How is methamphetamine abused?

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

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Methamphetamine is structurally similar to amphetamine and the neurotransmitter dopamine, 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 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. This results in methamphetamine being present in the brain longer, which ultimately leads to prolonged stimulant effects. And although both methamphetamine and cocaine increase levels of the brain chemical dopamine, animal studies reveal much higher levels of dopamine following administration of methamphetamine due to the different mechanisms of action within nerve cells in response to these drugs. Cocaine prolongs dopamine actions in the brain by blocking dopamine re-uptake. While at low doses, methamphetamine blocks dopamine re-uptake, methamphetamine also increases the release of dopamine, leading to much higher concentrations in the synapse, which can be toxic to nerve terminals.

 

Methamphetamine vs. Cocaine

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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.

Dopamine Pathways

In the brain, dopamine plays an important role in the regulation of reward and movement. As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral 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 release dopamine into the striatum.

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Long-term methamphetamine abuse has many negative consequences, including addiction. Addiction is a chronic, relapsing disease, characterized by compulsive drug seeking and use, accompanied by functional and molecular changes in the brain. In addition to being addicted to methamphetamine, chronic abusers exhibit symptoms that can include anxiety, confusion, insomnia, mood disturbances, and violent behavior. They also can 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 methamphetamine abuse has ceased, and stress has been shown to precipitate spontaneous recurrence of methamphetamine psychosis in formerly psychotic methamphetamine abusers.

With chronic abuse, tolerance to methamphetamine's pleasurable effects can develop. In an effort to intensify the desired effects, abusers may take higher doses of the drug, take it more frequently, or change their method of drug intake. 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.

Recovery of Brain Dopamine Transporters in Chronic Methamphetamine (METH) Abusers

Chronic methamphetamine abuse also significantly changes the brain. Specifically, brain imaging studies have demonstrated alterations in the activity of the dopamine system that are associated with reduced motor speed and impaired verbal learning. Recent 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.

Fortunately, some of the effects of chronic methamphetamine abuse appear to be, at least partially, reversible. A recent neuroimaging study showed recovery in some brain regions following prolonged abstinence (2 years, but not 6 months). This was associated with improved performance on motor and verbal memory tests. However, function in other brain regions did not display recovery even after 2 years of abstinence, indicating that some methamphetamine-induced changes are very long-lasting. Moreover, the increased risk of stroke from the abuse of methamphetamine can lead to irreversible damage to 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

Long-term effects may include: Addiction Psychosis, including: paranoia hallucinations repetitive motor activity Changes in brain structure and function Memory Loss Aggressive or violent behavior Mood disturbances Severe dental problems Weight loss