RESUMO
Methamphetamine (METH) addiction can damage the central nervous system, resulting in cognitive impairment and memory deficits. Low target effects have limited the utility of anti-addiction drugs because the presence of the blood-brain barrier hinders the effective delivery of drugs to the brain. Angiopep-2 can recognize and target low-density lipoprotein receptor-associated protein 1 (LRP-1) on the surface of cerebral capillary endothelial cells, causing cross-cell phagocytosis, and thus has high blood-brain barrier transport capacity. Resveratrol (RSV) has been found to be a neuroprotective agent in many nervous system diseases. In our study, we modified Angiopep-2 on the surface of the erythrocyte membrane to obtain a modified erythrocyte membrane (Ang-RBCm) and coated RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) nanoparticles with Ang-RBCm (Ang-RBCm@RSVNPs) to treat METH addiction. Our results showed that Ang-RBCm@RSVNPs can penetrate the blood-brain barrier and accumulate in the brain better than free RSV. Besides, mice treatetd with Ang-RBCm@RSVNPs showed less preference to METH-paired chamber and no noticeable tissue toxicity or abnormality was found in H&E staining images. Electrophysiological experiments demonstrated Ang-RBCm@RSVNPs could elevate synaptic plasticity impaired by METH. These indicated that Ang-RBCm@RSVNPs has better anti-addiction and neuroprotective effects. Therefore, Ang-RBCm@RSVNPs has great potential in the treatment of METH addiction.
Assuntos
Barreira Hematoencefálica , Metanfetamina , Sistemas de Liberação de Fármacos por Nanopartículas , Resveratrol , Resveratrol/administração & dosagem , Resveratrol/farmacocinética , Resveratrol/farmacologia , Resveratrol/química , Animais , Metanfetamina/administração & dosagem , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Masculino , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL , Peptídeos/administração & dosagem , Peptídeos/química , Nanopartículas/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodosRESUMO
PURPOSE OF REVIEW: We apply the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for substance use disorders (SUDs) to the herbal product kratom. Similarities and differences between kratom use disorder (KUD) and other SUDs are explored, along with assessment, diagnostic, and therapeutic recommendations for KUD. RECENT FINDINGS: Literature reports of "kratom addiction" or KUD rarely specify the criteria by which patients were diagnosed. Individuals meeting DSM-5 KUD criteria typically do so via tolerance and withdrawal, using more than intended, and craving, not functional or âpsychosocial disruption, which occur rarely. Most clinicians who use medication to treat patients with isolated KUD select buprenorphine formulations, although there are no controlled studies showing that buprenorphine is safe or efficacious in this patient population. Diagnosis and treatment decisions for KUD should be systematic. We propose an algorithm that takes into consideration whether KUD occurs with comorbid opioid use disorder.
Assuntos
Mitragyna , Transtornos Relacionados ao Uso de Substâncias , Humanos , Mitragyna/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Tratamento de Substituição de Opiáceos/métodosAssuntos
Comportamento Aditivo , Proteínas da Membrana Plasmática de Transporte de Dopamina , Terapia de Alvo Molecular , Transtornos Relacionados ao Uso de Substâncias , Humanos , Comportamento Aditivo/tratamento farmacológico , Comportamento Aditivo/metabolismo , Cocaína/metabolismo , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Terapia de Alvo Molecular/tendências , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/metabolismoRESUMO
ABSTRACT: Substance use disorder (SUD) continues to be a leading cause of morbidity and mortality with limited treatments. There is interest in expanding the use of GLP-1 agonists in treating SUD. However, evidence for safety and efficacy in humans is limited. This review aims to bridge the existing knowledge gap by establishing a baseline of literature in this area to inform future trials and clinical practice. Our inclusion criteria were English peer-reviewed manuscripts reporting on use of GLP-1, GIP, and/or glucagon receptor agonists in treatment of SUDs, excluding case studies. The literature search was performed in accordance to PRISMA guidelines. Five studies were included in this review examining the use of this medication in tobacco use disorder, alcohol use disorder, and cocaine use disorder. No studies regarding substance withdrawal syndrome were identified. The included studies varied widely in terms of patient selection, dose/formulation of GLP-1 agonists, and follow-up. The results of this scoping review are mixed, with 3 studies demonstrating positive results and 2 studies finding no efficacy of this medication on SUD outcomes. It is premature to prescribe this medication off-label to patients. Further research is needed to determine the efficacy of GLP-1 agonists in treating SUD.
Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Tabagismo/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Alcoolismo/tratamento farmacológicoRESUMO
Addiction is a chronic relapsing disease with high morbidity and mortality. Treatments for addiction include pharmacological and psychosocial interventions; however, currently available medications are limited in number and efficacy. The glucagon-like-peptide-1 (GLP-1) system is emerging as a potential novel pharmacotherapeutic target for alcohol and other substance use disorders (ASUDs). In this review, we summarize and discuss the wealth of available evidence from testing GLP-1 receptor (GLP-1R) agonist medications in preclinical models and humans with ASUDs, possible mechanisms underlying the impact of GLP-1R agonists on alcohol/substance use, gaps in knowledge, and future directions. Most of the research with GLP-1R agonists has been conducted in relation to alcohol use; psychostimulants, opioids, and nicotine have also been investigated. Preclinical evidence suggests that GLP-1R agonists reduce alcohol/substance use and other related outcomes. The main proposed mechanisms are related to reward processing, stress, and cognitive function, as well as broader mechanisms related to satiety, changes in gastric motility, and glucose homeostasis. More in-depth mechanistic studies are warranted. Clinical studies have been limited and their findings have been less conclusive; however, most support the safety and potential efficacy of GLP-1R agonists in ASUD treatment. Identifying preferred compounds, as well as possible subgroups who are most responsive to GLP-1R agonists are some of the key research questions to translate the promising preclinical data into clinical settings. Several clinical trials are underway to test GLP-1R agonists in people with ASUDs.
Assuntos
Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Transtornos Relacionados ao Uso de Substâncias , Humanos , Animais , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológicoRESUMO
Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research.
Assuntos
Alucinógenos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Alucinógenos/uso terapêutico , Alucinógenos/efeitos adversos , Alucinógenos/farmacologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Pesquisa BiomédicaRESUMO
Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neurobehavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical experiences in individuals who use drugs. In this review, we provide a comprehensive update on both frequently utilized and novel behavioral models of addiction with a focus on translational value to the clinical experience and highlight the need for preclinical research to follow epidemiological trends in drug use patterns to stay abreast of clinical treatment needs. We then note areas in which models could be improved to enhance the medications development pipeline through efforts to enhance translation of preclinical models. Next, we describe neuroscience efforts that can be leveraged to identify novel biological mechanisms to enhance medications development efforts for SUDs, focusing specifically on advances in brain transcriptomics approaches that can provide comprehensive screening and identification of novel targets. Together, the confluence of this review demonstrates the need for careful selection of behavioral models and methodological parameters that better approximate the clinical experience combined with cutting edge neuroscience techniques to advance the medications development pipeline for SUDs.
Assuntos
Modelos Animais de Doenças , Transtornos Relacionados ao Uso de Substâncias , Pesquisa Translacional Biomédica , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Animais , Humanos , Avaliação Pré-Clínica de Medicamentos , Comportamento Aditivo/tratamento farmacológicoRESUMO
Cannabidiol (CBD) has been investigated for several therapeutic applications, having reached the clinics for the treatment of certain types of epilepsies. This chapter reviews the potential of CBD for the treatment of substance use disorders (SUD). We will present a brief introduction on SUD and current treatments. In the second part, preclinical and clinical studies with CBD are discussed, focusing on its potential therapeutic application for SUD. Next, we will consider the potential molecular mechanism of action of CBD in SUD. Finally, we will summarize the main findings and perspectives in this field. There is a lack of studies on CBD and SUD in comparison to the extensive literature investigating the use of this phytocannabinoid for other neurological and psychiatric disorders, such as epilepsy. However, the few studies available do suggest a promising role of CBD in the pharmacotherapy of SUD, particularly related to cocaine and other psychostimulant drugs.
Assuntos
Canabidiol , Transtornos Relacionados ao Uso de Substâncias , Canabidiol/uso terapêutico , Canabidiol/farmacologia , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , AnimaisRESUMO
OBJECTIVES: There has been limited evidence synthesis examining treatment of ketamine use disorder. We aimed to conduct a systematic review to assess the efficacy and tolerability of pharmacological interventions in the management of ketamine use disorder. METHODS: We searched MEDLINE, EMBASE, PsychINFO, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to November 14, 2023, for studies of any design that reported on any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and assessed outcome quality using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. We planned to combine outcomes using random-effects meta-analysis, where this was not possible results were reported narratively. RESULTS: Twelve studies met the inclusion criteria reporting on 368 participants. These comprised 1 controlled trial, 2 retrospective case series, and 9 case reports. Two studies reported on ketamine intoxication, 6 on withdrawal, and 4 on craving/relapse prevention. All studies reported only descriptive outcomes, and all evidence was of very low quality. Benzodiazepine regimens and haloperidol were reported to have potential utility in intoxication and withdrawal, whereas naltrexone, lamotrigine, and a combination of paliperidone palmitate and bupropion were reported to have potential utility in craving/relapse prevention. CONCLUSIONS: There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention.
Assuntos
Ketamina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Ketamina/uso terapêutico , Ketamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Naltrexona/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Bupropiona/uso terapêutico , Bupropiona/efeitos adversosRESUMO
Peptide drugs are a promising alternative to classical small molecule therapeutics with diverse applications, ranging from antibiotic resistant infection to prostate cancer. Oxytocin (OT) is a highly evolutionarily conserved peptide neurohormone and has been of interest for pharmaceutical use since 1909. Despite their increased safety profile relative to most small molecule drugs, peptides are poor candidates based on the pharmacokinetic (PK) properties from their peptide nature. Broad application of OT as a drug has been limited by these same PK issues. Several strategies have been proposed to overcome these limitations, among them glycosylation, which was used in combination with other sequence modifications to produce robust antinociception in mouse models, increased selectivity and potency at the OT receptor, and improved stability in rats.
Assuntos
Desenho de Fármacos , Glicosídeos , Ocitocina , Dor , Ocitocina/uso terapêutico , Ocitocina/farmacocinética , Animais , Ratos , Camundongos , Dor/tratamento farmacológico , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Humanos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Glicosilação , Receptores de Ocitocina/metabolismoAssuntos
Gabapentina , Ketamina , Topiramato , Humanos , Gabapentina/uso terapêutico , Gabapentina/administração & dosagem , Ketamina/uso terapêutico , Ketamina/administração & dosagem , Topiramato/uso terapêutico , Topiramato/administração & dosagem , Adulto , Masculino , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Feminino , Quimioterapia CombinadaRESUMO
RATIONALE: Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. OBJECTIVE: Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. METHODS: Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability. RESULTS: In vitro, ITI-333 is a potent 5-HT2A receptor antagonist (Ki = 8 nM) and a biased, partial agonist at µ-opioid (MOP) receptors (Ki = 11 nM; lacking ß-arrestin agonism) with lesser antagonist activity at adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT2A receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys. CONCLUSIONS: ITI-333 acts as a potent 5-HT2A receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.
Assuntos
Síndrome de Abstinência a Substâncias , Animais , Camundongos , Masculino , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Ratos , Humanos , Ratos Sprague-Dawley , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Relação Dose-Resposta a Droga , Oxicodona/farmacologia , Oxicodona/administração & dosagem , Analgésicos Opioides/farmacologia , Analgésicos Opioides/administração & dosagem , Autoadministração , Cricetulus , Células CHORESUMO
INTRODUCTION: The neuroimmune system has emerged as a novel target for the treatment of substance use disorders (SUDs), with immunomodulation producing encouraging therapeutic benefits in both preclinical and clinical settings. AREAS COVERED: In this review, we describe the mechanism of action and immune response to methamphetamine, opioids, cocaine, and alcohol. We then discuss off-label use of immunomodulators as adjunctive therapeutics in the treatment of neuropsychiatric disorders, demonstrating their potential efficacy in affective and behavioral disorders. We then discuss in detail the mechanism of action and recent findings regarding the use of ibudilast, minocycline, probenecid, dexmedetomidine, pioglitazone, and cannabidiol to treat (SUDs). These immunomodulators are currently being investigated in clinical trials described herein, specifically for their potential to decrease substance use, withdrawal severity, central and peripheral inflammation, comorbid neuropsychiatric disorder symptomology, as well as their ability to improve cognitive outcomes. EXPERT OPINION: We argue that although mixed, findings from recent preclinical and clinical studies underscore the potential benefit of immunomodulation in the treatment of the behavioral, cognitive, and inflammatory processes that underlie compulsive substance use.
Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/imunologia , Animais , Fatores Imunológicos/uso terapêutico , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/farmacologia , Uso Off-Label , Alcoolismo/tratamento farmacológico , Alcoolismo/imunologia , ImunomodulaçãoRESUMO
This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin's recognition as a "breakthrough therapy" by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided.
Assuntos
Transtorno Depressivo Maior , Alucinógenos , Psilocibina , Transtornos Relacionados ao Uso de Substâncias , Psilocibina/uso terapêutico , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Alucinógenos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Assistentes Sociais/psicologia , Papel Profissional , Estados Unidos , Serviço Social/métodosRESUMO
Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes.
Assuntos
Antioxidantes , Peroxidação de Lipídeos , Estresse Oxidativo , Transtornos Relacionados ao Uso de Substâncias , Humanos , Antioxidantes/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Animais , NeurobiologiaRESUMO
World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction.
Assuntos
Produtos Biológicos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Animais , Comportamento Aditivo/tratamento farmacológicoRESUMO
Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N'-dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5-HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy-assisted psilocybin applications for life-threatening cancer-related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment-resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects-especially in depression, trauma disorders and substance use disorders-within the framework of ethical considerations.
Assuntos
Alucinógenos , Transtornos Relacionados ao Uso de Substâncias , Alucinógenos/uso terapêutico , Alucinógenos/farmacologia , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Depressão/tratamento farmacológico , Animais , Dietilamida do Ácido Lisérgico/uso terapêutico , Dietilamida do Ácido Lisérgico/farmacologia , Psilocibina/uso terapêutico , Psilocibina/farmacologia , Transtorno Depressivo/tratamento farmacológicoRESUMO
This Medical News story examines other potential uses of GLP-1 receptor agonists, the popular type 2 diabetes and weight-loss drugs.
Assuntos
Doença de Alzheimer , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Transtornos Relacionados ao Uso de Substâncias , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença Crônica/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológicoRESUMO
Substance use disorders (SUD) are chronic relapsing disorders governed by continually shifting cycles of positive drug reward experiences and drug withdrawal-induced negative experiences. A large body of research points to plasticity within systems regulating emotional, motivational, and cognitive processes as drivers of continued compulsive pursuit and consumption of substances despite negative consequences. This plasticity is observed at all levels of analysis from molecules to networks, providing multiple avenues for intervention in SUD. The cytoskeleton and its regulatory proteins within neurons and glia are fundamental to the structural and functional integrity of brain processes and are potentially the major drivers of the morphological and behavioral plasticity associated with substance use. In this review, we discuss preclinical studies that provide support for targeting the brain cytoskeleton as a therapeutic approach to SUD. We focus on the interplay between actin cytoskeleton dynamics and exposure to cocaine, methamphetamine, alcohol, opioids, and nicotine and highlight preclinical studies pointing to a wide range of potential therapeutic targets, such as nonmuscle myosin II, Rac1, cofilin, prosapip 1, and drebrin. These studies broaden our understanding of substance-induced plasticity driving behaviors associated with SUD and provide new research directions for the development of SUD therapeutics.
Assuntos
Síndrome de Abstinência a Substâncias , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Citoesqueleto , Citoesqueleto de Actina/metabolismo , Encéfalo , Síndrome de Abstinência a Substâncias/metabolismoRESUMO
Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.