Cerebral blood flow effects of acute intravenous heroin administration.

We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

Decreased frontal white-matter volume in chronic substance abuse.

There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.

Magnetic seizure therapy improves mood in refractory major depression.

This report describes the successful treatment of a patient suffering from an episode of drug-resistant major depression using magnetic seizure therapy (MST). The patient suffered from recurrent major depression since adolescence. MST is a novel brain stimulation method using transcranial magnetic stimulation at convulsive parameters in order to induce therapeutic seizures under general anesthesia in the same setting used for electroconvulsive therapy (ECT). The first use of therapeutic magnetic seizure induction in a psychiatric patient took place at the University Hospital in Bern, Switzerland, in May 2000. Results of a recent randomized, within-subject, double-masked trial comparing ECT and MST in 10 patients indicate that MST appears to have less subjective and objective side effects, is associated with faster recovery of orientation, and is superior to ECT on measures of attention, retrograde amnesia, and category fluency. ECT has an unparalleled and well-documented efficacy in severe depression but is associated with cognitive side effects. MST is currently under study in several centers with respect to its antidepressant efficacy. We report here on the treatment of a patient with refractory major depression (DSM IV-R), who underwent a series of 12 sessions of MST in an inpatient setting. Baseline Hamilton Depression Rating Scale (HRSD-21) of 33 and Beck Depression Inventory (BDI) of 40 decreased to 6 and 11 respectively, 1 week after completion of the MST trial. Measures of cognitive functions support the hypothesis that MST is associated with a less severe profile of cognitive side effects. [(99m)Tc]-HMPAO SPECT studies (baseline and 4 days after the completion of the MST trial) point to a raise of blood flow at baseline in the left fronto-parietal region and the brainstem. Our preliminary data support the prospect of antidepressant efficacy of MST and point to a benign cognitive side-effect profile in a patient suffering from severe treatment-resistant major depression.