Effects of Methamphetamine Abuse on Neurotransmission

Methamphetamine is a synthetically derived substance with a high potential for abuse and dependence (Nordahl et al., 2003; Volkow et al., 2001). The abuse of methamphetamine has grown rapidly throughout the United States since the early 1990’s. The widespread availability of methamphetamine is largely due to the fact that it can be manufactured using chemicals found at a local hardware or drugstore. According to the U.S. Drug Enforcement Agency (DEA), “among the controlled substances manufactured underground in the United States, methamphetamine is the most prevalent, and it is one of the commonly abused controlled substances that can be made in the home” (Nordahl et al., 2003, p. 318). The national increase in methamphetamine abuse led to the development of the Comprehensive Methamphetamine Control Act of 1996 and the Methamphetamine and Club Drug Anti-Proliferation Act of 2000 (Nordahl et al., 2003). These acts of national legislation were designed to increase the awareness of methamphetamine use and the dangers associated with its abuse.

The national rise in methamphetamine abuse also led to a public demand for the discovery and understanding of the n

The neurotoxic effects of methamphetamine are associated with significant changes in the mesostriatum and prefrontal cortex regions of the brain (Nordahl et al., 2003). The depletion of dopamine in these regions is related to impaired performance on tests measuring various cognitive tasks. Dopamine depletion in the mesostriatum is associated with decreased reaction time, while damage to the prefrontal cortex causes problems with the establishment of attentional sets. According to Nordahl et al. (2003), methamphetamine abusers show impairments in verbal memory and motor functioning when compared to non-abusers. They also perform significantly worse on tests of memory recall and tests that measure manipulation of information. Tasks that measure abstract reasoning and shifting strategies also indicate neurocognitive impairments in methamphetamine-dependent individuals. In general, methamphetamine abusers have difficulty sustaining attention and appear susceptible to distraction. This is most likely related to their difficulty in suppressing irrelevant task information.

The information from the PET scans was then compared to the performance on neuropsychological tests designed to measure psychomotor deficits in the frontal lobe and striatum. The analysis revealed that reductions in dopamine transporters are related to impaired performance on tasks measuring motor responses and memory changes. The degree of dopamine transporter reduction is able to predict the performance on motor and memory tests, meaning that low measures of dopamine transporters resulted in poorer performance. There is also an indication that an interaction exists between age and dopamine transporter reductions in methamphetamine abusers. Volkow et al. also proposed the possibility that nicotine acts as a protective agent against the neurotoxic effects of methamphetamine. The evidence from this study supports the belief that methamphetamine abuse leads to dopamine transporter reduction that then causes psychomotor impairment.

Methamphetamine is a synthetically derived stimulant with highly reinforcing effects. Large amounts of methamphetamine are able to rapidly cross the blood-brain barrier due to its high lipid solubility, causing it to be rapidly addicting (Nordahl et al., 2003). When taken in low doses, methamphetamines increase energy levels, causing enhanced attentiveness and alertness. When taken in high doses, methamphetamines create feelings of euphoria and a sense of well-being, often facilitating an enhanced self-esteem. The side effects include suppressed appetite, insomnia, restlessness, and irritability. Long-term use of methamphetamines can cause impairments to sexual functioning, compulsive behaviors, and extreme paranoia. The paranoia can develop into an actual psychosis with symptoms that are identical to paranoid schizophrenia. Withdrawal symptoms occur after long-term use of methamphetamines has been stopped. Individuals may experience feelings of irritability, agitation, and lack of motivation, in addition to experiencing extreme cravings for the drug.

In a study conducted by Volkow et al. (2001a), methamphetamine abusers underwent positron emission tomography (PET) scans in order to measure changes in the dopamine transporter and determine their role in psychomotor functioning. The PET scans produced images of two areas within the striatum region, identified as the caudate and putamen, as well as the cerebellum region, which were used to measure dopamine transporter availability. The image analysis revealed that dopamine transporter availability in both the caudate and putamen was significantly lower in methamphetamine abusers. Volkow et al. also found significant correlations in the caudate and putamen regions between the years of methamphetamine abuse and dopamine transporter levels.

It is still uncertain as to the relationship between dopamine transport recovery and the cognitive impairments caused by dopamine depletion (Zic

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