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Neuropharmacology Sep 2023This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue...
This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.
Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Substance-Related Disorders; Anxiety
PubMed: 37247807
DOI: 10.1016/j.neuropharm.2023.109610 -
Current Neuropharmacology 2024This narrative state-of-the-art review paper describes the progress in the understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over the last four... (Review)
Review
This narrative state-of-the-art review paper describes the progress in the understanding and treatment of Posttraumatic Stress Disorder (PTSD). Over the last four decades, the scientific landscape has matured, with many interdisciplinary contributions to understanding its diagnosis, etiology, and epidemiology. Advances in genetics, neurobiology, stress pathophysiology, and brain imaging have made it apparent that chronic PTSD is a systemic disorder with high allostatic load. The current state of PTSD treatment includes a wide variety of pharmacological and psychotherapeutic approaches, of which many are evidence-based. However, the myriad challenges inherent in the disorder, such as individual and systemic barriers to good treatment outcome, comorbidity, emotional dysregulation, suicidality, dissociation, substance use, and trauma-related guilt and shame, often render treatment response suboptimal. These challenges are discussed as drivers for emerging novel treatment approaches, including early interventions in the Golden Hours, pharmacological and psychotherapeutic interventions, medication augmentation interventions, the use of psychedelics, as well as interventions targeting the brain and nervous system. All of this aims to improve symptom relief and clinical outcomes. Finally, a phase orientation to treatment is recognized as a tool to strategize treatment of the disorder, and position interventions in step with the progression of the pathophysiology. Revisions to guidelines and systems of care will be needed to incorporate innovative treatments as evidence emerges and they become mainstream. This generation is well-positioned to address the devastating and often chronic disabling impact of traumatic stress events through holistic, cutting-edge clinical efforts and interdisciplinary research.
Topics: Humans; Stress Disorders, Post-Traumatic; Psychotropic Drugs; Treatment Outcome; Substance-Related Disorders; Brain
PubMed: 37132142
DOI: 10.2174/1570159X21666230428091433 -
Ugeskrift For Laeger Oct 2023Studies indicate that cocaine abuse in Denmark is rising. The drug can damage the midface's nasal tissues, cartilage, and bone. Diagnosing the cocaine-induced midline... (Review)
Review
Studies indicate that cocaine abuse in Denmark is rising. The drug can damage the midface's nasal tissues, cartilage, and bone. Diagnosing the cocaine-induced midline destructive lesions condition is difficult as patients may not admit to drug use. Thus, this review finds that physicians should ask about cocaine abuse in younger patients who present with midline destructions of unknown origin. Mild symptoms are reversible with total abstinence, which is why it is important to involve addiction services early. Besides drug abstinence, comprehensive treatment involves assistance from GPs, physiatrists, rhinologists, and plastic surgeons.
Topics: Humans; Cocaine-Related Disorders; Nose; Cocaine; Substance-Related Disorders; Diagnosis, Differential
PubMed: 37874002
DOI: No ID Found -
Tidsskrift For Den Norske Laegeforening... Mar 2024The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment.
BACKGROUND
The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment.
CASE PRESENTATION
A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary.
INTERPRETATION
The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.
Topics: Male; Humans; Benzodiazepines; Designer Drugs; Substance-Related Disorders; Substance Abuse Detection; Psychotropic Drugs
PubMed: 38506014
DOI: 10.4045/tidsskr.23.0668 -
International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
Genes Sep 2023Substance use disorders (SUD), like many neuropsychiatric conditions, are a heterogeneous group of disorders with similar symptomatology but often different...
Substance use disorders (SUD), like many neuropsychiatric conditions, are a heterogeneous group of disorders with similar symptomatology but often different pathoetiology [...].
Topics: Humans; Substance-Related Disorders; Genomics
PubMed: 37761900
DOI: 10.3390/genes14091760 -
Biomedicine & Pharmacotherapy =... Jan 2024Drug addiction is a complex disease affected by numerous genetic and environmental factors. Brain regions in reward pathway, neuronal adaptations, genetic and epigenetic... (Review)
Review
Drug addiction is a complex disease affected by numerous genetic and environmental factors. Brain regions in reward pathway, neuronal adaptations, genetic and epigenetic interactions causing transcriptional enhancement or repression of multiple genes induce different addiction phenotypes for varying duration. Addictive drug use causes epigenetic alterations and similarly epigenetic changes induced by environment can promote addiction. Epigenetic mechanisms include DNA methylation and post-translational modifications like methylation, acetylation, phosphorylation, ubiquitylation, sumoylation, dopaminylation and crotonylation of histones, and ADP-ribosylation. Non-coding RNAs also induce epigenetic changes. This review discusses these above areas and stresses the need for exploring epidrugs as a treatment alternative and adjunct, considering the limited success of current addiction treatment strategies. Epigenome editing complexes have lately been effective in eukaryotic systems. Targeted DNA cleavage techniques such as CRISPR-Cas9 system, CRISPR-dCas9 complexes, transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs) have been exploited as targeted DNA recognition or anchoring platforms, fused with epigenetic writer or eraser proteins and delivered by transfection or transduction methods. Efficacy of epidrugs is seen in various neuropsychiatric conditions and initial results in addiction treatment involving model organisms are remarkable. Epidrugs present a promising alternative treatment for addiction.
Topics: Humans; Epigenomics; Histones; DNA Methylation; Epigenesis, Genetic; Substance-Related Disorders
PubMed: 38043446
DOI: 10.1016/j.biopha.2023.115951 -
International Journal of Molecular... May 2024Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive... (Review)
Review
Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.
Topics: Humans; Dopamine; Animals; Substance-Related Disorders; Neuronal Plasticity; Synaptic Transmission
PubMed: 38791331
DOI: 10.3390/ijms25105293 -
Journal of Integrative Neuroscience Oct 2023Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the... (Review)
Review
Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the cerebellum, and evidence from neuroimaging and behavioral studies has suggested the role of cerebellum in drug reward, which has received increasing attention. Furthermore, emerging technological developments have aided in clarifying the various circuits and functions of the cerebellum. Exploring the role of the cerebellum in drug reward can improve our understanding of the mechanism underlying addiction and facilitate the development of new treatment schemes. This review summarizes the anatomy of the cerebellum and its connections to brain regions considered important in addiction. Subsequently, we investigate the neurological reasons elucidating why the cerebellum is a potential target for drug reward. Additionally, we expound the molecular targets of addictive drugs in the cerebellum, mainly glutamate and endocannabinoids. Unlike previous studies, this article focuses on the influence of alcohol, nicotine, morphine, cannabis, and cocaine on the cerebellum from multiple viewpoints, including imaging and behavioral changes, molecular signals, neurotransmitters, and synaptic transmission. We aim to clarify some drug-induced cerebellar changes to supplement the previous research regarding the relationship between addiction and the cerebellum. Finally, we discuss the limitations and prospects of drug reward research on the cerebellum to provide novel insights into studying the cerebellum and its role in addiction. We recommend that future addiction network models should include the cerebellum to provide new therapeutic targets for treating addiction.
Topics: Humans; Substance-Related Disorders; Cerebellum; Behavior, Addictive; Brain; Reward
PubMed: 38176941
DOI: 10.31083/j.jin2206147 -
Genes Nov 2023Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them,... (Review)
Review
Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.
Topics: Humans; Adolescent; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Brain; Neuroimaging; Drug Misuse
PubMed: 38136935
DOI: 10.3390/genes14122113