Basics of Heroin and Opioid Abuse

Prescription Opioid Abuse: A First Step to Heroin Use?

Prescription opioid pain medications such as Oxycontin and Vicodin can have effects similar to heroin when taken in doses or in ways other than prescribed, and they are currently among the most commonly abused drugs in the United States. Research now suggests that abuse of these drugs may open the door to heroin abuse.Nearly half of young people who inject heroin surveyed in three recent studies reported abusing prescription opioids before starting to use heroin. Some individuals reported taking up heroin because it is cheaper and easier to obtain than prescription opioids.

Many of these young people also report that crushing prescription opioid pills to snort or inject the powder provided their initiation into these methods of drug administration.

Heroin is an opioid drug that is synthesized from morphine, a naturally occurring substance extracted from the seed pod of the Asian opium poppy plant. Heroin usually appears as a white or brown powder or as a black sticky substance, known as “black tar heroin.”

In 2011, 4.2 million Americans aged 12 or older (or 1.6 percent) had used heroin at least once in their lives. It is estimated that about 23 percent of individuals who use heroin become dependent on it.

How Is Heroin Used?

Heroin can be injected, inhaled by snorting or sniffing, or smoked. All three routes of administration deliver the drug to the brain very rapidly, which contributes to its health risks and to its high risk for addiction, which is a chronic relapsing disease caused by changes in the brain and characterized by uncontrollable drug-seeking no matter the consequences.

How Does Heroin Affect the Brain?

When it enters the brain, heroin is converted back into morphine, which binds to molecules on cells known as opioid receptors. These receptors are located in many areas of the brain (and in the body), especially those involved in the perception of pain and in reward. Opioid receptors are also located in the brain stem, which controls automatic processes critical for life, such as blood pressure, arousal, and respiration.

Heroin overdoses frequently involve a suppression of breathing. This can affect the amount of oxygen that reaches the brain, a condition called hypoxia. Hypoxia can have short- and long-term psychological and neurological effects, including coma and permanent brain damage.

After an intravenous injection of heroin, users report feeling a surge of euphoria (“rush”) accompanied by dry mouth, a warm flushing of the skin, heaviness of the extremities, and clouded mental functioning. Following this initial euphoria, the user goes “on the nod,” an alternately wakeful and drowsy state. Users who do not inject the drug may not experience the initial rush, but other effects are the same.

Researchers are also investigating the long-term effects of opioid addiction on the brain. One result is tolerance, in which more of the drug is needed to achieve the same intensity of effect. Another result is dependence, characterized by the need to continue use of the drug to avoid withdrawal symptoms. Studies have shown some deterioration of the brain’s white matter due to heroin use, which may affect decision-making abilities, the ability to regulate behavior, and responses to stressful situations.

Injection Drug Use and HIV and HCV Infection

People who inject drugs are at high risk of contracting HIV and hepatitis C (HCV). This is because these diseases are transmitted through contact with blood or other bodily fluids, which can occur when sharing needles or other injection drug use equipment. (HCV is the most common blood-borne infection in the Unites States.) HIV (and less often HCV) can also be contracted during unprotected sex, which drug use makes more likely.

Because of the strong link between drug abuse and the spread of infectious disease, drug abuse treatment can be an effective way to prevent the latter. People in drug abuse treatment, which often includes risk reduction counseling, stop or reduce their drug use and related risk behaviors, including risky injection practices and unsafe sex. (See box, “Treating Heroin Addiction.”)

What Are the Other Health Effects of Heroin?

Heroin abuse is associated with a number of serious health conditions, including fatal overdose, spontaneous abortion, and infectious diseases like hepatitis and HIV (see box, “Injection Drug Use and HIV and HCV Infection”). Chronic users may develop collapsed veins, infection of the heart lining and valves, abscesses, constipation and gastrointestinal cramping, and liver or kidney disease. Pulmonary complications, including various types of pneumonia, may result from the poor health of the user as well as from heroin’s effects on breathing.

In addition to the effects of the drug itself, street heroin often contains toxic contaminants or additives that can clog blood vessels leading to the lungs, liver, kidneys, or brain, causing permanent damage to vital organs.

Treating Heroin Addiction

A range of treatments including behavioral therapies and medications are effective at helping patients stop using heroin and return to stable and productive lives.

Medications include buprenorphine and methadone, both of which work by binding to the same cell receptors as heroin but more weakly, helping a person wean off the drug and reduce craving; and naltrexone, which blocks opioid receptors and prevents the drug from having an effect (patients sometimes have trouble complying with naltrexone treatment, but a new long-acting version given by injection in a doctor’s office may increase this treatment’s efficacy). Another drug called naloxone is sometimes used as an emergency treatment to counteract the effects of heroin overdose.

For more information, see NIDA’s handbook, Principles of Drug Addiction Treatment.

Chronic use of heroin leads to physical dependence, a state in which the body has adapted to the presence of the drug. If a dependent user reduces or stops use of the drug abruptly, he or she may experience severe symptoms of withdrawal. These symptoms—which can begin as early as a few hours after the last drug administration—can include restlessness, muscle and bone pain, insomnia, diarrhea and vomiting, cold flashes with goose bumps (“cold turkey”), and kicking movements (“kicking the habit”). Users also experience severe craving for the drug during withdrawal, which can precipitate continued abuse and/or relapse.

Besides the risk of spontaneous abortion, heroin abuse during pregnancy (together with related factors like poor nutrition and inadequate prenatal care) is also associated with low birth weight, an important risk factor for later delays in development. Additionally, if the mother is regularly abusing the drug, the infant may be born physically dependent on heroin and could suffer from neonatal abstinence syndrome (NAS), a drug withdrawal syndrome in infants that requires hospitalization. According to a recent study, treating opioid-addicted pregnant mothers with buprenorphine (a medication for opioid dependence) can reduce NAS symptoms in babies and shorten their hospital stays.

Learn More

For additional information on heroin, please refer to the following sources on NIDA’s Web site:

This publication is available for your use and may be reproduced in its entirety without permission from NIDA. Citation of the source is appreciated, using the following language: Source: National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services.

This page was last updated October 2014.

Source: NIDA, NIH

Methamphetamine DrugFacts Summary

Methamphetamine (also called meth, crystal, chalk, and ice, among other terms) is an extremely addictive stimulant drug that is chemically similar to amphetamine. It takes the form of a white, odorless, bitter-tasting crystalline powder.

How Is Methamphetamine Abused?

Methamphetamine is taken orally, smoked, snorted, or dissolved in water or alcohol and injected. Smoking or injecting the drug delivers it very quickly to the brain, where it produces an immediate, intense euphoria. Because the pleasure also fades quickly, users often take repeated doses, in a “binge and crash” pattern.

How Does Methamphetamine Affect the Brain?

Methamphetamine increases the amount of the neurotransmitter dopamine, leading to high levels of that chemical in the brain. Dopamine is involved in reward, motivation, the experience of pleasure, and motor function. Methamphetamine’s ability to release dopamine rapidly in reward regions of the brain produces the euphoric “rush” or “flash” that many users experience. Repeated methamphetamine use can easily lead to addiction—a chronic, relapsing disease characterized by compulsive drug seeking and use.

Is Meth a Prescription Drug?

Methamphetamine can be prescribed by a doctor to treat attention deficit hyperactivity disorder and other conditions, although it is rarely used medically, and only at doses much lower than those typically abused. It is classified as a Schedule II drug, meaning it has high potential for abuse and is available only through a prescription that cannot be refilled.

People who use methamphetamine long-term may experience anxiety, confusion, insomnia, and mood disturbances and display violent behavior. They may also show symptoms of psychosis, such as paranoia, visual and auditory hallucinations, and delusions (for example, the sensation of insects crawling under the skin).

Chronic methamphetamine use is accompanied by chemical and molecular changes in the brain. Imaging studies have shown changes in the activity of the dopamine system that are associated with reduced motor skills and impaired verbal learning. In studies of chronic methamphetamine users, severe structural and functional changes have been found in areas of the brain associated with emotion and memory, which may account for many of the emotional and cognitive problems observed in these individuals.

Some of these brain changes persist long after methamphetamine use is stopped, although some may reverse after being off the drug for a sustained period (e.g., more than 1 year).

How is Meth Made?

Most of the methamphetamine abused in the United States is manufactured in “superlabs” here or, more often, in Mexico. But the drug is also easily made in small clandestine laboratories, with relatively inexpensive over-the-counter ingredients such as pseudoephedrine, a common ingredient in cold medicines. To curb production of methamphetamine, pharmacies and other retail stores are required by law to keep logs of purchases of products containing pseudoephedrine; individuals may only purchase a limited amount of those products on a single day.

Methamphetamine production also involves a number of other, very hazardous chemicals. Toxicity from these chemicals can remain in the environment around a methamphetamine production lab long after the lab has been shut down, causing a wide range of health problems for people living in the area.

What Are the Other Health Effects of Methamphetamine?

Taking even small amounts of methamphetamine can result in many of the same physical effects as those of other stimulants, such as cocaine or amphetamines. These include increased wakefulness, increased physical activity, decreased appetite, increased respiration, rapid heart rate, irregular heartbeat, increased blood pressure, and increased body temperature.

Long-term methamphetamine use has many negative consequences for physical health, including extreme weight loss, severe dental problems (“meth mouth”), and skin sores caused by scratching.

Methamphetamine use also raises the risk of contracting infectious diseases like HIV and hepatitis B and C. These can be contracted both by sharing contaminated drug injection equipment and through unsafe sex. Regardless of how it is taken, methamphetamine alters judgment and inhibition and can lead people to engage in these and other types of risky behavior.

Methamphetamine use may also worsen the progression of HIV/AIDS and its consequences. Studies indicate that HIV causes more injury to neurons and greater cognitive impairment in individuals who are HIV-positive and use methamphetamine than it does in HIV-positive people who do not use the drug.

NIDA, NIH

Methamphetamine

Letter from the Director

The abuse of methamphetamine—a potent and highly addictive stimulant—remains an extremely serious problem in the United States. According to data from the 2012 National Survey on Drug Use and Health (NSDUH), over 12 million people (4.7 percent of the population) have tried methamphetamine at least once. NSDUH also reports that approximately 1.2 million people used methamphetamine in the year leading up to the survey.

The consequences of methamphetamine abuse are terrible for the individual––psychologically, medically, and socially. Abusing the drug can cause memory loss, aggression, psychotic behavior, damage to the cardiovascular system, malnutrition, and severe dental problems. Methamphetamine abuse has also been shown to contribute to increased transmission of infectious diseases, such as hepatitis and HIV/AIDS.

Beyond its devastating effects on individual health, methamphetamine abuse threatens whole communities, causing new waves of crime, unemployment, child neglect or abuse, and other social ills. A 2009 report from the RAND Corporation noted that methamphetamine abuse cost the Nation approximately $23.4 billion in 2005.

But the good news is that methamphetamine abuse can be prevented and addiction to the drug can be treated. People can and do recover over time if they have ready access to effective treatments that address the multitude of problems resulting from their abuse of methamphetamine.

The primary goals of the National Institute on Drug Abuse (NIDA) are to apply what our scientists learn from drug abuse research to develop new treatment approaches and enhance existing ones, and to bring these effective treatments to the communities that need them.

In this newly updated Research Report, we provide an overview of the latest scientific information on methamphetamine. Our intent is to illustrate for readers the damaging effects of methamphetamine abuse and to inform them about effective prevention and treatment interventions.

Nora D.Volkow, M.D.
Director
National Institute on Drug Abuse

What is methamphetamine?

Methamphetamine is a powerful, highly addictive stimulant that affects the central nervous system. Also known as meth, chalk, ice, and crystal, among many other terms, it takes the form of a white, odorless, bitter-tasting crystalline powder that easily dissolves in water or alcohol.

Methamphetamine was developed early in the 20th century from its parent drug, amphetamine, and was used originally in nasal decongestants and bronchial inhalers. Like amphetamine, methamphetamine causes increased activity and talkativeness, decreased appetite, and a pleasurable sense of well-being or euphoria. However, methamphetamine differs from amphetamine in that, at comparable doses, much greater amounts of the drug get into the brain, making it a more potent stimulant. It also has longer-lasting and more harmful effects on the central nervous system. These characteristics make it a drug with high potential for widespread abuse.

Methamphetamine has been classified by the U.S. Drug Enforcement Administration as a Schedule II stimulant, which makes it legally available only through a nonrefillable prescription. Medically it may be indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and as a short-term component of weight-loss treatments, but these uses are limited and it is rarely prescribed; also, the prescribed doses are far lower than those typically abused.

What is the scope of methamphetamine abuse in the United States?

A photo of a paramedic putting an oxygen mask on a patient.

According to the 2012 National Survey on Drug Use and Health (NSDUH), approximately 1.2 million people (0.4 percent of the population) reported using methamphetamine in the past year, and 440,000 (0.2 percent) reported using it in the past month. This represents a decrease from previous years: In 2006 731,000 (0.3 percent) reported past-month use. In 2012, there were 133,000 new users of methamphetamine age 12 or older—the same as the previous year but continuing a general downward trend across the past decade. The average age of new methamphetamine users in 2012 was 19.7 years old.

The 2012 Monitoring the Future (MTF) survey of adolescent drug use and attitudes reported that about 1 percent of 8th, 10th, and 12th graders had used methamphetamine within the past year. These data indicate that 10th and 12th graders are using methamphetamine less than they did 5 years ago, but that use by 8th graders has not dropped significantly in that time. Overall, however, use of methamphetamine by adolescents has declined significantly since 1999, when this drug was first added to the survey.

According to the Drug Abuse Warning Network (DAWN), which collects information on drug-related episodes from hospital emergency departments (EDs) throughout the Nation, methamphetamine accounted for about 103,000 ED visits in 2011; it was the fourth most mentioned illicit drug in ED visits following cocaine, marijuana, and heroin. While still high, this number represents a decrease from the 132,576 ED visits for methamphetamine abuse measured in 2004.

The Treatment Episode Data Set (TEDS) provides information on admissions to substance abuse treatment facilities that are licensed or certified by State substance abuse agencies. According to TEDS data, nationwide treatment admissions for methamphetamine abuse dropped from 8.1 percent in 2005 to 5.6 percent in 2011. The majority of primary methamphetamine admissions were male (53 percent), and about two-thirds (68 percent) were non-Hispanic Whites.

While national trends are showing declines, methamphetamine abuse continues to exhibit regional variability. The strongest effects are felt in the West and parts of the Midwest, according to the National Institute on Drug Abuse’s (NIDA’s) Community Epidemiology Work Group (CEWG), a network of researchers that provides information about the nature and patterns of drug abuse across the United States. For example, in the first half of 2012, methamphetamine ranked first in drugrelated treatment admissions in Hawaii and San Diego, second in San Francisco, and third in Denver and Phoenix.

How is methamphetamine abused?

Methamphetamine comes in several forms and can be smoked, inhaled (snorted), injected, or orally ingested. The preferred method of abusing the drug varies by geographical region and has changed over time. Smoking methamphetamine is currently the most common way of ingesting it, according to CEWG data.

Smoking or injecting methamphetamine puts the drug very quickly into the bloodstream and brain, causing an immediate, intense “rush” and amplifying the drug’s addiction potential and adverse health consequences. The rush, or “flash,” lasts only a few minutes and is described as extremely pleasurable. Snorting or oral ingestion produces euphoria—a high, but not an intense rush. Snorting produces effects within 3 to 5 minutes, and oral ingestion produces effects within 15 to 20 minutes.

As with many stimulants, methamphetamine is most often abused in a “binge and crash” pattern. Because the pleasurable effects of methamphetamine disappear even before the drug concentration in the blood falls significantly, users try to maintain the high by taking more of the drug. In some cases, abusers indulge in a form of binging known as a “run,” foregoing food and sleep while continuing to take the drug for up to several days.

How is methamphetamine manufactured?

Most of the methamphetamine abused in this country is manufactured in “superlabs” here or, usually, in Mexico. But the drug is also easily made in small clandestine laboratories, with relatively inexpensive over-the-counter ingredients such as pseudoephedrine, a common ingredient in cold medications. To curb production of methamphetamine, Congress passed the Combat Methamphetamine Epidemic Act in 2005, which requires that pharmacies and other retail stores keep logs of purchases of products containing pseudoephedrine and limits the amount of those products an individual can purchase per day. A few States have even made pseudoephedrine available only with a prescription. Mexico has also tightened its restrictions on this and other methamphetamine precursor chemicals. But manufacturers adapt to these restrictions via small- or large-scale “smurfing” operations: obtaining pseudoephedrine from multiple sources, below the legal thresholds, using multiple false identifications. Manufacturers in Mexico are also increasingly using a different production process (called P2P, from the precursor chemical phenyl-2-propanone) that does not require pseudoephedrine.

Methamphetamine production also involves a number of other easily obtained chemicals that are hazardous, such as acetone, anhydrous ammonia (fertilizer), ether, red phosphorus, and lithium. Toxicity from these chemicals can remain in the environment around a methamphetamine production lab long after the lab has been shut down, causing a wide range of damaging effects to health. Because of these dangers, the U.S. Environmental Protection Agency has provided guidance on cleanup and remediation of methamphetamine labs.

How is methamphetamine different from other stimulants, such as cocaine?

The methamphetamine molecule is structurally similar to amphetamine and to the neurotransmitter dopamine, a brain chemical that plays an important role in the regulation of reward, but it is quite different from cocaine. Although these stimulants have similar behavioral and physiological effects, there are some major differences in the basic mechanisms of how they work.

In contrast to cocaine, which is quickly removed from and almost completely metabolized in the body, methamphetamine has a much longer duration of action, and a larger percentage of the drug remains unchanged in the body. Methamphetamine therefore remains in the brain longer, which ultimately leads to prolonged stimulant effects. Although both methamphetamine and cocaine increase levels of dopamine, administration of methamphetamine in animal studies leads to much higher levels of dopamine, because nerve cells respond differently to the two drugs. Cocaine prolongs dopamine actions in the brain by blocking the re-absorption (re-uptake) of the neurotransmitter by signaling nerve cells. At low doses, methamphetamine also blocks the re-uptake of dopamine, but it also increases the release of dopamine, leading to much higher concentrations in the synapse (the gap between neurons), which can be toxic to nerve terminals.

Figure 1. Methamphetamine versus Cocaine
Methamphetamine	Cocaine
Stimulant	Stimulant and local anesthetic
Man-made	Plant-derived
Smoking produces a long-lasting high	Smoking produces a brief high
50% of the drug is removed from the body in 12 hours	50% of the drug is removed from the body in 1 hour
Increases dopamine release and blocks dopamine re-uptake	Blocks dopamine re-uptake
Limited medical use for ADHD, narcolepsy, and weight loss	Limited medical use as a local anesthetic in some surgical procedures

What are the immediate (short-term) effects of methamphetamine abuse?

As a powerful stimulant, methamphetamine, even in small doses, can increase wakefulness and physical activity and decrease appetite. Methamphetamine can also cause a variety of cardiovascular problems, including rapid heart rate, irregular heartbeat, and increased blood pressure. Hyperthermia (elevated body temperature) and convulsions may occur with methamphetamine overdose, and if not treated immediately, can result in death.

Most of the pleasurable effects of methamphetamine are believed to result from the release of very high levels of the neurotransmitter dopamine. Dopamine is involved in motivation, the experience of pleasure, and motor function, and is a common mechanism of action for most drugs of abuse. The elevated release of dopamine produced by methamphetamine is also thought to contribute to the drug's deleterious effects on nerve terminals in the brain.

Short-term effects may include:

Increased attention and decreased fatigue
Increased activity and wakefulness
Decreased appetite
Euphoria and rush
Increased respiration
Rapid/irregular heartbeat
Hyperthermia

What are the long-term effects of methamphetamine abuse?

Long-term methamphetamine abuse has many negative consequences, including addiction. Addiction is a chronic, relapsing disease, characterized by compulsive drug seeking and use and accompanied by functional and molecular changes in the brain.

As is the case with many drugs, tolerance to methamphetamine’s pleasurable effects develops when it is taken repeatedly. Abusers often need to take higher doses of the drug, take it more frequently, or change how they take it in an effort to get the desired effect. Chronic methamphetamine abusers may develop difficulty feeling any pleasure other than that provided by the drug, fueling further abuse. Withdrawal from methamphetamine occurs when a chronic abuser stops taking the drug; symptoms of withdrawal include depression, anxiety, fatigue, and an intense craving for the drug.

In addition to being addicted to methamphetamine, chronic abusers may exhibit symptoms that can include significant anxiety, confusion, insomnia, mood disturbances, and violent behavior. They also may display a number of psychotic features, including paranoia, visual and auditory hallucinations, and delusions (for example, the sensation of insects creeping under the skin). Psychotic symptoms can sometimes last for months or years after a person has quit abusing methamphetamine, and stress has been shown to precipitate spontaneous recurrence of methamphetamine psychosis in formerly psychotic methamphetamine abusers.

These and other problems reflect significant changes in the brain caused by abuse of methamphetamine. Neuroimaging studies have demonstrated alterations in the activity of the dopamine system that are associated with reduced motor speed and impaired verbal learning. Studies in chronic methamphetamine abusers have also revealed severe structural and functional changes in areas of the brain associated with emotion and memory, which may account for many of the emotional and cognitive problems observed in chronic methamphetamine abusers.

PET images showing damage to Dopamine transporters in a meth abuser after 1 months abstinence, significant reduction in activity compared to normal brain, but after 24 months abstinence, transporters have nearly returned to normal

Recovery of Brain Dopamine Transporters in Chronic Methamphetamine (METH) Abusers
Methamphetamine abuse greatly reduces the binding of dopamine to dopamine transporters (highlighted in red and green) in the striatum, a brain area important in memory and movement. With prolonged abstinence, dopamine transporters in this area can be restored.

Methamphetamine abuse also has been shown to have negative effects on non-neural brain cells called microglia. These cells support brain health by defending the brain against infectious agents and removing damaged neurons. Too much activity of the microglial cells, however, can assault healthy neurons. A study using brain imaging found more than double the levels of microglial cells in former methamphetamine abusers compared to people with no history of methamphetamine abuse, which could explain some of the neurotoxic effects of methamphetamine.

Some of the neurobiological effects of chronic methamphetamine abuse appear to be at least partially reversible. In the aforementioned study, abstinence from methamphetamine resulted in less excess microglial activation over time, and abusers who had remained methamphetamine- free for 2 years exhibited microglial activation levels similar to the study’s control subjects. Another neuroimaging study showed neuronal recovery in some brain regions following prolonged abstinence (14 but not 6 months). This recovery was associated with improved performance on motor and verbal memory tests. But function in other brain regions did not recover even after 14 months of abstinence, indicating that some methamphetamineinduced changes are very long lasting. Moreover, methamphetamine use can increase one’s risk of stroke, which can cause irreversible damage to the brain. A recent study even showed higher incidence of Parkinson’s disease among past users of methamphetamine.

In addition to the neurological and behavioral consequences of methamphetamine abuse, long-term users also suffer physical effects, including weight loss, severe tooth decay and tooth loss (“meth mouth”), and skin sores. The dental problems may be caused by a combination of poor nutrition and dental hygiene as well as dry mouth and teeth grinding caused by the drug. Skin sores are the result of picking and scratching the skin to get rid of insects imagined to be crawling under it.

Long-term effects may include:

Addiction
Psychosis, including:
- paranoia
- hallucinations
- repetitive motor activity
Changes in brain structure and function
Deficits in thinking and motor skills
Increased distractibility
Memory loss
Aggressive or violent behavior
Mood disturbances
Severe dental problems
Weight loss

What are the risks of methamphetamine abuse during pregnancy?

Our knowledge of the effects of methamphetamine abuse during pregnancy is limited because studies of this issue have used small samples and have not been able to account for the possibility that mothers used other drugs besides methamphetamine. But the available research points to increased rates of premature delivery, placental abruption (separation of the placental lining from the uterus), and various effects on babies prenatally exposed to methamphetamine, including small size, lethargy, and heart and brain abnormalities. A large ongoing NIDA-funded study is examining developmental outcomes in children born to mothers who abused methamphetamine. Thus far, researchers have found neurobehavioral problems such as decreased arousal and increased stress and subtle but significant attention impairments in these children.

Are people who abuse methamphetamine at risk for contracting HIV/AIDS and hepatitis B and C?

Methamphetamine abuse raises the risk of contracting or transmitting HIV and hepatitis B and C—not only for individuals who inject the drug but also for noninjecting methamphetamine abusers. Among injecting drug users, HIV and other infectious diseases are spread primarily through the re-use or sharing of contaminated syringes, needles, or related paraphernalia. But regardless of how methamphetamine is taken, its intoxicating effects can alter judgment and inhibition and lead people to engage in unsafe behaviors like unprotected sex.

Methamphetamine abuse is associated with a culture of risky sexual behavior, both among men who have sex with men and in heterosexual populations, a link that may be attributed to the fact that methamphetamine and related stimulants can increase libido. (Although paradoxically, long-term methamphetamine abuse may be associated with decreased sexual functioning, at least in men.) The combination of injection practices and sexual risk-taking may result in HIV becoming a greater problem among methamphetamine abusers than among other drug abusers, and some epidemiologic reports are already showing this trend. For example, while the link between HIV infection and methamphetamine abuse has not yet been established for heterosexuals, data show an association between methamphetamine abuse and the spread of HIV among men who have sex with men.

Methamphetamine abuse may also worsen the progression of HIV disease and its consequences. In animal studies, methamphetamine has been shown to increase viral replication. Clinical studies in humans suggest that current methamphetamine users taking highly active antiretroviral therapy (HAART) to treat HIV may be at greater risk of developing AIDS than non-users, possibly as a result of poor medication adherence. Methamphetamine abusers with HIV also have shown greater neuronal injury and cognitive impairment due to HIV, compared with those who do not abuse the drug.

NIDA-funded research has found that, through drug abuse treatment, prevention, and community-based outreach programs, drug abusers can change their HIV risk behaviors. Drug abuse and drug-related risk behaviors, such as needle sharing and unsafe sexual practices, can be reduced significantly, thus decreasing the risk of exposure to HIV and other infectious diseases. Therefore, drug abuse treatment is HIV prevention.

A diagram of the brain demonstrating dopamine, as a major chemical messenger in the reward pathway.

Dopamine Pathways

In the brain, dopamine plays an important role in the regulation of reward and movement. As a major chemical messenger in the reward pathway, dopamine is manufactured in nerve cell bodies located within a group of neurons called the ventral tegmental area and is released in the nucleus accumbens, sometimes called the “pleasure center” because of its role in producing rewarding feelings, as well as in the prefrontal cortex, which is responsible for higher cognitive functions like decision-making and selfcontrol. Dopamine’s regulation of motor functions is linked to a separate pathway: Cell bodies in the substantia nigra manufacture and release dopamine into the striatum, which is involved in executing and inhibiting movements and reward-seeking behavior.

What treatments are effective for people who abuse methamphetamine?

The most effective treatments for methamphetamine addiction at this point are behavioral therapies, such as cognitive-behavioral and contingency-management interventions. For example, the Matrix Model, a 16-week comprehensive behavioral treatment approach that combines behavioral therapy, family education, individual counseling, 12-Step support, drug testing, and encouragement for non-drug-related activities, has been shown to be effective in reducing methamphetamine abuse. Contingency management interventions, which provide tangible incentives in exchange for engaging in treatment and maintaining abstinence, have also been shown to be effective. Motivational Incentives for Enhancing Drug Abuse Recovery (MIEDAR), an incentivebased method for promoting cocaine and methamphetamine abstinence, has demonstrated efficacy in methamphetamine abusers through NIDA’s National Drug Abuse Clinical Trials Network.

Although medications have proven effective in treating some substance use disorders, there are currently no medications that counteract the specific effects of methamphetamine or that prolong abstinence from and reduce the abuse of methamphetamine by an individual addicted to the drug. NIDA has made research in the development of medications to treat addiction to stimulants and other drugs a priority, however. One approach being tried is to target the activity of glial cells. A drug called AV411 (ibudilast) that suppresses the neuroinflammatory actions of glial cells has been shown to inhibit methamphetamine selfadministration in rats and is now being fast-tracked in clinical trials to establish its safety and effectiveness in humans with methamphetamine addiction. Also under study are approaches that use the body’s immune system to neutralize the drug in the bloodstream before it reaches the brain. These approaches include injecting a user with antimethamphetamine antibodies or with vaccines that would stimulate the body to produce its own such antibodies. Researchers have begun a clinical study to establish the safety of an antimethamphetamine monoclonal antibody known as mAb7F9 in human methamphetamine users.

Glossary

Addiction: A chronic, relapsing disease characterized by compulsive drug seeking and use despite serious adverse consequences, and by long-lasting changes in the brain.

Anesthetic: An agent that causes insensitivity to pain and is used for surgeries and other medical procedures.

Attention deficit hyperactivity disorder (ADHD): A disorder that typically presents in early childhood, characterized by inattention, hyperactivity, and impulsivity.

Central nervous system (CNS): The brain and spinal cord.

Craving: A powerful, often uncontrollable desire for drugs.

Dopamine: A brain chemical, classified as a neurotransmitter, found in regions that regulate movement, emotion, motivation, and pleasure.

Neurotransmitter: A chemical produced by neurons that carry messages from one nerve cell to another.

Psychosis: A mental disorder characterized by delusional or disordered thinking detached from reality; symptoms often include hallucinations.

Rush: A surge of pleasure (euphoria) that rapidly follows the administration of some drugs.

Stimulants: A class of drugs that enhance the activity of monoamines (such as dopamine and norepinephrine) in the brain, increasing arousal, heart rate, blood pressure, and respiration, and decreasing appetite; includes some medications used to treat attention deficit hyperactivity disorder (e.g., methylphenidate and amphetamines), as well as cocaine and methamphetamine.

Tolerance: A condition in which higher doses of a drug are required to produce the same effect achieved during initial use; often associated with physical dependence.

Toxic: Causing temporary or permanent effects detrimental to the functioning of a body organ or group of organs.

Withdrawal: Symptoms that occur after chronic use of a drug is reduced abruptly or stopped.

Source: NIDA, NIH

Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

A new study adds to the copious existing evidence that chronic exposure to addictive drugs alters the brain in ways that make quitting difficult. NIDA-supported researchers showed that, in monkeys, methamphetamine alters brain structures involved in decision-making and impairs the ability to suppress habitual behaviors that have become useless or counterproductive. The two effects were correlated, indicating that the structural change underlies the decline in mental flexibility.

Human chronic methamphetamine users have been shown to differ from nonusers in the same ways that the post-exposure monkeys differed from their pre-exposure selves. The researchers’ use of monkeys as study subjects enabled them to address a question that human studies cannot: Did the drug cause those differences, or were they present before the individuals initiated use of the drug? The study results strongly suggest that the drug is significantly, if not wholly, responsible.

Before and After Methamphetamine

A defining feature of addiction to methamphetamine is that the addicted individual keeps on taking the drug despite the negative health and social effects of doing so. Psychological testing of addicted individuals has linked their difficulty quitting to a weakness in inhibitory control—a reduced ability to stop repeating previously learned behaviors. Brain imaging studies have also shown that, compared to nonusers, chronic users of the drug have, on average, more gray matter in the putamen and less gray matter in the prefrontal cortex (PFC) brain regions.

To clarify the relationships among these observations, Dr. David Jentsch, graduate students Stephanie Groman and Angelica Morales, and colleagues at the University of California, Los Angeles (UCLA) exposed 7 adult male vervet monkeys to methamphetamine in a 31-day regimen of escalating doses that simulates chronic use of the drug in humans. The researchers tested the monkeys’ cognition before, during, and after the methamphetamine exposure, and obtained magnetic resonance images (MRI) of the brain before and after the exposure.

Figure 1. Reversal Trial Studies the Impact of Methamphetamine on Monkeys’ Mental Flexibility The trial evaluates an animal’s mental flexibility for ignoring an old cue and learning a new cue. An association between a food reward (a banana) and a visual cue (a symbol on the box containing the fruit) is established during the acquisition and retention phases. During the reversal phase, the researchers place the fruit into a new box (with a different symbol) and measure the number of trials it takes the animal to learn the new cue?reward association.
Text Description of Graphic

Before methamphetamine exposure, the experimental monkeys performed as well on a test of inhibitory control as 7 control monkeys that received only saline injections. When retested after 3 weeks on the methamphetamine regimen, their performance had declined significantly. In the test, the researchers trained the animals to point to one of three symbols to receive a fruit reward, then switched the reward to another symbol. The methamphetamine-exposed monkeys took many more tries to shift from pointing to the first symbol to pointing to the other (see Figure 1).

Similarly, the MRIs of the experimental monkeys’ putamen matched those of the control monkeys’ prior to methamphetamine exposure, but differed after exposure. Analysis of the images revealed significant increases in gray matter in the right putamen.

The researchers hypothesized that the expansion of putamen gray matter could explain the monkeys’ compromised test performance. A primary role of the putamen is to initiate established or habitual responses to familiar situations or stimuli. In the normal shaping of behavior, other brain structures, in particular the PFC, functionally inhibit the putamen from initiating those responses in circumstances where they are inappropriate. However, an enlarged putamen may override this input and trigger habitual responses even when they are useless or harmful.

Figure 2. Methamphetamine-Induced Gray Matter Changes Correlate With Poor Performance on a Learning Task Most methamphetamine-exposed monkeys showed a decline in performance on a reversal task from baseline (i.e., from before they were exposed to the drug), while most saline-treated monkeys showed an improved performance. The methamphetamine-exposed monkeys’ decline in performance correlated (indicated by the solid blue line) with a change in gray matter in the right putamen. The changes in the number of reversal task trials were determined by assessing animals before and after exposure to methamphetamine or saline. The change in gray matter was measured by comparing signal intensities in MRI scans before and after the drug and control treatments.
Text Description of Graphic

To test this hypothesis, Dr. Jentsch and colleagues plotted the experimental monkeys’ decline in performance on the test of inhibitory control against their increase in putamen gray matter. The results were confirmatory: The animals that showed the greatest increases in putamen size were slowest to adjust to the altered reward structure (see Figure 2).

“When the brain’s structural integrity is dysregulated in the striatum [the brain region that contains the putamen], we think the animal’s behavior is unleashed from inhibitory control,” Dr. Jentsch says.

Dr. Jentsch notes that reduced gray matter in the PFC, as occurs in human methamphetamine users, would be expected to further weaken inhibitory control over habitual responses. Although the researchers anticipated that methamphetamine would cause contraction of the experimental monkeys’ PFC, there was no statistical change measured in the study, possibly because of the relatively small number of monkeys involved in the study. Alternatively, he adds, there is some evidence that changes in PFC observed in humans result from other habits associated with methamphetamine use, such as tobacco smoking.

Can the Brain Recover?

The UCLA study’s findings underscore the importance of the PFC–putamen circuitry in methamphetamine addiction. “These results provide a causal mechanism for why methamphetamine addiction is so hard to treat and has a significant chance of relapse early in treatment,” says Dr. James Bjork of NIDA’s Clinical Neuroscience Branch. “It’s a double whammy if the part of the brain that normally controls risky behavior is weakened while the habit-sustaining center is chemically beefed up and on overdrive.”

With their impact on behavior, these brain centers constitute potential prime targets for interventions to help people regain control over their drug use. Such interventions could range from medications that correct abnormalities in neurotransmitters and other chemicals in these brain regions to aerobic exercise and training of self-control, both of which may alter PFC–putamen structure and function.

“Going forward,” Dr. Jentsch says, “questions that need to be answered are: What are the cellular and molecular events in the striatum that initiate the whole chain of structural and behavioral changes?” Last year, the UCLA researchers turned up a possible clue: In a study using positron emission tomography (PET) imaging, methamphetamine-exposed monkeys had fewer dopamine transporters and D₂ receptors in the putamen and related brain structures, compared to unexposed monkeys.

Another topic on Dr. Jentsch’s research agenda is the source of individual differences in drug use. Among the drug-exposed monkeys in their trial, for example, increases in putamen volume ranged from less than 2 percent in one animal to 11 percent in another, with corresponding differences in performance on the test of inhibitory control. This mirrors the circumstance among human chronic users of the drug.

"Where are these individual differences in drug use coming from? What makes the drug-susceptible brains different from the resilient brains?” Dr. Jentsch asks. “These questions are important because the answers will enable us to identify individuals with greater risk for being damaged by methamphetamine, and target them with preventive efforts that include educating them about the potential impact of the drug on their brains.” As a first step in this quest, the UCLA team has fully sequenced the genomes of the colony of vervet monkeys from which these study subjects were obtained. They will analyze these data for gene variants that associate with the observed differences in drug responses.

Ultimately, can methamphetamine’s disruptive effects on the brain be reversed? In the UCLA study, the methamphetamine-induced changes persisted through the final cognitive and behavioral assessments, which occurred 3 weeks after the animals received their last dose of the drug. Therefore, Dr. Jentsch says, to answer this question, future studies should track primate brains through longer abstinence.

“Methamphetamine dependence is currently a problem with no good medical treatments,” Dr. Jentsch notes. “When you say a disease like methamphetamine dependence is costly, it’s not just costing money, but lives, productivity, happiness, and joy. Its impact bleeds through families and society.”

This study was supported by NIH grants DA022539, DA020598, DA024635, DA028812, and DA033117.

Sources

Groman, S.M.; Morales A.M.; Lee, B.; London, E.D.; Jentsch, J.D. Methamphetamine-induced increases in putamen gray matter associate with inhibitory control. Psychopharmacology 229(3):527-538, 2013. Abstract

Groman, S.M.; Lee, B.; Seu, E.; James, A.S.; Feiler, K.; Mandelkern, M.A.; London, E.D.; Jentsch, J.D. Dysregulation of D₂-mediated dopamine transmission in monkeys after chronic escalating methamphetamine exposure. The Journal of Neuroscience 32(17):5843–5852, 2012. Full text

Source: NIDA, NIH

Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

Ketoprofen, an anti-inflammatory agent commonly prescribed to treat arthritis, reduces neuronal damage in rats that have been exposed to chronic stress and methamphetamine. If this finding of a recent NIDA-supported study extrapolates to humans, anti-inflammatory medications may gain a place in the treatment of methamphetamine addiction.

Chronic exposure to methamphetamine damages dopamine and serotonin terminals on neurons in the striatum, reducing levels of these neurotransmitters and impairing communication between neurons in this brain area. Past studies have shown that stress worsens the damage.

Drs. Nicole Northrop and Bryan Yamamoto, of the University of Toledo, Ohio, gave animals ketoprofen to investigate the role of inflammation in producing these effects, which contribute to methamphetamine users’ cognitive and behavioral problems. Their results indicate that neurotransmitter depletion in animals exposed to both methamphetamine and stress has two components, related to the two exposures. They implicate ketoprofen’s main target, the pro-inflammatory enzyme cyclooxygenase (COX-1/COX-2), in the stress-related component, and they indicate that a different mechanism underlies the methamphetamine-related component.

Partial Rescue

Drs. Northrop and Yamamoto have been conducting broad research on the impact of inflammation on brain health. They, along with others, have shown that stress increases COX-2 in the brain and that COX-2 activity promotes inflammation that can be toxic to brain cells. In the present study, they hypothesized that these effects are the link between stress and neuronal damage in methamphetamine abusers.

Ketoprofen provided the researchers with a tool to test their hypothesis. The medication inhibits COX-1/COX-2. If the hypothesis were correct, the medication should alleviate the stress-induced inflammatory response and resulting exacerbation of neuronal damage.

Figure 1. Chronic Stress Elevates Levels of Neuroinflammatory COX-2 Protein in the Rat Brain Rats were stressed or left unstressed for 10 days, and levels of the COX-2 protein, a neuroinflammatory mediator, were measured in the hippocampus (blue bars) and striatum (green bars) of these animals. Units for COX-2 expression on the y-axis represent percentages relative to the “no stress” treatments. In the stressed animals, the amount of COX-2 was increased by almost 80 percent in the hippocampus and by about 30 percent in the striatum relative to the levels in these brain regions in the unstressed animals.

The researchers exposed rats to chronic stress, methamphetamine, or chronic stress followed by methamphetamine. To put rats into a condition of chronic stress, the researchers subjected them to a 10-day regimen of randomly timed cage agitation, food and water deprivation, cold, and isolation. This regimen increased COX-2 in the striatum by 32 percent (Figure 1).

Ketoprofen did not affect neurotransmitter levels among rats that were exposed to chronic stress alone or methamphetamine alone. However, it prevented the incremental damage produced by chronic stress among the animals that underwent both the stress regimen and methamphetamine exposure (see Figure 2). Without ketoprofen, chronic stress added a further 49 percent and 35 percent, respectively, to the striatal dopamine and serotonin depletions observed among animals that received methamphetamine alone. With ketoprofen, there was no significant difference.

The anti-inflammatory medication worked equally well whether the researchers gave it to the animals during the stress regimen or during methamphetamine administration. Hence, the anti-inflammatory treatment alleviated the adverse impact of stress even when it was administered after the stressful experience.

Figure 2. Ketoprofen Alleviates Stress-Related Exacerbations of Methamphetamine-Induced Dopamine Depletions in the Striatum Stress exacerbated methamphetamine-induced depletion of dopamine levels in the striatum of the rat brain, and ketoprofen canceled the exacerbation. Rats were subjected to stress or handled normally (“no stress” controls) and then injected 4 times with 7.5 mg/kg methamphetamine or saline every 2 hours; rats treated with ketoprofen were injected with 5 mg/kg of the drug 1 hour before each methamphetamine or saline injection.
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A Double-Whammy for the Brain

The precise mechanism whereby COX-2 activation promotes neuronal damage remains unclear. The Ohio researchers tested and disproved one hypothesis. Based on the observation that COX-2 enhances prostaglandin production, they posited that the resulting increased prostaglandin activity might set off toxic reactions at neuronal EP1 prostaglandin receptors. However, when they administered an agent that inactivates the EP1 receptor, stress still aggravated the methamphetamine-related neurotransmitter depletion.

“There must be some other role for COX-2 activity to produce neuroinflammation,” says Dr. Yamamoto.

His current leading hypothesis draws on two well-established observations: Methamphetamine acutely increases dopamine levels in the striatum, and COX-2 converts dopamine into quinones, highly reactive chemicals that damage neurons. Hence, stress-related increases in COX-2 might combine with methamphetamine-related elevations in dopamine to produce a bumper crop of destructive quinones.

Dr. Yamamoto says that this scenario is consistent with another finding from the study: Although ketoprofen protected neurotransmitter levels in the striatum, it did not do so in the hippocampus, even though stress increased hippocampal COX-2 by 77 percent. Compared to the striatum, dopamine levels are low in the hippocampus, providing little substrate for COX-2 to convert into quinones.

Treating Drug-Induced Neuroinflammation

Drs. Yamamoto and Northrop and colleagues have previously shown that the combination of stress and methamphetamine compromises the integrity of the blood–brain barrier—the protective cell layer that lines the capillaries in the brain and prevents large molecules and pathogens, including bacteria and viruses, from entering the brain. In those studies, ketoprofen alleviated long-term blood?brain barrier disruption caused by the combination of methamphetamine and stress, but not by methamphetamine alone.

The parallel findings of these studies raise the possibility that treatment with ketoprofen or other anti-inflammatory agents might alleviate some of methamphetamine users’ neuronal damage and resulting problems. Ketoprofen has been clinically approved for human use, so if further research supports the use of anti-inflammatory drugs to mitigate the neurotoxicity of methamphetamine, human trials could begin promptly.

For the present, however, Dr. Yamamoto concurs with Dr. Jerry Frankenheim of NIDA’s Functional Neuroscience Research Branch, who cautions, “There is not yet enough evidence to warrant the use of anti-inflammatory drugs to protect against inflammation resulting from methamphetamine and stress.” Dr. Frankenheim adds, “The Toledo team’s preclinical study was cleverly designed to identify the mechanisms by which stress increases the neurotoxicity of methamphetamine, but not to identify a treatment.” Moreover, he notes that ketoprofen did not protect the hippocampus, and ketoprofen has side effects, including gastrointestinal bleeding.

Implications Beyond Drug Abuse

The finding that neuroinflammation can damage dopamine and serotonin neurons may be important for many neurodegenerative disorders. “Even though this study focused on methamphetamine, a lot of the underlying mechanisms we’re investigating are similar to those thought to be at work in neurodegenerative diseases in which inflammation has been implicated, such as Parkinson’s and Alzheimer’s,” says Dr. Yamamoto. “Perhaps injuries produced by drugs of abuse may not be much different from damage exhibited by these disease conditions.”

In addition, Dr. Yamamoto says, researchers need to consider how inflammation outside the brain might contribute to inflammation in the brain. “We’ve always considered the brain in isolation—that drugs act directly in the brain to produce these effects,” he says. “But the cross talk between the brain and the rest of the body also needs to be investigated further.” Dr. Yamamoto points to a previous research finding that liver damage contributes to methamphetamine-induced brain damage.

Dr. Frankenheim agrees: “Neuroinflammation is a frontier research area right now,” he says. “From many studies of neurodegenerative and psychiatric disorders, a common theme is emerging: Neuroinflammation damages the brain, and more experiments along the lines of this work should be done.”

This study was supported by NIH grant DA007606.

Sources:

Northrop, N.A. and Yamamoto B.K. Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine. Neuropharmacology 72:96–105, 2013. Abstract

Northrop, N.A. and Yamamoto B.K. Persistent neuroinflammatory effects of serial exposure to stress and methamphetamine on the blood-brain barrier. Journal of Neuroimmune Pharmacology 7(4):951–968, 2012.

Source: NIDA, NIH

Mind Over Matter: Methamphetamine

Mind Over Matter: The Brain's Response to Methamphetamine cover

Methamphetamine comes in many different forms and is snorted, swallowed, injected, or smoked. Methamphetamine can cause lots of harmful things, including inability to sleep, paranoia, aggressiveness, and hallucinations.

The Brain's Response to Methamphetamine

canoe

Hi, my name's Sara Bellum. Welcome to my magazine series exploring the brain's response to drugs. In this issue, we'll investigate many fascinating facts about the stimulant drug Methamphetamine. Some of this information was only recently discovered by leading scientists.

Speed, meth, chalk, crystal, ice, glass - these are all names for the drug Methamphetamine. Methamphetamine comes in many different forms and is snorted, swallowed, injected, or smoked. The smokable form is known as "ice" or "crystal," due to its appearance.

Methamphetamine is a powerful drug. It acts by changing how the brain works. It also speeds up many functions in the body. Methamphetamine has a chemical structure that is similar to another drug called amphetamine that I explore in my magazine on stimulants. Methamphetamine can cause lots of harmful things, including inability to sleep, paranoia, aggressiveness, and hallucinations. I'll tell you more about these later.

How Does Methamphetamine Cause Its Effects?

illustration shows neurotransmitters communicating over a synapse

No matter how Methamphetamine is used, it eventually ends up in the bloodstream where it is circulated throughout the brain. Methamphetamine can affect lots of brain structures, but the ones it affects the most are the ones that contain a chemical called dopamine. The reason for this is that the shape, size, and chemical structure of Methamphetamine and dopamine are similar. Before I tell you more about dopamine and Methamphetamine, I'd better tell you how nerve cells work.

Your brain is made up of billions of nerve cells (or neurons). Neurons come in all shapes and sizes, but most have three important parts: a cell body that contains the nucleus and directs the activities of the neuron; dendrites, short fibers that receive messages from other neurons and relay them to the cell body; and an axon, a long single fiber that carries messages from the cell body to dendrites of other neurons.

Axons of one neuron and the dendrites of a neighboring neuron are located very close to each other, but they don't actually touch. Therefore, to communicate with each other they use chemical messengers known as neurotransmitters. When one neuron wants to send a message to another neuron it releases a neurotransmitter from its axon into the small space that separates the two neurons. This space is called a synapse. The neurotransmitter crosses the synapse and attaches to specific places on the dendrites of the neighboring neuron called receptors. Once the neurotransmitter has relayed its message, it is either destroyed or taken back up into the first neuron where it is recycled for use again.

There are many different neurotransmitters, but the one that is most affected by Methamphetamine is dopamine. Dopamine is sometimes called the pleasure neurotransmitter because it helps you feel good from things like playing soccer, eating a big piece of chocolate cake, or riding a roller coaster. When something pleasurable happens, certain axons release lots of dopamine. The dopamine attaches to receptors on dendrites of neighboring neurons and passes on the pleasure message. This process is stopped when dopamine is released from the receptors and pumped back into the neuron that released it where it is stored for later use.

Methamphetamine Changes the Brain

Usually neurons recycle dopamine. But Methamphetamine is able to fool neurons into taking it up just like they would dopamine. Once inside a neuron, Methamphetamine causes that neuron to release lots of dopamine. All this dopamine causes the person to feel an extra sense of pleasure that can last all day. But eventually these pleasurable effects stop. They are followed by unpleasant feelings called a "crash" that often lead a person to use more of the drug. If a person continues to use Methamphetamine, they will have a difficult time feeling pleasure from anything. Imagine no longer enjoying your favorite food or an afternoon with your friends.

Methamphetamine Has Lots of Other Effects

Because it is similar to dopamine, Methamphetamine can change the function of any neuron that contains dopamine. And if this weren't enough, Methamphetamine can also affect neurons that contain two other neurotransmitters called serotonin and norepinephrine. All of this means that Methamphetamine can change how lots of things in the brain and the body work. Even small amounts of Methamphetamine can cause a person to be more awake and active, lose their appetite, and become irritable and aggressive. Methamphetamine also causes a person's blood pressure to increase and their heart to beat faster.

What Happens If a Person Uses Methamphetamine for a Long Time?

brain in the doghouse

Scientists are using brain imaging techniques, like positron emission tomography (called PET for short), to study the brains of human Methamphetamine users. They have discovered that even three years after long-time Methamphetamine users had quit using the drug, their dopamine neurons were still damaged. Scientists don't know yet whether this damage is permanent, but this research shows that changes in the brain from Methamphetamine use can last a long time. Research with animals has shown that the drug Methamphetamine can also damage neurons that contain serotonin. This damage also continues long after the drug use is stopped.

These changes in dopamine and serotonin neurons may explain some of the effects of Methamphetamine. If a person uses Methamphetamine for a long time, they may become paranoid. They may also hear and see things that aren't there. These are called hallucinations. Because Methamphetamine causes big increases in blood pressure, someone using it for a long time may also have permanent damage to blood vessels in the brain. This can lead to strokes caused by bleeding in the brain.

The Search Continues

girl with arm around dog

Researchers are only beginning to understand how Methamphetamine acts in the brain and body. When they learn more about how Methamphetamine causes its effects, they may be able to develop treatments that prevent or reverse the damage this drug can cause. Maybe someday you'll make the next major breakthrough.

Mind Over Matter is produced by the National Institute on Drug Abuse, National Institutes of Health. These materials are in the public domain and may be reproduced without permission. Citation of the source is appreciated. NIH Publication No.03-4394. Printed 2000, 2003.

Source: NIDA, NIH

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