N-methyl-2-pyrrolidone (NMP) and γ-hydroxybutyrate acid (GHB) are synthetic solvents detected in the recreational drug market. GHB has sedative/hypnotic properties and is used for criminal purposes to compromise reaction ability and commit drug-facilitated sexual assaults and other crimes. NMP is a strong solubilizing solvent that has been used alone or mixed with GHB in case of abuse and robberies

Anxiety and trauma-related disorders are highly prevalent worldwide, and are associated with altered associative fear learning. Despite the effectiveness of exposure therapy, which aims to reduce associative fear responses, relapse rates remain high. This is due, in part, to the context specificity of exposure therapy, which is a form of extinction. Many studies show that fear relapses when mice are

Rationale Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation

Rationale Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables like soybeans that share a common chemical structure. Previous studies have described that synthetic derivatives from the natural isoflavone daidzin can modulate cocaine addiction, by a mechanism suggested to involve aldehyde-dehydrogenase

Rationale A growing body of research suggests that substance use disorder (SUD) may be characterized as disorders of decision making. However, drug choice studies assessing drug-associated decision making often lack more complex and dynamic conditions that better approximate contexts outside the laboratory and may lead to incomplete conclusions regarding the nature of drug-associated value. Objectives

Background Depression causes significant debilitating symptoms and economic burden. Current management is challenged by slow onset of action and modest efficacies of antidepressants; thus, the search for newer antidepressants remains relevant. We evaluated the antidepressant effects of a kaurene diterpene, xylopic acid (XA), in zebrafish and mouse models. Methods The chronic unpredictable stress (CUS)

Rationale Noradrenaline (NE) is closely related to attentive performance and impulsive control. However, the potential sex differences regarding attention and impulsivity under the noradrenergic modulation have been largely neglected. Therefore, our study aimed to investigate whether male and female rats exhibit differential responses to NE-related drugs during the five-choice serial reaction time

Rationale Preclinical and clinical reports suggest that ferulic acid (FA), a plant-derived phenylpropanoid, is effective against mental health problems such as agitation, anxiety, and irritability in humans, without causing adverse side effects. However, the mechanism of action is unknown. Objective The aim of the study is to investigate the mechanism underlying the ameliorative effects of FA on mental

Rationale As a treatment for cognitive dysfunction in schizophrenia, oxytocin nasal sprays potentially improve social cognition, facial expression recognition, and sense of smell. Mismatch negativity (MMN) is an event-related potential (ERP) reflecting auditory discrimination while MMN deficits reflect cognitive function decline in schizophrenia. Objectives To determine whether oxytocin nasal spray

Rationale Cannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus expectancy factors. Objectives We evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses. Methods In this randomized crossover

Rationale Methamnetamine (MNA; PAL-1046) is a new psychoactive substance that acts as a full biogenic amine transporter (BAT) substrate. BAT substrates promote neurotransmitter release from the nerve terminal and can be abused as stimulants. However, scientific information on the abuse potential of methamnetamine is lacking. Objective We evaluated the abuse liability of methamnetamine. Methods The

Rationale Amyloid β peptide (Aβ) triggers a series of pathological events including microglial activation, oxidative stress, and inflammation-causing neuronal death and typical pathological changes in Alzheimer’s disease (AD). Objectives This study aimed to investigate the therapeutic effects and mechanism of bulbocodin D for AD in vivo. Methods In this study, Morris water maze (MWM) analysis was used

Rationale Major depressive disorder (MDD) is a debilitating disorder with adverse effects on mood, memory, and quality of life. Objectives In this study, the antidepressant potential of glatiramer acetate (GA), a drug used in the management of multiple sclerosis, was investigated in acute and chronic models of depression in male mice. The acute antidepressant screening was performed with the forced

Rationale Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies. Objectives The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine

Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urological toxicity (KIUT) is associated with sub-anesthetic

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine

Rationale There is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices. Objective We sought to determine whether young female carriers

Rationale Elevated whole-blood serotonin (5-HT) is a robust biomarker in ~ 30% of patients with autism spectrum disorders, in which repetitive behavior is a core symptom. Furthermore, elevated whole-blood 5-HT has also been described in patients with pediatric obsessive-compulsive disorder. The 5-HT1B receptor is associated with repetitive behaviors seen in both disorders. Chronic blockade of serotonin

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed

Rationale Nucleus cuneiformis (NC), a reticular nucleus of the midbrain, is a part of the descending pain modulatory system and therefore has an important role in pain perception. Objectives Considering the abundance of GABAA and cannabinoid receptors in the NC and also the bidirectional roles for GABA in controlling nociception, the present study examined the effects of bilateral intra-NC microinjection

Paeonol is a biologically active component purified from the root bark of Cortex Moutan that exerts pharmacological effects on the cervical cancer. In this study, we aim to evaluate the anti-cervical cancer capacity of paeonol and to investigate the mechanism driving its anti-cervical cancer effect. Paeonol administration markedly restrained the proliferation and caused apoptosis in HeLa cells. Furthermore

Background There is urgent need for new medications for psychiatric disorders. Mental illness is expected to become the leading cause of disability worldwide by 2030. Yet, the last two decades have seen the pharmaceutical industry withdraw from psychiatric drug discovery after costly late-stage trial failures in which clinical efficacy predicted pre-clinically has not materialised, leading to a crisis

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study

Rationale The use of psychotropic drugs in the paediatric population has not been the subject of many studies, due to the fact that this population is generally not included in clinical trials and these drugs are not authorized for use on minors. Objectives This study aims to provide an accurate description of psychotropic drug use in children and adolescents in the North of Europe and Catalonia. Methods

Rationale The relationship between age, ethanol intake, and the hedonic value of ethanol is key to understanding the motivation to consume ethanol. Objective It is uncertain whether ethanol drinking during adolescence changes ethanol’s hedonic value into adulthood. Methods The current study compared voluntary intermittent ethanol consumption (IAE; 2-bottle choice; 20%v/v) among adolescent and adult

Rationale Inhibition is a core executive function and refers to the ability to deliberately suppress attention, behavior, thoughts, and/or emotions and instead act in a specific manner. While acute alcohol exposure has been shown to impair response inhibition in the stop-signal and Go/NoGo tasks, reported alcohol effects on attentional inhibition in the Stroop task are inconsistent. Notably, studies

Introduction The classical effects of exogenous opioids, such as morphine, are predominantly mediated through μ-opioid receptors. The chronic use of morphine induces anxiety-like behavior causing functional changes in the mesolimbic dopaminergic system. The mixed μ/κ-agonist, nalbuphine, used either as an analgesic or as an adjuvant with morphine, produces different and opposite effects. However, whether

Rationale The flashing lights and sounds of modern casinos are alluring and may contribute to the addictive nature of gambling. Such cues can have a profound impact on the noradrenaline (NA) system, which could therefore be a viable therapeutic target for gambling disorder (GD). While there is substantial evidence to support the involvement of NA in the impulsive symptoms of GD, its function in mediating

Rationale Over the past decade, adolescent cigarette smoking has been declining. However, adolescent nicotine consumption via electronic cigarettes is rapidly gaining popularity. Earlier onset nicotine use is associated with increased risk of dependence. A bidirectional relationship between nicotine and stress exists; perceived stress is a predictor for nicotine use, and stress reduction is a commonly

Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced

Background Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing. Aims We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward

Rationale Rumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through

Rationale The medical uses of cannabidiol (CBD), a constituent of the Cannabis sativa, have accelerated the legal and social acceptance for CBD-based medications but has also given the momentum for questioning whether the long-term use of CBD during the early years of life may induce adverse neurobiological effects in adulthood, including sleep disturbances. Given the critical window for neuroplasticity

Background The use of sedatives or hypnotics and the recurrence of depression have not been adequately explored. This study investigated the roles of sedative-hypnotics in patients with major depressive disorder (MDD). Various characteristics of sedative-hypnotic use were tested as risk factors for recurrence. Methods Clinical records of 15,510 patients with major depressive disorder who prescribed

Introduction Alzheimer’s disease (AD) is a progressive brain disorder accompanied with synaptic failures and decline in cognitive and learning processes. Protease-activated receptor 1 (PAR1) is the major thrombin receptor in the brain that is implicated in synaptic plasticity and memory formation. In the current study, we hypothesized that inhibition of PAR1 would theoretically prevent amyloid beta

Rationale Aberrations in the stress response are associated with posttraumatic stress disorder (PTSD) symptom development, maintenance, and severity. Gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter, may play a key role in stress recovery. Objectives In this preliminary study, we examined whether plasma GABA levels differed between women with PTSD and trauma-exposed healthy

Adolescence is known for its high level of risk-taking, and neurobiological alterations during this period may predispose to psychoactive drug initiation and progression into more severe use patterns. Stress is a risk factor for drug consumption, and post-weaning social isolation increases drug self-administration in rodents. This review aimed to provide an overview of the effects of adolescent social

Rationale Alcohol priming can modulate the value of rewards, as observed through the effects of acute alcohol administration on cue reactivity. However, little is known about the psychophysiological mechanisms driving these effects. Here, we examine how alcohol-induced changes in bodily states shape the development of implicit attentional biases and explicit cue reactivity. Objectives To characterize

Rationale Benzodiazepines induce electroencephalography (EEG) changes in rodents and humans that are associated with distinct behavioral effects and have been proposed as quantitative biomarkers for GABAA receptor modulation. Specifically, central EEG beta and occipital EEG delta activity have been associated with anxiolysis and sedation, respectively. The extent to which nonhuman primates show the

Depression resulted as an important factor associated with the myocardial infarction (MI) prognosis. Patients with MI also have a higher risk for developing depression. Although the issue of depression after MI has become a matter of clinical concern, the molecular mechanism underlying depression after MI remains unclear, whereby several strategies suggested have not got ideal effects, such as selective

Rationale Depressed individuals demonstrate debilitating symptoms, including depressed mood, anhedonia, and effort-related deficits. Effort-related decision-making can be measured through providing subjects with a choice between high effort/reward and low effort/reward options, which is a dopamine (DA)–dependent behavior. While previous research has shown sex differences in depression rates, this has

Rationale Opioid and GABAA receptors are both located in central nociceptive pathways, and compounds that activate these receptors have pain-relieving properties. To date, the interactive effects of concurrent administration of these compounds in preclinical models of pain-like behaviors have not been assessed. Objective The purpose of this study was to examine the interactive effects of the μ-opioid

Rationale Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia

Objective To investigate the protective effect of phosphatidylserine liposomes (PSL) on post-stroke (ST) injuries such as neuroinflammation and depression in mice. Methods Brain ischemia was induced via the right unilateral common carotid artery occlusion model. Then, behavioral assessments including the forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like

A Correction to this paper has been published: https://doi.org/10.1007/s00213-021-05778-y

Rationale Co-witness discussion is common and often witnesses are under the influence of alcohol. As such, it is important to understand how such factors may influence eyewitness testimony. Objectives We combined a co-witness memory paradigm with an alcohol administration paradigm to examine the influence of alcohol and dyadic discussion on remembering a mock crime. Methods Intoxicated and sober dyads

Rationale Cognitive dysfunction is frequent in major depressive disorder (MDD), and brain-derived neurotrophic factor (BDNF) is involved both in regulation of cognition and in therapeutic response in MDD. Objectives The aim of this study was to determine if baseline plasma BDNF might predict change in cognitive function in MDD patients treated with vortioxetine or escitalopram, and whether the alterations

Rationale Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. Objectives and methods We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants

A Correction to this paper has been published: https://doi.org/10.1007/s00213-021-05794-y

Rationale and objective SJP-005 (ketotifen and ibuprofen) is being developed as a potential new treatment for opioid withdrawal. Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2–12) effects of SJP-005 on discontinuation-induced morphine withdrawal. Methods Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice

Rationale Samelisant (SUVN-G3031) is a potent and selective histamine H3 receptor (H3R) inverse agonist with good brain penetration and oral bioavailability. Objectives Pharmacological and neurochemical characterisation to support the utility of Samelisant (SUVN-G3031) in the treatment of sleep-related disorders like narcolepsy. Methods Samelisant (SUVN-G3031) was tested in rat brain microdialysis

Rationale With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. Objectives The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance, subjective drug effects, cardiovascular measures, and

Clinical evidence shows that chronic pain and depression often accompany each other, but the underlying pathogenesis of comorbid chronic pain and depression remains mostly undetermined. Biotechnology is gradually revealing the phenotype and function of microglia, with great progress regarding microglia’s role in neurodegeneration, depression, chronic pain, and other conditions. This article summarizes

Rationale Past research suggests that people with opioid dependence show increased consumption of sweet food, but it is unclear if this is influenced by altered taste preference and/or taste perception. Objectives We tested whether people prescribed opioid substitution therapy (OST) exhibited a shift in preference towards sweeter flavours, and altered perception of sweetness, and explored whether these

Background Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. Methods Seventy-one patients with treatment-resistant depression were

Rationale Cannabinoid type 1 receptors (CB1Rs) are widely expressed within the brain’s reward circuits and are implicated in regulating drug induced behavioral adaptations. Understanding how CB1R signaling in discrete circuits and cell types contributes to drug-related behavior provides further insight into the pathology of substance use disorders. Objective and methods We sought to determine how cell

Rationale Ursolic acid (UA) has exhibited anti-inflammatory and anti-oxidative drug effects. Objectives In the research, we assessed the effects of UA on Nthy-ori 3-1 cells stimulated by IL-1β and attempted to elucidate the mechanisms underlying the effects. Methods Autoimmune thyroiditis (AIT) was simulated using Nthy-ori 3-1 cells by IL-1β (10 μM) treatment. UA (20 μM) was applied to ameliorate the

Rationale Fragile X syndrome (FXS), the most prevalent genetic form of intellectual disability, is characterized by intellectual impairment, impaired sociability, aggression, self-injury, hyperactivity, and attention deficits. A consequence of the hyperactivity and attention deficits is that individuals with FXS are frequently diagnosed with attention deficit hyperactivity disorder (ADHD) and treated

Rationale Antipsychotics help alleviate the positive symptoms associated with schizophrenia; however, their debilitating side effects have spurred the search for better treatment options. Novel compounds can be screened for antipsychotic potential in neuronal cell cultures and following acute N-methyl-D-aspartate (NMDA) receptor blockade with non-competitive antagonists such as MK-801 in rodent behavioral

Rationale Previous research suggests that sleep polysomnography and EEG endpoints can be used to assess GABAergic activity; however, the impact of GABAB receptor positive allosteric modulators on sleep endpoints remains unclear. Objectives This phase 1 study compared a single dose of ASP8062 (35 mg or 70 mg), a GABAB receptor positive allosteric modulator, with placebo and paroxetine (40 mg). Methods