New psychoactive substances: concerted efforts and common legislative answers for stemming a growing health hazard

OBJECTIVE: New psychoactive substances (NPS), are a range of drugs designed to mimic the effects of established illicit drugs, being legal at the time of their distribution in illicit markets. The review aims to shed a light on the growing threat caused by NPS, and on the dynamics and developments that have led to their spread, including the risk of new adulteration practices which can cause a serious health threat, due to their increased toxicity, e.g., through fentanyl and its analogs. MATERIALS AND METHODS: An overview of statistical trends relative to NPS use has been provided, in addition to regulatory and legislative approaches in several countries and recommendations and data from International institutions: UN Office on Drugs and Crime, United Nations Commission on Narcotic Drugs, WHO, European Parliament, European Monitoring Centre for Drugs and Drug Addiction, Europol and international collaborative efforts such as the Trans European Drug Information (TEDI) project and the Spanish Energy Control. RESULTS: Given the elusive nature of NPS, spontaneous pharmacovigilance reporting systems are needed to identify new trends of drug abuse. Broad-ranging legislative initiatives are needed in order to set common international standards (e.g., the European Parliament Regulation 2017/2101, with information exchange, an early warning system and risk assessment procedure for NPS) to tackle a potentially catastrophic and growing threat. CONCLUSIONS: By virtue of all the complexities and hurdles that have to be overcome in the fight against NPS, and to assist national governments in their identification and reporting, supranational organizations can come to play a key role. Only through international measures, supplementing national legislative initiatives, can this multi-faceted problem be effectively addressed and information about NPS be gathered and disseminated in a timely fashion

Synthetic cathinones related fatalities: an update

Synthetic cathinones, more commonly known as "bath salts", are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide.  In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years.OBJECTIVE: Synthetic cathinones, more commonly known as “bath salts”, are synthetic drugs chemically related to cathinone, a psychostimulant found in the khat plant. They are the first most consumed products among new psychoactive substances, which cause psychostimulant and hallucinogenic effects determining a number of fatalities worldwide. In this paper, we have systematically reviewed cases of synthetic cathinones-related fatalities analytically confirmed, which have occurred in the last few years. MATERIALS AND METHODS: Relevant scientific articles were identified in Medline, Cochrane Central, Scopus, Web of Science and Institutional/ government websites up to November 2017 using the following keywords: synthetic cathinones, mephedrone, methylenedioxypyrovalerone, MDPV, methylone, ethylone, buthylone, fatal intoxication, fatalities and death. RESULTS: In total, 20 citations met the criteria for inclusion, representing several fatal cases with analytically confirmed synthetic cathinones in biological sample/s of the deceased. The death was attributed to hyperthermia, hypertension, cardiac arrest and more in general to the classic serotonin syndrome. Only rarely did the concentration of the parent drug causing fatality overcome the value of 1 mg/L in post-mortem biological fluids. CONCLUSIONS: Abuse of synthetic cathinones still represents a serious public health issue. Systematic clinical studies on both the animal and human model are lacking; therefore, the only available data are from the users who experience the possible hazardous consequences. Analytical methodologies for the identification of parent compounds and eventual metabolites both in ante-mortem and post-mortem cases need to be developed and validated. Analytical data should be shared through different communication platforms with the aim of stopping this serious health threat for drug users

Medical use of cannabis: italian and european legislation

This review illustrates some brief considerations of the medical use of cannabis recently issued in Italy. History and uses of cannabis throughout centuries and different countries are illustrated together with a description of botany and active phytocannabinoids. Then, medical use of cannabis anti-pain treatment for patients resistant to conventional therapies is described in case of chronic neuropathic pain, spasticity, for anticinetosic and antiemetic effect in nausea and vomiting caused by chemotherapy, for appetite stimulating effect in cachexia, anorexia, loss of appetite in cancer patients or patients with AIDS and in anorexia nervosa, hypotensive effect in glaucoma resistant to conventional therapies and for reduction of involuntary body and facial movements in Gilles de la Tourette syndrome. Italian most recent legislation on medical cannabis is detailed with some law proposals, also showing the inconsistent legislation within European Union. Some final considerations of future studies are also reported

Ethical and medico-legal remarks on uterus transplantation: may it solve uterine factor infertility?

Uterus transplantation was firstly tested with animal trials sixty-five years ago. Despite several successful attempts in human subjects, the different procedures still lay at the experimental stage, in need of further studies and investigations before they can be considered as standard clinical practices. Uterus transplant cannot be regarded as a life-saving procedure, but rather a method to restore woman ability to procreate, when lost, thus improving her quality of life. Uterus transplant is a complex surgical procedure and presents significant health threats. Medical staff should therefore always obtain informed consent from patients, emphasizing such risks. Before that, women undergoing uterine transplants should be thoroughly informed about the hazards inherent to the procedure and especially about the dangers of immunosuppressant drugs, administered after the surgery which may injure the fetus, eventually formed in the restored organ and even lead to its death, thus nullifying the purpose of the transplant itself. Therefore, the risk-benefit ratio of uterus transplantation needs to be carefully assessed and described

Nootropics use in the workplace. Psychiatric and ethical aftermath towards the new frontier of bioengineering

OBJECTIVE: The authors have sought to expound upon and shed a light on the rise of nootropics, which have gradually taken on a more and more relevant role in workplaces and academic settings. MATERIALS AND METHODS: Multidisciplinary databases have been delved into by entering the following keys: "nootropics", "cognitive enhancement", "workplace", "productivity", "ethics", "bioengineering". In addition, a broad-ranging search has been undertaken on institutional websites in order to identify relevant analysis and recommendations issued by international institutions and agencies. Papers and reports have been independently pored over by each author. This search strategy has led to the identification of 988 sources but only 64 were considered appropriate for the purposes of the paper after being selected by at least 3 of the authors, independently. RESULTS: The notion of an artificially enhanced work performance - carried out by the 'superworker' - is particularly noteworthy and resonates with the conception of contemporary work on so many different levels: the rising need and demands for higher degrees of flexibility and productivity on the job, the implications of a '24/7' society, where more and more services are available at any time, the ever greater emphasis on entrepreneurial spirit, individual self-reliance and self-improvement, and last but not least, the impact of an ageing society on economic standards and performance. CONCLUSIONS: Moreover, it is worth mentioning that human enhancement technologies will predictably and increasingly go hand in hand with gene editing, bioengineering, cybernetics and nanotechnology. Applications are virtually boundless, and may ultimately affect all human traits (physical strength, endurance, vision, intelligence and even personality and mood)

New trends of substance abuse during COVID-19 pandemic: an international perspective

In the late 2019, an epidemic of cases with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has spread from China to the rest of the world, resulting in a global pandemic (COronaVIrus Disease 19, COVID-19 pandemic). Starting from the first months of 2020, several restrictions have been imposed by governments to face the public health threat, impacting the usual patterns of drug abuse throughout the world (1). The temporary border closure affected the usual illicit drug route of shipping from country to country, resulting in scarcity of classic street drugs (2). Moreover, restrictive measures internationally adopted by several countries made necessary to close all the usual recreational settings in which stimulants drugs are commonly abused. On the contrary, since in house drugs abuse became the most feasible option, other private encounters might have caught on, such as chemsex (3). In particular this phenomenon, which originated mainly in the large cities of Northern Europe, has gradually spread across the continent and is now a worrying reality in western European countries. Other rising trends of substance abuse include cognitive enhancers and new psychoactive substances (4, 5). Furthermore, the consequent social isolation and the likely limited access to detoxification centers caused additional psychological distress, pushing drug addicts toward alternative psychotropic drugs, possibly through illegal online marketplaces. An international overview of the new trends of drug abuse during the current COVID-19 pandemic and the related health risks are hereby discussed, taking into consideration different points of view

Advancements in uterus transplant: new scenarios and future implications

Women suffering from Uterine Factor infertility (UFI) arising from congenital conditions (e.g., Rokitansky-Kuster-Hauser syndrome) or hysterectomy can fulfill their wish to achieve motherhood only by resorting to surro gacy, which is, however, banned in most countries. Medical research has long been looking into uterus transplant (UTx), which may constitute a valuable alternative for such patients. Following decades of animal testing and clinical trials, several successful pregnancies have been car ried to term. Yet UTx is still to be considered as an experimental procedure. The report's authors believe UTx has the potential to become a main stream surgical practice, but for the time being, several ethical issues need to be weighed in be fore it does

Commentary- Increasing abuse of anabolic steroids and chemsex drugs as performance and image-enhancing agents

Anabolic Androgenic Steroids (AAS) are a family of synthetic “Appearance and Performance Enhancing Drugs” (APED) derived from natural sex hormones, such as testosterone and its derivatives or precursors (e.g., dihydrotestosterone)1 . Whereas testosterone is the androgen responsible for the development of male secondary sex characteristics and elicits both anabolic and androgenic effects, AAS mostly simulate the anabolic effect of endogenous testosterone, and induce only partial androgenic effects2 . In the 1930s, anabolic steroids were shown to facilitate muscular growthhand consequently became rapidly popular among bodybuilders and other athletes, and were already widespread in the 1960s. AAS have been and still are among the doping agents most frequently misused by athletes, regardless of the type of sport, both in preparations containing natural anabolic drugs [e.g., testosterone and dehydroepiandrosterone (DHEA)] and in those with synthetic substances (e.g., dianazole, nandrolone, stanozolol and tetrahydrogestrinone

The COVID-19 pandemic and contact tracing technologies, between upholding the right to health and personal data protection

Countries responded to the COVID-19 pandemic with various levels of restrictions and lockdown in an effort to save lives and prevent the saturation and collapse of national health systems. Unfortunately, the blockades have entailed hefty socioeconomic costs. In order to contrast the spread of the virus, states have used contact tracing technology, in the form of mobile phone applications designed to track close contacts of those infected with COVID-19. Recent research has shown the effectiveness of this solution, particularly when used in conjunction with manual tracking. Nonetheless, the contact tracing app raises concerns due to the potential privacy implications. The authors have delved into the European legislation that protects privacy through the principles of proportionality and minimization, arguing that in order to quickly resolve the pandemic caused by COVID-19, one cannot blindly trust the exclusive help of technology. Instead, we need the involvement of health personnel, scientists, and no less importantly, the citizenry's sense of solidarity and the duty to abide by the rules of social distancing, the use of protective devices and hygiene rules to protect public health

Cognitive enhancing drugs: a future challenge for the workplace?

In medical practice, cognitive enhancers (also called nootropics) are defined as therapeutic drugs treating specific cognition impairments in patients with attention deficit hyperactivity disorder, Alzheimer’s disease, stroke schizophrenia or aging. However, the non-medical use of cognitive enhancers with the aim of increasing mental alertness and concentration, improving memory, fighting wakefulness and boosting energy has been spreading worldwide2. In this concern, scarce investigations have been carried out on the possible risks of chronic non-medical use of nootropics, and these risks seem to be largely overlooked, especially among students3. Considering the ever more competitive nature of modern societies, which also reverberates into workplaces, cognitive enhancers are reasonably expected to become even more common over time4. Nonetheless, long-term consequences are as yet unknown. Cognitive enhancers, used by healthy individuals, are widely known as nootropics: they consist of drugs, supplements and other substances that are allegedly known to improve cognitive function, particularly executive functions, and to strengthen memory, creativity or even motivation. Pharmaceutical substances and compounds known as ‘cognitive-enhancers’ allegedly boost mental performance and the ability to focus and keep concentration. In broader terms, such drugs are often claimed to heighten and foster the acquisition of motor capabilities and affective skills (i.e., one’s ability to deal with anxiety stemming from performing certain work tasks or eliciting feelings of trust and affiliation). It is worth noting, however, that no drugs are licensed by medical authorities to be recommended and prescribed as ‘cognitive enhancers’. Thus, the definition of ‘performance-enhancing drug’ is usually linked to the off-label use of drugs prescribed for specific medical conditions. These substances are usually stimulants that preferentially target the catecholamines of the prefrontal cortex of the brain to induce their effects5. Historically, amphetamines have been the first drugs used off-label for the purpose of fostering memory consolidation and increasing concentration6. Since these substances are legally controlled as drugs of abuse, they can only be obtained on illegal markets. This purchase channel is also used to obtain methylphenidate, which is undoubtedly the most misused drug as cognitive enhancer5,7. Mostly prescribed for treating Attention Deficit Hyperactive disorder (ADHD) and narcolepsy, methylphenidate has been scheduled as an illegal drug in many countries for its abuse liability and side effects, resulting in a rapid expansion of methylphenidate legal analogs onto the drug market. Alternative prescription drugs for the treatment of narcolepsy and ADHD, such as modafinil and armodafinil, are also used as cognitive enhancers8. Finally, two last drugs should be mentioned among nootropics: atomoxetine, a selective nor-adrenaline reuptake inhibitor licensed for the treatment of children with methylphenidate-resistant ADHD or undergoing methylphenidate side effects9, and donepezil, a second-generation acetylcholinesterase inhibitor licensed for the treatment of mild to moderately severe symptoms of Alzheimer-related dementia10. At the same time, there has been renewed interest in older prescription drugs (e.g., beta blockers, to decrease performance anxiety) and illicit psychostimulants (e.g., cocaine, amphetamines), sometimes in different forms or doses. Whereas there is still little consensus on the actual effectiveness and nature of the cognitive benefits of the above-mentioned drugs in healthy subjects13, their use to enhance the level of performance in specific workplaces has been reported for decades14. In fact, cognitive enhancement has been a mainstay of military research in the US since the Second World War with the use of amphetamines, modafinil and other cognitive enhancers in the most recent military operations (e.g., Vietnam war, Korean war, operations Desert Shield and Desert Storm in Iraq, later sustained military operations in the Middle East)15,16. Whereas the military use of cognitive enhancers has been known for many years, not only in the US but internationally. More recent studies reported that other occupations present a high prevalence of use: medical doctors and health professionals (e.g., surgeons, surgical technicians’ anesthetists), transportation workers (e.g., truck drivers, car drivers, taxi drivers), financial traders, clinical investigators, research managers and lawyers. Finally, the increase of precarious and part-time home works has been recently associated to psychological discomfort and an increase in prescriptions of psychotropic drugs, and a rise in the misuse of cognitive enhancers can be hypothesized17-19. Another important factor to be taken into account is the role of the internet as a source of information through web forums and as a way of obtaining those substances. Such dynamics also constitute a cultural shift in the way drugs are obtained and consumed: they are anonymously received and safer than street drugs trafficking, although the actual composition and nature of the substances cannot be precisely ascertained. This latter fact creates a gap of information on the diagnosis of misuse in cases of possible intoxications and fatalities, since neither analytical screening nor confirmation methodologies are currently available for documenting exposure to those profuse and chemically diverse substances. In addition, apart from intoxications and fatalities, it has to be reminded that several of these substances present a potential for abuse liability and abstinence symptoms, which, instead of improving work pressure and overload, can worsen the environmental situation. In conclusion, we wish to draw the attention of the whole scientific community and policy makers to the increasing importance of the misuse of cognitive enhancers, and to improve public awareness of the phenomenon and contextual political strategies to stop this incoming threat for the health of current and future worker