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Метамфетамин айс

Methamphetamine \\\\\\\\\\\\\\\\\[note 1\\\\\\\\\\\\\\\\\] contracted from N - methylamphetamine is a potent central nervous system CNS stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. It is rarely prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant , among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy. Dextromethamphetamine is a much stronger CNS stimulant than levomethamphetamine. Both methamphetamine and dextromethamphetamine are illicitly trafficked and sold owing to their potential for recreational use. The highest prevalence of illegal methamphetamine use occurs in parts of Asia, Oceania, and in the United States, where racemic methamphetamine, levomethamphetamine, and dextromethamphetamine are classified as schedule II controlled substances. Levomethamphetamine is available as an over-the-counter OTC drug for use as an inhaled nasal decongestant in the United States. While dextromethamphetamine is a more potent drug, racemic methamphetamine is sometimes illicitly produced due to the relative ease of synthesis and limited availability of chemical precursors. In low to moderate doses, methamphetamine can elevate mood , increase alertness, concentration and energy in fatigued individuals, reduce appetite, and promote weight loss. At relatively high doses, it can induce psychosis , breakdown of skeletal muscle , seizures and bleeding in the brain. Chronic high-dose use can precipitate unpredictable and rapid mood swings , stimulant psychosis e. Heavy recreational use of methamphetamine may lead to a post-acute-withdrawal syndrome , which can persist for months beyond the typical withdrawal period. Unlike amphetamine , methamphetamine is neurotoxic to human midbrain dopaminergic neurons. Methamphetamine belongs to the substituted phenethylamine and substituted amphetamine chemical classes. It is related to the other dimethylphenethylamines as a positional isomer of these compounds, which share the common chemical formula: In the United States, dextromethamphetamine hydrochloride, under the trade name Desoxyn , has been approved by the FDA for treating ADHD and obesity in both adults and children; \\\\\\\\\\\\\\\\\[24\\\\\\\\\\\\\\\\\] \\\\\\\\\\\\\\\\\[25\\\\\\\\\\\\\\\\\] however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use. As methamphetamine is associated with a high potential for misuse, the drug is regulated under the Controlled Substances Act and is listed under Schedule II in the United States. Methamphetamine is often used recreationally for its effects as a potent euphoriant and stimulant as well as aphrodisiac qualities. According to a National Geographic TV documentary on methamphetamine, an entire subculture known as party and play is based around sexual activity and methamphetamine use. Methamphetamine is contraindicated in individuals with a history of substance use disorder , heart disease , or severe agitation or anxiety, or in individuals currently experiencing arteriosclerosis , glaucoma , hyperthyroidism , or severe hypertension. The physical effects of methamphetamine can include loss of appetite , hyperactivity, dilated pupils , flushed skin , excessive sweating , increased movement , dry mouth and teeth grinding leading to ' meth mouth ' , headache, irregular heartbeat usually as accelerated heartbeat or slowed heartbeat , rapid breathing , high blood pressure , low blood pressure , high body temperature , diarrhea, constipation, blurred vision , dizziness , twitching , numbness , tremors , dry skin, acne , and pale appearance. Methamphetamine users and addicts may lose their teeth abnormally quickly, regardless of the route of administration, from a condition informally known as meth mouth. They suggest the side effect has been exaggerated and stylized to create a stereotype of current users as a deterrence for new ones. Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners, an association more pronounced in HIV-positive participants. Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle. The psychological effects of methamphetamine can include euphoria , dysphoria , changes in libido , alertness , apprehension and concentration , decreased sense of fatigue, insomnia or wakefulness , self-confidence , sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors. Unlike amphetamine , methamphetamine is directly neurotoxic to dopamine neurons in both lab animals and humans. Magnetic resonance imaging studies on human methamphetamine users have also found evidence of neurodegeneration, or adverse neuroplastic changes in brain structure and function. A review concluded that the behaviour resulting from the use of methamphetamine is likely caused in part from the neurotoxic effects of the drug. Excitotoxicity , oxidative stress , metabolic compromise, UPS dysfunction, protein nitration, endoplasmic reticulum stress , p53 expression and other processes contributed to this neurotoxicity. A methamphetamine overdose may result in a wide range of symptoms. Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms e. Acute methamphetamine intoxication is largely managed by treating the symptoms and treatments may initially include administration of activated charcoal and sedation. Antipsychotics such as haloperidol are useful in treating agitation and psychosis from methamphetamine overdose. Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens. The frequent persistence of addiction suggests that long-lasting changes in gene expression may occur in particular regions of the brain, and may contribute importantly to the addiction phenotype. Recently a crucial role has been found for epigenetic mechanisms in driving lasting changes in gene expression in the brain. A review in \\\\\\\\\\\\\\\\\[84\\\\\\\\\\\\\\\\\] summarized a number of studies involving chronic methamphetamine use in rodents. Epigenetic alterations were observed in the brain 'reward' regions, including the ventral tegmental area , the nucleus accumbens , the dorsal striatum , the hippocampus , and the prefrontal cortex. Chronic methamphetamine use caused gene-specific histone acetylations, deacetylations and methylations. Gene-specific DNA methylations in particular regions of the brain were also observed. The various epigenetic alterations caused downregulations or upregulations of specific genes important in addiction. For instance, chronic methamphetamine use caused methylation of the lysine in position 4 of histone 3 located at the promoters of the c-fos and the C-C chemokine receptor 2 ccr2 genes, activating those genes in the nucleus accumbens NAc. In methamphetamine addicted rats, epigenetic regulation through reduced acetylation of histones, in brain striatal neurons, caused reduced transcription of glutamate receptors. Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addictions in general. Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 TAAR1 , a G protein-coupled receptor GPCR that regulates brain catecholamine systems. In addition to the plasma membrane monoamine transporters, methamphetamine inhibits uptake and induces efflux of neurotransmitters and other substrates at the vesicular monoamine transporters, VMAT1 and VMAT2. Following oral administration, methamphetamine is well-absorbed into the bloodstream, with peak plasma methamphetamine concentrations achieved in approximately 3. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination. Methamphetamine and amphetamine are often measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics. Methamphetamine is a chiral compound with two enantiomers, dextromethamphetamine and levomethamphetamine. At room temperature, the free base of methamphetamine is a clear and colorless liquid with an odor characteristic of geranium leaves. Bleach exposure time and concentration are correlated with destruction of methamphetamine. Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart \\\\\\\\\\\\\\\\\[\\\\\\\\\\\\\\\\\] or reductive amination methods. During World War II, methamphetamine was sold in tablet form under the brand name Pervitin not to be confused with Perviton , which is a synonym for Phenatine , produced by the Berlin-based Temmler pharmaceutical company. It was used extensively by all branches of the combined Wehrmacht armed forces of the Third Reich , and was popular with Luftwaffe pilots in particular, for its performance-enhancing stimulant effects and to induce extended wakefulness. Side effects were so serious that the army sharply cut back its usage in Suffering from a drug hangover and looking more like a zombie than a great warrior, he had to recover from the side effects. Obetrol , patented by Obetrol Pharmaceuticals in the s and indicated for treatment of obesity , was one of the first brands of pharmaceutical methamphetamine products. The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. It has been suggested, based on animal research, that Calcitriol, the active metabolite of vitamin D, can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of methamphetamine. From Wikipedia, the free encyclopedia. This article is about the free base and salts of methamphetamine. For other uses, see Meth disambiguation. C Risk not ruled out. N C Cc1ccccc1 C C. Party and play and the Recreational routes of methamphetamine administration. Signaling cascade in the nucleus accumbens that results in psychostimulant addiction v t e. Metabolic pathways of methamphetamine in humans \\\\\\\\\\\\\\\\\[sources 2\\\\\\\\\\\\\\\\\]. Further information on illicit amphetamine synthesis: Method of methamphetamine synthesis of methamphetamine via reductive amination. Methods of methamphetamine synthesis via the Leuckart reaction. History and culture of substituted amphetamines. Legal status of methamphetamine. Breaking Bad , a TV series centered on illicit methamphetamine synthesis Faces of Meth , a drug prevention project Methamphetamine in the United States Montana Meth Project , a Montana-based organization aiming to reduce meth use among teenagers Rolling meth lab , a transportable laboratory that is used to illegally produce methamphetamine Ya ba , Southeast Asian tablets containing a mixture of methamphetamine and caffeine. Text color Transcription factors. Hearings, Ninety-second Congress, first session, pursuant to S. Retrieved 1 January We made a decision in January of to cease the manufacture of injectable methamphetamines. Methamphetamine, a central nervous system stimulant drug, is p-hydroxylated by CYP2D6 to less active p-OH-methamphetamine. United States Food and Drug Administration. Retrieved 30 December National Center for Biotechnology Information. Retrieved 31 December Manual of forensic emergency medicine: Jones and Bartlett Publishers. Predicted — EP Suite'. Retrieved 3 January Retrieved 1 September Uses, Symptoms, Signs and Addiction Treatment'. Retrieved 16 January Code of Federal Regulations Title Subchapter D — Drugs for human use. Retrieved 7 March Topical nasal decongestants -- i For products containing levmetamfetamine identified in The product delivers in each milliliters of air 0. Retrieved 2 January A Foundation for Clinical Neuroscience 2nd ed. Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons. Neuroimaging studies have revealed that METH can indeed cause neurodegenerative changes in the brains of human addicts Aron and Paulus, ; Chang et al. These abnormalities include persistent decreases in the levels of dopamine transporters DAT in the orbitofrontal cortex, dorsolateral prefrontal cortex, and the caudate-putamen McCann et al. The density of serotonin transporters 5-HTT is also decreased in the midbrain, caudate, putamen, hypothalamus, thalamus, the orbitofrontal, temporal, and cingulate cortices of METH-dependent individuals Sekine et al. Neuropsychological studies have detected deficits in attention, working memory, and decision-making in chronic METH addicts There is compelling evidence that the negative neuropsychiatric consequences of METH abuse are due, at least in part, to drug-induced neuropathological changes in the brains of these METH-exposed individuals These include loss of gray matter in the cingulate, limbic and paralimbic cortices, significant shrinkage of hippocampi, and hypertrophy of white matter Thompson et al. Elevated choline levels, which are indicative of increased cellular membrane synthesis and turnover are also evident in the frontal gray matter of METH abusers Ernst et al. Retrieved 6 January Archived from the original on June Retrieved 15 December Retrieved 15 January Archived from the original PDF on 16 August Merck Manual for Health Care Professionals. Retrieved 8 May Glia including astrocytes, microglia, and oligodendrocytes , which constitute the majority of cells in the brain, have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mids, and only relatively recently have they been gaining their due respect. Collectively, these pathological processes contribute to neurotoxicity e. They are present in the organs that mediate the actions of METH e. In the brain, METH acts primarily on the dopaminergic system to cause acute locomotor stimulant, subchronic sensitized, and neurotoxic effects. The Journal of Pharmacology and Experimental Therapeutics. A promising target for the treatment of psychostimulant addiction'. Curr Drug Abuse Rev. Retrieved 11 June Shoptaw SJ, Ali R, eds. A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis. A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects 2nd ed. Retrieved 20 April Reinforcement and Addictive Disorders'. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict. Mount Sinai School of Medicine. Retrieved 9 February A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders DSM-5 referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe. A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure. Chronic exposure to psychostimulants increases glutamatergic \\\\\\\\\\\\\\\\\[signaling\\\\\\\\\\\\\\\\\] from the prefrontal cortex to the NAc. Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex PFC , as well as projections from midbrain dopamine neurons. Previous studies have demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses Goto and Grace, Retrieved 31 October Most addictive drugs increase extracellular concentrations of dopamine DA in nucleus accumbens NAc and medial prefrontal cortex mPFC , projection areas of mesocorticolimbic DA neurons and key components of the 'brain reward circuit'. Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain. The net result is gene activation and increased CDK5 expression. The net result is c-fos gene repression. Transcriptional mechanisms of addiction: Signal Transduction in the Brain'. Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse Cosgrove et al. There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers Daniel et al. In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in or compulsive engagement in non-drug rewards such as gambling, shopping, or sex Evans et al. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens NAc , thereby causing development and expression of addictive behavior. Sexual behavior is highly rewarding Tenk et al. Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density Meisel and Mullins, ; Pitchers et al. Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis Pitchers et al. J Subst Abuse Treat. Currently, cognitive—behavioral therapies are the most successful treatment available for preventing the relapse of psychostimulant use. Expert Rev Clin Pharmacol. Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. To date, no pharmacological treatment has been approved for \\\\\\\\\\\\\\\\\[addiction\\\\\\\\\\\\\\\\\], and psychotherapy remains the mainstay of treatment. Excitatory and Inhibitory Amino Acids'. The NMDA receptor is unique among all neurotransmitter receptors in that its activation requires the simultaneous binding of two different agonists. In addition to the binding of glutamate at the conventional agonist-binding site, the binding of glycine appears to be required for receptor activation. Because neither of these agonists alone can open this ion channel, glutamate and glycine are referred to as coagonists of the NMDA receptor. The physiologic significance of the glycine binding site is unclear because the normal extracellular concentration of glycine is believed to be saturating. However, recent evidence suggests that D-serine may be the endogenous agonist for this site. Drug Use and Abuse'. Merck Manual Home Health Handbook. Retrieved 26 September The prevalence of this withdrawal syndrome is extremely common Cantwell ; Gossop with International Union of Basic and Clinical Pharmacology. Retrieved 8 December AMPH also increases intracellular calcium Gnegy et al. AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties \\\\\\\\\\\\\\\\\[80\\\\\\\\\\\\\\\\\], although the mechanisms do not appear to be identical for each drug \\\\\\\\\\\\\\\\\[81\\\\\\\\\\\\\\\\\]. Retrieved 29 May Retrieved 5 October Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine active and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. The simplest unsubstituted phenylisopropylamine, 1-phenylaminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: Amphetamine can also undergo aromatic hydroxylation to p -hydroxyamphetamine. Stereochemical course of the reaction' PDF. Retrieved 6 November Hydroxyamphetamine was administered orally to five human subjects The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues. Unfortunately, at the present time one cannot be completely certain that the hydroxylation of hydroxyamphetamine in vivo is accomplished by the same enzyme which converts dopamine to noradrenaline. Retrieved 7 May Retrieved 15 October Retrieved 12 October Disposition of toxic drugs and chemicals in man. A Study of Degradation and Transformation Effects'. Retrieved 17 October The Journal of Organic Chemistry. Alcohol and Drug Misuse: A Handbook for Students and Health Professionals. Vermont Department of Health. Retrieved 29 January Der Spiegel, 6 May A Short History of Drugs and War. The Many Lives of Amphetamine 1 ed. New York University Press. Retrieved 4 November Archived from the original on 30 November Archived from the original on 7 July Retrieved 15 May Retrieved 11 November International Narcotics Control Board. Archived from the original PDF on 5 December Retrieved 19 November Annals of the New York Academy of Sciences. Amphetamine dependence Meth mouth Prenatal methamphetamine exposure. United States Native Americans Australia. Calea zacatechichi Silene capensis. Coffee break Coffeehouse Latte art Tea house. Abuse Date rape drug Impaired driving Drug harmfulness Effects of cannabis Addiction Dependence Prevention Opioid replacement therapy Rehabilitation Responsible use Drug-related crime Fetal alcohol spectrum disorder Long-term effects of cannabis Neurotoxicity Overdose Passive smoking of tobacco or other substances. Alcohol legality Alcohol consumption Anabolic steroid legality Cannabis legality Annual use Lifetime use Cigarette consumption Cocaine legality Cocaine use Methamphetamine legality Opiates use Psilocybin mushrooms legality Salvia legality. Adapromine Amantadine Bromantane Memantine Rimantadine. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. SoRI Adrenergic release blockers: Human trace amine-associated receptor ligands. N , N -Dimethylethylamine Trimethylamine. Retrieved from ' https: Views Read View source View history. In other projects Wikimedia Commons Wikinews. This page was last edited on 5 September , at By using this site, you agree to the Terms of Use and Privacy Policy. Signaling cascade in the nucleus accumbens that results in psychostimulant addiction v t e Note: Nuclear pore Nuclear membrane Plasma membrane Ca v 1. Following presynaptic dopamine and glutamate co-release by such psychostimulants, \\\\\\\\\\\\\\\\\[64\\\\\\\\\\\\\\\\\] \\\\\\\\\\\\\\\\\[65\\\\\\\\\\\\\\\\\] postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP-dependent pathway and a calcium-dependent pathway that ultimately result in increased CREB phosphorylation. Psychostimulant conditioned place preference. Reinstatement of drug-seeking behavior. CREB phosphorylation in the nucleus accumbens. Sensitized dopamine response in the nucleus accumbens. Altered striatal dopamine signaling. Altered striatal opioid signaling. Changes in striatal opioid peptides. Number of dendrites in the nucleus accumbens. Dendritic spine density in the nucleus accumbens. Metabolic pathways of methamphetamine in humans \\\\\\\\\\\\\\\\\[sources 2\\\\\\\\\\\\\\\\\] Methamphetamine 4-Hydroxymethamphetamine 4-Hydroxyphenylacetone Phenylacetone Benzoic acid Hippuric acid Amphetamine Norephedrine 4-Hydroxyamphetamine 4-Hydroxynorephedrine The primary metabolites of methamphetamine are amphetamine and 4-hydroxymethamphetamine. Wikimedia Commons has media related to Methamphetamine.

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