Drug addiction is a chronic, relapsing brain disorder. The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies. The aim of the present study was to prospectively assess brain structural markers for escalating drug use in two independent samples of occasional amphetamine-type stimulant users. At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine (cumulative lifetime use ≤10 units) underwent structural brain imaging and were followed up at 12 months and 24 months (Study 1, n = 38; Study 2, n = 28). Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period. Participants in both samples who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and, additionally, in the basolateral amygdala (Study 1) and dorsal striatum (Study 2). In both samples the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months. Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine. These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant use.
A fatal case of nicotine intoxication by oral intake of a nicotine solution, sold via the Internet, is reported. The concentrated nicotine solution (72 mg/mL) is usually diluted with polypropylene, polyethylene glycol or glycerine, respectively, in order to allow the user to generate their own solution for vaporisation in electronic cigarettes (e-juice). A 34-year-old man was found lifeless by his parents, who reported that their son had been in good health and had shown no hints of suicidal behaviour. The medicolegal autopsy revealed unspecific findings. Toxicological analysis revealed nicotine concentrations of 5.5 mg/L in femoral venous blood, 136 mg/L in heart blood, 12.0 mg/kg in brain tissue, 42.6 mg/kg in kidney tissue, 89.5 mg/kg in lung tissue and a total amount of 3,950 mg in the gastric contents. Cotinine concentrations were 0.9 mg/L in femoral venous blood, 7.6 mg/L in heart blood, 0.4 mg/kg in brain tissue, 0.9 mg/kg in kidney tissue and 0.8 mg/kg in lung tissue. No cotinine was detected in the gastric contents. The nicotine level measured in the femoral blood was in good accordance with the levels reported in other fatal cases caused by oral or patch application of nicotine. Moreover, the high level of nicotine in lung and kidney tissue, compared to that within femoral blood, strikingly emphasises the strong effect of post-mortem redistribution, underlined by the comparably low concentration of nicotine in the brain. The extremely high level of nicotine in the heart blood is more likely due to the high concentration in the gastric contents, due to oral intake, and by accumulation of the basic substance in the acidic gastric contents. This further highlights the effect of post-mortem redistribution. The mother of the deceased later admitted that her son had been suffering from psychosis and that she found a package containing five nicotine solution vials of the brand "Titanium Ice" (of 50 mL each). Three of the vials were empty. The nicotine concentration in the e-juice Titanium Ice was confirmed by HPLC analysis.
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