub-categories. For the first time, this study developed six ML models, which were suitable for both desktop and portable spectrometers, to classify eight categories of NPS and eight synthetic cannabinoids sub-categories. These models can be applied for the fast, accurate, cost-effective, and on-site non-targeted screening of newly emerging NPS with no reference data available.
Topics: Spectroscopy, Fourier Transform Infrared; Cannabinoids; Psychotropic Drugs; Tryptamines; Fentanyl
PubMed: 37327724
DOI: 10.1016/j.forsciint.2023.111761 -
European Journal of Pharmacology Aug 2023Antipsychotic drugs of different chemical/pharmacological families show preferential dopamine (DA) D receptor (D-R) vs. D receptor (D-R) affinity, with the exception of...
Antipsychotic drugs of different chemical/pharmacological families show preferential dopamine (DA) D receptor (D-R) vs. D receptor (D-R) affinity, with the exception of clozapine, the gold standard of schizophrenia treatment, which shows a comparable affinity for both DA receptors. Here, we examined the ability of Lu AF35700 (preferential D-R>D-R antagonist), to reverse the alterations in thalamo-cortical activity induced by phencyclidine (PCP), used as a pharmacological model of schizophrenia. Lu AF35700 reversed the PCP-induced alteration of neuronal discharge and low frequency oscillation (LFO, 0.15-4 Hz) in thalamo-cortical networks. Likewise, Lu AF35700 prevented the increased c-fos mRNA expression induced by PCP in thalamo-cortical regions of awake rats. We next examined the contribution of D-R and D-R to the antipsychotic reversal of PCP effects. The D-R antagonist haloperidol reversed PCP effects on thalamic discharge rate and LFO. Remarkably, the combination of sub-effective doses of haloperidol and SCH-23390 (DA D-R antagonist) fully reversed the PCP-induced fall in thalamo-cortical LFO. However, unlike with haloperidol, SCH-23390 elicited different degrees of potentiation of the effects of low clozapine and Lu AF35700 doses. Overall, the present data support a synergistic interaction between both DA receptors to reverse the PCP-induced alterations of oscillatory activity in thalamo-cortical networks, possibly due to their simultaneous blockade in direct and indirect pathways of basal ganglia. The mild potentiation induced by SCH-23390 in the case of clozapine and Lu AF35700 suggests that, at effective doses, these agents reverse PCP effects through the simultaneous blockade of both DA receptors.
Topics: Rats; Animals; Phencyclidine; Clozapine; Haloperidol; Dopamine; Antipsychotic Agents; Dopamine Antagonists; Receptors, Dopamine D1
PubMed: 37295763
DOI: 10.1016/j.ejphar.2023.175802 -
ACS Chemical Neuroscience Jun 2023Dextromethorphan (DXM) was introduced in 1958 as the first non-opioid cough suppressant and is indicated for multiple psychiatric disorders. It has been the most used... (Review)
Review
Dextromethorphan (DXM) was introduced in 1958 as the first non-opioid cough suppressant and is indicated for multiple psychiatric disorders. It has been the most used over-the-counter cough suppressant since its emergence. However, individuals quickly noticed an intoxicating and psychedelic effect if they ingested large doses. DXM's antagonism at -methyl-d-aspartate receptors (NMDAr) is thought to underly its efficacy in treating acute cough, but supratherapeutic doses mimic the activity of dissociative hallucinogens, such as phencyclidine and ketamine. In this Review we will discuss DXM's synthesis, manufacturing information, drug metabolism, pharmacology, adverse effects, recreational use, abuse potential, and its history and importance in therapy to present DXM as a true classic in chemical neuroscience.
Topics: Humans; Antitussive Agents; Dextromethorphan; Hallucinogens; Phencyclidine; Ketamine; Receptors, N-Methyl-D-Aspartate
PubMed: 37290117
DOI: 10.1021/acschemneuro.3c00088 -
Cureus May 2023Recreational drug use is a significant public health concern in various countries. It is well understood that usage of psychedelics/hallucinogens, such as lysergic acid...
Recreational drug use is a significant public health concern in various countries. It is well understood that usage of psychedelics/hallucinogens, such as lysergic acid diethylamide (LSD), ecstasy, phencyclidine (PCP), and psilocybin-containing mushrooms, has increased significantly over the last few decades, particularly in adolescents and young adults, yet the effects of these recreational drugs are poorly understood. Psilocybin has recently been studied as an alternative to traditional antidepressant therapies with potentially benign side effects. Here, we present the case of a 48-year-old male with a past medical history of attention-deficit/hyperactivity disorder on lisdexamfetamine who presented after a syncopal episode witnessed by his wife at home. He was found to be in ventricular fibrillation and subsequently had an extensive workup with cardiac magnetic resonance imaging (MRI), ischemic evaluation, and electrophysiology, which were unrevealing. He then received an automatic implantable cardiac defibrillator and was incidentally found to have hereditary hemochromatosis on outpatient follow-up. His polypharmacy may have potentially led to catecholamine release, leading to ventricular arrhythmia.
PubMed: 37288212
DOI: 10.7759/cureus.38669 -
Journal of Analytical Toxicology Jul 20233-Hydroxyphencyclidine (3-OH-PCP) is a hydroxy derivative of phencyclidine, synthesized in 1978 to investigate the structure-activity relationship of phencyclidine...
3-Hydroxyphencyclidine (3-OH-PCP) is a hydroxy derivative of phencyclidine, synthesized in 1978 to investigate the structure-activity relationship of phencyclidine derivates. In vitro studies have shown that 3-OH-PCP, like phencyclidine, acts on the N-methyl-D-aspartate receptor and has a higher affinity for this receptor than phencyclidine. The authors report the case of a 38-year-old man, known for drug addiction, found dead at home with two plastic bags of powders found near his body. Using liquid chromatography coupled to tandem mass spectrometry, peripheral blood toxicological analysis revealed consumption of 3-OH-PCP with a concentration of 3-OH-PCP being 524 ng/mL. Blood also tested positive for nordiazepam, methylphenidate, amisulpride, methadone and benzoylecgonine, all at concentrations near those observed after recreational abuse. The blood concentration of 3-OH-PCP is the highest ever reported in the literature. Hair testing also revealed 3-OH-PCP, at 174 pg/mg, which may correspond to a chronic consumption of this molecule. A nuclear magnetic resonance analysis of the two powders highlighted 3-OH-PCP and 5-methoxy-dimethyltryptamine, estimated to have a purity of 85.4 and 91.3%, respectively, using the Electronic Reference To access In vivo Concentrations method.
Topics: Male; Humans; Adult; Phencyclidine; Powders; Substance-Related Disorders; Hair
PubMed: 37279962
DOI: 10.1093/jat/bkad031 -
Biochemical and Biophysical Research... Jul 2023Repeated administration of drugs of abuse leads to progressively greater behavioral responses; this phenomenon is referred to as behavioral sensitization. MK-801 blocks...
Repeated administration of drugs of abuse leads to progressively greater behavioral responses; this phenomenon is referred to as behavioral sensitization. MK-801 blocks the N-methyl-d-aspartate (NMDA) receptor and elicits behavioral sensitization. Ketamine and phencyclidine, are also NMDA antagonists and have well-documented abuse potential. This study investigated the characteristics of MK-801-induced behavioral sensitization and found that it induced sensitization rapidly; only five consecutive treatments were required. The optimal dose for robust sensitization was also identified, which corresponded to the typical doses of abused NMDA antagonists (i.e., between the doses inducing antidepressant and anesthetic effects). Following MK-801-induced behavioral sensitization, changes were observed in the expression and/or phosphorylation of NMDA receptor subunits. While the expression of early growth response protein 1, which serves as a marker of neuronal activation, was affected by MK-801 sensitization, extracellular signal-regulated kinase phosphorylation was not associated with MK-801 treatment.
Topics: Animals; Dizocilpine Maleate; N-Methylaspartate; Behavior, Animal; Phencyclidine; Receptors, N-Methyl-D-Aspartate
PubMed: 37201359
DOI: 10.1016/j.bbrc.2023.05.009 -
Drug Testing and Analysis Jan 20243-Methoxyeticyclidine (3-MeO-PCE), a phencyclidine-type substance, has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine and an involvement in...
In vitro and in vivo metabolism of 3-Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography-high-resolution mass spectrometry.
3-Methoxyeticyclidine (3-MeO-PCE), a phencyclidine-type substance, has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine and an involvement in fatal intoxication cases. The aim of this study was to identify new biomarkers and biotransformation pathways for 3-MeO-PCE. In vitro models were established using zebrafish and human liver microsomes for analysis of the phases I and II metabolites of 3-MeO-PCE by liquid chromatography-high-resolution mass spectrometry. Urine samples of known 3-MeO-PCE consumers in forensic cases were then subjected to analysis. Overall, 14 metabolites were identified in zebrafish and human liver microsomes, allowing postulation of the following metabolic pathways: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, combination, and glucuronidation or sulfation. 3-MeO-PCE and three metabolites (M2, M3, and M6) were detected in urine. We recommended M2 (the hydroxylation product) as a potential biomarker for documenting 3-MeO-PCE intake in clinical and forensic cases.
Topics: Animals; Humans; Microsomes, Liver; Zebrafish; Phencyclidine; Tandem Mass Spectrometry; Chromatography, Liquid; Ketamine
PubMed: 37125436
DOI: 10.1002/dta.3488 -
Frontiers in Cellular Neuroscience 2023N-methyl D-aspartate receptor (NMDAR) hypofunction is a pathophysiological mechanism relevant for schizophrenia. Acute administration of the NMDAR antagonist...
N-methyl D-aspartate receptor (NMDAR) hypofunction is a pathophysiological mechanism relevant for schizophrenia. Acute administration of the NMDAR antagonist phencyclidine (PCP) induces psychosis in patients and animals while subchronic PCP (sPCP) produces cognitive dysfunction for weeks. We investigated the neural correlates of memory and auditory impairments in mice treated with sPCP and the rescuing abilities of the atypical antipsychotic drug risperidone administered daily for two weeks. We recorded neural activities in the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC) during memory acquisition, short-term, and long-term memory in the novel object recognition test and during auditory processing and mismatch negativity (MMN) and examined the effects of sPCP and sPCP followed by risperidone. We found that the information about the familiar object and its short-term storage were associated with mPFC→dHPC high gamma connectivity (phase slope index) whereas long-term memory retrieval depended on dHPC→mPFC theta connectivity. sPCP impaired short-term and long-term memories, which were associated with increased theta power in the mPFC, decreased gamma power and theta-gamma coupling in the dHPC, and disrupted mPFC-dHPC connectivity. Risperidone rescued the memory deficits and partly restored hippocampal desynchronization but did not ameliorate mPFC and circuit connectivity alterations. sPCP also impaired auditory processing and its neural correlates (evoked potentials and MMN) in the mPFC, which were also partly rescued by risperidone. Our study suggests that the mPFC and the dHPC disconnect during NMDAR hypofunction, possibly underlying cognitive impairment in schizophrenia, and that risperidone targets this circuit to ameliorate cognitive abilities in patients.
PubMed: 37066076
DOI: 10.3389/fncel.2023.1152248