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Frontiers in Pharmacology 2021Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such... (Review)
Review
Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.
PubMed: 35197848
DOI: 10.3389/fphar.2021.775073 -
Journal of Advanced Research Dec 2023Tea (Camellia sinensis) has a rich history and is widely consumed across many countries, and is categorized into green tea, white tea, oolong tea, yellow tea, black tea,... (Review)
Review
BACKGROUND
Tea (Camellia sinensis) has a rich history and is widely consumed across many countries, and is categorized into green tea, white tea, oolong tea, yellow tea, black tea, and dark tea based on the level of fermentation. Based on a review of previous literature, the commonly recognized bioactive substances in tea include tea polyphenols, amino acids, polysaccharides, alkaloids, terpenoids, macro minerals, trace elements, and vitamins, which have been known to have various potential health benefits, such as anticancer, antioxidant, anti-inflammatory, anti-diabetes, and anti-obesity properties, cardiovascular protection, immune regulation, and control of the intestinal microbiota. Most studies have only pointed out the characteristics of tea's bioactivities, so a comprehensive summary of the pharmacological characteristics and mechanisms of tea's bioactivities and their use risks are vital.
AIM OF REVIEW
This paper aims to summarize tea's bioactive substances of tea and their pharmacological characteristics and mechanisms, providing a scientific basis for the application of bioactive substances in tea and outlining future research directions for the study of bioactive substances in tea.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review summarizes the main biologically active substances, pharmacological effects, and mechanisms and discusses the potential risks. It may help researchers grasp more comprehensive progress in the study of tea bioactive substances to further promote the application of tea as a natural bioactive substance in the medical field.
PubMed: 38056775
DOI: 10.1016/j.jare.2023.12.004 -
Pharmaceuticals (Basel, Switzerland) May 2022The genus Arrabidaea, consisting of ~170 species, belongs to the family Bignoniaceae, distributed around the Neotropics and temperate zone. The center of diversity of... (Review)
Review
The genus Arrabidaea, consisting of ~170 species, belongs to the family Bignoniaceae, distributed around the Neotropics and temperate zone. The center of diversity of the family is in Brazil, where 56 genera and about 340 species exist. Most species of the genus Arrabidaea are traditionally utilized as diuretics and antiseptics, as well as for treating intestinal colic, diarrhea, kidney stones, rheumatoid arthritis, wounds, and enterocolitis. The genus is chemically diverse with different substance classes; most of them are triterpenes, phenolic acids, and flavonoids, and they exhibit valuable pharmacological properties, such as antitumor, antioxidant, leishmanicidal, trypanocidal, anti-inflammatory, and healing properties. This review presents information on the chemical constituents isolated from seven Arrabidaea species, and the pharmacological activities of the extracts, fractions and pure substances isolated since 1994, obtained from electronic databases. The various constituents present in the different species of this genus demonstrate a wide pharmacological potential for the development of new therapeutic agents, however its potential has been underestimated.
PubMed: 35745577
DOI: 10.3390/ph15060658 -
CMAJ : Canadian Medical Association... Nov 2023Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of...
BACKGROUND
Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants.
METHODS
We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC.
RESULTS
Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation.
INTERPRETATION
Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.
Topics: Adult; Humans; Depressive Disorder, Major; Pharmacogenetics; Depression; Cost-Benefit Analysis; Antidepressive Agents; Quality-Adjusted Life Years; British Columbia
PubMed: 37963621
DOI: 10.1503/cmaj.221785 -
Fundamental & Clinical Pharmacology Oct 2022Little is known about psychoactive substance use in students, apart from tobacco, alcohol, and cannabis. This study investigated the prevalence of substance use and...
Little is known about psychoactive substance use in students, apart from tobacco, alcohol, and cannabis. This study investigated the prevalence of substance use and overlap between various psychoactive substances in students. This cross-sectional study was conducted in 10 066 students included in the i-Share cohort between January 1, 2015, and December 31, 2017. The baseline questionnaire was the key source of information. Psychoactive substances of interest (PSI) were cannabis, cocaine, amphetamines, nitrous oxide, poppers, and MDMA. Their patterns of use were categorized as lifetime, past year, and current use. The use of other psychoactive substances including alcohol and tobacco was described in PSI users and non-users. Most participants were female (75%), and their average age was 21 years. Lifetime use of at least one PSI was reported by 65.5% of participants. Cannabis was the most frequently used substance both over lifetime (57% of students) and past year (35%), followed by poppers and nitrous oxide (28% and 26% of students over lifetime, respectively). Among polydrug users (n = 1242), 65% used only nitrous oxide and poppers, showing a strong link between these two substances. Regular alcohol use, binge drinking, and current tobacco use were higher in PSI users than in non-users. Substance use was higher than previously found in both French and European studies in young people. Nitrous oxide use was particularly high. Regular alcohol use, binge drinking, and tobacco use could be used as markers to identify students at risk of PSI use to be targeted by prevention programs.
Topics: Adolescent; Adult; Binge Drinking; Cannabis; Cross-Sectional Studies; Ethanol; Female; Humans; Male; Nitrous Oxide; Prevalence; Students; Substance-Related Disorders; Young Adult
PubMed: 35194825
DOI: 10.1111/fcp.12771 -
Cureus Jul 2021Individuals with schizophrenia are particularly vulnerable to substance abuse problems. Comorbidity with substance use disorders (SUDs) frequently results in early death... (Review)
Review
Individuals with schizophrenia are particularly vulnerable to substance abuse problems. Comorbidity with substance use disorders (SUDs) frequently results in early death and increased dysfunction observed in schizophrenia. This dual diagnosis can be explained through multiple general mechanisms. Tobacco, alcohol, cannabis, and cocaine are substances widely used by individuals with schizophrenia. This study highlights the predictors, mechanisms responsible for the relationship between substance use disorder and schizophrenia and how it can help with the treatment of both disorders. The publications were rigorously reviewed after being found in multiple databases. The study's inclusion criteria were research published within the last five years, publications written in English, full-text availability, and human studies. A total of ten papers were selected for examination from a total of 9,106 articles found using the search method across several databases. This study follows the rules listed within the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist 2009. The information gathered from these published studies was used to investigate the elements that contribute to the link between schizophrenia and substance abuse. Here, we evaluate a close relationship between schizophrenia and substance use disorders. The articles studied exhibit a bidirectional association between the two disorders in most individuals. From our analysis, the comorbidity between the two disorders is partially due to shared polygenic liability. Individuals with schizophrenia have dysfunctional Mesocorticolimbic brain reward circuits indicating a history of substance use. An underlying genetic vulnerability to schizophrenia may be triggered by extensive cannabis usage at a young age. A combination of psychological and pharmacological interventions for both disorders can significantly improve the outcome.
PubMed: 34513357
DOI: 10.7759/cureus.16722 -
Handbook of Experimental Pharmacology 2020Excessive abuse of psychoactive substances is one of the leading contributors to morbidity and mortality worldwide. In this book chapter, we review translational... (Review)
Review
Excessive abuse of psychoactive substances is one of the leading contributors to morbidity and mortality worldwide. In this book chapter, we review translational research strategies that are applied in the pursuit of new and more effective therapeutics for substance use disorder (SUD). The complex, multidimensional nature of psychiatric disorders like SUD presents difficult challenges to investigators. While animal models are critical for outlining the mechanistic relationships between defined behaviors and genetic and/or molecular changes, the heterogeneous pathophysiology of brain diseases is uniquely human, necessitating the use of human studies and translational research schemes. Translational research describes a cross-species approach in which findings from human patient-based data can be used to guide molecular genetic investigations in preclinical animal models in order to delineate the mechanisms of reward circuitry changes in the addicted state. Results from animal studies can then inform clinical investigations toward the development of novel treatments for SUD. Here we describe the strategies that are used to identify and functionally validate genetic variants in the human genome which may contribute to increased risk for SUD, starting from early candidate gene approaches to more recent genome-wide association studies. We will next examine studies aimed at understanding how transcriptional and epigenetic dysregulation in SUD can persistently alter cellular function in the disease state. In our discussion, we then focus on examples from the literature illustrating molecular genetic methodologies that have been applied to studies of different substances of abuse - from alcohol and nicotine to stimulants and opioids - in order to exemplify how these approaches can both delineate the underlying molecular systems driving drug addiction and provide insights into the genetic basis of SUD.
Topics: Animals; Genome-Wide Association Study; Humans; Reward; Substance-Related Disorders; Translational Research, Biomedical
PubMed: 31628598
DOI: 10.1007/164_2019_259 -
Journal of Medicinal Chemistry Nov 2020This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health... (Review)
Review
This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.
Topics: Animals; Cannabidiol; Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Placebo Effect
PubMed: 32804502
DOI: 10.1021/acs.jmedchem.0c00724 -
Biomedicine & Pharmacotherapy =... Dec 2023Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly,... (Review)
Review
Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range of CVDs have been reported, each of which diverges significantly, exhibiting sophisticated types of pathogenesis (e.g., inflammatory, oxidative stress, and disorders in cardiomyocyte metabolism). Compared with conventional treatments in modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages in the treatment of CVDs. TCM can be utilized to develop effective strategies for addressing the challenges of CVD, with fewer side effects and higher therapeutic efficiency. Astragaloside IV (AS-IV) has been confirmed as one of the major active ingredients found in Astragalus membranaceus (a Chinese herbal medicine that has been extensively employed clinically for the treatments of CVDs). Since recent studies have shown that AS-IV in CVD treatments has achieved promising results, the substance has aroused great attention and further discussions in the field. The present review aims to summarize the recent pharmacological advances in employing AS-IV in the treatment of CVDs.
Topics: Humans; Medicine, Chinese Traditional; Drugs, Chinese Herbal; Saponins; Triterpenes; Cardiovascular Diseases
PubMed: 37875045
DOI: 10.1016/j.biopha.2023.115752