MRS glutamate measures reflect heroin craving

New MR spectroscopy findings indicate that changes in brain glutamate levels reflect changes in heroin craving among addicts during methadone maintenance therapy. MRS may eventually help predict if addicts will relapse after treatment.

Animal studies have previously shown that glutamate is involved in the development and expression of drug addiction. Drug exposure and withdrawal change the glutamate levels in the anterior cingulate cortex, ventral striatum, thalamus, and hippocampus.

Dr. Mark Greenwald and colleagues at Wayne State University established for the first time in a pilot study that glutamate changes can be measured in humans. Their data, presented by coauthor Dr. Jeffrey Stanley, demonstrate a significant correlation between glutamate levels and heroin craving during methadone detoxification therapy.

Six heroin addicts, five men and one woman, were involved. Their ages ranged from 31 to 55 years. Two healthy age-matched controls also participated.

Baseline H-1 MR spectroscopic scans, performed on a 4T Bruker scanner, were completed several days after the start of treatment. Methadone administrations had been ramped up and stabilized at a dose of 100 mg/day. Following a standard treatment regimen, dosage was then reduced to 25 mg/day for five subjects. For one male subject, the dose was cut to 10 mg/day.

Follow-up MRS evaluations were performed about one month after the baseline scan, several weeks after the dose had been scaled down. Imaging data were acquired during a required three-day hospital stay while methadone use and drug cravings were closely monitored.

Imaging was performed using a short T1 PRESS sequence. Voxels with the dimensions of 2 x 1.5 x 1.5 mm were placed in the midline anterior cingulate cortex and thalamus.

All patients showed significantly lower glutamate levels in the anterior cingulate while they received the high methadone dosage than during lower dose administrations (p<0.05). The same trend was observed in the thalamus, but the change was not statistically significant, Stanley said.

Three patients were taking cocaine during methadone treatment, and two of them showed the greatest change in glutamate during the transition between high- to low-dose methadone therapy, Stanley said. The cocaine users also showed a higher heroin craving during high-dose methadone treatment.

The results are preliminary, but they show a strong correlation between the change in glutamate level and the intensity of drug craving (r = 0.85, p<0.4). They suggest that observed changes in glutamate could be used as a biomarker for opiate-dependent states, according to Stanley.

Confirmation will come with additional trials involving more patients. Key questions for future work will include whether glutamate measures with MRS can be used to monitor treatment and predict its success, he said.