Ya Ba Tablets Abuse & Harmful After Effects On Body Even Minds

Ya Ba Tablets Abuse & It's Harmful After Effects On Body Even Minds !

Ya ba (also yaba, yaa baa ; Thai: literally "mad drug"; Burmese:  formerly known as ya ma , are tablets containing a mixture of  Methamphetamine and caffeine.

"From ya khayan (energy pill) in its early days to ya maa (horse medicine), the drug was named ya ba (crazy pill) in 1996".  It was given to horses when pulling carts up steep hills and for other strenuous work in Shan State (Mayanmar).

Ya ba is sometimes called bhul bhuliya in India. The name commonly used for it in the Philippines and Indonesia is shabú. In north Thailand it is often referred to as "chocalee" due to a somewhat sweet taste ya ba pills leave in the mouth. The name commonly used for it in China is Ma-goo  or  Ma-guo, usually as a Sexual stimulant in recent years. Methamphetamine  is  Engineered to Trick your brain. It can keep you awake, stop you from eating and can make you Feel ‘Brave’(!).  Yaba has a very strong stimulating effects. When smoked, the drug creates an intense effect similar to that of crack cocaine. Only that its lasts much longer.

In Bangkok Yaba helped to boom the street sex industry by massive proportion. In the Red Light District it created a 24 hour market for sex. A 17 year old female sex worker explained to National Geographic ‘More Yaba meant I can have more ‘boyfriends’ and more ‘boyfriends’ meant more money. When I don’t have it, I feel tired and hungry. With a couple of smoke again however, I am wide awake, relaxed, not worried. It feels good’. The money they earned from the sex industry was usually sent home. But when they were starting to become dependent on Yaba, the money that they once used to send back home was now being used for something else: for buying ‘more yabas’. The beginning of the Viscous circle of addiction! Methamphetamine : The more you use, the more you need. Young potential students drained their potential into sex industries and were expert in the consumption of it even at the age of 15.

Thailand went crazy with the continuous spread of the ‘YA BA’ (Thai)- translated in English-‘THE CRAZY MEDICINE’, and the Government after estimating that 3 million people were consuming it on regular basis launched brutal crackdown on the Yaba industry and the addicts in 2003 under the banner ‘all out attack on drugs’, killing almost 2000 suspected drug dealers in three months time.

 In Bangladesh it's colloqually known as Baba.

Appearance & Use :

Ya ba is typically produced in a round pill form. There are many different versions of ya ba, and the most common are red, orange, or lime green in color and carry logos such as "R" or "WY". They are small and round, roughly 6 millimetres (0.24 in) in diameter (similar size to Smint but round), which means they can be packed inside a plastic soda straw for easy transportation or in a reusable "mint" container.

Ya ba tablets typically are consumed orally. Another common method is called "chasing the dragon". Users place the ya ba tablet on aluminum foil and heat it from below. As the tablet melts, vapors rise and are inhaled. The drug also may be administered by crushing the tablets into powder, which is then snorted or mixed with a solvent and injected. When swallowed in pill form the duration of the drug's effect is between 8–16 hours, as compared to 1–3 hours when smoked, while the intensity is considerably reduced. The peak of the drug's effect is followed by a come down period lasting 6–10 hours, during which the user may have difficulty sleeping or eating. Many users report that it takes them up to 24 hours after consumption to be able to fall asleep.

Ya ba is not commonly injected as many intravenous users favour the pure product instead (methamphetamine, called "ice" in Southeast Asia). This illegal drug is especially popular in Thailand, where it is imported from Burma or Laos even though it is sometimes manufactured locally in Thailand.

Typical ya ba users are working males, aged 16–40 years old, and its use is not uncommon among both female and male prostitutes in Thailand and Cambodia.

Burma (Myanmar) is the largest producer of methamphetamine in the world, with the majority of ya ba found in Thailand being produced in Burma, particularly in the Golden Triangle and northeastern Shan State, which borders Thailand, Laos, and China. In 2010, Burma trafficked 1 billion tablets to neighboring Thailand. Ethnic militias and rebel groups (in particular the United Wa State Army) are responsible for much of this production; however, the Burmese military units are believed to be heavily involved in the trafficking of the drugs.

Ya ba tablets were formerly sold at gas stations and were commonly used by long-haul drivers to stay awake. After many horrific long-distance bus accidents, they were outlawed by the Thai government in 1970. The deposed Prime Minister Thaksin Shinawatra's campaign from 2003 on to eliminate drug-trafficking further helped to curtail widespread use. In particular, use of the drug by bus drivers and truckers is not as widespread as it was in the 1980s.

      Ya Ba  Abuse & Users After Effects :

As a result of the Thai government crackdown, restricted supply has had an effect on prices, further curtailing the popular use of ya ba. In 1999–2000, when buying a straw-full (around 20 pills) in Chiang Rai Province, north Thailand, ya ba was sold for around THB10 per pill and commonly used on the go-go circuit and by young "MTV" clubbers.  Retail prices have risen  from THB100–150 (US$3–4) to THB250–450 per pill as a result of the crackdown, though it remains a popular party drug.

In 2000, ya ba was smuggled across the porous border with Myanmar and from the neighbouring Chiang Rai and Chiang Mai Provinces of Thailand. Illegal traffickers often marketed or promoted their product by claiming that the pills contained up to 6% heroin. Rumour suggested it was produced by the corrupt personnel of Wa State Army in Burma.

In 2014, it was reported that Thailand's northeast provinces have seen a 700% increase in the number of people arrested for meth since 2008, according to data from the Narcotics Suppression Bureau.^[4] In 2013, authorities counted more than 33,000 meth-related arrests in the northeast. The rapid growth of ya ba use in Isan mirrors that which is occurring across Asia, which now accounts for more than 50% of global amphetamine-type stimulant users. 

On 16 June 2016, the National Council for Peace and Order, the military junta ruling Thailand, stated that it was planning to legalise ya ba in the country. 

      Ya Ba  Abuse &  After Effects :

In 2006, ya ba ma consumption became fashionable for the well-to-do in Bangladesh. A series of highly publicized drug raids in 2007 by authorities implicated some well-known business people. Although the extent of ya ba abuse in Bangladesh is not precisely known, seizures of the drug by authorities are frequent.  It is also believed those who use it on a regular basis are frequently involved in the distribution of the drug, either directly or indirectly.  It is commonly known in Bangladesh as "pill", "BABA", "gari", "guti", and "bori", among other street names. 

In February 2010 it was reported that increasingly large quantities of ya ba were being smuggled into Israel by Thai migrant workers, leading to fears that its use would spread to the Israeli club scene, where ecstasy use is already common.  In recent years, it has also been used by immigrant populations in the United States, and occasionally as a club drug replacing ecstasy.

Methamphetamine :

Methamphetamine  (contracted from N-methylamphetamine) 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 was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine.    Methamphetamine properly refers to a specific chemical, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms. It is rarely prescribed due to 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. Internationally, the production, distribution, sale, and possession of methamphetamine is restricted or banned in many countries, due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty.

Ya Ba  Abuse &  Harmful  After Effects :

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 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, breakdown of skeletal muscle, seizures andbleeding in the brain. Chronic high-dose use can precipitate unpredictable and rapid mood swings, prominent delusions and violent behavior. Recreationally, methamphetamine's ability to increase energy has been reported to lift mood and increase sexual desireto 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 isneurotoxic to human midbrain dopaminergic neurons.^[18] It has also been shown to damage serotonin neurons in the CNS.^[19][20]This damage includes adverse changes in brain structure and function, such as reductions in grey matter volume in several brain regions and adverse changes in markers of metabolic integrity.

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: C₁₀H₁₅N₁.

Medical :

In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treatingADHD and obesity in both adults and children;  however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use.  Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia.  In the United States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal decongestant products.

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 hydrochloride dispensed in the United States is required to include a boxed warning regarding its potential for recreational misuse and addiction liability.

Recreational :

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 methamphetamine use".  Members of this San Francisco sub-culture, which consists almost entirely of gay male methamphetamine users, will typically meet up through internet dating sites and have sex.  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 sleepiness). Methamphetamine use has also been noted among men having sex with men in New York City.

Desoxyn tablets – pharmaceutical methamphetamine hydrochloride

Crystal meth – illicit methamphetamine hydrochloride

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. The USFDA states that individuals who have experienced hypersensitivity reactions to other stimulants in the past or are currently taking monoamine oxidase inhibitors should not take methamphetamine. The USFDA also advises individuals with bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome to monitor their symptoms while taking methamphetamine.  Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of growing children and adolescents during treatment.

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 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 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 lose their teeth abnormally quickly, regardless of the route of administration, from 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.  According to the American Dental Association, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high-calorie, carbonated beverages and bruxism (teeth grinding and clenching)". As dry mouth is also a common side effect of other stimulants, which are not known to contribute severe tooth decay, many researchers suggest that methamphetamine associated tooth decay is more due to users' other choices. They suggest the side effect has been exaggerated and stylized to create a stereotype of current users to deter new ones.

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.   These findings suggest that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors, behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men.  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.   Methamphetamine may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually transmitted infection.

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, decreased sense of fatigue,insomnia or wakefulness, self-confidence, sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors. Methamphetamine use also has a high association with anxiety, depression, amphetamine psychosis, suicide, and violent behaviors.

Neurotoxicity and neuroimmune response :

This diagram depicts the neuroimmune mechanisms that mediate methamphetamine-induced neurodegeneration in the human brain. The NF-κB-mediated neuroimmune response to methamphetamine use which results in the increased permeability of the blood–brain barrierarises through its binding at and activation of sigma-1 receptors, the increased production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern molecules (DAMPs), the dysregulation of glutamate transporters(specifically, EAAT1 and EAAT2) and glucose metabolism, and excessive Ca²⁺ ion influx in glial cells and dopamine neurons.

Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons in both lab animals and humans.  Moreover, methamphetamine neurotoxicity is associated with an increased risk ofParkinson's disease, an effect which partially arises through excessive cytosolic and synaptic production ofreactive oxygen species and autoxidation of dopamine.   In addition to dopaminergic neurotoxicity, a review of evidence in humans also indicated that high-dose methamphetamine 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-inducedneurotoxicity 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 ofhippocampi, and reduced gray matter in the cingulate cortex, limbic cortex, and paralimbic cortex in recreational methamphetamine users.  Moreover, evidence suggests that adverse changes in the level ofbiomarkers of metabolic integrity and synthesis occur in recreational users, such as a reduction in N-acetylaspartate and creatine levels and elevated levels of choline and myoinositol.

Methamphetamine has been shown to activate TAAR1 in human astrocytes and generate cAMP as a result.  Activation of astrocyte-localized TAAR1 appears to function as a mechanism by which methamphetamine attenuates membrane-bound EAAT2 (SLC1A2) levels and function in these cells.

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 no urine output, cardiogenic shock, bleeding in the brain, circulatory collapse, dangerously high body temperature, pulmonary hypertension, kidney failure, rapid muscle breakdown, serotonin syndrome, and a form of stereotypy ("tweaking").  A methamphetamine overdose will likely also result in mild brain damage due todopaminergic and serotonergic neurotoxicity.  Death from methamphetamine poisoning is typically preceded by convulsions and coma.

Psychosis :

The main section for this topic is on the page Stimulant psychosis, in the section Substituted amphetamines.

Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms (e.g. paranoia, hallucinations, delirium, delusions).  ACochrane 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.  There is not enough evidence on hemodialysis or peritoneal dialysis in cases of methamphetamine intoxication to determine their usefulness.  Forced acid diuresis (e.g., with vitamin C) will increase methamphetamine excretion but is not recommended as it may increase the risk of aggravating acidosis, or cause seizures or rhabdomyolysis. Hypertension presents a risk for intracranial hemorrhage 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.

Antipsychotics such as haloperidol are useful in treating agitation and psychosis from methamphetamine overdose.   Beta blockers with lipophilic properties and CNS penetration such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity.  The mixed alpha- and beta-blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine.  The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta-blockers for treatment of methamphetamine toxicity.

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 up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.  Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness orsleepiness, and vivid or lucid dreams.

Interactions :

Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6 inhibitors will prolong the elimination half-life of methamphetamine.  Methamphetamine also interacts with monoamine oxidase inhibitors (MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous.  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 antihypertensives 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  ::

This illustration depicts the normal operation of the dopaminergic  terminal to the left, and the dopaminergic terminal in the presence of methamphetamine to the right. Methamphetamine reverses the action of the dopamine transporter (DAT) by activating TAAR1 (not shown). TAAR1 activation also causes some of the dopamine transporters to move into the presynaptic neuron and cease transport (not shown). At VMAT2 (labeled VMAT), methamphetamine causes dopamine efflux (release).

Pharmacodynamics :

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.   Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT).  When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters.  Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux.   TAAR1 also has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels.   TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter.  

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.    In neurons, methamphetamine induces monoamine neurotransmitter efflux through VMAT2, resulting in the outflow of monoamines fromsynaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron.    Other transporters that methamphetamine is known to inhibit are SLC22A3 and SLC22A5.   SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter.  

Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ₁ than σ₂, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B).   Methamphetamine is known to inhibit the CYP2D6 liver enzyme as well.   Dextromethamphetamine is a stronger psychostimulant(approximately ten times on striatal dopamine), but levomethamphetamine 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,   but shorter psychodynamic effect for levomethamphetamine.

Pharmacokinetics ::

Following oral administration, methamphetamine is well-absorbed into the bloodstream, 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 IV 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.

CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize methamphetamine or its metabolites in humans.  The primary metabolites are amphetamine and 4-hydroxymethamphetamine; other minor metabolites include:4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of amphetamine.   Among these metabolites, the active sympathomimetics are amphetamine, 4‑hydroxyamphetamine,  4‑hydroxynorephedrine,  4-hydroxymethamphetamine,  and norephedrine.  

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.   The known metabolic pathways include:

Metabolic pathways of methamphetamine

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.   Human microbiota, particularly Lactobacillus, Enterococcus, and Clostridium species, contribute to the metabolism of methamphetamine via an enzyme which N-demethylates methamphetamine and 4-hydroxymethamphetamine into amphetamine and 4-hydroxyamphetamine respectively.

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 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 levomethamphetamine, 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.

Chemistry :

Pure shards of methamphetamine hydrochloride, also known as crystal meth

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.   It issoluble 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 °C (338 to 347 °F) 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 :

Bleach exposure time and concentration are correlated with destruction of methamphetamine.  Methamphetamine in soils has shown to be a persistent pollutant.  Methamphetamine is largely degraded within 30 days in a study of bioreactors under exposure to light inwastewater.

Synthesis :

Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart  or reductive amination methods.  In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of N-methylformamide to produce the formyl amide of methamphetamine plus carbon dioxide and methylamine as side products.   In this reaction, an iminium cation is formed as an intermediate which is reduced by the second equivalent of N-methylformamide.  The intermediate formyl amide is then hydrolyzed under acidic aqueous conditions to yield methamphetamine as the final product.  Alternatively, phenylacetone can be reacted with methylamine under reducing conditions to yield methamphetamine.

Methamphetamine synthesis

Method of methamphetamine synthesis of methamphetamine via reductive amination

Methods of methamphetamine synthesis via the Leuckart reaction

History, society, and culture :

Pervitin, a methamphetamine brand used by German soldiers during World War II, was dispensed in these tablet containers.

Amphetamine, discovered before methamphetamine, was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine. Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanesechemist Nagai Nagayoshi. Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.

During World War II, methamphetamine was sold in tablet form under the brand name Pervitin, produced by the Berlin-based Temmlerpharmaceutical 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. Pervitin became colloquially known among the German troops as "Stuka-Tablets" (Stuka-Tabletten) and "Herman-Göring-Pills" (Hermann-Göring-Pillen).

Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of obesity, was one of the first brands of pharmaceutical methamphetamine products.  Due to the psychological and stimulant effects of methamphetamine, Obetrol became a popular diet pill in America in the 1950s and 1960s. Eventually, as the addictive properties of the drug became known, governments began to strictly regulate the production and distribution of methamphetamine. For example, during the early 1970s in the United States, methamphetamine became aschedule II controlled substance under the Controlled Substances Act. Currently, methamphetamine is sold under the trade name Desoxyn, trademarked by the Danish pharmaceutical company Lundbeck.  As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company 

Legal Status :

The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Methamphetamine has been placed in schedule II of the United Nations Convention on Psychotropic Substances treaty.

Australia :

Methamphetamine is a Schedule 8 prohibited substance in Australia under the Poisons Standard (July 2016).^[142] A schedule 8 substance is a controlled Drug – Substances which should be available for use but require restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence.

In Western Australia under the Misuse of Drugs Act 1981 4.0g of Methamphetamine is the amount of prohibited drugs determining a court of trial, 2.0g is the amount of Methamphetamine required for the presumption of intention to sell or supply and 28.0g is the amount of Methamphetamine required for purposes of drug trafficking 

Research

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.

References :

1.   Amphetamine legislation 1971: Hearings, Ninety-second Congress, first session, pursuant to S. Res. 32, section 12, investigation of juvenile delinquency in the United States (PDF). U.S.  January 2016. 

2.    "The Neuroprotective Potential of low-dose Methamphetamine in preclinical models of stroke and traumatic brain injury". , 2013

3.    "Toxicity". Methamphetamine. PubChem Compound. National Center for Biotechnology Information. Retrieved 31 December 2013. USA

4.     "Adderall XR Prescribing Information" (PDF). United States Food and Drug Administration. December 2013. pp. 12–13. Retrieved 30 December 2013.

5.     "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. 

6.   Manual of forensic emergency medicine : a guide for clinicians. 

7.  "The clinical toxicology of metamfetamine". Clinical Toxicology (Philadelphia.). 

8.   "Properties: Predicted ". Methmphetamine. Chemspider. January2013.

9.   "Chemical and Physical Properties". Methamphetamine. PubChem Compound. National Center for Biotechnology Information. December 2013.

10.  "Methamphetamine". Drug profiles. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).  September 2011.