N,α-Dimethylphenethylamine
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Methamphetamine (contracted from ) is a potent
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
(CNS)
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
that is mainly used as a
recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...
or performance-enhancing drug and less commonly as a
second-line treatment A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications an ...
for
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD). It has also been researched as a potential treatment for
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumati ...
. Methamphetamine was discovered in 1893 and exists as two
enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
s: levo-methamphetamine and dextro-methamphetamine. ''Methamphetamine'' properly refers to a specific chemical substance, the
racemic In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...
free base In chemistry, a free base (freebase, free-base) is a term for the neutral form of an amine or other Lewis base. The term is used in the pharmaceutical industry in contrast to salt-based formulations like hydrochlorides. The amine is often an ...
, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, but the
hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...
salt, commonly called crystal meth, is widely used. Methamphetamine is rarely prescribed over concerns involving its potential for recreational use as an
aphrodisiac An aphrodisiac is a substance that increases libido, sexual desire, sexual attraction, sexual pleasure, or sexual behavior. These substances range from a variety of plants, spices, and foods to synthetic chemicals. Natural aphrodisiacs, such as ...
and
euphoriant Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy such as
Adderall Adderall and Mydayis are trade names for a combination drug containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and l ...
and
Vyvanse Lisdexamfetamine, sold under the brand names Vyvanse and Elvanse among others, is a stimulant medication that is used as a treatment for attention deficit hyperactivity disorder (ADHD) in children and adults and for moderate-to-severe binge e ...
. While pharmaceutical formulations of methamphetamine in the United States are labeled as methamphetamine hydrochloride, they contain dextromethamphetamine as the
active ingredient An active ingredient is any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. ...
. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine. Both racemic 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 Oceania, and in the United States, where racemic methamphetamine and dextromethamphetamine are classified as Schedule II controlled substances.
Levomethamphetamine Levomethamphetamine (International Nonproprietary Name, INN: levmetamfetamine) is an optical isomer of methamphetamine primarily used as a Topical decongestant, topical nasal decongestant. Levomethamphetamine is used to treat nasal congestion f ...
is available as an
over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...
(OTC) drug for use as an inhaled
nasal decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...
in the United States. Internationally, the production, distribution, sale, and possession of methamphetamine is restricted or banned in many countries, owing to its placement in schedule II of the
United Nations Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics signed in Vienna, Austria on 21 February 1 ...
treaty. While dextromethamphetamine is a more potent drug, racemic methamphetamine is illicitly produced more often, owing to the relative ease of
synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...
and regulatory limits of
chemical precursor In chemistry, a precursor is a compound that participates in a chemical reaction that produces another compound. In biochemistry, the term "precursor" often refers more specifically to a chemical compound preceding another in a metabolic pathway, ...
availability. 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 In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
, breakdown of skeletal muscle,
seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
, and bleeding in the brain. Chronic high-dose use can precipitate unpredictable and rapid
mood swing A mood swing is an extreme or sudden change of mood. Such changes can play a positive or a disruptive part in promoting problem solving and in producing flexible forward planning. When mood swings are severe, they may be categorized as part ...
s,
stimulant psychosis Stimulant psychosis is a mental disorder characterized by psychotic symptoms such as hallucinations, paranoid ideation, delusions, disorganized thinking, and grossly disorganized behaviour. It typically occurs following an overdose or several ...
(e.g.,
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...
,
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s,
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
, and
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s), and
violent behavior Violence is characterized as the use of physical force by humans to cause harm to other living beings, or property, such as pain, injury, disablement, death, damage and destruction. The World Health Organization (WHO) defines violence as ...
. 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 while binging the drug. Methamphetamine is known to possess a high
addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...
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). Discontinuing methamphetamine after heavy use may lead to a
post-acute-withdrawal syndrome Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, opioids, benzodiazepines, barbiturates, and other substances. Infants born to mothers who used substances of depen ...
, which can persist for months beyond the typical withdrawal period. At high doses, methamphetamine is
neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
to human
midbrain The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum. It is functionally associated with vision, hearing, mo ...
dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...
neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s and, to a lesser extent,
serotonergic A serotonergic substance, medication, or receptor protein is one that affects neurotransmission pathways that involve serotonin, as follows: * Serotonergic drugs ** Serotonin receptor agonists ** Serotonin receptor antagonists ** Serotonin reupta ...
neurons. Methamphetamine neurotoxicity causes adverse changes in brain structure and function, such as reductions in
grey matter Grey matter, or gray matter in American English, is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil ( dendrites and unmyelinated axons), glial cells ( astrocytes and oligodendrocytes), synapses, ...
volume in several brain regions, as well as adverse changes in markers of metabolic integrity. Methamphetamine belongs to the
substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...
and
substituted amphetamine Substituted amphetamines, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...
chemical classes. It is related to the other
dimethylphenethylamine Dimethylphenethylamine may refer to: * α,α-Dimethylphenethylamine (phentermine) * ''N'',α-Dimethylphenethylamine (methamphetamine) * ''N'',β-Dimethylphenethylamine (phenpromethamine) * 2,α-Dimethylphenethylamine (ortetamine) * 3,α-Dimeth ...
s as a
positional isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...
of these compounds, which share the common
chemical formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...
.


Uses


Medical

In the United States, methamphetamine hydrochloride, sold under the brand name Desoxyn, is
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
-approved for the treatment of
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD); however, the FDA notes that the limited therapeutic usefulness of methamphetamine should be weighed against the risks associated with its use. To avoid toxicity and risk of side effects, FDA guidelines recommend an initial dose of methamphetamine at doses 5–10 mg/day for ADHD in adults and children over six years of age, and may be increased at weekly intervals of 5 mg, up to 25 mg/day, until optimum clinical response is found; the usual effective dose is around 20–25 mg/day. Methamphetamine is sometimes prescribed
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...
for
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
,
narcolepsy Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...
, and
idiopathic hypersomnia Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic hypersomnia was first described by Bedrich Roth in 1976, and it can be divided into t ...
. In the United States, methamphetamine's levorotary form is available in some
over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...
(OTC)
nasal decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...
products. Although the pharmaceutical name "methamphetamine hydrochloride" may suggest a
racemic mixture In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...
, Desoxyn contains
enantiopure In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities which are mirror images of each other and non-superpos ...
dextromethamphetamine, which is a more potent
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
than both levomethamphetamine and racemic methamphetamine. This naming convention deviates from the standard practice observed with other stimulants, such as
Adderall Adderall and Mydayis are trade names for a combination drug containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and l ...
and
dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
, where the dextrorotary
enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
is explicitly identified as an
active ingredient An active ingredient is any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. ...
in both
generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...
and brand-name pharmaceuticals. As methamphetamine is associated with a high potential for misuse, the drug is regulated under the
Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
and is listed under Schedule II in the United States. Methamphetamine hydrochloride dispensed in the United States is required to include a
boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...
regarding its potential for
recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...
misuse and
addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...
liability. Desoxyn and Desoxyn Gradumet are both pharmaceutical forms of the drug. The latter is no longer produced and is an
extended-release Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a spe ...
form of the drug, flattening the curve of the effect of the drug while extending it.


Recreational

Methamphetamine is often used recreationally for its effects as a potent
euphoriant Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
and stimulant as well as
aphrodisiac An aphrodisiac is a substance that increases libido, sexual desire, sexual attraction, sexual pleasure, or sexual behavior. These substances range from a variety of plants, spices, and foods to synthetic chemicals. Natural aphrodisiacs, such as ...
qualities. According to a
National Geographic ''National Geographic'' (formerly ''The National Geographic Magazine'', sometimes branded as ''Nat Geo'') is an American monthly magazine published by National Geographic Partners. The magazine was founded in 1888 as a scholarly journal, nine ...
TV documentary on methamphetamine, an entire subculture known as
party and play Party and play (PnP), also known as chemsex or wired play, refers to the practice of consuming drugs to enhance sexual activity. This sexual subculture involves recreational drug users engaging in high-risk sexual behaviors under the influence ...
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 Online dating, also known as internet dating, virtual dating, or mobile app dating, is a method used by people with a goal of searching for and interacting with potential romantic or sexual partners, via the internet. An online dating service ...
sites and have sex. Because of its strong stimulant and aphrodisiac effects and inhibitory effect on
ejaculation Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the penis through the urethra. It is the final stage and natural objective of male sexual stimulation, and an essential component of natural conception. ...
, 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 Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
(excessive daytime sleepiness). The party and play subculture is prevalent in major US cities such as San Francisco and New York City.


Contraindications

Methamphetamine is
contraindicated In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...
in individuals with a history of
substance use disorder Substance use disorder (SUD) is the persistent use of drugs despite substantial harm and adverse consequences to self and others. Related terms include ''substance use problems'' and ''problematic drug or alcohol use''. Along with substance-ind ...
,
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
, or severe agitation or anxiety, or in individuals currently experiencing
arteriosclerosis Arteriosclerosis, literally meaning "hardening of the arteries", is an umbrella term for a vascular disorder characterized by abnormal thickening, hardening, and loss of elasticity of the walls of arteries; this process gradually restricts th ...
,
glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
,
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
, or severe
hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
. The FDA states that individuals who have experienced
hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...
reactions to other stimulants in the past or are currently taking
monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...
s should not take methamphetamine. The FDA also advises individuals with
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
, depression, elevated
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
, liver or kidney problems,
mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...
,
psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
,
Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...
,
seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
,
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
problems,
tic A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture. Tics can be invisible to the obs ...
s, or
Tourette syndrome Tourette syndrome (TS), or simply Tourette's, is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Common tics are blinkin ...
to monitor their symptoms while taking methamphetamine. Owing to the potential for stunted growth, the FDA advises monitoring the height and weight of growing children and adolescents during treatment.


Adverse effects


Physical


Cardiovascular

Methamphetamine is a sympathomimetic drug that causes
vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...
and
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
. Methamphetamine also promotes abnormal extra heart beats and irregular heart rhythms some of which may be life-threatening.


Other physical effects

The effects can also include
loss of appetite Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...
, hyperactivity,
dilated pupils Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. It may also b ...
,
flushed skin Flushing is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished from blushing, since blushing is psychosomatic, milder, generally restricted to the face ...
,
excessive sweating Hyperhidrosis is a medical condition in which a person exhibits excessive sweating, more than is required for the regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deteriorate the quality of life of the ...
, increased movement, dry mouth and
teeth grinding Bruxism is excessive teeth grinding or jaw clenching. It is an oral parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of bruxism (both sleep and a ...
(potentially leading to condition informally known as ''
meth mouth Meth mouth is a colloquial term used to describe severe tooth decay and tooth loss, as well as tooth fracture, acid erosion, and other oral problems that are often correlated with extended use of the drug methamphetamine. The condition is though ...
''), headache, rapid breathing, high body temperature, diarrhea, constipation,
blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...
,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...
, twitching,
numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to Sensory receptor, sensory stimuli. In everyday speech this is generally r ...
,
tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
s, dry skin,
acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
, and pale appearance. Long-term meth users may have sores on their skin; these may be caused by scratching due to
itchiness An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
or the belief that insects are crawling under their skin, and the damage is compounded by poor diet and hygiene. Numerous deaths related to methamphetamine overdoses have been reported. Additionally, " stmortem examinations of human tissues have linked use of the drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis", which may be caused "by a considerable rise in the formation of
ceramides Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component ...
, pro-inflammatory molecules that can foster cell aging and death."


Dental and oral health ("meth mouth")

Methamphetamine users, particularly heavy users, may lose their teeth abnormally quickly, regardless of the route of administration, from a condition informally known as
meth mouth Meth mouth is a colloquial term used to describe severe tooth decay and tooth loss, as well as tooth fracture, acid erosion, and other oral problems that are often correlated with extended use of the drug methamphetamine. The condition is though ...
. 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 The American Dental Association (ADA) is an American professional dental association. Established in 1859 and with over 159,000 current members, ADA is the world's largest and oldest national dental association. The organization lobbies on behal ...
, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in
xerostomia Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...
(dry mouth), extended periods of poor
oral hygiene Oral hygiene is the practice of keeping one's oral cavity clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and adopting good hygiene habits. It is important that oral hygiene be carr ...
, frequent consumption of high-calorie, carbonated beverages and
bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...
(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 The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
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 Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...
in men. Methamphetamine may also cause sores and abrasions in the mouth via
bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...
, 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 Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
,
dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and uneas ...
, changes in
libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...
,
alertness Alertness is a state of active attention characterized by high sensory awareness. Someone who is alert is vigilant and promptly meets danger or emergency, or is quick to perceive and act. Alertness is a psychological and physiological state. Lac ...
, apprehension and
concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...
, decreased sense of fatigue,
insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
or
wakefulness Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, ...
,
self-confidence Confidence is the feeling of belief or trust that a person or thing is reliable. * * * Self-confidence is trust in oneself. Self-confidence involves a positive belief that one can generally accomplish what one wishes to do in the future. Sel ...
, sociability, irritability, restlessness,
grandiosity In psychology, grandiosity is a sense of superiority, uniqueness, or invulnerability that is unrealistic and not based on personal capability. It may be expressed by exaggerated beliefs regarding one's abilities, the belief that few other peopl ...
and repetitive and obsessive behaviors. Peculiar to methamphetamine and related stimulants is "
punding Punding is compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting objects. It can also apply to digital objects, such as computer files and data. The term was originally coined to desc ...
", persistent non-goal-directed repetitive activity. Methamphetamine use also has a high association with
anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, depression, amphetamine psychosis,
suicide Suicide is the act of intentionally causing one's own death. Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...
, and violent behaviors.


Neurotoxicity

Methamphetamine is directly
neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
to dopaminergic neurons in both lab animals and humans.
Excitotoxicity In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...
,
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
, metabolic compromise, UPS dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression and other processes contributed to this neurotoxicity. In line with its dopaminergic neurotoxicity, methamphetamine use is associated with a higher risk of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
. In addition to its dopaminergic neurotoxicity, a review of evidence in humans indicated that high-dose methamphetamine use can also be neurotoxic to
serotonergic A serotonergic substance, medication, or receptor protein is one that affects neurotransmission pathways that involve serotonin, as follows: * Serotonergic drugs ** Serotonin receptor agonists ** Serotonin receptor antagonists ** Serotonin reupta ...
neurons. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. Withdrawal of methamphetamine in dependent persons may lead to post-acute withdrawal which persists months beyond the typical withdrawal period.
Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
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 A hyperintensity or T2 hyperintensity is an area of high intensity on types of magnetic resonance imaging (MRI) scans of the brain of a human or of another mammal that reflect lesions produced largely by demyelination and axonal loss. These smal ...
and
hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Although hypertro ...
of
white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
, marked shrinkage of hippocampi, and reduced
gray matter Grey matter, or gray matter in American English, is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and ...
in the
cingulate cortex The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cin ...
, limbic cortex, and
paralimbic cortex The paralimbic cortex is an area of three-layered cortex that includes the following regions: the piriform cortex, entorhinal cortex, the parahippocampal cortex on the medial surface of the temporal lobe, and the cingulate cortex just above the c ...
in recreational methamphetamine users. Moreover, evidence suggests that adverse changes in the level of
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
s of metabolic integrity and synthesis occur in recreational users, such as a reduction in ''N''-acetylaspartate and
creatine Creatine ( or ) is an organic compound with the nominal formula . It exists in various tautomers in solutions (among which are neutral form and various zwitterionic forms). Creatine is found in vertebrates, where it facilitates recycling of ...
levels and elevated levels of
choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...
and myoinositol. Methamphetamine has been shown to activate
TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...
in human
astrocytes Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...
and generate
cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...
as a result. Activation of astrocyte-localized TAAR1 appears to function as a mechanism by which methamphetamine attenuates membrane-bound
EAAT2 Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the ''SLC1A2'' gene. Alternatively spliced transcript variants of thi ...
(SLC1A2) levels and function in these cells.
Methamphetamine binds to and activates both
sigma receptor Sigma receptors (σ-receptors) are protein receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 rec ...
subtypes, σ1 and σ2, with micromolar affinity. Sigma receptor activation may promote methamphetamine-induced neurotoxicity by facilitating
hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
, increasing dopamine synthesis and release, influencing microglial activation, and modulating
apoptotic Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...
signaling cascades and the formation of reactive oxygen species.


Addiction

Current models of addiction from chronic drug use involve alterations in
gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
in certain parts of the brain, particularly the
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
. The most important
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s that produce these alterations are
ΔFosB Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: FOS, F ...
,
cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...
response element binding protein (
CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...
), and nuclear factor kappa B ( NFκB). ΔFosB plays a crucial role in the development of drug addictions, since its overexpression in
D1-type The D1-like receptors are a subfamily of dopamine receptors that bind the endogenous neurotransmitter dopamine. The D1-like subfamily consists of two G protein–coupled receptors that are coupled to Gs and mediate excitatory neurotransmission ...
medium spiny neuron Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of inhibitory GABAergic neuron representing approximately 90% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons h ...
s in the nucleus accumbens is
necessary and sufficient In logic and mathematics, necessity and sufficiency are terms used to describe a material conditional, conditional or implicational relationship between two Statement (logic), statements. For example, in the Conditional sentence, conditional stat ...
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. It has been implicated in addictions to
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
,
cannabinoid Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...
s,
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
,
methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...
,
nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
,
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s,
phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hall ...
,
propofol Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Nu ...
, and substituted amphetamines, among others. ΔJunD, a transcription factor, and EHMT2, G9a, a histone methyltransferase enzyme, both directly oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its expression). Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug use (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs inducible gene, induce expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sex addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sex addictions (i.e., drug-induced compulsive sexual behaviors) are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic#Supplements and drugs, dopaminergic drugs, such as amphetamine or methamphetamine.


Epigenetic factors

Methamphetamine addiction is persistent for many individuals, with 61% of individuals treated for addiction relapsing within one year. About half of those with methamphetamine addiction continue with use over a ten-year period, while the other half reduce use starting at about one to four years after initial use. The frequent persistence of addiction suggests that long-lasting changes in Regulation of gene expression#Regulation of transcription in addiction, gene expression may occur in particular regions of the brain, and may contribute importantly to the addiction phenotype. In 2014, a crucial role was found for epigenetics, epigenetic mechanisms in driving lasting changes in gene expression in the brain. A review in 2015 summarized a number of studies involving chronic methamphetamine use in rodents. Epigenetic alterations were observed in the brain Mesolimbic pathway, reward pathways, including areas like ventral tegmental area,
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
, and dorsal striatum, the hippocampus, and the prefrontal cortex. Chronic methamphetamine use caused gene-specific histone acetylation and deacetylation, histone acetylations, deacetylations and Histone methylation, methylations. Gene-specific DNA methylations in particular regions of the brain were also observed. The various epigenetic alterations caused downregulation and upregulation, downregulations or upregulations of specific genes important in addiction. For instance, chronic methamphetamine use caused Histone methylation#Function, methylation of the lysine in position 4 of histone 3 located at the Promoter (genetics), promoters of the ''c-fos'' and the ''CCR2, C-C chemokine receptor 2 (ccr2)'' genes, activating those genes in the nucleus accumbens (NAc). c-fos is well known to be important in
addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...
. The ''ccr2'' gene is also important in addiction, since mutational inactivation of this gene impairs addiction. In methamphetamine addicted rats, epigenetic regulation through reduced acetylation of histones, in brain striatal neurons, caused reduced transcription of glutamate receptor#Conditions with demonstrated associations to glutamate receptors, glutamate receptors. Glutamate receptors play an important role in regulating the reinforcing effects of addictive drugs. Administration of methamphetamine to rodents causes DNA damage (naturally occurring), DNA damage in their brain, particularly in the
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
region. During repair of such DNA damages, persistent chromatin alterations may occur such as in the DNA methylation, methylation of DNA or the acetylation or histone methylation, methylation of histones at the sites of repair. These alterations can be epigenetics, epigenetic scars in the chromatin that contribute to the persistent epigenetic changes found in methamphetamine addiction.


Treatment and management

A 2018 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.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these. , there is no effective pharmacotherapy for methamphetamine addiction. A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in randomized controlled trials (RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion, mirtazapine, sertraline), antipsychotics (aripiprazole), anticonvulsants (topiramate, baclofen, gabapentin), naltrexone, varenicline, citicoline, ondansetron, prometa, riluzole, atomoxetine, dextroamphetamine, and modafinil. Opioid agonist therapy, Medication-Assisted Treatment (MAT) combines FDA-approved medications with behavioral therapies to address substance use disorders. This approach aims to reduce cravings and withdrawal symptoms, supporting individuals in their recovery process.


Dependence and withdrawal

Drug tolerance, 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 (mood), Depression from methamphetamine withdrawal lasts longer and is more severe than that of
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
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, Craving (withdrawal), drug craving, Dysphoria, dysphoric mood, Fatigue (medical), fatigue, hyperphagia, increased appetite, increased movement or psychomotor retardation, decreased movement, anhedonia, lack of motivation, insomnia, sleeplessness or hypersomnia, sleepiness, and Lucid dream, vivid or lucid dreams. Methamphetamine that is present in a mother's bloodstream can pass through the placenta to a fetus and be secreted into breast milk. Infants born to methamphetamine-abusing mothers may experience a neonatal withdrawal syndrome, with symptoms involving of abnormal sleep patterns, poor feeding, tremors, and hypertonia. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.


Neonatal

Unlike other drugs, babies with Drugs in pregnancy#Methamphetamine, prenatal exposure to methamphetamine do not show immediate signs of withdrawal. Instead, cognitive and behavioral problems start emerging when the children reach school age. A prospective cohort study of 330 children showed that at the age of 3, children with methamphetamine exposure showed increased emotional reactivity, as well as more signs of anxiety and depression; and at the age of 5, children showed higher rates of externalizing disorders and
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD).


Overdose

Methamphetamine overdose is a diverse term. It frequently refers to the exaggeration of the unusual effects with features such as irritability, agitation, hallucinations and paranoia. The cardiovascular effects are typically not noticed in young healthy people. Hypertension and tachycardia are not apparent unless measured. A moderate overdose of methamphetamine may induce symptoms such as: Cardiac dysrhythmia, abnormal heart rhythm, confusion, dysuria, difficult or painful urination, high or low blood pressure, high body temperature, hyperreflexia, over-active or over-responsive reflexes, myalgia, muscle aches, severe Psychomotor agitation, agitation, rapid breathing,
tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...
, urinary hesitancy, and urinary retention, an inability to pass urine. An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, anuria, substantially reduced or no urine output, cardiogenic shock, bleeding in the brain, circulatory collapse, hyperpyrexia, hyperpy rexia (i.e., dangerously high body temperature), pulmonary hypertension, kidney failure, rhabdomyolysis, rapid muscle breakdown, serotonin syndrome, and a form of stereotypy#Associated terms, stereotypy ("tweaking"). A methamphetamine overdose will likely also result in mild brain damage owing to dopaminergic and Serotonin, serotonergic neurotoxicity. Death from methamphetamine poisoning is typically preceded by convulsions and coma.


Psychosis

Use of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms (e.g.,
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...
,
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s,
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
, and
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s). A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine use-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. Stimulant psychosis#Substituted amphetamines, Amphetamine psychosis may also develop occasionally as a treatment-emergent side effect.


Death from overdose

The CDC reported that the number of deaths in the United States involving psychostimulants with abuse potential to be 23,837 in 2020 and 32,537 in 2021. This category code (ICD–10 of T43.6) includes primarily methamphetamine but also other stimulants such as amphetamine, and methylphenidate. The mechanism of death in these cases is not reported in these statistics and is difficult to know. Unlike fentanyl which causes respiratory depression, methamphetamine is not a respiratory depressant. Some deaths are as a result of intracranial hemorrhage and some deaths are cardiovascular in nature including flash pulmonary edema and ventricular fibrillation.


Emergency treatment

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 blocker, 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.


Interactions

Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6#Ligands, 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
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
s as well. Methamphetamine may counteract the effects of antihypertensives and antipsychotics owing 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. Owing to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine. Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
,
euphoriant Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
, and sympathomimetic effects of
dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
in humans. Similarly, norepinephrine–dopamine reuptake inhibitors (NRIs) like
methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...
and bupropion prevent norepinephrine and dopamine release induced by amphetamines and bupropion has been found to reduce the subjective and sympathomimetic effects of methamphetamine in humans.


Pharmacology


Pharmacodynamics

Methamphetamine has been identified as a potent full agonist of TAAR1, 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 endocytosis, 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 has been shown to reduce the action potential, firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels. TAAR1 activation by methamphetamine in
astrocytes Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...
appears to negatively modulate the membrane expression and function of
EAAT2 Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the ''SLC1A2'' gene. Alternatively spliced transcript variants of thi ...
, a type of glutamate transporter. In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release. This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters. Other Membrane transport protein, 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 receptor Sigma receptors (σ-receptors) are protein receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 rec ...
s with a greater binding affinity, affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Sigma receptor activation by methamphetamine may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger Peripheral nervous system, peripheral effects, a longer half-life, and longer perceived effects among heavy substance users. At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis, but levomethamphetamine has shorter psychodynamic effects.


Pharmacokinetics

The bioavailability of methamphetamine is 67% oral administration, orally, 79% intranasal administration, intranasally, 67 to 90% via inhalational administration, inhalation (smoking), and 100% intravenous administration, intravenously. 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. Because of the high lipophilicity of methamphetamine due to its methyl group, 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. Methamphetamine 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 elimination half-life of methamphetamine varies with a range of 5–30hours, but it is on average 9 to 12hours in most studies. The elimination half-life of methamphetamine does not vary by route of administration, but is subject to substantial interindividual variability. CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, 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 pholedrine, 4-hydroxymethamphetamine; other minor metabolites include: , , , benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of amphetamine. Among these metabolites, the active sympathomimetics are amphetamine, , , , and norephedrine. Methamphetamine is a CYP2D6 inhibitor. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination. The known metabolic pathways include:


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 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

Methamphetamine is a chirality (chemistry), chiral compound with two enantiomers, dextromethamphetamine and levomethamphetamine. At room temperature, the
free base In chemistry, a free base (freebase, free-base) is a term for the neutral form of an amine or other Lewis base. The term is used in the pharmaceutical industry in contrast to salt-based formulations like hydrochlorides. The amine is often an ...
of methamphetamine is a clear and colorless liquid with an odor 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 and, at room temperature, occurs as white crystals or a white Crystallinity, crystalline powder. The hydrochloride salt is also freely soluble in ethanol and water. The crystal structure of either enantiomer is monoclinic with P21 space group; at , it has lattice parameters ''a'' = 7.10 Angstrom, Å, ''b'' = 7.29 Å, ''c'' = 10.81 Å, and ''β'' = 97.29°.


Degradation

A 2011 study into the destruction of methamphetamine using bleach showed that effectiveness is correlated with exposure time and concentration. A year-long study (also from 2011) showed that methamphetamine in soils is a persistent pollutant. In a 2013 study of bioreactors in wastewater, methamphetamine was found to be largely degraded within 30 days under exposure to light.


Synthesis

Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart reaction, Leuckart or reductive amination methods. In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of 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 Redox, reduced by the second equivalent of . 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.


History, society, and culture

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 Japanese chemist Nagai Nagayoshi. Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via redox, reduction of ephedrine using red phosphorus and iodine. From 1938, methamphetamine was marketed on a large scale in Germany as a nonprescription drug under the brand name ''Pervitin'', produced by the Berlin-based Temmler pharmaceutical company. It was used by all branches of the combined Wehrmacht, armed forces of the Third Reich, for its stimulant effects and to induce extended
wakefulness Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, ...
. Pervitin became colloquially known among the German troops as "Stuka-Tablets" (''Stuka-Tabletten'') and "Hermann Göring, Herman-Göring-Pills" (''Hermann-Göring-Pillen''), as a snide allusion to Göring's widely-known addiction to drugs. However, the side effects, particularly the withdrawal symptoms, were so serious that the army sharply cut back its usage in 1940. By 1941, usage was restricted to a doctor's prescription, and the military tightly controlled its distribution. Soldiers would only receive a couple of tablets at a time, and were discouraged from using them in combat. Historian Łukasz Kamieński says, Some soldiers turned violent, committing war crimes against civilians; others attacked their own officers. At the end of the war, it was used as part of a new drug: D-IX. Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
, was one of the first brands of pharmaceutical methamphetamine products. Because of 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 a Controlled Substances Act#Schedule II controlled substances, schedule II controlled substance under the
Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
. As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company Recordati.


Trafficking

The Golden Triangle (Southeast Asia), specifically Shan State, Myanmar, is the world's leading producer of methamphetamine as production has shifted to Yaba (drug), ''ya ba'' and crystalline methamphetamine, including for export to the United States and across East and Southeast Asia and the Pacific. Concerning the accelerating synthetic drug production in the region, the Cantonese Chinese syndicate Sam Gor, also known as , is understood to be the main international crime syndicate responsible for this shift. It is made up of members of five different triads. Sam Gor is primarily involved in drug trafficking, earning at least $8 billion per year. Sam Gor is alleged to control 40% of the Asia-Pacific methamphetamine market, while also trafficking heroin and ketamine. The organization is active in a variety of countries, including Myanmar, Thailand, New Zealand, Australia, Japan, China, and Taiwan. Sam Gor previously produced meth in Southern China and is now believed to manufacture mainly in the Golden Triangle (Southeast Asia), Golden Triangle, specifically Shan State, Myanmar, responsible for much of the massive surge of crystal meth in circa 2019. The group is understood to be headed by Tse Chi Lop, a gangster born in Guangzhou, China who also holds a Canadian passport. Liu Zhaohua was another individual involved in the production and trafficking of methamphetamine until his arrest in 2005. It was estimated over 18 tonnes of methamphetamine were produced under his watch.


Legal status

The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. In some jurisdictions, it is legally available as a prescription medication. Methamphetamine has been placed in schedule II of the United Nations Convention on Psychotropic Substances treaty, indicating that it has limited medical use.


Research

Animal models have shown that low-dose methamphetamine improves cognitive and behavioural functioning following TBI (
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumati ...
). This is in contrast to high, repeated doses which cause neurotoxicity. These models demonstrate that low-dose methamphetamine increases neurogenesis and reduces apoptosis in the dentate gyrus of the hippocampus following TBI. It has also been found that TBI patients testing positive for methamphetamine at the time of emergency department admission have lower rates of mortality. 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. Protection against methamphetamine-induced neurotoxicity has also been observed following administration of ascorbic acid (vitamin C), cobalamin (vitamin B12), and vitamin E.


See also

* 18-Methoxycoronaridine, 18-MC * ''Breaking Bad'', a TV drama series centered on illicit methamphetamine synthesis * Drug checking * Faces of Meth, a drug prevention project * Famprofazone, a non-steroidal anti-inflammatory drug yielding methamphetamine as a major metabolite * Harm reduction * Methamphetamine and Native Americans * Methamphetamine use in Australia, Methamphetamine in Australia * Methamphetamine in Bangladesh * Illegal drug trade in the Philippines#Methamphetamine production, Methamphetamine in the Philippines * Methamphetamine in the United States * Montana Meth Project, a Montana-based organization aiming to reduce meth use among teenagers * Recreational drug use * Rolling meth lab, a transportable laboratory that is used to illegally produce methamphetamine * Ya ba, Southeast Asian tablets containing a mixture of methamphetamine and caffeine


Footnotes


Reference notes


References


Further reading

* * *


External links


Methamphetamine Poison Information Monograph

Drug Trafficking: Aryan Brotherhood Methamphetamine Operation Dismantled
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