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Sleep Jun 2021Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have... (Review)
Review
Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of methamphetamine, acute and long-term sleep impairments are of major concern, posing a significant therapeutic challenge, and a cause of addiction relapse. Unraveling mechanisms and functional correlates of methamphetamine-related sleep and circadian disruption are, therefore, of key relevance to translational and clinical psychiatry. In this article, we review the mounting evidence for the acute and long-term impairements of sleep-wake behavior and circadian activity caused by single or recurring methamphetamine usage and withdrawal. Factors contributing to the severity of sleep loss and related cognitive deficit, with risks of relapse are discussed. Key molecular players mediating methamphetamine-induced dopamine release and neuromodulation are considered, with wake-promoting effects in mesolimbic circuits. The effects on various sleep phases and related changes in dopamine levels in selected subcortical structures are reviewed and compared to other psychostimulants with similar action mechanisms. A critical appraisal is presented of the therapeutic use of modafinil, countering sleep, and circadian rhythm impairments. Finally, emerging knowledge gaps and methodical limitations are highlighted along with the areas for future research and therapeutic translation.
Topics: Central Nervous System Stimulants; Dopamine; Methamphetamine; Modafinil; Sleep
PubMed: 33406259
DOI: 10.1093/sleep/zsab001 -
Experimental Neurology Sep 2021Methamphetamine users are typically young adults, placing them at risk for significant drug-related harms. Neurological harms include stroke and Parkinson's disease,... (Review)
Review
INTRODUCTION
Methamphetamine users are typically young adults, placing them at risk for significant drug-related harms. Neurological harms include stroke and Parkinson's disease, both of which may develop prematurely in the context of methamphetamine use.
MATERIAL AND METHODS
We conducted a narrative review examining the evidence first, for stroke under 45 years and second, early onset of Parkinson's disease (PD) and parkinsonism related to methamphetamine use. We summarise epidemiological factors and common clinical features, before examining in detail the underlying pathology and causal mechanisms.
RESULTS AND DISCUSSION
Methamphetamine use among young people (<45 years) is associated with heightened risk for haemorrhagic stroke. Compared to age-matched all-cause fatal stroke, haemorrhage secondary to aneurysmal rupture is more common among young people with methamphetamine-related stroke and is associated with significantly poorer prognosis. Aetiology is related primarily to both acute and chronic hypertension associated with methamphetamine's sympathomimetic action. Evidence from a variety of sources supports a link between methamphetamine use and increased risk for the development of PD and parkinsonism, and with their early onset in a subset of individuals. Despite this, direct evidence of degeneration of dopaminergic neurons in methamphetamine users has not been demonstrated to date.
CONCLUSIONS
Stroke and Parkinson's Disease/parkinsonism are neurological harms observed prematurely in methamphetamine users.
Topics: Amphetamine-Related Disorders; Central Nervous System Stimulants; Humans; Methamphetamine; Parkinson Disease, Secondary; Risk Factors; Stroke
PubMed: 34166684
DOI: 10.1016/j.expneurol.2021.113793 -
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 -
JPMA. the Journal of the Pakistan... May 2023Clinical picture of patients taking methamphetamine for long duration includes rampant caries of the smooth surfaces of the whole dentition. The increasing use of... (Review)
Review
Clinical picture of patients taking methamphetamine for long duration includes rampant caries of the smooth surfaces of the whole dentition. The increasing use of methamphetamine in homosexuals is leading to the spread of HIV (human immunodeficiency virus). Easy availability and rapidly spreading nature of this drug (methamphetamine) results in worldwide increase of patients with medical and dental problems. Its effect on human dentition is highly damaging as patients with a beautiful smile begin to present a horrible picture of black, broken, and painful teeth within one year of methamphetamine use. Restoration of aesthetics and function of these teeth is not an easy task, and usually the first step to deal with this condition is counselling the patient to stop using this drug. Knowledge of methamphetamine-induced undesirable effects on the human body is important for the general dental practitioner as referral to mental health services is necessary in this condition.
Topics: Male; Humans; Methamphetamine; Dental Caries; Dentists; Amphetamine-Related Disorders; Professional Role
PubMed: 37218237
DOI: 10.47391/JPMA.6368 -
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 -
International Journal of Molecular... Feb 2023Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward,... (Review)
Review
Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users' mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed.
Topics: Animals; Humans; Tryptophan; Substance-Related Disorders; Brain; Behavior, Addictive; Central Nervous System Stimulants; Methamphetamine; Mammals
PubMed: 36769059
DOI: 10.3390/ijms24032737 -
Drug and Alcohol Review Nov 2021We examine how smoking and injecting methamphetamine change over time and correlate with specific health and social outcomes.
INTRODUCTION
We examine how smoking and injecting methamphetamine change over time and correlate with specific health and social outcomes.
METHODS
Panel data from a longitudinal cohort dependent on methamphetamine (N = 444; 891 months). Random effects regression models examined the relationship between smoking and/or injecting methamphetamine and past month outcomes (substance use, ≥daily injection, needle/syringe sharing, psychological distress, poor mental and physical health, sexual behaviour, psychotic symptoms, violent behaviour and crime). Effects were adjusted for between-group differences at baseline.
RESULTS
At baseline, 56% of participants only injected methamphetamine in the past month, 18% only smoked and 26% both injected and smoked (concurrent injecting and smoking). Compared to injecting only, concurrent injecting and smoking was associated with more days of methamphetamine use (b = 1.3, P < 0.001; adjusted [A] b = 1.2, P < 0.001), more frequent injection [odds ratio (OR) 1.8, P = 0.013; adjusted OR (AOR) 1.6, P = 0.042], violent behaviour (OR 2.1, P = 0.001; AOR 1.8, P = 0.013] and crime (OR 3.1, P < 0.001; AOR 2.5, P < 0.001). Non-injecting related outcomes did not differ significantly for only smoking versus only injecting. There was no significant transition from injecting methamphetamine at baseline to non-injecting methamphetamine use at follow up, or from exclusively smoking methamphetamine at baseline to any methamphetamine injection at follow up.
DISCUSSION AND CONCLUSION
Efforts are needed to address heavier methamphetamine use, more frequent drug injection and elevated violent behaviour and crime among people who concurrently smoke and inject methamphetamine.
Topics: Humans; Methamphetamine; Needle Sharing; Risk-Taking; Smoking; Substance Abuse, Intravenous
PubMed: 34365687
DOI: 10.1111/dar.13364 -
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