This article is about the free base and salts of methamphetamine. "Meth" and "crystal meth" redirect here. For other uses, see Meth (disambiguation).
|Synonyms||N-methylamphetamine, N,α-dimethylphenethylamine, desoxyephedrine|
|Medical: oral (ingestion), intravenous|
Recreational: oral, intravenous, intramuscular, subcutaneous, smoke inhalation, insufflation, rectal, vaginal
|Protein binding||Varies widely|
|Metabolism||CYP2D6 and FMO3|
|Onset of action||Rapid|
|Biological half-life||5–30 hours|
|Duration of action||10–20 hours|
|Chemical and physical data|
|Molar mass||149.24 g·mol−1|
|3D model (JSmol)|
|Melting point||3 °C (37 °F) (predicted)|
|Boiling point||212 °C (414 °F) at 760 mmHg|
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. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine.[note 2]Methamphetamine properly refers to a specific chemical, the racemicfree base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms. 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.[note 3] 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. 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 weight loss. At higher 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.g., paranoia, hallucinations, delirium, and delusions) and violent behavior. Recreationally, methamphetamine'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 possess a high addiction liability (i.e., a high likelihood that long-term or high dose use will lead to compulsive drug use) and high dependence liability (i.e. a high likelihood that withdrawal symptoms will 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 human midbraindopaminergicneurons. It has also been shown to damage serotonin neurons in the CNS. 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 amphetaminechemical classes. It is related to the other dimethylphenethylamines as a positional isomer of these compounds, which share the common chemical formula: C10H15N1.
In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD 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.[note 3]
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.
See also: Party and play and the Recreational routes of methamphetamine administration
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. Participants in this subculture, which consists almost entirely of homosexual 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). The party and play subculture is prevalent in major US cities such as San Francisco and New York City.
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 FDA 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 FDA 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 FDA advises monitoring the height and weight of growing children and adolescents during treatment.
The physical effects of methamphetamine can include loss of appetite; hyperactivity; dilated pupils ( Mydriasis ); 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 or low blood pressure; high body temperature; diarrhea or constipation; blurred vision; dizziness; twitching; muscle cramps, spasms, pain or stiffness; numbness; tremors; dry skin; acne; and pale appearance or flushed skin. Especially characteristic of chronic high-dose use are excoriation disorder, or abnormal scratching and skin picking,[unreliable medical source] and formication, the sensation that insects are crawling on the skin. Muscle cramps such as "charley horse", sometimes severe and prolonged, can occur both in short-term use and more dangerously in long-term use due to electrolyte imbalance from poor diet and dehydration. 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 percent of cases.
Main article: 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 as a deterrence for 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.
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. Peculiar to methamphetamine and related stimulants is "punding", persistent non-goal-directed repetitive activity. Methamphetamine use also has a high association with anxiety, depression, amphetamine psychosis, suicide, and violent behaviors.
Neurotoxicity and neuroimmune response
This section is incomplete. This is because coverage of this review and the effects of meth on neuroglia are missing. Please help to improve it, or discuss the issue on the talk page.(November 2015)
Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons in both lab animals and humans. Moreover, methamphetamine neurotoxicity is associated with an increased risk of Parkinson's disease, an effect which partially arises through excessive cytosolic and synaptic production of reactive 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-induced neurotoxicity to dopamineneurons, 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 matter in the cingulate cortex, limbic cortex, and paralimbic cortex in recreational methamphetamine users. Moreover, evidence suggests that adverse changes in the level of biomarkers 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.
Methamphetamine binds to and activates both sigma receptor subtypes, σ1 and σ2, in the brain. Sigma receptor activation by methamphetamine promotes methamphetamine-induced neurotoxicity by facilitating hyperthermia, increasing dopamine synthesis and release, influencing microglial activation, and modulating apoptotic signaling cascades and the formation of reactive oxygen species.
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, hyperpyrexia (i.e., dangerously high body temperature), pulmonary hypertension, kidney failure, rapid muscle breakdown, serotonin syndrome, and a form of stereotypy ("tweaking").[sources 1] 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.
Main section: Stimulant psychosis § Substituted amphetamines
Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms (e.g., paranoia, hallucinations, delirium, and 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.
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 (i.e., bleeding in the brain) 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.
|Addiction and dependence glossary|
Signaling cascade in the nucleus accumbens that results in psychostimulant addiction
This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamine and glutamateco-release by such psychostimulants,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. Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help of corepressors;c-Fosrepression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for 1–2 months, slowly accumulates following repeated high-dose exposure to stimulants through this process. ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.
Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens. The most important transcription factors[note 4] that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NFκB). ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in D1-typemedium spiny neurons in the nucleus accumbens is necessary and sufficient[note 5] for most of the behavioral and neural adaptations that arise from addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.
Desoxyn tablets – pharmaceutical methamphetamine hydrochloride
Crystal meth – illicit methamphetamine hydrochloride
Red Phosphorous/Iodine Methamphetamine Synthesisby Placebo
Ok, this is an amalgamation of many peoples methods! I beleive this to be the best, simplest, fastest, and cleanest method for producing meth-amphetamine, in the highest yeilds possible for RP/I2/E reaction! Remember, each and every step gives small losses, and this method has the least steps! It is a culmination of efforts by, Worlock, CHEMMAN, and maybe a few tiny touches by me! I re-iterate, I don't want any congratulations except for the write-up itself!
You will need these things, and no substitutions allowed! If you can't get this shit, you aint ready to make the best Go-Go in town! This is a refinement of all methods, and the next step up from Push Pull, But nobody should be dicouraged from attempting this, as you will probably find it easier! PH paper, isn't even necessary!
This post is one method from Go to Whoah! This post has to be followed from GO to Whoah! Otherwise you can run into trouble, as povidone is not removed in this extraction! It will be removed at the end! Each step was chosen to compliment the next! Understand?
- Various jars
- 2L pyrex vessel
- 2L 2 neck round flat bottom flask
- 1 condenser, I reccomend a coil condenser but a liebig will suffice!
- 1 sloping splashhead or better still, a steam distillation sloping splashhead!
- A steam pressure cooker, that has releif valve at top
- Hotplate, electric of course!
- Filter paper, Bucner and vacuum would be nice too!
- 1 glass stopper
- lengths of clear pvc tubing
- Pot with vegetable oil, that can fit your reaction vessel
Reagents (All must be clean and anhydrous!)
- Iodine crystals
- Red Phosphorous
- Pseudo-ephedrine, or ephedrine
Extraction of pfed
Ok, this method will deal with the Hcl salt of pfed, and a streamlined version of "the cure"! All pills are dumped into a large jar and double the volume of methanol poured on top! This is stirred vigourously and let to settle, in the fridge seems to speed it up! After top methanol layer has cleared it is carefully decanted off. This procedure is repeated 3 times. All methanol pulls are put together and reduced on a hotplate. As methanol gets down to last little bit, it is taken off heat Then a portion of acetone, twice your remaing liquid is dropped in. This forces the pfed crystals to crash out. Then remaining liquid is carefully evaped off.
Now you have your crude/dirty pfed Hcl. Next we will be doing successive toluene washes So put your pfed crystals in a pyrex (heat proof glass) Now add toluene to a safe level that can be lightly boiled on hotplate After about 5 mins boiling with stirring. Take off heat and let settle a minute. Now carefully pour off toluene into a filter to catch any remnants of pfed that may follow. Now if you get the toluene that has our contaminents in it and add some water You will see the crap crash from the toluene into the water This is the crap that came thru with the methanol pull!
So as we continue to do multiple toluene washes, We will continue to test the toluene after pouring it off, To see how we are progressing with the cleanup! When we have reached a point where no crap comes out of the toluene, With the addition of water, then we are ready to try acetone! Usually about 3 boils in toluene, but of course it depends how much your using! So, as before we will add a portion of acetone and boil lightly! Now when we pour off the acetone, we will add a tiny amount of water and some NaOH This is our final test, when you do this and no crap falls out of acetone you are ready!
This will be the cleanest pfed you have ever seen, guarenteed! AND, yeilds should be >90% if your careful! 95% is good.
Smallest reaction to be attempted, especially by newbees, is 1oz of pfed! So that even taking into account sloppiness, lack of experience and losses along the way You should get some product!
Ratios of reagents are, 3:3:1 or 1:1:1/3 ie.E:I:RP aka, equal amounts of Iodine and pfed, and a third as much RP! Comprenda!
Ok first prepare yourself an icebath! Yes icecubes and water in a sink or bucket! Now, many will say you should add this first or that first! Well after much reading of different peoples methods, I say.... Chuck the whole shebang in together, while your flask is on ice, Lift and swirl ingredients together, while maintaing on ice! Put your condenser on top and start water running thru, from bottom to top! Now, the idea is to get the reaction going in the most controlled way possible. Now you want to let reagents react in the icebath, if at all, Then move vessel from icebath to room temp, If things look like they're going too fast, put back in ice bath, You want to keep the reaction going but only at a nice slow, controlled pace! This is also necessary to control vapour in the condenser! Thick and or dis-colored smoke is bad! and plumes of smoke will escape from condenser As things progress at a nice slow pace, as things slow too much you can start applying heat! So prepare an oilbath and bring to about 50c, now if there is no more action in your vessel You can move it to the oilbath, and same as before, when things slow down, Adjust heat up, to say 100c then 150c for one hour, to make sure reaction has completed The whole time you should be watching to keep a nice reflux going, and not too much vapour is escaping from condenser!
Now remove from heat and disconnect condenser, Now add ice water to quench reaction, reason for ice water is to calm the reaction down when NaOH is added Now its up to you if you want to filter out RP or leave till the end I would leave it, it will be washed nicely by next process and be easier to filter! Now add lots of NaOH to bring reaction mix to positive 14PH You cannot over-basify as meth won't be destroyed, its a tough MF!
Now you need to set up your glassware for steam distillation! So attach steam distillation sloping splashhead to top hole of flask! Now attach plastic hose to steam inlet and other end, on release valve of pressure cooker that is full of water! Now attach condenser on end of splashhead, and rig up some kind of prop for it to stay up! Now place a jar at the end of condenser to catch our distillate! Now you want to heat both the pressure cooker, and the reaction flask! Now sit back and get ready for one of the most beautiful sites and smells! The meth freebase that is sitting on the top of your aqueous layer in flask will vapourise and be carried across and be condensed in the condenser and trickle down into your jar It will sit atop a bottom layer of water! After the last of the oil has come across, change jars and leave the setup to run for another hour Just to make sure you got it all! Any povidone from the pills will be stuck behind in the reaction vessel It has been noted that some polymer that may have been left from extraction, may follow the steam!
So, now we have a jar of water, with this sweet clear oil sitting on top! Now options are to add Hcl acid slowly with stirring until oil layer disappears and then evap the whole lot to get crystals! Or, as I found, you may have some polymer that has come over with the steam and is now sitting in the water layer, and it looks cloudy! So I don't want to evap all that, it will just concentrate the shit in there (plus its very time consuming evapping water, plus you risk losing some meth as the water evaps) So, I think you should just throw a little toluene into jar, and then seperate! Now your absolutly pure meth freebase is in your toluene! Now you can either gas, for instant clean meth, or Add minimal DH2O and then acidify to PH7, shake, seperate and evap water for crystals! repeat this step if you do it this way, as some more may come in second go!
Now with this process from start to finish, you shouldn't need to re-crystallise As your product should be the cleanest shit anybody has ever seen anyway! But you may want to for the purpose of growing nice big crystals! In which case, add just enough hot methanol to dissolve all your meth and then place in freezer. The secret is, the slower the evap, the bigger the crystals! So a nice slow room temp evap over several days might be fun!
Enjoy, and do not attempt anything above, before you completely understand what you are doing! You must have a sound understanding of the basics first!