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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(CNS)
stimulant that is mainly used as a
recreational drug and less commonly as a
second-line treatment for
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
and
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
.
Methamphetamine was discovered in 1893 and exists as two
enantiomers:
levo-methamphetamine and dextro-methamphetamine. ''Methamphetamine'' properly refers to a specific chemical substance, the
racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts 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 racemates. ...
free base
Free base (freebase, free-base) is the conjugate base ( deprotonated) form of an amine, as opposed to its conjugate acid ( protonated) form. The amine is often an alkaloid, such as nicotine, cocaine, morphine, and ephedrine, or derivatives ther ...
, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms. It is rarely prescribed over concerns involving human
neurotoxicity
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 – specificall ...
and potential for recreational use as an
aphrodisiac
An aphrodisiac is a substance that increases sexual desire, sexual attraction, sexual pleasure, or sexual behavior. Substances range from a variety of plants, spices, foods, and synthetic chemicals. Natural aphrodisiacs like cannabis or cocai ...
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 called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio ...
and
Vyvanse
Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eating ...
. 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
LevomethamphetamineOther names include l-methamphetamine, levodesoxyephedrine, l-desoxyephedrine, levmetamfetamine ( INN and USAN). is the levorotatory (L-enantiomer) form of methamphetamine. Levomethamphetamine is a sympathomimetic vasoconstri ...
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 prescr ...
(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 ...
treaty. While dextromethamphetamine is a more potent drug, racemic methamphetamine is illicitly produced more often, owing to the relative ease of
synthesis and regulatory limits of
chemical precursor 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
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
,
breakdown of skeletal muscle,
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
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 part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be categorized as par ...
s,
stimulant psychosis (e.g.,
paranoia
Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy co ...
,
hallucination
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s,
delirium, and
delusion
A delusion is a false 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 som ...
s) and
violent behavior
Violence is the use of physical force so as to injure, abuse, damage, or destroy. Other definitions are also used, such as the World Health Organization's definition of violence as "the intentional use of physical force or power, threatened o ...
. 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 engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
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). Withdrawal from 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, opiates, benzodiazepines, antidepressants, and other substances. Infants born to mothers who used substances of depen ...
, which can persist for months beyond the typical withdrawal period. 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 – specificall ...
to human
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
dopaminergic neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
s at high doses. Methamphetamine has been shown to have a higher affinity and, as a result, higher toxicity toward
serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
neurons than
amphetamine.
Methamphetamine neurotoxicity causes adverse changes in brain structure and function, such as reductions in
grey matter
Grey matter 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 capillaries. Grey matter is distingu ...
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 compounds of phenethylamine which can be formed by ...
and
substituted amphetamine 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-Dimethyl ...
s as a
positional isomer
In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct bonds between them. The term meta ...
of these compounds, which share the common
chemical formula
In chemistry, 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 symbol ...
.
Uses
Medical
![Desoxyn Package of 100 Pills](https://upload.wikimedia.org/wikipedia/commons/0/06/Desoxyn_Package_of_100_Pills.jpg)
In the United States, methamphetamine hydrochloride, under the trade name ''Desoxyn'', has been approved by the FDA for treating
ADHD and
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
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
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...
and
idiopathic hypersomnia
Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). The condition typically becomes evident in early adulthood and most patients diagnosed with IH will ...
.
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 prescr ...
(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.
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
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 pleasur ...
misuse and
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
liability.
Desoxyn and Desoxyn Gradumet are both pharmaceutical forms of the drug. The latter is no longer produced and is a gradual-release 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 sexual desire, sexual attraction, sexual pleasure, or sexual behavior. Substances range from a variety of plants, spices, foods, and synthetic chemicals. Natural aphrodisiacs like cannabis or cocai ...
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
Online dating, also known as Internet dating, Virtual dating, or Mobile app dating, is a relatively recent method used by people with a goal of searching for and interacting with potential romantic or sexual partners, via the internet. An onlin ...
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 male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential compone ...
, 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 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 reason to use a certain tre ...
in individuals with a history of
substance use disorder,
heart disease, or severe
agitation or anxiety, or in individuals currently experiencing
arteriosclerosis
Arteriosclerosis is the thickening, hardening, and loss of elasticity of the walls of arteries. This process gradually restricts the blood flow to one's organs and tissues and can lead to severe health risks brought on by atherosclerosis, which ...
,
glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
,
hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...
, or severe
hypertension.
The FDA states that individuals who have experienced
hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
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
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
,
depression, elevated
blood pressure, liver or kidney problems,
mania,
psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
,
Raynaud's phenomenon
Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...
,
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
,
thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
problems,
tic
A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...
s, or
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or 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) ...
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
The physical effects of methamphetamine can include
loss of appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
, 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.
Normally, as ...
,
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, despite a close physiological relation between them, from blushing, which is milder, ge ...
,
excessive sweating,
increased movement, dry mouth and
teeth grinding (leading to "
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 symptomatic to extended use of the drug methamphetamine. The condition is though ...
"), headache,
irregular heartbeat
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
(usually as
accelerated heartbeat or
slowed heartbeat),
rapid breathing
Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing.
In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...
,
high blood pressure
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
,
high body temperature, diarrhea, constipation,
blurred vision,
dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a common medical c ...
,
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 stimuli. In everyday speech this is generally referred to as num ...
,
tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
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, black ...
, and
pale appearance.
Long-term meth users may have
sores on their skin;
these may be caused by scratching due to
itchiness
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
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.
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
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 symptomatic to 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 association established in 1859 which has more than 161,000 members. Based in the American Dental Association Building in the Near North Side of Chicago, the ADA is the world's ...
, 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 dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.
This symptom is very common and is often seen as a side ef ...
(dry mouth), extended periods of poor oral hygiene
Oral hygiene is the practice of keeping one's mouth clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and cleaning between the teeth. It is important that oral hygiene be carried out ...
, 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
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...
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, 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.
Fatal
Doses of 200 mg or more of methamphetamine are considered fatal.
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 unea ...
, changes in libido
Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...
, alertness
Alertness is the state of active attention by high sensory awareness such as being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related for psychology . A lack of alertness is a symptom of a ...
, 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'', an ...
, decreased sense of fatigue, insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
or wakefulness
Wakefulness is a daily recurring Human brain, 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 ...
, self-confidence
Confidence is a state of being clear-headed either that a hypothesis or prediction is correct or that a chosen course of action is the best or most effective. Confidence comes from a Latin word 'fidere' which means "to trust"; therefore, having ...
, sociability, irritability, restlessness, grandiosity
In the field of psychology, the term grandiosity refers to an unrealistic sense of superiority, characterized by a sustained view of one's self as better than others, which is expressed by disdainfully criticising them (contempt), overinflating ...
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 household objects. The term was originally coined to describe complex prolonged, purposeless, and stereotyped behaviou ...
", persistent non-goal-directed repetitive activity. Methamphetamine use also has a high association with anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, depression, amphetamine psychosis
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or ...
, suicide
Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and s ...
, and violent behaviors.
Neurotoxic and neuroimmunological
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 – specificall ...
to dopaminergic neurons in both lab animals and humans. Excitotoxicity
In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...
, oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
, metabolic compromise, UPS dysfunction, protein nitration, endoplasmic reticulum stress Beta cells are heavily engaged in the synthesis and secretion of insulin. They are therefore particularly sensitive to endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR). Severe or prolonged episodes of ER st ...
, 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 long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. In addition to its dopaminergic neurotoxicity, a review of evidence in humans indicated that high-dose methamphetamine use can also be neurotoxic to serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
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 form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
studies on human methamphetamine users have also found evidence of neurodegeneration, or adverse neuroplastic
Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of Neural circuit, neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that diffe ...
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.Updated by Linda J ...
of white matter
White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution ...
, marked shrinkage of hippocampi, and reduced gray matter
Grey matter 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 capillaries. Grey matter is distingui ...
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 ci ...
, limbic cortex
The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time.Integrating time from experience in the ...
, and paralimbic cortex
The paralimbic cortex is an area of three-layered Cerebral cortex, cortex that includes the following regions: the piriform cortex, entorhinal cortex, the parahippocampal cortex on the Anatomical terms of location#Left and right (lateral), and med ...
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 (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...
levels and elevated levels of choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but re ...
and myoinositol
Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors an ...
.
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 an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
in human astrocytes
Astrocytes (from Ancient Greek , , "star" + , , "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 endo ...
and generate cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
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 cell surface 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, ...
subtypes, σ1 and σ2, with micromolar affinity. Sigma receptor activation may promote methamphetamine-induced neurotoxicity by facilitating hyperthermia
Hyperthermia, also known simply 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 ...
, increasing dopamine synthesis and release, influencing microglial activation, and modulating apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
signaling cascades and the formation of reactive oxygen species.
Addictive
Current models of addiction from chronic drug use involve alterations in gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
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 hypotha ...
. 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 of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
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:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
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 GABAergic inhibitory cell representing 95% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons have two primary ...
s in the nucleus accumbens is necessary and sufficient
In logic and mathematics, necessity and sufficiency are terms used to describe a conditional or implicational relationship between two statements. For example, in the conditional statement: "If then ", is necessary for , because the truth of ...
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 most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
, cannabinoid
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
s, cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
, methylphenidate
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...
, 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 substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s, phencyclidine
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptio ...
, propofol
Propofol, marketed as Diprivan, among other names, is a short-acting medication that results in a decreased level of consciousness and a lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation f ...
, and substituted amphetamines
Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...
, among others.
ΔJunD
Under the early Caliphates, a ''jund'' ( ar, جند; plural ''ajnad'', اجناد) was a military division, which became applied to Arab military colonies in the Muslim conquests, conquered lands and, most notably, to the provinces into which Bila ...
, a transcription factor, and G9a
Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the ''EHMT2'' gene. G9a catalyzes the mono- and di-methylated states of histone H3 at lysine residue 9 ...
, a histone methyltransferase
Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...
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 vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...
s 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 reward
Behavioral addiction is a form of addiction that involves a compulsion to engage in a rewarding non- substance-related behavior – sometimes called a natural reward – despite any negative consequences to the person's physical, mental, social ...
s, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs 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 addiction
According to proponents of the concept, sexual addiction, also known as sex addiction, is a state characterized by compulsive participation or engagement in sexual activity, particularly sexual intercourse, despite negative consequences. The con ...
s, 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
Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dop ...
which occurs in some patients taking 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 gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
may occur in particular regions of the brain, and may contribute importantly to the addiction phenotype. In 2014, a crucial role was found for epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
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 reward pathways, including areas like ventral tegmental area
The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is 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 hypotha ...
, and dorsal striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...
, the hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, and the prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
. Chronic methamphetamine use caused gene-specific histone acetylations, deacetylations and methylations. Gene-specific DNA methylations in particular regions of the brain were also observed. The various epigenetic alterations caused downregulations or upregulations of specific genes important in addiction. For instance, chronic methamphetamine use caused methylation of the lysine in position 4 of histone 3 located at the promoters of the ''c-fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...
'' and the '' 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 engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
. 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
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
of histones, in brain striatal neurons, caused reduced transcription of glutamate receptors
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous syste ...
. Glutamate receptors play an important role in regulating the reinforcing effects of misused illicit drugs.
Administration of methamphetamine to rodents causes DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
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 hypotha ...
region. During repair of such DNA damages, persistent chromatin alterations may occur such as in the methylation of DNA or the acetylation or methylation of histones at the sites of repair. These alterations can be epigenetic scars in the chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
that contribute to the persistent epigenetic changes found in methamphetamine addiction.
Treatment and management
A 2018 systematic review and network meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy
Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...
with both contingency management
Contingency management (CM) is the application of the three-term contingency (or operant conditioning), which uses stimulus control and consequences to change behavior. CM originally derived from the science of applied behavior analysis (ABA), bu ...
and community reinforcement approach
Community reinforcement approach and family training (CRAFT) is a behavior therapy approach in psychotherapy for treating addiction developed by Robert J. Meyers in the late 1970s. Meyers worked with Nathan Azrin in the early 1970s whilst he was de ...
had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included monotherapy
Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...
with contingency management or community reinforcement approach, cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
, 12-step program
Twelve-step programs are international mutual aid programs supporting recovery from substance addictions, behavioral addictions and compulsions. Developed in the 1930s, the first twelve-step program, Alcoholics Anonymous (AA), aided its members ...
s, non-contingent reward-based therapies, psychodynamic therapy
Psychodynamics, also known as psychodynamic psychology, in its broadest sense, is an approach to psychology that emphasizes systematic study of the psychological forces underlying human behavior, feelings, and emotions and how they might relate t ...
, and other combination therapies involving these.
, there is no effective pharmacotherapy
Pharmacotherapy is therapy using pharmaceutical drugs, as distinguished from therapy using surgery (surgical therapy), radiation (radiation therapy), movement ( physical therapy), or other modes. Among physicians, sometimes the term ''medical the ...
for methamphetamine addiction. A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in 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
Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is o ...
, sertraline
Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differe ...
), antipsychotics (aripiprazole
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
), anticonvulsants (topiramate
Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...
, baclofen
Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...
, gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
), naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
, varenicline
Varenicline (trade name Chantix and Champix) is a medication used for smoking cessation. Varenicline is also used for the treatment of dry eye disease.
The most common side-effects include nausea (feeling sick), insomnia (difficulty sleeping), a ...
, citicoline
Citicoline ( INN), also known as cytidine diphosphate-choline (CDP-Choline) or cytidine 5'-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is na ...
, ondansetron
Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery. It is also effective for treating gastroenteritis. It can be given by ...
, prometa
Gabasync is an ineffective treatment promoted for methamphetamine addiction, although it had also been claimed to be effective for dependence on alcohol or cocaine. It was marketed as PROMETA. The treatment, based loosely on the research of Span ...
, riluzole, atomoxetine
Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to impro ...
, dextroamphetamine, and modafinil
Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...
.
Dependence and withdrawal
Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. In dependent users, withdrawal symptoms are positively correlated with the level of drug tolerance. Depression from methamphetamine withdrawal lasts longer and is more severe than that of cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
withdrawal.
According to the current Cochrane review on drug dependence and withdrawal in recreational users of methamphetamine, "when chronic heavy users abruptly discontinue ethamphetamine
Etilamfetamine (trade names Apetinil and Adiparthrol; also known as ''N''-ethylamphetamine) is a stimulant drug of the phenethylamine and amphetamine chemical classes. It was invented in the early 20th century and was subsequently used as an a ...
use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose". Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, increased appetite
Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
, and vivid or lucid dreams.
Methamphetamine that is present in a mother's bloodstream
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
can pass through the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
to a fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
and be secreted into breast milk
Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...
. Infants born to methamphetamine-abusing mothers may experience a neonatal withdrawal
Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by ''in utero'' exposure to drugs of dependence, most commonly opioids. Common signs an ...
syndrome, with symptoms involving of abnormal sleep patterns, poor feeding, tremors, and hypertonia
Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending ...
. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.
Neonatal
Unlike other drugs, babies with prenatal exposure to methamphetamine do not show immediate signs of withdrawal. Instead, cognitive and behavioral problems start emerging when the children reach school age.[Babies born to meth-affected mothers seem well behaved, but their passive nature masks a serious problem](_blank)
Elicia Kennedy, ABC News Online
ABC News, or ABC News and Current Affairs, is a public news service produced by the Australian Broadcasting Corporation. Broadcasting within Australia and the rest of the world, the service covers both local and world affairs.
The division of ...
, 3 January 2020
A prospective cohort study
A prospective cohort study is a longitudinal cohort study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome. F ...
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 and attention deficit/hyperactivity disorders.
Overdose
A methamphetamine overdose may result in a wide range of symptoms. A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
, 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
Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing.
In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...
, tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
, urinary hesitancy
Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...
, and an inability to pass urine. An extremely large overdose may produce symptoms such as adrenergic storm
An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenaline and noradrenaline (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It ...
, methamphetamine psychosis
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, Thought disorder, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs follow ...
, substantially reduced or no urine output, cardiogenic shock
Cardiogenic shock (CS) is a medical emergency resulting from inadequate blood flow due to the dysfunction of the ventricles of the heart.Textbooks of Internal MedicinHarrison's Principles of Internal Medicine 16th Edition, The McGraw-Hill Compan ...
, bleeding in the brain, circulatory collapse
Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...
, hyperpyrexia
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
(i.e., dangerously high body temperature), pulmonary hypertension, kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, rapid muscle breakdown, serotonin syndrome
Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...
, and a form of stereotypy
A stereotypy (, or ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are ...
("tweaking"). A methamphetamine overdose will likely also result in mild brain damage
Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating t ...
owing to dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...
and serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
neurotoxicity. Death from methamphetamine poisoning is typically preceded by convulsions and coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
.
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 or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy co ...
, hallucination
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s, delirium, and delusion
A delusion is a false 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 som ...
s). A Cochrane Collaboration
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
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
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
medications effectively resolve the symptoms of acute amphetamine psychosis. Amphetamine psychosis
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or ...
may also develop occasionally as a treatment-emergent side effect.
Emergency treatment
Acute methamphetamine intoxication is largely managed by treating the symptoms and treatments may initially include administration of activated charcoal
"Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016).
Background
In an interv ...
and sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
. There is not enough evidence on hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
or peritoneal dialysis
Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...
in cases of methamphetamine intoxication to determine their usefulness. Forced acid diuresis (e.g., with vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
) 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
Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds ( intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds. ...
(i.e., bleeding in the brain) and, if severe, is typically treated with intravenous phentolamine
Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist.
Mechanism
Its primary action is vasodilation due to α1 blockade.
Non-selective α-blockers can cause a much more pronounced ...
or nitroprusside
Sodium nitroprusside (SNP), sold under the brand name Nitropress among others, is a medication used to lower blood pressure. This may be done if the blood pressure is very high and resulting in symptoms, in certain types of heart failure, and ...
. Blood pressure often drops gradually following sufficient sedation with a benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
and providing a calming environment.
Antipsychotics such as haloperidol
Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
are useful in treating agitation and psychosis from methamphetamine overdose. Beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s with lipophilic properties and CNS penetration such as metoprolol
Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...
and labetalol
Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...
may be useful for treating CNS and cardiovascular toxicity. The mixed alpha- and beta-blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
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
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
, so CYP2D6 inhibitors
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
will prolong the elimination half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of methamphetamine. Methamphetamine also interacts with monoamine oxidase inhibitors
Monoamine oxidase inhibitors (MAOIs) are a 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 antidepressants, espec ...
(MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous. Methamphetamine may decrease the effects of sedative
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...
s and depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
s and increase the effects of antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s and other stimulants as well. Methamphetamine may counteract the effects of antihypertensives
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that r ...
and antipsychotic
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
s 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 inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
They are the most potent inhibitors ...
s, which reduce gastric acid
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...
, are known to interact with methamphetamine.
Pharmacology
Pharmacodynamics
Methamphetamine has been identified as a potent full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of trace amine-associated receptor 1
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 an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
(TAAR1), a G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPCR) that regulates brain catecholamine
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a subst ...
systems. Activation of TAAR1 increases cyclic adenosine monophosphate
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
(cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter
The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopam ...
(DAT), norepinephrine transporter
The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene.
NET is a monoamine transporter and is responsible for the sodium- ...
(NET), and serotonin transporter
The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...
(SERT). When methamphetamine binds to TAAR1, it triggers transporter phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
via protein kinase A
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...
(PKA) and protein kinase C
In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
(PKC) signaling, ultimately resulting in the internalization
Internalization ( or internalisation) is the process of making something internal, with more specific meanings in various fields. It is the opposite of externalization.
Psychology and sociology
In psychology, internalization is the outcome of ...
or reverse function of monoamine transporter
Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible for ...
s. Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase
CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, t ...
(CAMK)-dependent signaling pathway, in turn producing dopamine efflux. TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channel
The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of lipid-gated inward-rectifier potassium ion channels which are activated (opened) by the signaling lipid PIP2 and a signal transduction cascade starting with ...
s. TAAR1 activation by methamphetamine in astrocytes
Astrocytes (from Ancient Greek , , "star" + , , "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 endo ...
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
Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the ex ...
.
In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
, which prevents monoamine uptake into the vesicles and promotes their release. This results in the outflow of monoamines from synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulse ...
s into the cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
(intracellular fluid) of the presynaptic neuron
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous sys ...
, and their subsequent release into the synaptic cleft by the phosphorylated transporters. Other transporters that methamphetamine is known to inhibit are SLC22A3
Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the ''SLC22A3'' gene.
Polyspecific organic cation transporter ...
and SLC22A5
SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane alo ...
. SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine
Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...
transporter.
Methamphetamine is also an agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the alpha-2 adrenergic receptor
The alpha-2 (α2) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some ...
s and sigma receptor
Sigma receptors (σ-receptors) are protein cell surface 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, ...
s with a greater affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Par ...
for σ1 than σ2, and inhibits monoamine oxidase A
Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, ...
(MAO-A) and monoamine oxidase B
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the ''MAOB'' gene.
The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. ...
(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
LevomethamphetamineOther names include l-methamphetamine, levodesoxyephedrine, l-desoxyephedrine, levmetamfetamine ( INN and USAN). is the levorotatory (L-enantiomer) form of methamphetamine. Levomethamphetamine is a sympathomimetic vasoconstri ...
has stronger peripheral
A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...
effects, a longer half-life, and longer perceived effects among addicts. At high doses, both enantiomers of methamphetamine can induce similar stereotypy
A stereotypy (, or ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are ...
and methamphetamine psychosis
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, Thought disorder, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs follow ...
, but levomethamphetamine has shorter psychodynamic effects.
Pharmacokinetics
The bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
of methamphetamine is 67% orally, 79% intranasally, 67 to 90% via inhalation
Inhalation (or Inspiration) happens when air or other gases enter the lungs.
Inhalation of air
Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...
(smoking
Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
), and 100% intravenously
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
. 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, it can readily move through the blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
faster than other stimulants, where it is more resistant to degradation by monoamine oxidase
Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...
. 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
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of methamphetamine varies with a range of 5–30hours, however it is on average 9 to 12hours in most studies. The elimination half-life of methamphetamine does not vary by route of administration
A route of administration in pharmacology and toxicology is the way by which a medication, drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance i ...
, but is subject to substantial interindividual variability
Genetic variation is the difference in DNA among individuals or the differences between populations. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources of genetic variation, ...
.
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
, dopamine β-hydroxylase
Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine.
The three substrates of ...
, flavin-containing monooxygenase 3
Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline monooxygenase -oxide-forming3 and trimethylamine monooxygenase, is a flavoprotein enzyme () that in humans is encoded by the ''FMO3'' gene.
This enzyme catalyzes the foll ...
, butyrate-CoA ligase
Butyryl-coenzyme A (or butyryl-CoA) is the coenzyme A-containing derivative of butyric acid. It is acted upon by butyryl-CoA dehydrogenase and an intermediary compound of ABE fermentation.
Butyryl-CoA is a precursor to and converted from crotonyl- ...
, and glycine N-acyltransferase
In enzymology, a glycine N-acyltransferase (GLYAT), also known as acyl-CoA:glycine N-acyltransferase (ACGNAT), () is an enzyme that catalyzes the chemical reaction
: \rightleftharpoons
Thus, the two substrates of this enzyme are acyl-CoA an ...
are the enzymes known to metabolize methamphetamine or its metabolites in humans. The primary metabolites are amphetamine and 4-hydroxymethamphetamine; other minor metabolites include: , , , benzoic acid
Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh ...
, hippuric acid
Hippuric acid ( Gr. ''hippos'', horse, ''ouron'', urine) is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenoli ...
, norephedrine
Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to contro ...
, and phenylacetone
Phenylacetone is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known a ...
, 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
A drug test is a technical analysis of a biological specimen, for example urine, hair, blood, breath, sweat, or oral fluid/saliva—to determine the presence or absence of specified parent drugs or their metabolites. Major applications of drug ...
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
LevomethamphetamineOther names include l-methamphetamine, levodesoxyephedrine, l-desoxyephedrine, levmetamfetamine ( INN and USAN). is the levorotatory (L-enantiomer) form of methamphetamine. Levomethamphetamine is a sympathomimetic vasoconstri ...
, 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 chiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
compound with two enantiomers, dextromethamphetamine and levomethamphetamine. At room temperature, the free base
Free base (freebase, free-base) is the conjugate base ( deprotonated) form of an amine, as opposed to its conjugate acid ( protonated) form. The amine is often an alkaloid, such as nicotine, cocaine, morphine, and ephedrine, or derivatives ther ...
of methamphetamine is a clear and colorless liquid with an odor characteristic of geranium leaves. It is soluble
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubil ...
in diethyl ether
Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...
and ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
as well as miscible
Miscibility () is the property of two substances to mix in all proportions (that is, to fully dissolve in each other at any concentration), forming a homogeneous mixture (a solution). The term is most often applied to liquids but also applies ...
with chloroform
Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...
.
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 crystalline
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macrosc ...
powder. The hydrochloride salt is also freely soluble in ethanol and water. Its crystal structure is monoclinic
In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic s ...
with P21 space group
In mathematics, physics and chemistry, a space group is the symmetry group of an object in space, usually in three dimensions. The elements of a space group (its symmetry operations) are the rigid transformations of an object that leave it unchan ...
; at , it has lattice parameter
A lattice constant or lattice parameter is one of the physical dimensions and angles that determine the geometry of the unit cells in a crystal lattice, and is proportional to the distance between atoms in the crystal. A simple cubic crystal has o ...
s ''a'' = 7.10 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
Wastewater is water generated after the use of freshwater, raw water, drinking water or saline water in a variety of deliberate applications or processes. Another definition of wastewater is "Used water from any combination of domestic, industr ...
, methamphetamine was found to be largely degraded within 30 days under exposure to light.
Synthesis
Racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts 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 racemates. ...
methamphetamine may be prepared starting from phenylacetone
Phenylacetone is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known a ...
by either the Leuckart or reductive amination
Reductive amination (also known as reductive alkylation) is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is considered ...
methods. In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of to produce the formyl amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
of methamphetamine plus carbon dioxide and methylamine
Methylamine is an organic compound with a formula of . This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine.
Methylamine is sold as a solution in methanol, ...
as side products. In this reaction, an iminium
In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology.
Structure
Iminium cations adopt alkene-like geometries. The central C=N unit is nearly coplanar with al ...
cation is formed as an intermediate which is reduced by the second equivalent of . The intermediate formyl amide is then hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
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
Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
in 1893 by Japanese chemist
A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe th ...
Nagai Nagayoshi. Three decades later, in 1919, methamphetamine hydrochloride was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus
Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...
and iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
.
Since 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
Temmler Werke GmbH was founded in Detmold in 1917 by Hermann Temmler. The Temmler Group is a German pharmaceutical company, which focuses on the production, sale and contract production of pharmaceutical products. In 2012 the Temmler Group was tak ...
pharmaceutical company. It was used by all branches of the combined armed forces
A military, also known collectively as armed forces, is a heavily armed, highly organized force primarily intended for warfare. It is typically authorized and maintained by a sovereign state, with its members identifiable by their distinct ...
of the Third Reich
Nazi Germany (lit. "National Socialist State"), ' (lit. "Nazi State") for short; also ' (lit. "National Socialist Germany") (officially known as the German Reich from 1933 until 1943, and the Greater German Reich from 1943 to 1945) was ...
, for its stimulant effects and to induce extended wakefulness
Wakefulness is a daily recurring Human brain, 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 ...
. Pervitin became colloquially known among the German troops as " Stuka-Tablets" (''Stuka-Tabletten'') and " 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
D-IX is a methamphetamine-based experimental Performance-enhancing drugs, performance enhancer developed by Nazi Germany in 1944 for military application. The researcher who rediscovered this project, Wolf Kemper, said that "the aim was to use D-IX ...
.
Obetrol
Obetrol was the brand name of a drug combining several amphetamine salts indicated for the treatment of exogenous obesity. It was originally sold by the American company Obetrol Pharmaceuticals. Obetrol was a popular diet pill in America in the ...
, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment of obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, 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 schedule II controlled substance
The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...
under the Controlled Substances Act. Currently, methamphetamine is sold under the trade name ''Desoxyn'', trademark
A trademark (also written trade mark or trade-mark) is a type of intellectual property consisting of a recognizable sign, design, or expression that identifies products or services from a particular source and distinguishes them from others ...
ed by the Danish pharmaceutical company Lundbeck
H. Lundbeck A/S (commonly known simply as Lundbeck) is a Danish international pharmaceutical company engaged in the research, development, manufacturing, marketing and sale of pharmaceuticals across the world. The company’s products are target ...
. As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company Recordati.
Trafficking
The Golden Triangle (Southeast Asia)
The Golden Triangle is the area where the borders of Thailand, Laos, and Myanmar meet at the confluence of the Ruak and Mekong rivers. The name "Golden Triangle"—coined by the CIA—is commonly used more broadly to refer to an area of approxim ...
, specifically Shan State
Shan State ( my, ရှမ်းပြည်နယ်, ; shn, မိူင်းတႆး, italics=no) also known by the Endonym and exonym, endonyms Shanland, Muang Tai, and Tailong, is a administrative divisions of Myanmar, state of Myanmar. ...
, Myanmar, is the world's leading producer of methamphetamine as production has shifted to Yaba 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 The Company, 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
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
and ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
. 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
Golden Triangle may refer to:
Places
Asia
* Golden Triangle (Southeast Asia), named for its opium production
* Golden Triangle (Yangtze), China, named for its rapid economic development
* Golden Triangle (India), comprising the popular tourist ...
, 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
Tse Chi Lop ( zh, , first=t, t=謝志樂, s=谢志乐, p=Xiè Zhìlè, j=Ze6 Zi3-lok6, born 1963) is the alleged drug lord, kingpin behind Asia-Pacific based international crime syndicate, crime supersyndicate Sam Gor, also referred to as "The C ...
, a gangster born in Guangzhou
Guangzhou (, ; ; or ; ), also known as Canton () and alternatively romanized as Kwongchow or Kwangchow, is the capital and largest city of Guangdong province in southern China. Located on the Pearl River about north-northwest of Hong Kon ...
, China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
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 jurisdiction
Jurisdiction (from Latin 'law' + 'declaration') is the legal term for the legal authority granted to a legal entity to enact justice. In federations like the United States, areas of jurisdiction apply to local, state, and federal levels.
Jur ...
s. Methamphetamine has been placed in schedule II of the United Nations
The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...
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, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...
treaty.
Research
It has been suggested, based on animal research, that calcitriol, the active metabolite of vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
, can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of methamphetamine.
See also
*18-MC
18-Methoxycoronaridine (18-MC, or MM-110) is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemists
Upul K. Bandarage and Martin E. Kuehne fro ...
* ''Breaking Bad
''Breaking Bad'' is an American crime drama television series created and produced by Vince Gilligan. Set and filmed in Albuquerque, New Mexico, the series follows Walter White (Bryan Cranston), an underpaid, overqualified, and dispirited hig ...
'', a TV drama series centered on illicit methamphetamine synthesis
* Drug checking Drug checking or pill testing is a way to reduce the harm from drug consumption by allowing users to find out the content and purity of substances that they intend to consume. This empowers users to make safer choices: to avoid more dangerous substa ...
* Faces of Meth, a drug prevention project
* Harm reduction
Harm reduction, or harm minimization, refers to a range of public health policies designed to lessen the negative social and/or physical consequences associated with various human behaviors, both legal and illegal. Harm reduction is used to de ...
* Methamphetamine in Australia
* Methamphetamine in Bangladesh Methamphetamine in Bangladesh is an illegal substance that is often consumed in the form of Yaba. Yaba is a drug made by combining methamphetamine and caffeine. They are sold as colorful pills. There are three forms of Yaba in Bangladesh, they are ...
* Methamphetamine in the Philippines
* Methamphetamine in the United States
Methamphetamine in the United States is regulated under Schedule II of the Controlled Substances Act. It is approved for pharmacological use in the treatment of attention deficit hyperactivity disorder, narcolepsy, and treatment-resistant obesit ...
* Montana Meth Project
The Montana Meth Project (MMP) is a Montana-based non-profit organization founded by businessman Thomas Siebel which seeks to reduce methamphetamine use, particularly among teenagers. The main venture of the MMP is a saturation-level advertising ...
, a Montana-based organization aiming to reduce meth use among teenagers
* Recreational drug use
Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...
* Rolling meth lab
A rolling meth lab is a transportable laboratory that is used to illegally produce methamphetamine.Staff writerMethamphetamine, meth-lab assessment and clean-up" ''Forensic Applications Consulting Technologies Inc.'' Retrieved on 2009-02-14. Ro ...
, a transportable laboratory that is used to illegally produce methamphetamine
* Ya ba
''Ya ba'' ( th, ยาบ้า, lo, ຢາບ້າ, literally 'crazy medicine'), formerly known as ''yama'' ( th, ยาม้า; literally 'horse drug'), also known as "bikers' coffee" and "kamikaze", are tablets containing a mixture of met ...
, Southeast Asian tablets containing a mixture of methamphetamine and caffeine
Explanatory notes
Image legend
Reference notes
References
Further reading
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External links
Methamphetamine Toxnet entry
Drug Trafficking: Aryan Brotherhood Methamphetamine Operation Dismantled
FBI
The Federal Bureau of Investigation (FBI) is the domestic Intelligence agency, intelligence and Security agency, security service of the United States and its principal Federal law enforcement in the United States, federal law enforcement age ...
Neurologic manifestations of chronic methamphetamine abuse
{{Authority control
1893 introductions
Anorectics
Aphrodisiacs
Attention deficit hyperactivity disorder management
Carbonic anhydrase activators
Cardiac stimulants
Euphoriants
Excitatory amino acid reuptake inhibitors
Japanese inventions
Management of obesity
Norepinephrine-dopamine releasing agents
Phenethylamines
Sigma agonists
Stimulants
Substituted amphetamines
Sympathomimetics
TAAR1 agonists
VMAT inhibitors