1 NIDA RRS Marijuana by userlpf

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            N A T I O N A L                              I N S T I T U T E              O N        D R U G           A B U S E




          Research Report                                                                                        S E R I E S
                        The abuse of methamphetamine—
                    a potent and highly addictive psycho-


                                                              METHAMPHETAMINE
                    stimulant—is a very serious problem
                    in the United States. Initially limited
                    to Hawaii and western parts of the
                    country, methamphetamine abuse
                    continues to spread eastward, with
                    rural and urban areas everywhere
                    increasingly affected. According to
                    one national survey, approximately
                                                                                 Abuse and Addiction
                    10 million people in the United States
                    have tried methamphetamine at
                    least once.
                                                              What is
                        Methamphetamine abuse leads to
                    devastating medical, psychological,
                                                              methamphetamine?

                                                              M
                    and social consequences. Adverse
                    health effects include memory loss,
                                                                       ethamphetamine is a         amphetamine a drug with high
                    aggression, psychotic behavior, heart              highly addictive stimu-     potential for widespread abuse.
                    damage, malnutrition, and severe                   lant that affects the          Methamphetamine is commonly
                    dental problems. Methamphetamine
                    abuse also contributes to increased       central nervous system. Although     known as “speed,” “meth,” and
                    transmission of infectious diseases,      most of the methamphetamine          “chalk.” In its smoked form, it
from the director




                    such as hepatitis and HIV/AIDS, and
                    can infuse whole communities with         used in this country comes from      is often referred to as “ice,”
                    new waves of crime, unemployment,         foreign or domestic superlabs,       “crystal,” “crank,” and “glass.” It
                    child neglect or abuse, and other         the drug is also easily made in      is a white, odorless, bitter-tasting
                    social ills.
                        The good news is that metham-         small clandestine laboratories,      crystalline powder that easily
                    phetamine abuse can be prevented          with relatively inexpensive over-    dissolves in water or alcohol.
                    and methamphetamine addiction
                    can be treated. People do recover,        the-counter ingredients. These       The drug was developed early
                    but only when effective treatments        factors combine to make meth-        last century from its parent drug,
                    that address the multitude of problems
                    resulting from methamphetamine
                    abuse are readily available. Primary
                    goals of the National Institute on                               Methamphetamine
                    Drug Abuse (NIDA) are to apply
                    what our scientists learn from
                    drug abuse research to develop new
                    and enhance existing treatment
                    approaches and to bring these effec-
                    tive treatments to the communities
                    that need them.
                        In this report, we provide an over-
                    view of the latest scientific findings    zycnzj.com/http://www.zycnzj.com/
                    on methamphetamine. Our intent is
                    to enlighten readers about the dam-
                    aging effects of methamphetamine
                    abuse and to inform prevention and
                    treatment efforts.
                    Nora D.Volkow, M.D.
                    Director
                    National Institute on Drug Abuse


                    U.S. Department of Health and Human Services                  • National      Institutes    of   Health
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2   NIDA RESEARCH REPORT SERIES


amphetamine, and was used
originally in nasal decongestants         Primary Methamphetamine/Amphetamine Admission
and bronchial inhalers. Like                Rates per 100,000 Population Aged 12 and Over
amphetamine, methamphetamine
causes increased activity and
talkativeness, decreased appetite,
and a general sense of well-being.
However, methamphetamine                  1992                                                                                    1994
differs from amphetamine in
that at comparable doses, much
higher levels of methampheta-
mine get into the brain, making
it a more potent stimulant drug.
It also has longer lasting and
more harmful effects on the               1999                                                                                    2002
central nervous system.
   Methamphetamine is a
Schedule II stimulant, which                                                            Incomplete Data   <3     10-23        KEY YEAR: 1992
                                                                                                          3-9    24 or more
means it has a high potential
                                          Source: Treatment Episode Data Set (TEDS), SAMHSA.
for abuse and is available only
through a prescription. It is
indicated for the treatment of          U.S., reported in January 2006                            methamphetamine use, and
narcolepsy (a sleep disorder)           that methamphetamine continues                            512,000 reported current (past-
and attention deficit hyperactivity     to be a problem in the West,                              month) use. Moreover, the 2005
disorder; but these medical uses        with indicators persisting at high                        Monitoring the Future (MTF)
are limited, and the doses are          levels in Honolulu, San Diego,                            survey of student drug use and
much lower than those typically         Seattle, San Francisco, and Los                           attitudes reported 4.5 percent of
abused.                                 Angeles; and that it continues                            high school seniors had used
                                        to spread to other areas of the                           methamphetamine within their
What is the                             country, including both rural
                                        and urban sections of the South
                                                                                                  lifetimes, while 8th-graders and
                                                                                                  10th-graders reported lifetime
scope of                                and Midwest. In fact, metham-                             use at 3.1 and 4.1 percent,
methamphetamine                         phetamine was reported to be                              respectively. However, neither
abuse in the                            the fastest growing problem in
                                        metropolitan Atlanta.
                                                                                                  of these surveys has documented
                                                                                                  an overall increase in the abuse
United States?                        zycnzj.com/http://www.zycnzj.com/
                                           According to the 2005 National                         of methamphetamine over the


N
       IDA’s Community                  Survey on Drug Use and Health                             past few years. In fact, both
       Epidemiology Work                (NSDUH), an estimated 10.4 mil-                           surveys showed recent declines
       Group (CEWG), an early           lion people age 12 or older (4.3                          in methamphetamine abuse
warning network of researchers          percent of the population) have                           among the Nation’s youth.
that provides information about         tried methamphetamine at some                                In contrast, evidence from
the nature and patterns of drug         time in their lives. Approximately                        emergency departments and
abuse in 21 major areas of the          1.3 million reported past-year                            treatment programs attest to
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                                                                                 NIDA RESEARCH REPORT SERIES             3
the growing impact of metham-
phetamine abuse in the country.
                                     How is                                     intense rush. Snorting produces
                                                                                effects within 3 to 5 minutes, and
The Drug Abuse Warning               methamphetamine                            oral ingestion produces effects
Network (DAWN), which collects       abused?                                    within 15 to 20 minutes.
information on drug-related                                                        As with similar stimulants,


                                     M
episodes from hospital emergency                ethamphetamine comes            methamphetamine most often
departments (EDs) throughout                    in many forms and can           is used in a “binge and crash”
the Nation, has reported a                      be smoked, snorted,             pattern. Because the pleasurable
greater than 50 percent increase     injected, or orally ingested.              effects of methamphetamine
in the number of ED visits related   The preferred method of                    disappear even before the drug
to methamphetamine abuse             methamphetamine abuse varies               concentration in the blood falls
between 1995 and 2002, reaching      by geographical region and has             significantly—users try to main-
approximately 73,000 ED visits,      changed over time. Smoking                 tain the high by taking more of
or 4 percent of all drug-related     methamphetamine, which leads               the drug. In some cases, abusers
visits in 2004.                      to very fast uptake of the drug            indulge in a form of binging
   Treatment admissions for          in the brain, has become more              known as a “run,” foregoing
methamphetamine abuse have           common in recent years,                    food and sleep while continuing
                                     amplifying methamphetamine’s               abuse for up to several days.
also increased substantially. In
                                     addiction potential and adverse
1992, there were approximately
                                     health consequences.
21,000 treatment admissions in
                                        The drug also alters mood in            How is
which methamphetamine/
amphetamine was identified
                                     different ways, depending on               methamphetamine
                                     how it is taken. Immediately
as the primary drug of abuse,        after smoking the drug or inject-          different from
representing more than 1 percent     ing it intravenously, the user             other stimulants,
of all treatment admissions during
the year. By 2004, the number
                                     experiences an intense rush
                                     or “flash” that lasts only a few
                                                                                such as cocaine?

                                                                                M
of methamphetamine treatment         minutes and is described as                        ethamphetamine is
admissions increased to greater      extremely pleasurable. Snorting                    structurally similar to
than 150,000, representing 8         or oral ingestion produces                         amphetamine and the
percent of all admissions.           euphoria—a high but not an                 neurotransmitter dopamine, but
   Moreover, this increased
involvement of methamphetamine               Methamphetamine                  vs. Cocaine
in drug treatment admissions has                                 Stimulant        Stimulant and local anesthetic
also been spreading across the
                                                          Man-made
                                     zycnzj.com/http://www.zycnzj.com/            Plant-derived
country. In 1992, only 5 states
                                       Smoking produces a long-lasting high       Smoking produces a brief high
reported high rates of treatment
admissions (i.e., >24 per 100,000         50% of the drug is removed from         50% of the drug is removed from
                                                      the body in 12 hours        the body in 1 hour
population) for primary meth-
                                      Increases dopamine release and blocks       Blocks dopamine re-uptake
amphetamine/amphetamine
                                                       dopamine re-uptake
problems; by 2002, this number
                                                        Limited medical use       Limited use as a local anesthetic in
increased to 21, more than a                                                      some surgical procedures
third of the states.
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4   NIDA RESEARCH REPORT SERIES


                                                                                                        higher concentrations in the
                                Dopamine Pathways
                                                                                                        synapse, which can be toxic to
                                                                                                        nerve terminals.


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

                                                                                                        A
                                                                                                               s a powerful stimulant,
                                                                                                               methamphetamine, even
                                                                                                               in small doses, can
                                                                                                        increase wakefulness and
                                                                                                        physical activity and decrease
                                                                                                        appetite. Methamphetamine can
                                                                                                        also cause a variety of cardiovas-
In the brain, dopamine plays an important role in the regulation of reward and movement. As part        cular problems, including rapid
of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral         heart rate, irregular heartbeat,
tegmental area (VTA) and is released in the nucleus accumbens and the prefrontal cortex. Its motor
functions are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture   and increased blood pressure.
and release dopamine into the striatum.                                                                 Hyperthermia (elevated body
                                                                                                        temperature) and convulsions
                                                                                                        may occur with methampheta-
it is quite different from cocaine.   although both methamphetamine                                     mine overdose, and if not treated
Although these stimulants have        and cocaine increase levels of                                    immediately, can result in death.
similar behavioral and physiolog-     the brain chemical dopamine,                                         Most of the pleasurable effects
ical effects, there are some major    animal studies reveal much                                        of methamphetamine are believed
differences in the basic mecha-       higher levels of dopamine                                         to result from the release of
nisms of how they work. In con-       following administration of                                       very high levels of the neuro-
trast to cocaine, which is quickly    methamphetamine due to the                                        transmitter dopamine. Dopamine
removed and almost completely         different mechanisms of action                                    is involved in motivation, the
metabolized in the body,              within nerve cells in response to                                 experience of pleasure, and
methamphetamine has a much          zycnzj.com/http://www.zycnzj.com/
                                      these drugs. Cocaine prolongs                                     motor function, and is a common
longer duration of action and a       dopamine actions in the brain                                     mechanism of action for most
larger percentage of the drug         by blocking dopamine re-uptake.                                   drugs of abuse. The elevated
remains unchanged in the body.        While at low doses, metham-                                       release of dopamine produced
This results in methamphetamine       phetamine blocks dopamine                                         by methamphetamine is also
being present in the brain longer,    re-uptake, methamphetamine                                        thought to contribute to the
which ultimately leads to pro-        also increases the release of                                     drug’s deleterious effects on
longed stimulant effects. And         dopamine, leading to much                                         nerve terminals in the brain.
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                                                                                                  NIDA RESEARCH REPORT SERIES    5
What are the                                            insects creeping under the skin).
                                                        Psychotic symptoms can some-
                                                                                                 imaging studies have demon-
                                                                                                 strated alterations in the activity
long-term                                               times last for months or years           of the dopamine system that are
effects of                                              after methamphetamine abuse
                                                        has ceased, and stress has been
                                                                                                 associated with reduced motor
                                                                                                 speed and impaired verbal
methamphetamine                                         shown to precipitate spontaneous         learning. Recent studies in
abuse?                                                  recurrence of methamphetamine            chronic methamphetamine
                                                        psychosis in formerly psychotic


L
     ong-term methamphetamine                           methamphetamine abusers.
     abuse has many negative                               With chronic abuse, tolerance
     consequences, including
                                                                                                      Short-Term Effects
                                                        to methamphetamine’s pleasura-                  May Include:
addiction. Addiction is a chronic,                      ble effects can develop. In an
relapsing disease, characterized                        effort to intensify the desired             Increased attention and
by compulsive drug seeking and                          effects, abusers may take higher              decreased fatigue
use, accompanied by functional                                                                      Increased activity and
                                                        doses of the drug, take it more
and molecular changes in the                                                                          wakefulness
                                                        frequently, or change their
brain. In addition to being                                                                         Decreased appetite
                                                        method of drug intake. With-
addicted to methamphetamine,
                                                        drawal from methamphetamine                 Euphoria and rush
chronic abusers exhibit symptoms
                                                        occurs when a chronic abuser                Increased respiration
that can include anxiety, con-
fusion, insomnia, mood distur-                          stops taking the drug; symptoms             Rapid/irregular
                                                        of withdrawal include depres-                 heartbeat
bances, and violent behavior.
They also can display a number                          sion, anxiety, fatigue, and an              Hyperthermia
of psychotic features, including                        intense craving for the drug.
paranoia, visual and auditory                              Chronic methamphetamine
hallucinations, and delusions                           abuse also significantly changes               Long-Term Effects
(for example, the sensation of                          the brain. Specifically, brain                   May Include:
                                                                                                    Addiction
                                                                                                    Psychosis, including:
           Recovery of Brain Dopamine Transporters
                                                                                                      • paranoia
         in Chronic Methamphetamine (METH) Abusers
                                                                                                      • hallucinations
                                                                                                      • repetitive motor
                                                                                                        activity
                                                                                                    Changes in brain
                                                                                                      structure and function
                                                       zycnzj.com/http://www.zycnzj.com/            Memory loss
                                                                                                    Aggressive or violent
                                                                                                      behavior
                                                                                                    Mood disturbances
         Normal Control                       METH Abuser                    METH Abuser            Severe dental
                                          (1 month abstinence)           (24 month abstinence)        problems
 Source: Volkow ND et al., Journal of Neuroscience 21:9414–9418, 2001.                              Weight loss
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6   NIDA RESEARCH REPORT SERIES


abusers have also revealed          to the NSDUH, less than 1 per-        infection with HIV and other
severe structural and functional    cent of pregnant women aged           infectious diseases is spread
changes in areas of the brain       15–44 had used methampheta-           primarily through the re-use of
associated with emotion and         mine in the past year, any use        contaminated syringes, needles,
memory, which may account           among this population is of           or other paraphernalia by more
for many of the emotional and       concern. Unfortunately, our           than one person. However,
cognitive problems observed in      knowledge of the effects of           regardless of how it is taken, the
chronic methamphetamine             methamphetamine during preg-          intoxicating effects of metham-
abusers.                            nancy is limited. The few human       phetamine can alter judgment
   Fortunately, some of the         studies that exist have shown         and inhibition and lead people
effects of chronic methamphet-      increased rates of premature          to engage in unsafe behaviors.
                                    delivery, placental abruption,
amine abuse appear to be, at                                                 Methamphetamine has become
                                    fetal growth retardation, and
least partially, reversible. A                                            associated with a culture of risky
                                    heart and brain abnormalities.
recent neuroimaging study                                                 sexual behavior, both among
                                    However, these studies are
showed recovery in some brain                                             men who have sex with men
                                    difficult to interpret due to
regions following prolonged                                               (MSM) and heterosexual popula-
                                    methodological issues, such as
abstinence (2 years, but not 6                                            tions. This link may be due to
                                    small sample size and maternal
months). This was associated                                              the fact that methamphetamine
                                    use of other drugs. Ongoing
with improved performance on                                              and related psychomotor
                                    research is continuing to study
motor and verbal memory tests.                                            stimulants can increase libido.
                                    developmental outcomes such
However, function in other                                                Paradoxically, long-term
                                    as cognition, social relationships,
brain regions did not display                                             methamphetamine abuse may be
                                    motor skills, and medical
recovery even after 2 years of      status of children exposed to         associated with decreased sexual
abstinence, indicating that some    methamphetamine before birth.         functioning, at least in men.
methamphetamine-induced                                                   The combination of injection and
changes are very long-lasting.                                            sexual risk-taking may result in
Moreover, the increased risk of     Are                                   HIV becoming a greater problem
stroke from the abuse of            methamphetamine                       among methamphetamine
methamphetamine can lead to
irreversible damage to the brain.   abusers at risk                       abusers than among opiate and
                                                                          other drug abusers, something
                                    for contracting                       that already seems to be occur-
What are                            HIV/AIDS and                          ring, according to some epidemi-
                                                                          ologic reports. For example,
the risks of                        hepatitis B and C?                    while the link between HIV
methamphetamine                   zycnzj.com/http://www.zycnzj.com/


                                    I
                                       ncreased HIV and hepatitis B       infection and methamphetamine
abuse during                           and C transmission are             abuse has not yet been estab-
                                       consequences of increased          lished for heterosexuals, data
pregnancy?                          methamphetamine abuse, not            show an association between



P
      renatal exposure to           only in individuals who inject the    methamphetamine abuse and the
      methamphetamine may           drug, but also in noninjecting        spread of HIV among MSM.
      also be a problem in the      methamphetamine abusers.                 Methamphetamine abuse may
United States. Although according   Among injection drug users,           also worsen the progression of
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                                                                           NIDA RESEARCH REPORT SERIES          7
HIV and its consequences. In        for nondrug-related activities,       house for Alcohol and Drug
animal studies, methamphetamine     has been shown to be effective        Information (NCADI) at
increased viral replication; in     in reducing methamphetamine           800–729–6686. Information
human methamphetamine               abuse. Contingency management         specialists are available to help
abusers, HIV caused greater         interventions, which provide          you locate information and
neuronal injury and cognitive       tangible incentives in exchange       resources.
impairment compared with            for engaging in treatment and            Fact sheets, including
                                    maintaining abstinence, have          InfoFacts, on the health effects of
nondrug abusers.
                                    also been shown to be effective.      methamphetamine, other drugs
   NIDA-funded research has
                                       There are currently no specific    of abuse, and other drug abuse
found that, through drug abuse
                                    medications that counteract the       topics are available on the NIDA
treatment, prevention, and
                                    effects of methamphetamine or         Web site (www.drugabuse.gov),
community-based outreach
                                    that prolong abstinence from and      and can be ordered free of
programs, drug abusers can                                                charge in English and Spanish
                                    reduce the abuse of metham-
change their HIV risk behaviors.                                          from NCADI at www.health.org.
                                    phetamine by an individual
Drug abuse can be eliminated        addicted to the drug. However,
and drug-related risk behaviors,    there are a number of medica-
such as needle-sharing and          tions that are FDA-approved for            Access information
unsafe sexual practices, can        other illnesses that might also be          on the Internet
be reduced significantly, thus      useful in treating methampheta-         • What’s new on the NIDA Web site
decreasing the risk of exposure     mine addiction. Recent study
to HIV and other infectious                                                 • Information on drugs of abuse
                                    findings reveal that bupropion,
diseases. Therefore, drug abuse     the anti-depressant marketed            • Publications and communications
treatment is HIV prevention.        as Wellbutrin, reduced the                (including NIDA Notes)
                                    methamphetamine-induced                 • Calendar of events
                                    “high” as well as drug cravings         • Links to NIDA organizational units
What treatments                     elicited by drug-related cues.          • Funding information
are effective for                   This medication and others are            (including program announcements
                                    currently in clinical trials, while
methamphetamine                     new compounds are being
                                                                              and deadlines)
                                                                            • International activities
abusers?                            developed and studied in
                                                                            • Links to related Web sites
                                    preclinical models.


A
       t this time, the most                                                  (access to Web sites of many other
       effective treatments for                                               organizations in the field)
       methamphetamine addic-       Where can I get
tion are behavioral therapies       further scientific                            NIDA Web Sites
such as cognitive behavioral        zycnzj.com/http://www.zycnzj.com/             www.drugabuse.gov
and contingency management          information about                            www.steroidabuse.gov
interventions. For example, the     methamphetamine                               www.clubdrugs.gov
                                                                                www.hiv.drugabuse.gov
Matrix Model, a comprehensive
behavioral treatment approach
                                    abuse?                                     www.inhalant.drugabuse.gov


                                    T
that combines behavioral therapy,        o learn more about
                                                                                        NCADI
family education, individual             methamphetamine and
                                                                               Web Site: www.health.org
counseling, 12-Step support,             other drugs of abuse,
                                                                               Phone No.: 800-729-6686
drug testing, and encouragement     contact the National Clearing-
                           zycnzj.com/ www.zycnzj.com

8  NIDA RESEARCH REPORT SERIES



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