Paola Cassandro

Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans

To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of human melatonin production, we studied the effects of the acute administration of the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24-33 years, underwent three experimental sessions in which they received orally 400 mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind design. The drug administration was done at 19:00 hours; thereafter, blood samples were collected over the night, in dark conditions with the help of a red light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one. The maximum suppression coincided with the highest plasma levels of valproic acid. These findings support the view that endogenous GABA may participate in the modulation of the activity of the human pineal gland.

Prolactin hyperresponsiveness to D-fenfluramine in drug-free schizophrenic patients: a placebo-controlled study.

BACKGROUND Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided. In the present study, we investigated the prolactin (PRL) response to the selective serotonin (5-HT) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects. METHODS Sixteen drug-free schizophrenics and 16 healthy subjects were randomized in a double-blind neuroendocrine test to D-fenfluramine (30 mg p.o.) or placebo. Blood PRL and cortisol concentrations were determined by radioimmunoassay, while plasma levels of D-fenfluramine were measured by mass spectrometry. RESULTS In schizophrenic patients, baseline plasma PRL levels were not different from controls, whereas plasma cortisol concentrations were significantly increased (p < .03). The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects (p < .005). Schizophrenics meeting Kanes criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients (p < .04). No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects. CONCLUSIONS These findings suggest a serotonergic hypersensitivity in chronic schizophrenia. This alteration seems to be peculiar to those patients refractory to typical neuroleptics.

Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence

Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. “Drug vaccines” aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, “cocaine and nicotine vaccines” have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.

A five years study on drug-related deaths in Campania (Italy)

OBJECTIVES The study regards n. 267 drug related deaths submitted to toxicological analyses for forensic purpose, since 2008 to 2012, at the Laboratory of Forensic Toxicology of the Second University of Napoli (SUN), Italy. Among the cases studied (94% males and 6% females) the 13.1% regards foreign citizens. METHODS For each case autopsy findings and all drugs detected were recorded. In addition other epidemiological data such as age, race, gender, place and circumstance of death were also supplied. A systematic toxicological analysis (STA) for illicit drug, other pharmaceuticals, new psychotropic substances and ethanol has been applied on the specimens collected at autopsy and all positive results were confirmed by a quantitative analysis (GC/MS or LC-MS/MS). RESULTS Toxicological results shows that simultaneous use of multiple illicit drugs was responsible of the largest mortality rate (57.7%), in both males and females. In the polydrug use the cocaine was the most detected substance. The association of heroin/cocaine was identified in the 22.5% of deaths. The finding of only one drug was correlated with an opiate drug for the 14.2% and with cocaine for the 4.5% of cases. The distribution by age and gender demonstrates an increase in deaths among males aged over 30 years and among women older than 35 years. The territorial distribution of the deaths in the different surrounding areas and in the residential quarters of the Naples city demonstrates that the 76% of deaths occurred in a place different from the usual residence. CONCLUSION Results obtained demonstrate that prevails, at present, the need to specifically explore the changing patterns of polydrug use among addicts, because studying the prevalence of mortality subsequent to the consumption of a single illicit drug may be insufficient to guide preventive policies in public health.

Alcohol and drugs use among drivers injured in road accidents in Campania (Italy): A 8-years retrospective analysis

A recent update of the Italian Road Traffic Law (RTL 41/2016), established severe penal sanctions when drivers, driving under the influence of alcohol (DUI) or drugs (DUID), are involved in road accident that results in death or injuries. A study was carried out to assess the trends of consumption of alcohol, illicit drugs or pharmaceutical among injured drivers suspected for DUI or DUID from 2009 to 2016 in the region of Campania (Italy). Confirmation toxicological analyses were performed on 780 blood samples and 1017 urine samples collected from 1797 injured drivers. These drivers all tested positive for alcohol or drug use through immunoassay screening applied at hospital emergency units and their biological samples transferred to the Forensic Reference Laboratory (FRL) for confirmation analysis. The GC/HS-FID methodology was used to test Blood Alcohol Concentration (BAC). Qualitative and quantitative analyses for drugs were performed using the GC/MS or LC-MS/MS methodology. The BAC >0.5g/L was confirmed in 91.5% of drivers suspected for DUI cases and in 93% of DUID respectively. In DUI cases, results show an increasing incidence of road accidents involving drivers with BAC above 1.5g/L while at concentrations above 0.8g/L alcohol and drugs are both used. Among the suspected DUID cases, the intake of alcohol in association with drugs has consistently increased over time and positive results on blood samples was confirmed for multiple drugs (20%) or cannabis and cocaine alone (18%) followed by benzodiazepines (6%) and methadone (3.5%) respectively. The majority of injured drivers suspected for DUID (1017 cases) did not authorize blood sampling, therefore only urine was analyzed showing the prevalent use of cannabis, followed by multiple drug>cocaine>benzodiazepines>opiates. Among 1797 drivers, suspected at screening for DUI or DUID, 15.4% of cases (64 blood and 213 urine samples) were not confirmed by GC/HS, GC/MS or LC-MS/MS analysis. In forensic toxicological investigations, it is mandatory to satisfy the best quality standards, which is not achievable if immunochemical screening is only performed on urine. Therefore, only confirmed positive results of alcohol or drugs on blood samples can represent conclusive evidence to demonstrate the DUI or DUID related offences. An improvement of the protocols currently applied in Italy for the assessment of DUI or DUID crimes is needed and the confirmation analysis on blood should be considered mandatory.