YABA

Methamphetamine is a strong central nervous system ( CNS ) stimulant that is mainly used as a recreational drug and less commonly as a treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine exists as two enantiomers: dextromethamphetamine and levomethamphetamine. Methamphetamine properly refers to a specific chemical, the racemic free base, which is an equal mixture of levomethamphetamine and dextroamphetamine in their pure amine forms. It is rarely prescribed due to concerns involving human neurotoxicity and potential for recreational used as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy. Dextroamphetamine is a much stronger central stimulant than levoamphetamine. Both enantiomers are neurotoxic and addictive.
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 and in the United States. Levomethamphetamine is available as an over- the- counter ( OTC ) drug for use as an inhaled nasal decongested in the United States. Internationally, the production, distribution,sale, and possession of methamphetamine is restricted or banned in many countries.
In low doses, methamphetamine can elevate mood, increase alertness, concentration and energy in fatigued individuals, reduce appetite and promote ( initial ) weight loss. At higher doses, it can induce psychosis, rhabdomyolysis, seizures and cerebral haemorrhage. Chronic high- dose use can precipitate unpredictable and rapid mood swings, prominent delusions and violent behaviors . Recreationally, methamphetamines’s ability to increase energy has been reported to lift mood and increase sexual desire to such an extent that users are able to engage in sexual activity continuously for several days. Methamphetamine is known to have a high addiction liability ( i.e., compulsive methamphetamine use ) and dependence liability ( i.e., withdrawal symptoms occur when methamphetamine use ceases ). 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 humans, damaging both dopamine and serotonin neurons in the CNS. This damage includes adverse changes in brain structure and function, such as reductions in grey mater volume in several brain regions and adverse changes in markers of metabolic integrity.
Uses
Recreational
Methamphetamine is often used recreationally for it’s effects as a potent euphoriant and stimulant as well as aphrodisiac qualities. Due to its strong stimulant and aphrodisiac effects and inhibitory effect on ejaculation, with repeated use, these sexual encounters will sometimes occur continuously for several days on end. The crash following the use of methamphetamine in this manner is very often severe, with marked hypersomnia ( excessive daytime sleeping ).
Contraindications
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 .
Side effects
Physical
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 ), rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhoea, constipation, blurred vision, dizziness, twitching, numbness, tremors , dry skin, acne, and pale appearance. Methamphetamine that is present in a mother’s bloodstream can pass through the placenta to a fetus and can also be secreted into breast milk. Infants born to methamphetamine- abusing mothers were found to have a significantly smaller gestational age- adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with neonatal withdrawal symptoms of agitation, vomiting and fast breathing. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.
Meth mouth
Methamphetamine users and addicts may loose their teeth abnormally quickly, regardless of the route of administration, form a condition informally known as meth mouth. The condition is generally most severe in users who inject the drug, rather than swallow, smoke, or inhale it.
Sexually transmitted infection
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. Methamphetamine use allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions as well as priapism in men.
Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle. The level of needle sharing among methamphetamine users is similar to that among other drug injection users.
Psychological
The psychological effects of methamphetamine can include euphoria, dysphoria, changes in libido, alertness, apprehension and concentration, decrease sense of fatigue, insomnia or wakefulness, self- confidence, sociability, irritability, restlessness, grandiosity and repetitive and abussive behaviors.
Neurotoxicity and neuroimmune response
Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons in both lab animals and humans. In addition to dopaminergic neurotoxicity, a review of evidence in humans also indicated that high-dose meth amphetamine use can be neurotoxic to serotonin neurons. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. As a result of methamphetamine- induced neurotoxicity to dopamine neurons, chronic use may also lead to post- acute withdrawal which persists months beyond the typical withdrawal period.
Magnetic resonance imaging studies on human methamphetamine users have also found evidence of neurodegeneration, or adverse neuroplastic changes in brain structure and function. In particular, methamphetamine appears to cause hyperintensity and hypertrophy of white matter, marked shrinkage of hippocampi, and reduced gray mater in the cingulate cortex, lambic cortex, and paralimbic cortex in recreational methamphetamine users.
Overdose
A methamphetamine overdose may result in a wide range of symptoms. A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm, confusion, difficult and/ or painful urination, high or low blood pressure, high body temperature, over- active and/ or over- responsive reflexes, muscle aches, severe agitation, rapid breathing, tremor, urinary hesitancy, and an inability to pass urine. An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, substantially reduced or nil urine output, carcinogenic shock, brain bleed, circulatory collapse , dangerously high body temperature, pulmonary hypertension, kidney failure, rhabdomyolysis, serotonin syndrome, and a form of stereotypy ( “tweaking” ). A methamphetamine overdose will likely also result in mild brain damage due to dopaminergic and serotonergic neurotoxicity. Death from methamphetamine poisoning is typically preceded by convulsions and coma.
Psychosis
Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms ( e.g., paranoia, hallucinations, delirium, delusions ). A cochrane collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse- induced psychosis states that about 5-15% of users fail to recover completely. The same review asserts that , based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Amphetamine psychosis may also develop occasionally as a treatment- emergent side effect.
Emergency treatment
The USFDA states that acute methamphetamine intoxication is largely managed by treating the symptoms and treatments may initially include administration of activated charcoal and sedation. Hypertension presents a risk for intracranial haemorrhage and, if severe, is typically treated with intravenous phentolamine or nitroprusside. Blood pressure often drops gradually following sufficient sedation with a benzodiazepine and providing a calming environment. Chlorpromazine may be useful in decreasing the stimulant and CNS effects of a methamphetamine overdose. The use of a nonselective betablocker may be required to control increased heart rate.
Addiction
Treatment and management
Cognitive behavioral therapy is currently the most effective clinical treatment for psychostimulant addictions in general.
Dependence and withdrawal
Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. In dependent users, withdrawal symptoms are positively correlated with the level of drug tolerance. Depression from methamphetamine

withdrawal lasts longer and is more severe than that of cocaine withdrawal.

According to the current Cochrane review on drug dependence and withdrawal in recreational users of methamphetamine, ” when chronic heavy users abruptly discontinue ( methamphetamine ) use, many report a time- limited withdrawal syndrome that occurs within 24 hours of their last dose. Withdrawal symptoms in chronic, high – dose users are frequent, occurring in upto 87.6% of cases, and persist for three to four weeks with a masked ” crash ” phase occurring during the fast week. Meth amphetamine withdrawal symptoms can include anxiety, drug craving, dysphoria mood, fatigue, increased appetite, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.
Interactions
Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of antidepressants and other stimulants as well. Methamphetamine may counteract the effects of anti hypertensives and antipsychotics due to its effects on the cardiovascular system and cognition respectively. The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite. Due to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine.
Pharmacology
Pharmacodynamics
Dextroamphetamine is a stronger psychostimulant ( approximately ten times on striatal dopamine ), but levoamphetamine has stronger peripheral effects, a longer half- life, and longer perceived effects among addicts. At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis.
Pharmacokinetics
Following oral administration, methamphetamine is well- absorbed into the blood stream, with peak plasma methamphetamine concentrations achieved in approximately 3.13-6.3 hours post ingestion. Methamphetamine is also well  absorbed following inhalation and following intranasal administration. Due to the high lipophilicity of methamphetamine, it can readily move through the blood- brain barrier faster than other stimulants, where it is more resistant to degradation by monoamine oxidase. The amphetamine metabolite peaks at 10-24 hours. It is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. When taken orally, 30-54% of the dose is excreted in urine as methamphetamine and 10-23% as amphetamine. Following intravenous doses, about 45% is excreted as methamphetamine and 7% as amphetamine. The half- life of methamphetamine is variable with a range of 5-30 hours.
Detection in biological fluids
Methamphetamine and amphetamine are often measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics. Chiral techniques may be employed to help distinguish the source of the drug to determine whether it was obtained illicitly or legally via prescription or prodrug. Chiral separation is needed to assess the possible contribution of levoamphetamine, which is an active ingredients in some OTC nasal decongestants, toward a positive test result. Dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.
Physical and chemical properties
Methamphetamine is a chiral compound with two enantiomers, dextroamphetamine and levoamphetamine. At room temperature, the free base of methamphetamine is a clear and colorless  liquid with an odour characteristic of geranium leaves. It is soluble in diethyl ether and ethanol as well as miscible with chloroform. In contrast, the methamphetamine hydrochloride- salt is odorless with a bitter taste. It has a melting point between 170 to 175 degree Celsius ( 338 to 347 degree Fahrenheit ) and, at room temperature, occurs as white crystals or a white crystalline powder. The hydrochloride salt is also freely soluble in ethanol and water.
Degradation
Beach exposure time and concentration are correlated with destruction of merhamphetamine. Methamphetamine in soils has shown to be a persistent pollutant. Methamphetamine is largely degraded with 30 days in a study of bioreactors under exposure to light in waste water.
Prof. A. K. M. Aminul Hoque
Ex- Prof. of Medicine
DMCH

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