Methamphetamine

Тема в разделе "Euphoric substances and stimulants", создана пользователем Charles Darwin, 3/5/14.

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    Charles Darwin

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    Methamphetamine

    (pronunciation:
    ; contracted from
    -
    ) is a
    and potent
    of the
    and
    that is used to treat
    (ADHD) and
    . Methamphetamine exists as two
    ,
    and
    . Dextromethamphetamine is a stronger
    (CNS) stimulant than
    ; however, both are addictive and produce the same toxicity symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the
    (USFDA) under the trade nameDesoxyn. Recreationally, methamphetamine is used to
    ,
    , and increase energy, allowing some users to engage in sexual activity continuously for several days straight.

    Methamphetamine may be sold illegally, either as pure dextromethamphetamine or in an
    mixture of the right and left handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are
    controlled substances in the United States. Similarly, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the
    treaty. In contrast,
    is an
    in the United States.

    In low doses, methamphetamine can cause an
    and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce
    ,
    and
    . Methamphetamine is known to have a high potential for
    and
    . Recreational use of methamphetamine may result in psychosis or lead to
    , a withdrawal syndrome that can persist for months beyond the typical withdrawal period.Unlike
    , methamphetamine is
    to humans, damaging both
    and
    neurons in the CNS.Entirely opposite to the long-term use of Амф, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in
    volume in several brain regions and adverse changes in markers of metabolic integrity.

    Medical

    In the United States, methamphetamine hydrochloride, under the trade nameDesoxyn, has been approved by the USFDA for treating
    and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children; however, the USFDA also indicates that the limited therapeutic usefulness of methamphetamine should be weighed against the inherent risks associated with its use. In the United States,
    is available in some over-the-counter nasal decongestant products, such as Vicks Vapoinhaler.

    As methamphetamine is associated with a high potential for misuse, the drug is regulated under the
    and is
    in the United States.
    Methamphetamine hydrochloride dispensed in the United States is required to include the following


    “Methamphetamine has a high potential for abuse and should be tried only in weight reduction programs where alternative therapy has been ineffective. Administration of Methamphetamine for prolonged periods may lead to drug dependence. The drug should be prescribed or dispensed sparingly. Misuse may cause sudden Dead and serious cardiovascular adverse events.”

    Recreational

    See also:
    and the

    Methamphetamine is often used recreationally for its effects as a potent
    ,
    , and stimulant. According to a
    TV documentary on methamphetamine, "an entire subculture known as party and play is based around methamphetamine use."Members of this sub-culture in
    , which consists almost entirely of homosexual male methamphetamine users, will typiCally meet up through internet dating sites and have sex. Due to its strong stimulant and aphrodisiac effects and inhibitory effect on
    , with repeated use, these sexual encounters will sometimes occur continuously for several days.The crash following the use of methamphetamine in this manner is very often severe, with marked
    .

    Contraindications

    Methamphetamine is
    in individuals with a history of
    ,Love
    , or severe
    or anxiety, or in individuals currently experiencing
    ,
    ,
    , or severe
    . The USFDA states that individuals who have experienced
    reactions to other stimulants in the past or are currently taking
    should not take methamphetamine. The USFDA also advises individuals with
    ,
    , elevated
    , liver or kidney problems,
    ,
    ,
    ,
    ,
    problems,
    , or
    to monitor their symptoms while taking methamphetamine. Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of growing children and adolescents during treatment.

    Side effects

    Physical

    The physical effects of methamphetamine can include
    , hyperactivity,
    ,
    ,
    ,
    , dry mouth and
    (leading to "
    "), headache,
    (usually as
    or
    ),
    ,
    ,
    ,
    , diarrhea, constipation,
    ,
    ,
    ,
    ,
    , dry skin,
    , and
    .Methamphetamine that is present in a mother's
    can pass through the
    to a
    and is or be secreted into
    . Infants born to methamphetamine-abusing mothers were found to have a significantly smaller
    age-adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with
    symptoms of agitation, vomiting and
    . This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.

    Meth mouth

    Main article:

    Methamphetamine users and addicts may lose their teeth abnormally quickly, regardless of the route of administration, from a condition informally known as
    . The condition is generally most severe in users who inject the drug, rather than those who smoke, ingest or inhale it. According to the
    , meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in
    (dry mouth), extended periods of poor
    , frequent consumption of high-calorie, carbonated beverages and
    (teeth grinding and clenching)."Many researchers suggest that meth-induced tooth decay is due to users' lifestyles, as dry mouth is also a side effect of prescription stimulants, which aren't known to cause serious tooth decay. They suggest that that the side effect has been exaggerated and stylized to deter potential users and stereotype current users.

    Psychological

    The psychological effects of methamphetamine can include
    ,
    , changes in
    ,
    , apprehension,
    , decreased sense of fatigue,
    or
    ,
    , sociability, irritability, restlessness,
    and
    behaviors. Methamphetamine use also has a high association with
    ,
    ,
    ,Bomb, and violent behaviors. Methamphetamine also has a very high
    risk.

    Neurotoxicity

    Unlike
    , methamphetamine is directly
    to dopamine neurons. Moreover, methamphetamine abuse is associated with an increased risk of
    due to excessive pre-synaptic dopamine
    , a mechanism of neurotoxicity. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to
    neurons. It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine. As a result of methamphetamine-induced
    to
    , chronic use may also lead to
    which persist beyond the withdrawal period for months, and even up to a year.

    Sexually transmitted infection

    Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners, an association more pronounced in HIV-positive participants. These findings suggest that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors, behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men. Methamphetamine use allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions as well as
    in men. Methamphetamine may also cause sores and abrasions in the mouth via
    , increasing the risk of sexually transmitted infection.

    Besides the sexual transmission of HIV, it may also be transmitted between users who
    . The level of needle sharing among methamphetamine users is similar to that among other drug injection users.

    Dependence, addiction, and withdrawal

    See also:

    is expected to develop with regular methamphetamine use and, when abused, this tolerance develops rapidly.

    The evidence on effective treatments for Амф and methamphetamine dependence and abuse is limited. In light of this,
    and
    appear to have some limited benefits in treating abuse and addiction, "no treatment has been demonstrated to be effective for the treatment of [methamphetamine] dependence and abuse."

    In highly dependent Амф and methamphetamine abusers, "when chronic heavy users abruptly discontinue [methamphetamine] use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week. Methamphetamine withdrawal symptoms can include anxiety,
    ,
    ,
    ,
    ,
    or
    ,
    ,
    or
    , and
    . Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse). The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of
    withdrawal.

    Overdose

    A methamphetamine overdose may result in a wide range of symptoms.Love A moderate overdose of methamphetamine may induce symptoms such as:
    , confusion,
    , high or low blood pressure, hyperthermia,
    ,
    , severe agitation,
    ,
    ,
    , and
    .
    An extremely large overdose may produce symptoms such as
    ,
    ,
    ,
    ,
    ,
    ,
    ,
    ,
    ,
    ,
    , and a form of
    ("tweaking").
    A methamphetamine overdose will likely also result in mild
    due to
    and
    neurotoxicity. Death from fatal methamphetamine poisoning is typiCally preceded by convulsions and
    .

    Emergency treatment

    The USFDA states that acute methamphetamine intoxication is largely managed by treating the symptoms and includes
    , administration of
    , and
    . There is not enough evidence on
    or
    in cases of methamphetamine intoxication to determine their usefulness.
    (e.g., with
    ) will increase methamphetamine excretion, but increases the risk of
    in the presence of
    . Intravenous (IV)
    may be useful for acute cases of severe hypertension if the condition complicates methamphetamine overdose. Blood pressure often drops gradually following sufficient sedation.
    may be useful in decreasing the stimulant and CNS effects of a methamphetamine overdose.

    Psychosis

    The main section for this topic is on the page
    , in the section
    .
    Abuse of methamphetamine can result in a stimulant psychosis which may present with a variety of symptoms (e.g.
    ,
    ,
    ). A
    review on treatment for Амф, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely. The same review asserts that, based upon at least one trial,
    medications effectively resolve the symptoms of acute Амф psychosis.
    may also develop occasionally as a treatment-emergent side effect.

    Interactions

    Methamphetamine is metabolized by the liver enzyme
    , so CYP2D6 inhibitors (e.g.,
    (SSRIs)) will prolong the
    of methamphetamine. Methmphetamine also interacts with
    (MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous. Methamphetamine may decrease the effects of
    and
    and increase the effects of
    and
    as well. Methamphetamine may counteract the effects of
    and
    due to its effects on the cardiovascular system and cognition respectively. The
    of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. SpecifiCally, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite.Due to the effect pH has on absorption,
    , which reduce gastric acid, are known to interact with methamphetamine.

    Pharmacology



    This illustration depicts the normal operation of the
    terminal to the left, and the dopaminergic terminal in presence of methamphetamine to the right. Methamphetamine reverses the action of the dopamine transporter (DAT) by activating
    (not shown). TAAR1 activation also causes some of the dopamine transporters to move into the presynaptic neuron and cease transport (not shown). At VMAT2 (labeled VMAT), methamphetamine causes dopamine efflux (release).

    Pharmacodynamics

    Like Амф, methamphetamine has been identified as a potent
    of
    (TAAR1), a
    (GPCR) that regulates brain
    systems. Activation of TAAR1, via
    , increases
    (cAMP) production and either completely inhibits or reverses the transport direction of the
    (DAT),
    (NET), and
    (SERT). When methamphetamine binds to TAAR1, it triggers transporter
    via
    (PKA) and
    (PKC) signaling, ultimately resulting in the
    or reverse function of
    . Other
    that methamphetamine is known to inhibit are
    (VMAT1),
    (VMAT2),
    , and
    . SLC22A3 is an extraneuronal monoamine transporter that is present in
    and SLC22A5 is a high-affinity
    transporter. When methamphetamine interacts with VMAT2, it induces a release of monoamines from the
    (vesicles that stores monoamines) into the
    (intracellular fluid) of the
    .

    Methamphetamine is also an
    of the
    and
    , and inhibits
    (VMAT1),
    (MAO-B), and
    (MAO-A). Methamphetamine is known to inhibit the CYP2D6 liver enzyme as well. Dextromethamphetamine is a stronger
    , but levomethamphetamine has a longer half-life and is
    -active with weaker effects (approximately one-tenth) on striatal dopamine and shorter perceived effects among addicts. At high doses, both enantiomers of methamphetamine can induce
    and
    , but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile.

    Although all of the mechanisms are not fully understood, methamphetamine is a known neurotoxin in both lab animals and humans. Beyond neurotoxicity,
    studies on human methamphetamine addicts and abusers indicate adverse
    changes, such as significant abnormalities in various brain structures. In particular, methamphetamine appears to cause
    and
    , marked shrinkage of
    , and a reduction in
    in the
    ,
    , and
    . Moreover, there are adverse changes in various metabolic markers of metabolic integrity or synthesis in methamphetamine abusers, such as reductions in
    and
    as well as elevated
    and
    levels.

    Comparison to Амф pharmacodynamics

    Both Амф and methamphetamine are potent
    stimulants with a few
    and affected transporters in common; however, there are important
    differences between the two compounds.Both compounds are potent
    (TAAR1) agonists (causing non-competitive inhibition of
    ,
    , and
    ) and inhibitors of
    ,
    , and
    .However, methamphetamine appears to bind at a different site at VMAT2 than Амф. Methamphetamine also inhibits
    , has
    activity at all
    and
    subtypes, and is directly toxic to dopamine neurons in humans, whereas there is no evidence of acute Амф toxicity in humans. Sigma receptor activity is known to potentiate the stimulant and neurotoxic effects of methamphetamine.

    In contrast to the adverse neuroplastic effects evident in methamphetamine addicts and abusers, long-term use of Амф or methylphenidate at therapeutic doses appears to produce beneficial changes in brain function and structure, such as normalization of the
    .
     
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    Charles Darwin, 3/5/14
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