Herbal highs: review on psychoactive effects and neuropharmacology

Background: A new trend among users of new psychoactive substances’ the consumption of “herbal highs”: plant parts containing psychoactive substances. Most of the substances extracted from herbs, in old centuries were at the centre of religious ceremonies of ancient civilizations. Currently, these herbal products are mainly sold by internet web sites and easily obtained since some of them have no legal restriction. Objective: We reviewed psychoactive effects and neuropharmacology of the most used “herbal highs” with characterized active principles, with studies reporting mechanisms of action, pharmacological and subjective effects, eventual secondary effects including intoxications and/or fatalities Method: The PubMed database was searched using the following key.words: herbal highs, Argyreia nervosa, Ipomoea violacea and Rivea corymbosa; Catha edulis; Datura stramonium; Piper methysticum; Mitragyna speciosa. Results: Psychoactive plants here reviewed have been known and used from ancient times, even if for some of them limited information still exist regarding subjective and neuropharmacological effects and consequent eventual toxicity when plants are used alone or in combination with “classical” drugs of abuse. Conclusion: Some “herbal highs” should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking

An “Escape Clock” for Estimating the Turnover of SIV DNA in Resting CD4+ T Cells

Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an “escape clock” approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT) SIV DNA present in early infection by CTL escape mutant (EM) strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication

Pharmacotoxicology and analytical issues of gamma-hydroxybutyric acid in clinical and forensic laboratory

Gamma-hydroxybutyric acid (GHB) can be considered both an endogenous metabolite and a precursor of the neurotransmitter gamma-aminobutyric acid (GABA) acting within the central nervous system as a neuromodulator. Pharmacologically, GHB is classified as a central nervous system depressant and its mechanism of action involves interaction and binding with GABA-B receptors. With the generic name of sodium oxybate, the sodium salt of GHB, is sold as a pharmaceutical product under the trade name of Xyrem® when prescribed for the treatment of people with narcolepsy and with the name of Alcover® when used to relieve alcohol withdrawal syndrome and treat alcohol dependence. Between the end of the 90s of the twentieth century and the beginning of the twenty-first one, the abuse of GHB became increasingly widespread in the recreational field. The substance, often consumed in combination with alcohol, cannabis, ecstasy (3,4-Methylenedioxymethamphetamine, MDMA), ketamine, has been converted in one of the most used "club drugs", becoming one of the most serious health issues in the emergency department of many European and extra-European Countries because of the initial difficult clinical management of the growing number of cases of intoxication. At the same time, there was an increase of cases of sexual assaults of victims who were unaware they had been given GHB as odourless and colourless sedative substance. In this narrative review, the three different aspects of GHB as endogenous neuromodulator, as prescription drug and as substance of abuse are illustrated. The main methods for qualitative and quantitative analysis in conventional and non-conventional biological matrices for clinical and forensic purposes are also describe

Determination of cannabinoids in oral fluid and urine of "light cannabis" consumers: a pilot study

Background In those countries where cannabis use is still illegal, some manufacturers started producing and selling "light cannabis": dried flowering tops containing the psychoactive principle Δ-9-tetrahydrocannabinol (THC) at concentrations lower than 0.2% together with variable concentration of cannabidiol (CBD). We here report a pilot study on the determination of cannabinoids in the oral fluid and urine of six individuals after smoking 1 g of "light cannabis". Methods On site screening for oral fluid samples was performed, as a laboratory immunoassay test for urine samples. A validated gas chromatography-mass spectrometry (GC-MS) method was then applied to quantify THC and CBD, independently from results of screening tests. Results On site screening for oral fluid samples, with a THC cut-off of 25 ng/mL gave negative results for all the individuals at different times after smoking. Similarly, negative results for urine samples screening from all the individuals were obtained. Confirmation analyses showed that oral fluid THC was in the concentration range from 2.5 to 21.5 ng/mL in the first 30 min after smoking and then values slowly decreased. CBD values were usually one order of magnitude higher than those of THC. THC-COOH, the principal urinary THC metabolite, presented the maximum urinary value of 1.8 ng/mL, while urinary CBD had a value of 15.1 ng/mL. Conclusions Consumers of a single 1 g dose of "light cannabis" did not result as positive in urine screening, assessing recent consumption, so that confirmation would not be required. Conversely, they might result as positive to oral fluid testing with some on-site kits, with THC cut-off lower than 25 ng/mL, at least in the first hour after smoking and hence confirmation analysis can be then required. No conclusions can be drawn of eventual chronic users

Recombinant norovirus GII.g/GII.12 gastroenteritis in children

Recombinant GII.g/GII.12 norovirus (NoV) strains emerged in 2008 in Australia and subsequently have been associated with gastroenteritis outbreaks worldwide. In the winter season 2009–2010 GII.12 strains caused 16% of the NoV outbreaks in the United States. During 2009–2010 we also identified GII.g/GII.12 strains during surveillance of sporadic cases of gastroenteritis in Italian children. Severity scores were calculated for the GII.g/GII.12 NoV infections using the Vesikari scale and in two out of three paediatric cases they exceeded the median value calculated for concomitant GII.4 infections. Upon sequence analysis, the Italian strains were found to be recombinant viruses and displayed different patterns of nucleotide polymorphisms. Phylodynamic analysis with other GII.g/GII.12 recombinants showed a high rate of evolution,comparable to the rates observed for GII.4 viruses. The mechanisms leading to worldwide emergence of GII.12 NoV strains in 2008–2010 are not clear. Monitoring of GII.12 NoV circulation is necessary to understand these mechanisms of evolution

Hepatotoxicity associated to synthetic cannabinoids use

Synthetic cannabinoids (SCs) are psychotropic compounds, chemically created in laboratory to mimic cannabinergic brain activity of delta-9 tetrahydrocannabinol. The consumption of these compounds for recreational purposes can lead to a variety of adverse effects on health including overdose and deaths. Increasingly popular as substances of abuse since the 2000s, SCs were produced initially to bind and study cannabinoid receptors (they also can be called synthetic cannabimimetics) failing in eliminating the psychoactive effects. Currently, SCs are misused by students and young adults as "natural products" because of their herbal aspect. Actually, these apparently innocuous recreational substances hide toxic effects to health. Reported side effects are cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, pulmonary and psychoactive including dependence and withdrawal. A few cases of SCs ingestion have also been associated with liver failure. We herein review the recent literature on the SCs toxicity with particular attention to liver damage aspects