Methamphetamine] (pronunciation: /ˌmɛθæmˈfɛtəmiːn/; contracted from N-methyl-alpha-methylphenethylamine) is a neurotoxin and potent psychostimulant of the phenethylamine and amphetamine classes that is used as a recreational drug and, rarely, to treat attention deficit hyperactivity disorder (ADHD) and obesity. Methamphetamine exists as two enantiomers, dextrorotaryand levorotary. Dextromethamphetamine is a stronger central nervous system (CNS) stimulant than levomethamphetamine; however, both are addictive and produce the same toxicity symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name Desoxyn. Recreationally, methamphetamine is used to increase sexual desire, lift the mood, and increase energy, allowing some users to engage in sexual activity continuously for several days straight.
Methamphetamine may be sold illegally, either as pure dextromethamphetamine or in an equal parts mixture of the right and left handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in the United States. Similarly, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In contrast, levomethamphetamine is an over-the-counter drug in the United States.
In low doses, methamphetamine can cause an elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis, rhabdomyolysis and cerebral hemorrhage. Methamphetamine is known to have a high potential for abuse and addiction. Recreational use of methamphetamine may result in psychosis or lead to post-withdrawal syndrome, a withdrawal syndrome that can persist for months beyond the typical withdrawal period. Unlike amphetamine, methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the CNS. Contrary to the long-term use of amphetamine, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.
Uses
Medical
In the United States, methamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the USFDA for treatingADHD and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children;however, the USFDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use. In the United States, methamphetamine's levorotary form is available in some over-the-counter nasal decongestant products, such as Vicks VapoInhaler.
As methamphetamine is associated with a high potential for misuse, the drug is regulated under the Controlled Substances Act and islisted 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. | ” |
Side effects
Physical
The physical effects of methamphetamine can include anorexia, hyperactivity, dilated pupils, flushed skin, excessive sweating, increased movement, dry mouth and bruxism(leading to "meth mouth"), headache, irregular heartbeat (usually as accelerated heartbeat or slowed heartbeat), rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, numbness, tremors, dry skin, acne, and pallor. Methamphetamine that is present in a mother'sbloodstream can pass through the placenta to a fetus and is or be secreted into breast milk. Infants born to methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with neonatal withdrawalsymptoms of agitation, vomiting and tachypnea. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.
Meth mouth
Main article: Meth mouth
Methamphetamine users and addicts may lose their teeth abnormally quickly, regardless of the route of administration, from a condition informally known as meth mouth. The condition is generally most severe in users who inject the drug, rather than those who smoke, ingest or inhale it. According to the American Dental Association, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high-calorie, carbonated beverages and bruxism (teeth grinding and clenching)". Many researchers suggest that meth-induced tooth decay is due to users' lifestyles, as dry mouth is also a side effect of prescription stimulants, which aren't known to cause serious tooth decay. They suggest that that the side effect has been exaggerated and stylized to deter potential users and stereotype current users.
Psychological
The psychological effects of methamphetamine can include euphoria, dysphoria, changes in libido, alertness, apprehension, concentration, decreased sense of fatigue, insomniaor wakefulness, self-confidence, sociability, irritability, restlessness, grandiosity and repetitive and obsessive behaviors. Methamphetamine use also has a high association with anxiety, depression, methamphetamine psychosis, suicide, and violent behaviors.Methamphetamine also has a very high addiction risk.
Dependence, addiction, and withdrawal
See also: ΔFosB
Tolerance is expected to develop with regular methamphetamine use and, when abused, this tolerance develops rapidly.
The evidence on effective treatments for amphetamine and methamphetamine dependence and abuse is limited. In light of this, fluoxetine andimipramine appear to have some limited benefits in treating abuse and addiction, "no treatment has been demonstrated to be effective for the treatment of [methamphetamine] dependence and abuse".
In highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue [methamphetamine] use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose". Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood,fatigue, increased appetite, increased movement or decreased movement,lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse). The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.
Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain. The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB). ΔFosB is the most significant, since its overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction; it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, andsubstituted amphetamines. ΔJunD is the transcription factor which directly opposes ΔFosB. Increases in nucleus accumbens ΔJunD expression can reduce or, with a large increase, even block most of the neural alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since natural rewards, like drugs of abuse, induce ΔFosB, chronic acquisition of these rewards can result in a similar pathological addictive state. Consequently, ΔFosB is the key transcription factor involved in amphetamine addiction, especially amphetamine-induced sex addictions. ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.
Neurotoxicity
Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons. Moreover, methamphetamine abuse is associated with an increased risk of Parkinson's disease due to excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to serotonin neurons. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. As a result of methamphetamine-induced neurotoxicity to dopamine neurons, chronic use may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year.
Sexually transmitted infection
Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners, an association more pronounced in HIV-positive participants.These findings suggest that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors, behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men. Methamphetamine use allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions as well as priapism in men. Methamphetamine may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually transmitted infection.
Besides the sexual transmission of HIV, it may also be transmitted between users who share a common needle. The level of needle sharing among methamphetamine users is similar to that among other drug injection users.
Overdose
A methamphetamine overdose may result in a wide range of symptoms. A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm, confusion, dysuria, high or low blood pressure, hyperthermia, hyperreflexia, myalgia, severe agitation, tachypnea, tremor, urinary hesitancy, and urinary retention. An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, anuria, cardiogenic shock, cerebral hemorrhage, circulatory collapse,hyperpyrexia, pulmonary hypertension, renal failure, rhabdomyolysis, serotonin syndrome, and a form of stereotypy ("tweaking").A methamphetamine overdose will likely also result in mild brain damage due to dopaminergic and serotonergic neurotoxicity. Death from methamphetamine poisoning is typically preceded by convulsions andcoma.
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