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ESC Heart Failure Apr 2020Abuse of crystal methamphetamine (MA) poses a growing problem for health services worldwide. This review summarizes the current literature on the effects of MA on the... (Review)
Review
AIMS
Abuse of crystal methamphetamine (MA) poses a growing problem for health services worldwide. This review summarizes the current literature on the effects of MA on the cardiovascular system.
METHODS AND RESULTS
This article is a presentation of a case report and review of the current literature. In Europe, especially the eastern countries and the eastern states of Germany are affected. MA increases the concentration of catecholamines in the synaptic gap leading to euphoria, alertness, and hunger suppression as well as psychiatric and gastrointestinal complications. MA consumption is associated with hypertension, acute and chronic myocardial toxicity, stroke, coronary artery disease, and sudden cardiac death. Although many aspects of the underlying pathophysiology remain unknown, catecholamine-mediated pathologies appear to play an important role. The duration of MA consumption is the most important determinant for the prognosis.
CONCLUSIONS
Awareness is needed as cardiac complications are important causes of morbidity and mortality in patients with MA consumption. Drug abstinence is the mainstay of therapy, cardiac and other complications should be treated according to the respective guidelines. Incompliance to therapy and frequent relapses are the main challenges for successful treatment. Further research is required to improve the understanding of this rapidly increasing cardiomyopathy.
Topics: Cardiovascular Diseases; Europe; Germany; Heart; Humans; Methamphetamine
PubMed: 31950731
DOI: 10.1002/ehf2.12572 -
Neuroscience and Biobehavioral Reviews Dec 2021Comorbid drug use, often alcohol with other drugs, poses significant health and societal concerns. Methamphetamine is among the illicit drugs most often co-used with... (Review)
Review
Comorbid drug use, often alcohol with other drugs, poses significant health and societal concerns. Methamphetamine is among the illicit drugs most often co-used with alcohol. The current review examines the animal literature for impacts of comorbid alcohol and methamphetamine exposure. We found evidence for additive or synergistic effects of combined or sequential exposure on behavior and physiology. Dopaminergic, serotonergic, and glutamatergic systems are all impacted by combined exposure to alcohol and methamphetamine and cyclooxygenase-2 activity plays an important role in their combined neurotoxic effects. Adverse consequences of comorbid exposure include altered brain development with prenatal exposure, impaired learning and memory, motor deficits, gastrotoxicity, hepatotoxicity, and augmented intake under some conditions. Given high susceptibility to drug experimentation in adolescence, studies of co-exposure during the adolescent period and of how adolescent exposure to one drug impacts later use or sensitivity to the other drug should be a priority. Further, to gain traction on prevention and treatment, additional research to identify motivational and neurobiological drivers and consequences of comorbid use is needed.
Topics: Animals; Ethanol; Female; Illicit Drugs; Methamphetamine; Models, Animal; Pregnancy; Substance-Related Disorders
PubMed: 34543650
DOI: 10.1016/j.neubiorev.2021.09.019 -
Oxidative Medicine and Cellular... 2018Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects. Understanding methamphetamine toxicity is key beyond the... (Review)
Review
Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects. Understanding methamphetamine toxicity is key beyond the field of drug abuse since it allows getting an insight into the molecular mechanisms which operate in a variety of neuropsychiatric disorders. In fact, key alterations produced by methamphetamine involve dopamine neurotransmission in a way, which is reminiscent of spontaneous neurodegeneration and psychiatric schizophrenia. Thus, understanding the molecular mechanisms operated by methamphetamine represents a wide window to understand both the addicted brain and a variety of neuropsychiatric disorders. This overlapping, which is already present when looking at the molecular and cellular events promoted immediately after methamphetamine intake, becomes impressive when plastic changes induced in the brain of methamphetamine-addicted patients are considered. Thus, the present manuscript is an attempt to encompass all the molecular events starting at the presynaptic dopamine terminals to reach the nucleus of postsynaptic neurons to explain how specific neurotransmitters and signaling cascades produce persistent genetic modifications, which shift neuronal phenotype and induce behavioral alterations. A special emphasis is posed on disclosing those early and delayed molecular events, which translate an altered neurotransmitter function into epigenetic events, which are derived from the translation of postsynaptic noncanonical signaling into altered gene regulation. All epigenetic effects are considered in light of their persistent changes induced in the postsynaptic neurons including sensitization and desensitization, priming, and shift of neuronal phenotype.
Topics: Epigenomics; Humans; Methamphetamine; Oxidative Stress
PubMed: 30140365
DOI: 10.1155/2018/4982453 -
ACS Chemical Neuroscience Oct 2018Methamphetamine has the second highest prevalence of drug abuse after cannabis, with estimates of 35 million users worldwide. The ( S)-(+)-enantiomer is the illicit... (Review)
Review
Methamphetamine has the second highest prevalence of drug abuse after cannabis, with estimates of 35 million users worldwide. The ( S)-(+)-enantiomer is the illicit drug, active neurostimulant, and eutomer, while the ( R)-(-)-enantiomer is contained in over the counter decongestants. While designated a schedule II drug in 1970, ( S)-(+)-methamphetamine is available by prescription for the treatment of attention-deficit disorder and obesity. The illicit use of ( S)-(+)-methamphetamine results in the sudden "rush" of stimulation to the motivation, movement, pleasure, and reward centers in the brain, caused by rapid release of dopamine. In this review, we will provide an overview of the synthesis, pharmacology, adverse effects, and drug metabolism of this widely abused psychostimulant that distinguish it as a DARK classic in Chemical Neuroscience.
Topics: Amphetamine-Related Disorders; Central Nervous System Stimulants; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Methamphetamine
PubMed: 29602278
DOI: 10.1021/acschemneuro.8b00123 -
International Journal of Environmental... Nov 2019Contamination of residential homes with methamphetamine is an emerging issue of significant concern to public health. Cooking or smoking methamphetamine in a residential... (Review)
Review
Contamination of residential homes with methamphetamine is an emerging issue of significant concern to public health. Cooking or smoking methamphetamine in a residential property contaminates the house, furnishings and personal possessions within it, with subsequent exposure through ingestion, dermal absorption and/or inhalation causing adverse health effects. Current guidelines identifying levels of methamphetamine contamination that require remediation vary between countries. There is also no international standard protocol for measuring levels of contamination and research has shown that different materials give rise to different recovery rates of methamphetamine. There are a number of currently used remediation methods; however, they have varying levels of success with limited studies comparing their long-term efficacies. Most importantly, there are few guidelines available that are based on a transparent, health risk-based approach, and there are many uncertainties on exposures and health effects, making it difficult to ensure the health of people residing in homes that have been used to cook or smoke methamphetamine are sufficiently protected. This manuscript presents the current state of knowledge regarding the contamination of residential homes with methamphetamine and identifies the current gaps in knowledge and priority areas for future research. The current regulatory approach to public health protection associated with exposure to residential premises contaminated with methamphetamine in Australia, New Zealand and the USA is also discussed.
Topics: Environmental Pollutants; Humans; Methamphetamine; Public Health; Substance-Related Disorders
PubMed: 31771211
DOI: 10.3390/ijerph16234676 -
Journal of Prosthodontics : Official... Jan 2015Overt dental disease is a distinguishing comorbidity associated with methamphetamine abuse, necessitating the need for special management to maximize treatment benefits.... (Review)
Review
Overt dental disease is a distinguishing comorbidity associated with methamphetamine abuse, necessitating the need for special management to maximize treatment benefits. As this highly addictive stimulant increases in popularity, it has become imperative that clinicians are equipped to thoughtfully provide comprehensive care for these patients. This article reviews the impact of methamphetamine to systemic and oral health and proposes a comprehensive treatment plan and sequence for the methamphetamine-dependent patient. A multidisciplinary approach is recommended. Destructive oral and psychological changes must be identified and controlled. A thorough risk assessment, caries control, and preventative plan should be established before initiating prosthodontic treatment. Patient motivation, support, and a timely recall schedule are integral for dental longevity.
Topics: Amphetamine-Related Disorders; Central Nervous System Stimulants; Dental Caries; Humans; Methamphetamine; Oral Health; Prosthodontics; Substance-Related Disorders
PubMed: 25627552
DOI: 10.1111/jopr.12245 -
Proceedings of the National Academy of... Jul 2023The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the...
The serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the target of both therapeutic antidepressant drugs and psychostimulant substances such as cocaine and methamphetamines, which are small molecules that perturb normal serotonergic transmission by interfering with serotonin transport. Despite decades of studies, important functional aspects of SERT such as the oligomerization state of native SERT and its interactions with potential proteins remain unresolved. Here, we develop methods to isolate SERT from porcine brain (pSERT) using a mild, nonionic detergent, utilize fluorescence-detection size-exclusion chromatography to investigate its oligomerization state and interactions with other proteins, and employ single-particle cryo-electron microscopy to elucidate the structures of pSERT in complexes with methamphetamine or cocaine, providing structural insights into psychostimulant recognition and accompanying pSERT conformations. Methamphetamine and cocaine both bind to the central site, stabilizing the transporter in an outward open conformation. We also identify densities attributable to multiple cholesterol or cholesteryl hemisuccinate (CHS) molecules, as well as to a detergent molecule bound to the pSERT allosteric site. Under our conditions of isolation, we find that pSERT is best described as a monomeric entity, isolated without interacting proteins, and is ensconced by multiple cholesterol or CHS molecules.
Topics: Animals; Swine; Serotonin Plasma Membrane Transport Proteins; Cryoelectron Microscopy; Detergents; Serotonin; Central Nervous System Stimulants; Cocaine; Methamphetamine
PubMed: 37436958
DOI: 10.1073/pnas.2304602120 -
American Journal of Cardiovascular... Jul 2022Methamphetamines are illicit drugs of the amphetamine-type stimulant class that have been increasing in popularity, availability, and purity in recent decades. As a... (Review)
Review
Methamphetamines are illicit drugs of the amphetamine-type stimulant class that have been increasing in popularity, availability, and purity in recent decades. As a result, rates of methamphetamine-associated cardiomyopathy (MAC) are rising globally. MAC is associated with high rates of sudden cardiac arrest, late presentation, and poor outcomes. This review discusses the medical management of MAC, including anticipated challenges specific to methamphetamine users. Not only are patients with MAC more likely to present at a younger age and with multisystem disease than patients with cardiomyopathy of other etiologies, but there may also be significant behavioral, psychosocial, financial, and system-based challenges to providing the best medical care. An individualized treatment plan that emphasizes methamphetamine abstinence as the foundation of therapy, as well as introducing optimal heart failure therapy and providing multidisciplinary support is likely to result in optimal outcomes. Given the potential reversibility of MAC, institution of guideline-directed heart failure therapy and patient support for adherence to therapy and abstinence from methamphetamines should be energetically pursued.
Topics: Cardiomyopathies; Central Nervous System Stimulants; Heart Failure; Humans; Methamphetamine
PubMed: 35157254
DOI: 10.1007/s40256-022-00523-y -
Psychiatry Research Nov 2022Methamphetamine (MA) is used worldwide and causes serious public health and social problems. MA affects the central nervous, cardiac, and immune systems, which causes...
Methamphetamine (MA) is used worldwide and causes serious public health and social problems. MA affects the central nervous, cardiac, and immune systems, which causes neuropsychiatric and cardiovascular diseases and infection. Epigenetic changes, including DNA methylation (DNAm), are associated with various clinical phenotypes of MA abuse. DNAm is related to biological aging and health risks; hence, we aimed to assess the changes in biological aging in MA dependence using the DNAm age and DNA methylation-based telomere length (DNAmTL). We used five measures of DNAm age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAmTL, and DNAm-based age-predictive factors (plasma proteins and blood cell composition). We compared patients with MA dependence and healthy controls (n = 24 each) using the DNAm profiles obtained from whole-blood samples. Patients with MA dependence showed significant acceleration in PhenoAge and GrimAge, as well as a trend for significant acceleration in DNAmTL. Following adjustment for confounding factors, MA dependence was significantly associated with accelerations in PhenoAge, GrimAge, and DNAmTL, as well as alterations in DNAm-based age-predictive factors (beta-2-microglobulin, granulocytes, and naive cluster of differentiation 4+ T cells). Our results suggested an acceleration of biological aging and specific changes in the DNAm of age- predictive factors in MA dependence.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Cardiovascular Diseases; Methamphetamine
PubMed: 36244160
DOI: 10.1016/j.psychres.2022.114901 -
International Review of Neurobiology 2022Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs... (Review)
Review
Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs adult-initiated exposure is incomplete. We consider the existing animal research in this area for (meth)amphetamines. Established for a number of phenotypes, is lower sensitivity of peri-adolescents than adults to acute effects of (meth)amphetamines, including neurotoxic effects of binge-level exposure. More variable are data for long-term consequences of peri-adolescent exposure on motivational and cognitive traits. Moreover, investigations often exclude an adult-initiated exposure group critical for answering questions about outcomes unique to peri-adolescent initiation. Despite this, it is clear from the animal research that (meth)amphetamine exposure during the peri-adolescent period, whether self- or other-administered, impacts brain motivational circuitry and cognitive function, and alters adult sensitivity to other drugs and natural rewards. Such consequences occurring in humans have the potential to predispose toward unfortunate and potentially disastrous family, social and livelihood outcomes.
Topics: Adolescent; Animals; Brain; Cognition; Humans; Methamphetamine; Models, Animal
PubMed: 34801166
DOI: 10.1016/bs.irn.2021.06.011