Methamphetamine (USAN) /ˌmɛθæmˈfɛtəmiːn/, also known as metamfetamine (INN), meth, ice, clouds, crystal, crystal meth, glass, tik, speed, N-methylamphetamine, methylamphetamine, and desoxyephedrine, is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs.
Methamphetamine occurs in two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has a longer half-life and is CNS-active with weaker (approx. one-tenth) effects on striatal dopamine and shorter psychodynamic effects. At high doses, both enantiomers of methamphetamine can induce stereotypy and psychosis, but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile. Although rarely prescribed, methamphetamine hydrochloride is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder and obesity under the trade name Desoxyn.
Illicitly, methamphetamine may be sold either as pure dextromethamphetamine or in a racemic mixture. Both dextromethamphetamine and racemic methamphetamine are Schedule II controlled substances in the United States, and similarly the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Internationally, methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty.
Contrary to popular misconception, methamphetamine in both powder and crystal form is a hydrochloride salt. The freebase form of methamphetamine (as well as amphetamine) is an oily liquid. The misconception started with the fact that heroin and cocaine are injected or snorted as salts, but they are smoked in freebase form. See also: crack cocaine.
In low dosages, methamphetamine can increase alertness, concentration, and energy in fatigued individuals. In higher doses, it can induce mania with accompanying euphoria, feelings of self-esteem and increased libido. Methamphetamine has a high potential for abuse and addiction, activating the psychological reward system by triggering a cascading release of dopamine in the brain characterized as Amphetamine/Stimulant psychosis.
Chronic abuse may also lead to post-withdrawal syndrome, a result of methamphetamine-induced neurotoxicity to dopaminergic neurons. Post-withdrawal syndrome can persist beyond the withdrawal period for months, and sometimes up to a year. In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose.
In United States, Methamphetamine has been approved by the Food and Drug Administration (FDA) in treating ADHD and exogenous obesity (obesity originating from factors outside of the patient’s control) in both adults and children.
Methamphetamine is sold under the name Desoxyn, trademarked by the Danish pharmaceutical company Lundbeck. As of January 2013, the Desoxyn trademark had been sold to Italian pharmaceutical company Recordati.
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 the following black box warning:
“Methamphetamine has a high potential for abuse and should be tried only in weight reduction programs where alternative therapy has been ineffective. Administration of Methamphetamine for prolonged periods may lead to drug dependence. The drug should be prescribed or dispensed sparingly. Misuse may cause sudden death and serious cardiovascular adverse events.”
Methamphetamine is used as a recreational drug for its euphoric and stimulant properties.
Physical effects can include anorexia, hyperactivity, dilated pupils, flushed skin, excessive sweating, restlessness, dry mouth and bruxism (leading to “meth mouth”), headache, accelerated heartbeat, slowed heartbeat, irregular heartbeat, rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, insomnia, numbness, palpitations, tremors, dry and/or itchy skin, acne, pallor, and – with chronic and/or high doses – convulsions, heart attack, stroke, and death.
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, increased energy, increased self-esteem, self-confidence, sociability, irritability, aggressiveness, psychosomatic disorders, psychomotor agitation, dermatillomania (compulsive skin picking), hair pulling, delusions of grandiosity, hallucinations, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and – with chronic use and/or high doses – amphetamine psychosis.
Withdrawal symptoms of methamphetamine primarily consist of fatigue, depression, and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of methamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, restlessness, excessive sleeping, vivid or lucid dreams, deep REM sleep, and suicidal ideation.
Methamphetamine use has a high association with depression and suicide as well as serious heart disease, amphetamine psychosis, anxiety, and violent behaviors. Methamphetamine also has a very high addiction risk.
Unlike cocaine and amphetamine, methamphetamine is directly neurotoxic to midbrain dopamine neurons. Moreover, methamphetamine use is associated with an increased risk of Parkinson’s disease due to the fact that uncontrolled dopamine effluxion is neurotoxic. Long-term dopamine upregulation occurring as a result of methamphetamine abuse can also cause neurotoxicity, which is believed to be responsible for causing persisting cognitive deficits, such as memory loss, impaired attention, and decreased executive function. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to serotonergic neurons.
As a result of methamphetamine-induced neurotoxicity to dopaminergic neurons, chronic use may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year. A study performed on female Japanese prison inmates suffering from methamphetamine addiction showed that 49% experienced “flashbacks” afterward and 21% experienced a psychosis resembling schizophrenia which persisted for longer than six months post-methamphetamine use; this amphetamine psychosis could be resistant to traditional treatment. Other studies in Japan show that those who experience methamphetamine-induced psychosis are much more likely to experience psychotic symptoms again if they use methamphetamine. In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose.
As with other amphetamines, tolerance to methamphetamine is not completely understood but is known to be sufficiently complex that it cannot be explained by any single mechanism. The extent of tolerance and the rate at which it develops vary widely between individuals, and even within one person. It is highly dependent on dosage, duration of use, and frequency of administration. Tolerance to the awakening effect of amphetamines does not readily develop, making them suitable for the treatment of narcolepsy.
Short-term tolerance can be caused by depleted levels of neurotransmitters within the synaptic vesicles available for release into the synaptic cleft following subsequent reuse (tachyphylaxis). Short-term tolerance typically lasts until neurotransmitter levels are fully replenished; because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. Prolonged overstimulation of dopamine receptors caused by methamphetamine may eventually cause the receptors to downregulate in order to compensate for increased levels of dopamine within the synaptic cleft. To compensate, larger quantities of the drug are needed in order to achieve the same level of effects.
Reverse tolerance or sensitization can also occur. The effect is well established, but the mechanism is not well understood.
Routes of Administration
Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases. These findings suggest the route of administration used affects the potential risk for psychological addiction independently of other risk factors, such as dosage and frequency of use. Intravenous injection is the fastest route of drug administration, causing blood concentrations to rise the most quickly, followed by smoking, suppository (anal or vaginal insertion), insufflation (snorting), and ingestion (swallowing). Ingestion does not produce a rush, an acute transcendent state of euphoria as forerunner to the high experienced with the use of methamphetamine, which is most pronounced with the intravenous route of administration. While the onset of the rush induced by injection can occur in as little as a few seconds, the oral route of administration requires approximately half an hour before the high sets in.
Injection carries relatively greater risks than other methods of administration. The hydrochloride salt of methamphetamine is soluble in water. Intravenous users may use any dose range, from less than 100 milligrams to over one gram, using a hypodermic needle, although it should be noted that typically street methamphetamine is “cut,” or diluted, with a water-soluble cutting material, which constitutes a significant portion of a given street methamphetamine dose. Intravenous users risk developing pulmonary embolism (PE), a blockage of the main artery of the lung or one of its branches, and commonly develop skin rashes (also known as “speed bumps”) or infections at the site of injection. As with the injection of any drug, if a group of users share a common needle without sterilization procedures, blood-borne diseases, such as HIV or hepatitis, can be transmitted.
Smoking amphetamines refers to vaporizing it to inhale the resulting fumes, not burning it to inhale the resulting smoke. It is commonly smoked in glass pipes made from glassblown Pyrex tubes and light bulbs. It can also be smoked off aluminium foil, which is heated underneath by a flame. This method is also known as “chasing the white dragon” (whereas smoking heroin is known as “chasing the dragon”). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension (PH)), or limited to injection users (pulmonary embolism (PE)).
Another popular route of administration to intake methamphetamine is insufflation (snorting). This method allows methamphetamine to be absorbed through the soft tissue of the mucous membrane in the sinus cavity, and then directly into the bloodstream, bypassing first-pass metabolism.
Suppository (anal or vaginal insertion) is a less popular method of administration used in the community with comparatively little research into its effects. Information on its use is largely anecdotal with reports of increased sexual pleasure and the effects of the drug lasting longer, though as methamphetamine is centrally active in the brain, these effects are likely experienced through the higher bioavailability of the drug in the bloodstream (second to injection) and the faster onset of action (than insufflation). Nicknames for the route of administration within some methamphetamine communities include a “butt rocket”, a “booty bump”, “potato thumping”, “turkey basting”, “plugging”, “boofing”, “suitcasing”, “hooping”, “keistering”, “shafting”, “bumming”, and “shelving” (vaginal).