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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 very 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 : C 10 H 15 N 1. 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; \\\\\\\\\[23\\\\\\\\\] \\\\\\\\\[24\\\\\\\\\] 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. 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 \\\\\\\\\[77\\\\\\\\\] 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. A systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had the highest efficacy i. As of December \\\\\\\\\[update\\\\\\\\\] , there is no effective pharmacotherapy for methamphetamine addiction. Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. While newborn babies addicted to opioids show the jittery signs of immediate withdrawal, methamphetamine-affected babies show little more than a tendency to sleep. Neonatologist Dr Ju Lee Oei of the University of New South Wales said not only were these babies often overlooked at birth, it was not until they approached school age that concerning behavioural and learning issues really started to emerge, by which time years of treatment opportunities had been missed. These children do not present with overt cerebral palsy or disability, but they have attention, behavioural and subtle cognitive losses that cannot be explained by anything else after accounting for lifestyle, environmental differences and genetic influences. Researcher and nurse, Dr Stacey Blythe , said 'Generally what would happen is the child presents as relatively healthy and they continue to grow and develop. 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. 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, a stimulant drug. For other uses, see Meth disambiguation. US : C Risk not ruled out. IUPAC name. Interactive image. N C Cc1ccccc1 C C. See also: Party and play and the Recreational routes of methamphetamine administration. Main article: Meth mouth. Signaling cascade in the nucleus accumbens that results in psychostimulant addiction v t e. Note: colored text contains article links. Nuclear pore. Nuclear membrane. Plasma membrane. Metabolic pathways of methamphetamine in humans \\\\\\\\\[sources 2\\\\\\\\\]. Benzoic acid. Hippuric acid. Methamphetamine synthesis. Method of methamphetamine synthesis of methamphetamine via reductive amination. Methods of methamphetamine synthesis via the Leuckart reaction. Main article: History and culture of substituted amphetamines. Main article: Legal status of methamphetamine. Levomethamphetamine and dextromethamphetamine are also known as L-methamphetamine , R -methamphetamine , or levmetamfetamine International Nonproprietary Name \\\\\\\\\[INN\\\\\\\\\] and D-methamphetamine , S -methamphetamine , or metamfetamine INN , respectively. Text color Transcription factors. Methamphetamine, a central nervous system stimulant drug, is p-hydroxylated by CYP2D6 to less active p-OH-methamphetamine. United States Food and Drug Administration. Shire US Inc. December Archived PDF from the original on 30 December Retrieved 30 December PubChem Compound. National Center for Biotechnology Information. Sudbury, Mass. Archived from the original on 18 March Retrieved 4 September Clinical Toxicology. Drug profiles. Archived from the original on 15 April Retrieved 27 November University of Alberta. Archived from the original on 4 March Retrieved 16 January Archived from the original on 7 December Retrieved 1 January Archived from the original on 28 January Pubchem Compound. Archived from the original on 6 October April Topical nasal decongestants -- i For products containing levmetamfetamine identified in The product delivers in each milliliters of air 0. NBC News. Associated Press. Archived from the original on 12 August Retrieved 12 September Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons. Behav Neurol. Brain Res. 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. Archived PDF from the original on 2 January Retrieved 6 January A critical review'. National Geographic Channel. August Archived from the original on 8 July Retrieved 7 July The Lancet. New York: McGraw-Hill. National Institute on Drug Abuse. National Institutes of Health , U. October Retrieved 15 March Medical News Today. Advanced Recovery Systems. American Dental Association. Archived from the original on June Retrieved 15 December AIDS and Behavior. Archived from the original on 4 June Retrieved 15 January Archived from the original PDF on 16 August Merck Manual for Health Care Professionals. Archived from the original on 6 May Retrieved 8 May Neurologic Clinics. Drug Alcohol Rev. Glial modulators as potential treatments of psychostimulant abuse. Advances in Pharmacology. 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. Neuroimmune basis of methamphetamine toxicity. International Review of Neurobiology. Collectively, these pathological processes contribute to neurotoxicity e. Curr Neuropharmacol. 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. Behavioural Neurology. The Journal of Pharmacology and Experimental Therapeutics. Pharmacol Rep. Archived PDF from the original on 16 July Retrieved 8 November Curr Drug Abuse Rev. Dialogues in Clinical Neuroscience. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. 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. Department of Neuroscience. Retrieved 9 February New England Journal of Medicine. Substance-use disorder: 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. Addiction: 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. The Journal of General Physiology. 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, KEGG Pathway. 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. Molecular Neurobiology. Nature Reviews Neuroscience. The net result is gene activation and increased CDK5 expression. The net result is c-fos gene repression. Clinical Psychopharmacology and Neuroscience. Drug Alcohol Abuse. 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. Archived from the original on 13 October Bibcode : PNAS.. Journal of Psychoactive Drugs. 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. Drug Alcohol Depend. J Subst Abuse Treat. Trends Pharmacol. PLOS Medicine. Expert Rev Clin Pharmacol. Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Addiction Abingdon, England. Merck Manual Home Health Handbook. Archived from the original on 17 February Retrieved 26 September Cochrane Database Syst. Shoptaw SJ ed. The prevalence of this withdrawal syndrome is extremely common Cantwell ; Gossop with American Family Physician. Emergency Central. Unbound Medicine. Archived from the original on 26 September Retrieved 11 June Archived PDF from the original on 4 July Retrieved 2 January 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. New York: Oxford University Press. Methamphetamine Toxicity. Archived from the original on 9 April Retrieved 20 April Bibcode : PNAS International Union of Basic and Clinical Pharmacology. Archived from the original on 29 June 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\\\\\\\\\]. University of Paris. Archived from the original on 29 May 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: cytochrome P and flavin monooxygenase. Amphetamine can also undergo aromatic hydroxylation to p -hydroxyamphetamine. Stereochemical course of the reaction' PDF. Archived PDF from the original on 7 October 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 12 October Clin Pharmacokinet. Disposition of toxic drugs and chemicals in man. Seal Beach, Ca. Archived from the original on 19 October Retrieved 17 October Bibcode : Chmsp.. Water Res. The Journal of Organic Chemistry. The Guardian. Archived from the original on 17 August Retrieved 17 August London: Routledge. Vermont Department of Health. Government of Vermont. Archived from the original on 26 June Retrieved 29 January ISRN Dentistry. Spiegel Online. Der Spiegel, 6 May Archived from the original on 19 December Retrieved 12 August Oxford University Press. Archived from the original on 23 March Retrieved 23 October New York University Press. Archived from the original on 5 April Retrieved 4 November Lundbeck: Desoxyn. Archived from the original on 30 November Recordati SP. Archived from the original on 7 July Retrieved 15 May New York: United Nations. Archived PDF from the original on 16 October Retrieved 11 November International Narcotics Control Board. United Nations. Archived from the original PDF on 5 December Retrieved 19 November Annals of the New York Academy of Sciences. Dexedrine ProCentra Zenzedi. Dextromethamphetamine Levomethamphetamine. Amphetamine dependence Meth mouth Prenatal methamphetamine exposure. United States Native Americans Australia. Recreational drug use. 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. ATC code : N06B. ADHD pharmacotherapies. Amphetamine Mixed amphetamine salts , Levoamphetamine , Dextroamphetamine , Lisdexamfetamine Methamphetamine Methylphenidate Dexmethylphenidate. Atomoxetine Modafinil. Clonidine Guanfacine. Amantadine Carbamazepine. Monoamine releasing agents. Oxazolines: 4-Methylaminorex Aminorex Clominorex Fluminorex. Others: Indeloxazine Viqualine. Human trace amine-associated receptor ligands. N , N -Dimethylethylamine Trimethylamine. Sigma receptor modulators. Monoamine neurotoxins. Categories : Methamphetamine Anorectics Aphrodisiacs Carbonic anhydrase activators Cardiac stimulants Euphoriants Excitatory amino acid reuptake inhibitors Japanese inventions Management of obesity Norepinephrine-dopamine releasing agents Phenethylamines Sigma agonists Stimulants Substituted amphetamines Sympathomimetics TAAR1 agonists Treatment and management of attention deficit hyperactivity disorder VMAT inhibitors introductions. Namespaces Article Talk. Views Read View source View history. In other projects Wikimedia Commons Wikinews. By using this site, you agree to the Terms of Use and Privacy Policy. Medical: oral ingestion Recreational: oral , intravenous , intramuscular , subcutaneous , smoke inhalation , insufflation , rectal , vaginal. Varies widely \\\\\\\\\[6\\\\\\\\\]. Rapid \\\\\\\\\[7\\\\\\\\\]. Signaling cascade in the nucleus accumbens that results in psychostimulant addiction v t e Note: colored text contains article links. Nuclear pore Nuclear membrane Plasma membrane Ca v 1. Following presynaptic dopamine and glutamate co-release by such psychostimulants, \\\\\\\\\[57\\\\\\\\\] \\\\\\\\\[58\\\\\\\\\] 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 cross-sensitization. Psychostimulant self-administration. 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 Dextromethamphetamine.
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