Background: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling cannabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug’s efficacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake. Methods: Relevant studies reporting CBD’s AEs or toxicity were identified from PubMed, Cochrane Central, and EMBASE through January 2019. Studies defining CBD’s beneficial effects were included to provide balance in estimating risk/benefit. Results: CBD is not risk-free. In animals, CBD AEs included developmental toxicity, embryo-fetal mortality, central nervous system inhibition and neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive system alterations, and hypotension, although at doses higher than recommended for human pharmacotherapies. Human CBD studies for epilepsy and psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormalities, diarrhea, fatigue, vomiting, and somnolence. Conclusion: CBD has proven therapeutic efficacy for serious conditions such as Dravet and Lennox-Gastaut syndromes and is likely to be recommended off label by physicians for other conditions. However, AEs and potential drug-drug interactions must be taken into consideration by clinicians prior to recommending off-label CBD.

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In recent years, the evaluation of in utero exposure to drugs of abuse has been achieved by testing biological matrices coming from the fetus or newborn (eg, meconium, fetal hair, cord blood, neonatal urine), the pregnant or nursing mother (eg, hair, blood, oral fluid, sweat, urine, breast milk), or from both the fetus and the mother (placenta, amniotic fluid). Overall, these matrices have the advantage of noninvasive collection (with the exception of amniotic fluid) and early detection of exposure from different gestational periods. Matrices such as amniotic fluid, meconium, fetal hair, and maternal hair provide a long historical record of prenatal exposure to certain drugs and can account for different periods of gestation: amniotic fluid from the early pregnancy, meconium for the second and third trimester of gestation, fetal hair for the third, and finally maternal hair (when long enough) for the whole pregnancy. Placenta may reveal the passage of a substance from the mother to the fetus. Cord blood and neonatal urine are useful for determining acute exposure to drugs of abuse in the period immediately previous to delivery. Drug detection in maternal blood, oral fluid, and sweat accounts only for acute consumption that occurred in the hours previous to collection and gives poor information concerning fetal exposure. Different immunoassays were used as screening methods for drug testing in the above-reported matrices or as unique analytical investigation tools when chromatographic techniques coupled to mass spectrometry were not commonly available. However, in the last decade, both liquid and gas chromatography-mass spectrometric methodologies have been routinely applied after appropriate extraction of drugs and their metabolites from these biological matrices.

Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.

After fewer than 3 years from the opening of the first Italian e-cigarette shop, more than 45 million Italians have heard about e-cigarettes, 3.5 million have tried e-cigaretts, and more than 600,000 Italians regularly use e-cigarettes. Three out of 4 e-cigarette users reported to have favorably modified their smoking habit; however, 90% of users did not quit smoking as a consequence of starting vaping e-cigarettes. Almost 900,000 Italian never-smokers, particularly young never-smokers, have tried this new and potentially addictive product at least once.

As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.

Up to now, little is known about the metabolic pathways of new fentanyl analogs that have recently emerged on the drug markets worldwide with high potential for producing addiction and severe adverse effects including coma and death. For some of the compounds, limited information on the metabolism has been published, however, for others so far no information is available. Considering the well characterized metabolism of the pharmaceutically used opioid fentanyl and the so far available data, the metabolism of the new fentanyl analogs can be anticipated to generally involve reactions like hydrolysis, hydroxylation (and further oxidation steps), N - and O -dealkylation and O -methylation. Furthermore, phase II metabolic reactions can be expected comprising glucuronide or sulfate conjugate formation. When analyzing blood and urine samples of acute intoxication cases or fatalities, the presence of metabolites can be crucial for confirmation of the uptake of such compounds and further interpretation. Here we present a review on the metabolic profiles of new fentanyl analogs responsible for a growing number of severe and fatal intoxications in the United States, Europe, Canada, Australia, and Japan in the last years, as assessed by a systematic search of the scientific literature and official reports.

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