Methamphetamine use can worsen brain damage caused by HIV infection

Long-term heavy use of methamphetamine can exacerbate the damage to brain cells caused by HIV, according to a study presented in the February edition of The American Journal of Psychiatry. Although both methamphetamine use and HIV infection contributed to brain damage, the study showed that their effects were additive, and not due to a more complex interaction between HIV and drug use.

Methamphetamine (‘crystal meth’ or ‘ice’) is a psychostimulant drug that is commonly used by HIV-positive and –negative people. It can be injected, smoked or ‘snorted’. The use of methamphetamine has been identified as an important factor in the spread of HIV, not only through unsafe injection practices, but also through its association with increased rates of unprotected sex in both men and women.

Studies have shown that long-term methamphetamine users exhibit similar changes in behaviour to patients with HIV-associated dementia. These include slowed reaction times and poor decision-making, memory, attention and concentration skills.

As previous investigations have suggested that similar toxic effects in the brain cause these psychological effects, this study set out to determine how methamphetamine use affected the development of brain abnormalities caused by HIV.

Investigators from Hawaii, California and Germany carried out brain scans on 68 HIV-positive and 75 HIV-negative volunteers. Twenty-four of the HIV-positive, and 36 of the HIV-negative subjects had a history of methamphetamine dependence or abuse. This was defined as methamphetamine use for at least a year as the primary drug of abuse, with an average dose of at least 0.25g per day on two or more days per week.

The investigators scanned three regions of each volunteer’s brain using a technique called proton magnetic resonance spectroscopy. This allowed them to measure the levels of the metabolite N-acetylaspartate, a marker of neurones, the electrically active cells that transmit signals through the brain. They also measured levels of choline and myo-inositol, which are found in the brain’s structural ‘glial’ cells.

Volunteers with a history of methamphetamine use showed lower concentrations of N-acetylaspartate in the ‘basal ganglia’ (-4%, p = 0.03), an area of the brain involved in the co-ordination of movement. In agreement with previous studies, this indicated that there had been damage to neurones in this brain region.

In contrast, methamphetamine users had higher levels of choline in the ‘frontal white matter’ (5%, p = 0.03) and the ‘frontal cortex’ (10%, p = 0.008). Myo-inositol levels were also 9% higher in the frontal cortex (p = 0.009), suggesting that inflammation had occurred in these areas of the brain, which are involved in thinking, planning and decision-making.

HIV infection caused similar patterns of change. The HIV-positive volunteers had lower levels of N-acetylaspartate in the frontal cortex (-5%, p = 0.001) and in the basal ganglia (-5%, p = 0.004) than the participants who were uninfected. They also had higher levels of myo-inositol in the frontal white matter (7%, p = 0.01).

In all three brain regions, there was an additive effect of methamphetamine and HIV on the levels of N-acetylaspartate (basal ganglia: -9%, p

“The HIV-positive subjects with a history of chronic methamphetamine use had the lowest concentration of N-acetylaspartate in all three brain regions studied, compared to the other three subject groups,” state the investigators. “This finding suggests significant neuronal loss or dysfunction in these brain regions."

Similarly, HIV and methamphetamine use had an additive effect on creatine levels in the basal ganglia (-7%, p = 0.007) and on myo-inositol in the frontal white matter (12%, p = 0.02).

The investigators speculate that the additive effect of HIV and methamphetamine may be related to the drug’s effect on the neurotransmitter dopamine. Methamphetamine causes the release of massive amounts of dopamine from the ends of neurones, notably in the basal ganglia. This release of dopamine often causes the ends of the neurones to shrivel and eventually die back. The researchers hypothesise that this release of dopamine can also stimulate HIV replication and worsen the damage caused by the drug.

“As predicted, the region most affected was the basal ganglia, which has the highest density of dopaminergic nerve terminals,” they explain. “One possible pathway to the combined neurotoxicity might be a methamphetamine-induced increase in extracellular dopamine, which in turn would activate HIV replication.”

These results from brain scans of living volunteers mirror previous findings from animal experiments and post mortem studies of human brain. “Future studies using other non-invasive neuroimaging techniques...may provide further insights into the in vivo pathophysiological changes associated with the combined effects of HIV and methamphetamine,” the investigators conclude.