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Opioid use results in thousands of overdose deaths each year. To address this crisis, we need a better understanding of the neurobiological mechanisms that drive opioid abuse. The noninvasive imaging tools positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and manganese-enhanced magnetic resonance imaging (MEMRI) can be used to identify how brain activity responds to acute opioid exposure and adapts to chronic drug treatment. These techniques can be performed in humans and animal models, and brain networks identified in animals closely map to the human brain. Animal models have the advantage of being able to systematically examine the independent effects of opioid exposure in a controlled environment accounting for the complex factors that drive opioid misuse in humans. This review synthesizes literature that utilized noninvasive neuroimaging tools (PET, fMRI, and MEMRI) measuring brain activity correlates in animals to understand the neurobiological consequences of exposure to abused opioids. A PubMed search in September 2023 identified 25 publications. These manuscripts were divided into 4 categories based on the route and duration of drug exposure (acute/chronic, active/passive administration). Within each category, the results were generally consistent across drug and imaging protocols. These papers cover a 20-year range and highlight the advancements in neuroimaging methodology during that time. These advances have enabled researchers to achieve greater resolution of brain regions altered by opioid exposure and to identify patterns of brain activation across regions (i.e., functional connectivity) and within subregions of structures. After describing the existing literature, we suggest areas where additional research is needed. [ABSTRACT FROM AUTHOR]

Aim: Much research has been conducted on the acute effects of nicotine on human cognitive performance, demonstrating both enhancing and impairing cognitive effects. With the relatively recent introduction of electronic cigarettes ('e-cigarettes') as a smoking cessation device, little is known about the cognitive effects of e-cigarettes specifically, either as a nicotine replacement device or in the absence of nicotine. The purpose of this review was to present an overview of evidence from empirical studies on the effect of e-cigarettes on cognitive function. Approach: Guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines (PRISMA-ScR), SCOPUS, PubMed, and EBSCOhost were searched from 2006, the year e-cigarettes were introduced, to June 2023 for relevant papers, along with reference lists checked for additional papers. Key findings: Seven experimental and four cross-sectional survey studies were identified and included. The majority of the studies only include regular and current cigarette smokers and primarily assessed the acute cognitive effect of e-cigarettes relative to nicotine. While the findings primarily suggest either no or positive effect of e-cigarettes on cognition in cigarette smokers, associations between e-cigarettes and cognitive impairments in memory, concentration and decision making were reported in both cigarette smokers and never-smokers. Implications and conclusions: The acute cognitive effect of e-cigarettes on regular cigarette smokers appears minimal. However, long-term cognitive effect and their effects on never-smokers are unclear. Given that the increased numbers of e-cigarette users are non-smokers and/or adolescents, research with those naïve to nicotine and a developmentally vulnerable adolescent population on its long-term effect is needed. [ABSTRACT FROM AUTHOR]

A list is presented of people who received awards for papers on original research in psychopharmacology that were cited the most in reviews published in the periodical "Psychopharmacology" between 2003 and 2006, including Danielle C. Turner, James D. Belluzzi and James N. C. Kew.

Rationale: The endocannabinoid system (ECS) belongs to the G protein-coupled receptor family of cell membranes and is associated with neuropsychiatric conditions, and neurodegenerative diseases. Cannabinoid 2 receptors (CB2) are expressed in the central nervous system (CNS) on microglia and subgroups of neurons and are involved in various behavioural processes via immunological and neural regulation. Objective: The objective of this paper is to summarize and explore the impact of CB2 receptors on neuronal modulation, their involvement in various neurological disorders, and their influence on mood, behavior, and cognitive function. Results: The activation of CB2 appears to protect the brain and its functions from damage under neuroinflammatory actions, making it an attractive target in a variety of neurological conditions such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD), and Huntington's disease (HD). During inflammation, there is an overexpression of CB2 receptors, and CB2 agonists show a strong anti-inflammatory effect. These results have sparked interest in the CB2 receptors as a potential target for neurodegenerative and neuroinflammatory disease treatment. Conclusion: In conclusion, CB2 receptors signalling shows promise for developing targeted interventions that could positively affect both immune and neuronal functions, ultimately influencing behavioral outcomes in both health and disease. [ABSTRACT FROM AUTHOR]

Dr. Pickens was remarkably productive during this time with more than 32 basic research papers on drug self-administration as well as 29 reviews and book chapters. In possibly the most influential of these papers, Pickens and Thompson ([6]) systematically studied the effects of cocaine dose and schedule of reinforcement on cocaine self-administration. Graph Roy W. Pickens died peacefully on May 25, 2022, at his home in Glen Allen, Virginia, where he and his wife Dace Svikis have lived since 1999. [Extracted from the article]

Rationale: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. Objectives: As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness. Results: The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored. Conclusions: PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration. [ABSTRACT FROM AUTHOR]

Rationale: Challenges in drug development for psychiatric disorders have left much room for the introduction of novel treatments with better therapeutic efficacies and indices. As a result, intense research has focused on identifying new targets for developing such pharmacotherapies. One of these targets may be the phosphodiesterase (PDE) class of enzymes, which play important roles in intracellular signaling. Due to their critical roles in cellular pathways, these enzymes affect diverse neurobiological functions from learning and memory formation to neuroinflammation. Objectives: In this paper, we reviewed studies on the use of PDE inhibitors (PDEIs) in preclinical models and clinical trials of psychiatric disorders including depression, anxiety, schizophrenia, post-traumatic stress disorder (PTSD), bipolar disorder (BP), sexual dysfunction, and feeding disorders. Results: PDEIs are able to improve symptoms of psychiatric disorders in preclinical models through activating the cAMP-PKA-CREB and cGMP-PKG pathways, attenuating neuroinflammation and oxidative stress, and stimulating neural plasticity. The most promising therapeutic candidates to emerge from these preclinical studies are PDE2 and PDE4 inhibitors for depression and anxiety and PDE1 and PDE10 inhibitors for schizophrenia. Furthermore, PDE3 and 4 inhibitors have shown promising results in clinical trials in patients with depression and schizophrenia. Conclusions: Larger and better designed clinical studies of PDEIs in schizophrenia, depression, and anxiety are warranted to facilitate their translation into the clinic. Regarding the other conditions discussed in this review (most notably PTSD and BP), better characterization of the effects of PDEIs in preclinical models is required before clinical studies. [ABSTRACT FROM AUTHOR]

In this extraordinary time of scientific discovery and heightened awareness of the burden of mental illness throughout the world, research to develop effective psychopharmacological treatments for diverse psychiatric diseases holds great promise. The special issue of the journal "Psychopharmacology" seeks to help fulfill these important promises by highlighting the importance of ethical considerations in psychopharmacological research and related areas. The issue has a three-part structure. First, it highlights pieces on ethical issues in basic and clinical research. Second, it includes papers and commentaries that focus on ethical considerations related to psychopharmacology studies and other forms of clinical research involving individuals who derive from special populations. Third, it provides two papers on approaches to psychopharmacological research ethics education that may be adopted in scientific training settings.

Rationale: Psychostimulants, including methylphenidate (MPH), are the mainstay of pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) in adults. Even though MPH is the most commonly used medication for ADHD these days, there are relatively few resources available that provide comprehensive insight into the pharmacological and clinical features of the compound. Objective: The aim of this paper is to provide an up-to-date outline of the pharmacology and clinical utility of MPH for ADHD in adult patients. Methods: While conducting the narrative review, we applied structured search strategies covering the two major online databases (MEDLINE and Cochrane Central Register of Controlled Trials). In addition, we performed handsearching of reference lists of relevant papers. Results: Methylphenidate exhibits multimodal mechanism of action, working primarily as a dopamine and noradrenaline reuptake inhibitor. It also protects the dopaminergic system against the ongoing 'wearing off' (by securing a substantial reserve pool of the neurotransmitter, stored in the presynaptic vesicles). In placebo-controlled trials, MPH was shown to be moderately effective both against the core ADHD symptoms (standardized mean difference [SMD], 0.49; 95% confidence interval [CI], 0.35–0.64), and the accompanying emotion regulation deficits (SMD, 0.34; 95% CI, 0.23–0.45). The most common adverse events related to long-term treatment with MPH are decreased appetite (~ 20%), dry mouth (15%), heart palpitations (13%), gastrointestinal infections (~ 10%), and agitation/feeling restless (~ 10%). Conclusions: There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD. [ABSTRACT FROM AUTHOR]

Rationale: Drug and natural rewarding stimuli activate the mesolimbic dopaminergic system. Both methamphetamine (Meth) and copulation to satiety importantly increase dopamine (DA) release in the nucleus accumbens (NAc), but with differences in magnitude. This paper analyzes the interaction between Meth administration and the intense sexual activity associated with sexual satiety. Objectives: To evaluate possible changes in Meth-induced behavioral effects and striatal DA-related protein expression due to sexual satiety. Methods: Meth-induced locomotor activity and conditioned place preference (CPP) were tested in sexually experienced male rats that copulated to satiety (S–S) or ejaculated once (1E) the day before or displayed no sexual activity (control group; C). DA receptors and DA transporter expression were determined by western blot in the striatum of animals of all sexual conditions treated with specific Meth doses. Results: Meth's locomotor and rewarding effects were exacerbated in S–S animals, while in 1E rats, only locomotor effects were enhanced. Sexual activity, by itself, modified DA-related protein expression in the NAc core and in the caudate-putamen (CPu), while Meth treatment alone changed their expression only in the NAc shell. Meth-induced changes in the NAc shell turned in the opposite direction when animals had sexual activity, and additional changes appeared in the NAc core and CPu of S–S rats. Conclusion: Sexual satiety sensitizes rats to Meth's behavioral effects and the Meth-induced striatal DA-related protein adaptations are modified by sexual activity, evidencing cross-sensitization between both stimuli. [ABSTRACT FROM AUTHOR]

Rationale: The use of psychedelics for medical and recreational purposes is rising. Contextual factors such as expectancy, intention, and sensory and social environment (set and setting) are widely recognized as moderating the effects of these substances. Nevertheless, clinical trials of microdosing — the ingestion of small, sub-hallucinogenic doses of psychedelics — rarely report their set and setting. This fact suggests that such factors are not considered important in the context of microdosing. Objective: This paper challenges this assumption and makes the case for the crucial relevance of set and setting in microdosing practice. Building on set and setting theory and placebo theory, we explain why set and setting are of crucial importance in the case of microdosing. Results: This reasoning helps elucidate the role of set and setting in determining the outcomes of microdosing and helps explain some of the contradictory results that have emerged in microdosing research in recent years. Conclusion: Set and setting are important constructs to be considered especially in the context of microdosing psychedelics. By reporting set and setting, the results of microdosing research can be made more reliable and consistent. [ABSTRACT FROM AUTHOR]

Rationale: Neurological conditions like Stroke and Alzheimer’s disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis’s potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.Objective: Neurological conditions like Stroke and Alzheimer’s disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis’s potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.Results: Neurological conditions like Stroke and Alzheimer’s disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis’s potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.Conclusion: Neurological conditions like Stroke and Alzheimer’s disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis’s potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes. [ABSTRACT FROM AUTHOR]

Human research with hallucinogens such as lysergic acid diethylamide (LSD) has been ongoing in the USA since 1949. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a “model psychosis”; as a direct antidepressant; and as an adjunct to psychotherapy. Studies with all drugs, including LSD, have always been conducted under federal regulatory controls, including the 1938 Food Drug and Cosmetic Act (FDCA; which ensured the safety of drugs) and the 1962 Kefauver-Harris Amendments to the FDCA (which described appropriate scientific methodology and ensured drug efficacy). This paper details how the 1962 Amendments introduced numerous safety and efficacy requirements that must be in satisfied during clinical drug research—and how human studies conducted with LSD in the 1960s struggled with their fulfillment. Information is provided from Senate hearings, case law, and interviews with key investigators. Examples are also drawn from scientific papers and symposia published during and since that period, with a focus on information from clinical studies conducted with LSD by psychiatrist Albert Kurland at the Spring Grove State Hospital, near Baltimore, MD. While Kurland largely conformed with these new regulations, other investigators often fell short of complying with scientific standards and federal requirements. Thus, the human hallucinogen studies of the 1960s are best understood as providing pilot data on safety and efficacy, as well as testable hypotheses for current hallucinogen studies conducted under modern scientific and regulatory standards. [ABSTRACT FROM AUTHOR]

Rationale: Current pharmacological approaches to treatment of post-traumatic stress disorder (PTSD) lack adequate effectiveness. As a result, identifying new molecular targets for drug development is necessary. Furthermore, fear learning and memory in PTSD can undergo different phases, such as fear acquisition, consolidation, and extinction. Each phase may involve different cellular pathways and brain regions. As a result, effective management of PTSD requires mindfulness of the timing of drug administration. One of the molecular targets currently under intense investigation is the N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR). However, despite the therapeutic efficacy of drugs targeting NMDAR, their translation into clinical use has been challenging due to their various side effects. One possible solution to this problem is to target signaling proteins downstream to NMDAR to improve targeting specificity. One of these proteins is the neuronal nitric oxide synthase (nNOS), which is activated following calcium influx through the NMDAR. Objective: In this paper, we review the literature on the pharmacological modulation of nNOS in animal models of PTSD to evaluate its therapeutic potential. Furthermore, we attempt to decipher the inconsistencies observed between the findings of these studies based on the specific phase of fear learning which they had targeted. Results: Inhibition of nNOS may inhibit fear acquisition and recall, while not having a significant effect on fear consolidation and extinction. However, it may improve extinction consolidation or reconsolidation blockade. Conclusions: Modulation of nNOS has therapeutic potential against PTSD and warrants further development for use in the clinical setting. [ABSTRACT FROM AUTHOR]

Rationale: The regular consumption of very small doses of psychedelic drugs (known as microdosing) has been a source of growing media and community attention in recent years. However, there is currently limited clinical and social research evidence on the potential role of microdosing as therapies for mental and substance use disorders. Objectives: This paper examined subjective experiences of microdosing psychedelics to improve mental health or to cease or reduce substance use, and examined sociodemographic and other covariates of perceived improvements in mental health that individuals attributed to microdosing. Methods: An international online survey was conducted in 2018 and examined people's experiences of using psychedelics for self-reported therapeutic or enhancement purposes. This paper focuses on 1102 respondents who reported current or past experience of psychedelic microdosing. Results: Twenty-one percent of respondents reported primarily microdosing as a therapy for depression, 7% for anxiety, 9% for other mental disorders and 2% for substance use cessation or reduction. Forty-four percent of respondents perceived that their mental health was "much better" as a consequence of microdosing. In a multivariate analysis, perceived improvements in mental health from microdosing were associated with a range of variables including gender, education, microdosing duration and motivations, and recent use of larger psychedelic doses. Conclusions: Given the promising findings of clinical trials of standard psychedelic doses as mental health therapies, clinical microdosing research is needed to determine its potential role in psychiatric treatment, and ongoing social research to better understand the use of microdosing as self-managed mental health and substance use therapies. [ABSTRACT FROM AUTHOR]

The therapeutic potential of medical cannabis to treat a variety of conditions is becoming increasingly recognised. Globally, a large number of countries have now legalised cannabis for medical uses and a substantial number of patients are able to access their medications. Yet in the UK, where medical cannabis was legalised in November 2018, only a handful of NHS prescriptions have been written, meaning that most patients are unable to access the medicine. Reasons for this are manyfold and include the perceived lack of clinical evidence due to the challenges of studying medical cannabis through randomised controlled trials. In order to develop the current evidence base, the importance of incorporating real-world data (RWD) to assess the effectiveness and efficacy of medical cannabis has gradually become recognised. The current paper provides a detailed outline of Project Twenty21 (T21), the UK's first medical cannabis registry, launched in August 2020. We provide the rationale for T21 and describe the methodology before reporting the characteristics of the 'first patients' enrolled in the registry. We describe the health status of all patients enrolled into the project during its first 7 months of operation and the sociodemographic characteristics and primary presenting conditions for these patients, as well as details of the medical cannabis prescribed to these individuals. By 12th March 2021, 678 people had been enrolled into T21; the majority (64%) were male and their average age was 38.7 years (range = 18–80). The most commonly reported primary conditions were chronic pain (55.6%) and anxiety disorders (32.0%) and they reported high levels of multi-morbidity, including high rates of insomnia and depression. We also present preliminary evidence from 75 patients followed up after 3 months indicating that receipt of legal, prescribed cannabis was associated with a significant increase in self-reported health, assessed using the visual analogue scale of the EQ-5D-5L (Cohen's d =.77, 95% CI =.51–1.03). Our initial findings complement reports from other large-scale databases globally, indicating that the current RWD is building up a pattern of evidence. With many clinicians demanding better and faster evidence to inform their decisions around prescribing medical cannabis, the current and future results of T21 will expand the existing evidence base on the effectiveness of cannabis-based medical products (CBMPs). [ABSTRACT FROM AUTHOR]

The potential of mitragynine to produce physiological dependence (withdrawal) was assessed using a rapid assessment procedure with male ICR mice exposed to heroin-admixed food followed by naloxone (subcutaneously, s.c.) precipitation of withdrawal. Initial studies indicated that 3 days of exposure to 3.0 mg/g of heroin-admixed food followed by naloxone (0.6 mg/kg) reliably precipitated withdrawal jumping and weight loss. Lower concentrations of heroin-admixed food and lower doses of naloxone produced fewer withdrawal signs. A longer exposure to heroin-admixed food did not produce significantly greater amounts of jumping or weight loss. Further, these withdrawal signs were dose-dependently reversed by s.c. administration of heroin immediately following naloxone administration. Mitragynine (s.c.) also dose-dependently suppressed naloxone-precipitated withdrawal signs. Additionally, both jumping and weight loss were suppressed over a comparable range of mitragynine doses when administered by gavage with a noticeably, but not significantly, higher potency than with s.c. administration. The ED50 values for mitragynine for the suppression of withdrawal by any route (354–911 μmol/kg) were greater than the minimally effective dose that decreased locomotor activity (251 μmol/kg) and from 40- to 104-fold greater than those for heroin. The results suggest inherent opioid dependence liability of mitragynine. The in vivo potency relations between mitragynine and heroin are consistent with a conclusion of dependence-producing effects, indicated by the suppression of withdrawal, comparable to standard opioid μ-receptor agonists, differing primarily in terms of potency. The present paper provides a method for the rapid assessment of physiological dependence liability applicable to other kratom plant constituents or any potential opioid dependence-producing agents. [ABSTRACT FROM AUTHOR]

Background: In this paper, we reviewed translational studies concerned with environmental influences on the rewarding effects of heroin versus cocaine in rats and humans with substance use disorder. These studies show that both experienced utility ('liking') and decision utility ('wanting') of heroin and cocaine shift in opposite directions as a function of the setting in which these drugs were used. Briefly, rats and humans prefer using heroin at home but cocaine outside the home. These findings appear to challenge prevailing theories of drug reward, which focus on the notion of shared substrate of action for drug of abuse, and in particular on their shared ability to facilitate dopaminergic transmission. Aims: Thus, in the second part of the paper, we verified whether our findings could be accounted for by available computational models of reward. To account for our findings, a model must include a component that could mediate the substance-specific influence of setting on drug reward Results: It appears of the extant models that none is fully compatible with the results of our studies. Conclusions: We hope that this paper will serve as stimulus to design computational models more attuned to the complex mechanisms responsible for the rewarding effects of drugs in real-world contexts. [ABSTRACT FROM AUTHOR]

Rationale: The functional analysis of the behavioral effects of drugs has lagged behind more biological research approaches in elucidating how drugs influence behavior. Part of the problem is the scarcity of mathematical models of responding under standardized behavioral procedures. A two-parameter model derived from the matching law to account for response rate as a function of reinforcement rate in single response alternative procedures provides a good description of responding under multi-component multiple variable interval (mult VI) schedules of reinforcement, both in the absence of drugs and in the presence of a variety of drugs. Objective: This paper explores how well the two-parameter model and its exponentiated variant (three-parameter model) describe drug effects on responding under mult VI schedules. Methods: Data from seven published papers concerning the effects of drugs on mult VI schedules are reanalyzed. Results: The three-parameter model describes the effects of drugs on responding more accurately than does the two-parameter model. The three-parameter model also describes well the type of relation between response rates under drug and no-drug conditions that the rate dependency hypothesis is usually invoked to explain. Conclusions: The three-parameter model can be improved by adding a parameter to account for base response rate, that is, response rate when reinforcement rate is zero. The parameters of the best descriptive model could be used to devise a classification system for the behavioral effects of drugs under mult VI schedules. The parameters should be conceptualized by relating the drug-induced changes in parameter value to converging changes in measurements of brain function. This would connect the behavioral and the biological analyses of drug action to the benefit of both research fields. [ABSTRACT FROM AUTHOR]

Depression is a leading cause of disability worldwide and improving its treatment is a core research priority for future programmes. A change in the view of psychological and biological processes, from seeing them as separate to complementing one another, has introduced new perspectives on pathological mechanisms of depression and treatment mode of action. This review presents a theoretical model that incorporated this novel approach, the cognitive neuropsychological hypothesis of antidepressant action. This model proposes that antidepressant treatments decrease the negative bias in the processing of emotionally salient information early in the course of antidepressant treatment, which leads to the clinically significant mood improvement later in treatment. The paper discusses the role of negative affective biases in the development of depression and response to antidepressant treatments. It also discusses whether the model can be applied to other antidepressant interventions and its potential translational value, including treatment choice, prediction of response and drug development. [ABSTRACT FROM AUTHOR]

Rationale: Cannabidiol (CBD) products lacking regulatory approval are being used to self-treat a myriad of conditions and for their unsubstantiated health benefits. The scientific evidence supporting these claims largely arises not from controlled clinical trials, but from the recognition that CBD has numerous biological targets. Yet, CBD is commonly consumed and often in over-the-counter products that are unapproved and of unknown composition. Epidiolex® is the only product that has undergone rigorous pharmacokinetic assessment and testing in clinical trials; it was approved as a non-scheduled drug by the U.S. Food and Drug Administration for the treatment of intractable childhood-onset seizures. However, studies investigating CBD for other medical conditions are limited in number and often lack the scientific rigor, controls, or sample sizes required to draw clinically meaningful conclusions. Although Epidiolex® is safe for human consumption, recent changes in regulation of commercially available CBD products have resulted in limited quality control and products marketed with unknown CBD bioavailability. Even scientifically rigorous studies have used different sources of CBD and different suspension vehicles for administration, making it difficult to compare results among studies and resolve mixed outcomes. Objectives: This paper reviews the molecular targets, pharmacokinetics, and safety and abuse liability of CBD; additionally, the extant evidence on its potential therapeutic effects for neurological disorders, pain, inflammation, conditions related to immune function, psychiatric disorders, and substance use are described. [ABSTRACT FROM AUTHOR]

This article focuses on misconceptions behind the usage of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). MDMA has elicited substantial interest not only from preclinical and clinical scientists, but also from major parts of the media such as newspapers and television. It has been stated that MDMA is a very dangerous drug when taken acutely. It is sometimes even proposed that any dose is potentially fatal, thereby ignoring the fact that MDMA, like all other drugs, obeys normal pharmacological principles. However, not a single experiment has produced absolute evidence that regular MDMA ingestion causes damage to the serotonin nerve endings in the human brain or results in impaired physiological performance or psychiatric problems.

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth. Rationale: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration. Objectives: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists. Method: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca). Results: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism. Conclusions: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics. [ABSTRACT FROM AUTHOR]

Rationale: Schizophrenia is a mental illness which is characterised by positive and negative symptoms and by cognitive impairments. While the major prevailing hypothesis is that altered dopaminergic and/or glutamatergic transmission contributes to this disease, there is evidence that the noradrenergic system also plays a role in its major symptoms. Objectives: In the present paper, we investigated the pro-cognitive effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) an endogenous neuroprotective compound, on ketamine-modelled schizophrenia in rats. Methods: We used an antagonist of NMDA receptors (ketamine) to model memory deficit symptoms in rats. Using the novel object recognition (NOR) test, we investigated the pro-cognitive effect of 1MeTIQ. Additionally, olanzapine, an atypical antipsychotic drug, was used as a standard to compare the pro-cognitive effects of the substances. In vivo microdialysis studies allowed us to verify the changes in the release of monoamines and their metabolites in the rat striatum. Results: Our study demonstrated that 1MeTIQ, similarly to olanzapine, exhibits a pro-cognitive effect in NOR test and enhances memory disturbed by ketamine treatment. Additionally, in vivo microdialysis studies have shown that ketamine powerfully increased noradrenaline release in the rat striatum, while 1MeTIQ and olanzapine completely antagonised this neurochemical effect. Conclusions: 1MeTIQ, as a possible pro-cognitive drug, in contrast to olanzapine, expresses beneficial neuroprotective activity in the brain, increasing concentration of the extraneuronal dopamine metabolite, 3-methoxytyramine (3-MT), which plays an important physiological role in the brain as an inhibitory regulator of catecholaminergic activity. Moreover, we first demonstrated the essential role of noradrenaline release in memory disturbances observed in the ketamine-model of schizophrenia, and its possible participation in negative symptoms of the schizophrenia. [ABSTRACT FROM AUTHOR]

The incorporation of microeconomics concepts into studies using self-administration procedures has provided critical insights into the factors that influence consumption of a wide range of food and drug reinforcers. In particular, the fitting of demand curves to consumption data provides a powerful analytic tool for computing objective metrics of behavior that can be compared across a wide range of reward types in both human and animal experiments. The results of these analyses depend crucially on the mathematical form used to fit the data. The most common choice is an exponential form proposed by Hursh and Silberberg, which is widely used and has provided fundamental insights into relationships between cost and consumption, but it also has some disadvantages. In this paper, we first briefly review the use of demand curves to quantify the motivating effects of food and drugs, then we describe the current methodology and highlight some potential issues that arise in its application. To address these issues, we propose a new mathematical framework for the analysis of consumption data, including a new functional form for the demand curve. We show that this proposed form gives good fits to data for a range of different reinforcers and experimental protocols, while allowing for straightforward calculation of key metrics of demand, including preferred consumption level, maximum response, price at maximum response, and price elasticity of demand. We provide software implementing our entire analysis pipeline, including data fits, data visualization, and the calculation of demand metrics. [ABSTRACT FROM AUTHOR]

Background: People with schizophrenia frequently have cognitive dysfunction, which does not respond to pharmacological interventions. Varenicline has been identified as a potential treatment option for nicotinic receptor dysfunction with a potential to treat cognitive impairment in schizophrenia. Methods: We conducted a systematic review of Pubmed, Embase, Psycinfo, CINAHL and the Cochrane Schizophrenia Trial Registry for randomised controlled trials of varenicline in people with schizophrenia for cognitive dysfunction. We excluded trials among people with dementia. We then undertook a meta-analysis with the primary outcome of difference in change of cognitive measures between varenicline and placebo as well as secondary outcomes of difference in rates of adverse events. We conducted a sensitivity analysis on smoking status and study duration. Results: We included four papers in the meta-analysis (n = 339). Varenicline was not superior to placebo for overall cognition (SMD = −0.022, 95% CI −0.154–0.110; Z = −0.333; p = 0.739), attention (SMD = −0.047, 95% CI −0.199–0.104; Z = −0.613; p = 0.540), executive function (SMD = −0.060, 95% CI −0.469–0.348; Z =− 0.290; p = 0.772) or processing speed (SMD = 0.038, 95% CI −0.232–0.308; Z = 0.279; p = 0.780). There was no difference in psychotic symptoms, but varenicline was associated with higher rates of nausea. Sensitivity analyses for smoking status and study duration did not alter the results. Conclusion: Within the present literature, varenicline does not appear to be a useful target compound for improving cognitive impairment in schizophrenia. Based on these results, a trial would need over 2500 participants to be powered to show statistically significant findings. [ABSTRACT FROM AUTHOR]

This historical review shows that the early history of cognitive psychopharmacology, originally labelled as “pharmacopsychology”, is closely linked to developments in experimental psychology and academic psychiatry. At the beginning of his scientific career, the German psychiatrist Emil Kraepelin (1856–1926) joined Wilhelm Wundt’s laboratory of experimental psychology at the University of Leipzig. Although Kraepelin was fired from his clinical position at the university’s psychiatric hospital, he completed his habilitation, the German equivalent of Ph.D., and started a series of pharmacological investigations in healthy volunteers using common recreational drugs (alcohol, coffee, tea) or medicinal products (amyl nitrite, chloral hydrate, chloroform, ethyl ether, morphine, paraldehyde) together with innovative psychological tasks. This paper reviews Kraepelin’s pharmacopsychological research and his methodological innovations, providing translations, for the first time, from original papers, his monograph On the Modulation of Simple Psychological Processes by Some Medicines and from other sources. Kraepelin’s contributions to psychopharmacology and clinical neuropsychology were far ahead of his time and his conceptual achievements have been largely neglected by modern psychiatry and cognitive neuroscience. [ABSTRACT FROM AUTHOR]

Stereotyped behavior in rats, consisting of compulsive, repetitive sniffing and gnawing, caused by high doses of amphetamine-like psychostimulants, may serve as an animal model for psychosis. Previous methods for measuring behavioral stereotypies of this kind have required continuous observation and rating of the behaviors or semiquantitative techniques that fail to produce a continuous record of the behaviors. The present paper describes a simple automated method that provides a continuous quantitative record of the specific gnawing behavior induced in rats by methylphenidate, an amphetamine-like psychostimulant. The apparatus described and the test procedures developed are compatible with a wide variety of common counters and recorders. [ABSTRACT FROM AUTHOR]