Simona Pichini

Istituto Superiore di Sanità | ISS · National Centra on Addiction and Doping

Background The comprehensive monitoring of licit and illicit drug consumption plays a crucial role in understanding the complexities of patient conditions and designing effective treatment strategies. In this study, the prevalence of psychoactive prescription drugs, classical illicit drugs, and new psychoactive substances (NPS) were objectively ass...

Cannabis can be related to respiratory diseases, but the relationship between smoking marijuana and the development of a pneumothorax has scarcely been investigated. We aimed to analyze, in patients with a history of cannabis smoking abuse submitted to lung apicectomy for a primary spontaneous pneumothorax (PSP), the correlation between the presenc...

In the present study an enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the first time for quantitative determination of the recreational drug of abuse methylone and its major metabolites in oral fluid. The simultaneous chemo- and enantioseparation of methylone and its major metab...

Background: During the last two years, hexahydrocannabinol (HHC), the hydrogenated derivative of tetrahydrocannabinol has been freely sold by internet websites as a "legal" replacement to THC and cannabis in a range of highly attractive branded and unbranded products, some of which are sold as "legal highs". Potentially, there could be a large dem...

This study presents a validated GC-MS/MS method for the detection and quantification of 4-chloromethcathinone or clephedrone (4-CMC), N-ethyl Pentedrone (NEP), and N-ethyl Hexedrone (NEH, also named HEXEN) in oral fluid and sweat and verifies its feasibility in determining human oral fluid concentrations and pharmacokinetics following the administr...

The growing interest in medical Cannabis-based therapies has increased in recent years and treatment of drugresistant epilepsy is one of the most relevant applications. In Italy, the use of medical Cannabis is regulated by Ministerial Decree 9/11/2015. Medical Cannabis consists of dried female flowering tops that contain, among others, at least 90...

Abstract: The aim of this study was to determine the excretion of methylone and its metabolites in sweat following the ingestion of increasing controlled doses of 50, 100, 150 and 200 mg of methylone to twelve healthy volunteers involved in a clinical trial. Methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylen...

The aim of this study was to investigate methylone and its metabolites concentration in oral fluid following controlled increasing doses, focusing on the effect of oral fluid pH. Samples were obtained from a clinical trial where twelve healthy volunteers participated after ingestion of 50, 100, 150 and 200 mg of methylone. Concentration of methylon...

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone re...

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placeb...

The need to identify and quantify a growing number of NPS represents a crucial challenge for toxicological and forensic purposes. Among biological specimens investigated for pharmaco-toxicological analyses, oral fluid (OF) provides greater advantages compared to blood to prove drug current use. OF is regarded with particular interest for drug scree...

“Light cannabis” is a product legally sold in Europe with Δ9-tetrahydrocannabinol (THC) concentration lower than 0.2% and variable cannabidiol (CBD) content. In this study, we aimed to assess the time-courses of THC and metabolites (11-nor-9-carboxy-THC and 11-hydroxy-THC) and CBD and metabolites (CBD-7-oic acid, 7-hydroxy-CBD, 6α-hydroxy-CBD, and...

Aim Variable individual responses and relationships between administered dose and CBD blood concentrations suggest therapeutic drug monitoring (TDM) as a valuable support for patient management. Currently, there is no published method for the simultaneous quantification of CBD, THC and their main active and inactive metabolites. The aim of this stu...

Aim Use of alcohol during pregnancy and subsequent fetal exposure can cause multiple perinatal disorders (prematurity at birth, withdrawal syndromes, tremors, hyperreflexia) and impaired physical and mental development in the later stages of life, known as fetal alcohol spectrum disorders (FADS) including as major expression of impairment fetal alc...

Aim Synthetic cathinones are commonly abused novel psychoactive substances (NPS) that are consumed alone or in combination with other psychoactive drugs via the oral, intranasal, or intravenous routes. These substances induce physiological and subjective effects typical of psychostimulant drugs, although with a faster onset and shorter duration whe...

Aim In compliance with the European Council Decision 2005/387/JHA, the Italian AntiDrug Policies Department designated the National Center for Addiction and Doping of the Istituto Superiore di Sanità (ISS) to organize and manage the National Early Warning System (NEWS) on New Psychoactive Substances (NPS) to promote a rapid exchange of information...

Purpose: Synthetic benzimidazole opioids (BO) are highly potent µ-opioid receptor agonists with heroin-like effects. Isotonitazene was first available in 2019 in the drug market, while new analogs have multiplied recently. The authors aimed to identify BO use trends and gather toxicological data from BO-related cases to assist in clinical and fore...

Cannabis is the most widely consumed illegal drug in the world and synthetic cannabinoids are increasingly gaining popularity and replacing traditional cannabis. These substances are a type of new psychoactive substance that mimics the cannabis effects but often are more severe. Since, people with opioids use disorder use widely cannabis, they are...

Δ9-tetrahydrocannabinol (Δ9-THC) isomers, especially Δ8-tetrahydrocannabinol (Δ8-THC), are increasing in foods, beverages, and e-cigarettes liquids. A major factor is passage of the Agriculture Improvement Act (AIA) that removed hemp containing less than 0.3% Δ9-THC from the definition of “marijuana” or cannabis. CBD-rich hemp flooded the market re...

The use of High Resolution Mass Spectrometry (HRMS) has increased over the past decade in clinical and forensic toxicology, especially for comprehensive screening approaches. Despite this, few guidelines of this field have specifically addressed HRMS issues concerning compound identification, validation, measurement uncertainty and quality assuranc...

Discovered in the United States of America (USA) in the 1960s, ketamine was introduced as an anaesthetic drug to specifically replace phencyclidine. Briefly, the substance moved from the medical world to recreational users, since it was discovered that intense psychedelic experiences were obtained with dosages lower than those prescribed for anesth...

Recently, several countries approved the use of cannabis flowering tops with standardized amount of ∆9-tetrahydrocannabinol (THC), cannabidiol (CBD) to treat several diseases. Therapeutic monitoring of medical cannabis products administered to patients for the established pathologies is rarely carried out. Previous few investigations have been deve...

(1) Background: Since the beginning of the 21st century, the large number and wide chemical variety of new psychoactive substances (NPS) that enter the market every year has become a public health problem. Given the rapidity with which the drug market is changing, many NPS are not clinically investigated and their effects and health risks are unkno...

Introduction: New synthetic opioids (NSO), a class of new psychoactive substances (NPS), have recently emerged and pose an upcoming global public health challenge. The effects produced by NSO are similar to those from morphine, but they present greater pharmacological potency and abuse potential. Due to the increasing number of fatal overdoses and...

For the first time, the present study employed hair testing to investigate the prevalence of classical drugs of abuse and new psychoactive substances use during gestation in a cohort of 300 Mexican pregnant women. An interview was conducted to collect data on sociodemographic aspects of the patients, and a 9 cm-long hair strand was taken from the b...

Currently, more than 1000 molecules have been classified as New Psychoactive Substances (NPSs), and it is reported that, every year, this number increases with new classes of compounds and/or newer generations of NPS families [...]

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children w...

Substance use in pregnancy is a global public health problem, both in developed and developing countries. Whereas information is available for major western countries, scarce data are present for the second ones. The objective assessment of pregnancy consumption of xenobiotic is provided by analysis of maternal hair, which can account for gestation...

BACKGROUND: For most people, gambling is a harmless activity, but for some it can be addictive with negative consequences. In Italy, there is no estimate of the prevalence of this phenomenon on large samples of the adult population METHODS: The purpose of this epidemiological study (N.=12,061) was to estimate the prevalence and to describe the Ital...

The use of ethyl alcohol during pregnancy and subsequent foetal exposure to this teratogen can cause developmental disorders of the foetus, such as growth retardation, craniofacial abnormalities, organ malformations and neurobehavioural abnormalities. These clinical manifestations are known as Foetal Alcohol Spectrum Disorder, whose most severe exp...

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects o...

Cannabidiol (CBD) is a promising therapeutic agent with analgesic, myorelaxant, and anti-epileptic actions. Recently, a purified form of CBD (Epidiolex®) has been approved by the European Medicines Agency (EMA) for the treatment of two highly-refractory childhood-onset epilepsies (Dravet and Lennox-Gastaut syndrome). Given the interindividual respo...

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance li...

Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the...

No analytical assay is currently available for the simultaneous determination of CBD major metabolites in serum or urine samples of individuals treated with medical cannabis or CBD-based pharmaceuticals. We developed and validated a method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) for qua...

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized m...

The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and deco...

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) scr...

Our understanding of tryptamines is poor due to the lack of data globally. Tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. Although their prevalence was low, it is increasing. There are few published data on the many new compounds, their mechanisms of action,...

Recently, several countries authorized the use of cannabis flowering tops (dried inflorescences) with a standardized amount of Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD) and their acidic precursors [Δ‐9‐tetrahydrocannabinolic acid A (THCA‐A) and cannabidiolic acid (CBDA)] to treat neurogenic pain. We studied the acute pharmacological effects...

Introduction: Turmeric is the common name for the rhizome of Curcuma longa L. In the recent years, food supplements containing turmeric have been marketed and widely used by an increasing number of consumers. Spontaneous reports of suspected adverse reactions to food supplements are collected within the Phytovigilance system. Methods: An ad hoc...

Cannabis products have been used for centuries by humans for recreational and medical purposes. Resent research, proposed the promising therapeutic potential of cannabis and related cannabinoids for a wide range of medical conditions, including psychiatric and neurological diseases. This Special Issue presents the latest updates on medicinal cannab...

To date, more than 800 molecules are classified as New Psychoactive Substances (NPS), and it is reported that this number increases every year. Whereas several cases of polydrug consumption which led to acute intoxication and death are reported, a lack of effective analytical screening method to detect NPS and classical drug of abuse in human matri...

Gambling is widely recognized as an important public health problem. Despite the rising use of stimulant substances among adolescents, there are still very few studies focusing on whether adolescents' use of stimulants is associated with their gambling behaviour. Therefore, the aim of this study was to investigate the association between gambling h...

Cannabidiol (CBD) is the second most abundant cannabinoid present in Cannabis sativa L. It is not associated with psychotropic activity and is capable to mitigate the psychotomimetic effects produced by tetrahydrocannabinol (THC). The latest cannabis decriminalization policies and the high applicability in therapeutic and technologic-industrial fie...

Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic potential of cannabis and paved the way fo...

Background “Light cannabis” is a product legally sold in Europe with Δ9-tetrahydrocannabinol (THC) concentration lower than 0.2% and variable cannabidiol (CBD) content. We studied THC and CBD excretion profiles in blood, oral fluid (OF) and urine after smoking one or four light cannabis cigarettes. Methods Blood, OF and urine samples were obtained...

Fetal Alcohol Spectrum Disorders (FASD) are a plethora of malformative conditions leading to mental retardation that affect newborns and children who have been exposed to alcohol during pregnancy or breastfeeding. FASD is a relevant topic for public health in Europe: European area is first in ranking for alcohol use during pregnancy with a prevalen...

Interest on keratinized matrix analysis for clinical and forensic purposes has been recently grown due to the wide temporary detection window for psychotropic and toxic substances entrapped after repeated consumption. The aim of this study was the development and full validation of an UHPLC-MS/MS screening method to quantify 119 molecules among mos...

Sampling and drug stability in oral fluid (OF) are crucial factors when interpreting forensic toxicological analysis, mainly because samples may not be analyzed immediately after collection, potentially altering drug concentrations. Therefore, the stability of some common drugs of abuse (morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgo...

Nail analysis can be performed as a substitute or complement to hair analysis for the retrospective determination of psychotropic drugs consumption in forensic contexts. The application of nail analysis in a "chemsex" context is reported herein. An ultra-performance liquid chromatography-tandem mass spectrometry method was developed to quantify the...

Purpose: The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome (NAS), preterm delivery, and stillbirths. Monitoring drug use during pregnancy is cruci...

Objectives The aim of this study was to elucidate the pathway of associations linking gambling, alcohol intake, smoking habit, cannabis consumption between each other and with demographic and socioeconomic variables. Setting and participants A survey was conducted in 2017 on a representative sample of 15 602 Italian 14-year-olds to 17-year-olds at...

Monitoring pharmacological active compounds in pharmaceutical preparations of medical cannabis and in conventional and non-conventional biological matrices of treated individuals use requires both a wide linear range and sensitive detection. We have developed and validated a fast and sensitive method using ultra-high performance liquid chromatograp...

In the last few years, a wide range of new psychoactive substances (NPS) have been produced and marketed to elude the controlled substance lists. These molecules enter the traditional illegal and web market with poor knowledge about their toxicity, mechanism of action, metabolism, abuse potential so that they are directly tested by the consumers. T...

Background: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum, and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis vs. illegal and medical cannabis use were also investigated. Methods: Sera were obtained at different t...

Purpose: Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abu...

The expression “ChemSex” generally refers to the use of γ‐hydroxybutyric acid (GHB), gamma‐butyrolactone (GBL) in combination with psychoactive illicit substances to facilitate sexual sessions lasting several hours or days, especially in the context of men who have sex with other men. We here present a fatal chemsex case involving GBL and the synth...

Background Currently, there is 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®...

Purpose: Drug use during pregnancy is a critical global challenge, capable of severe impacts on neonatal development. However, the consumption of cannabis and synthetic cannabinoids is on the rise in pregnant women. Obstetric complications with increased risks of miscarriage, fetal growth restriction, and brain development impairment, have been as...

In the field of forensic toxicology, the use of non-destructive and easy-to-use analytical techniques deserves remarkable attention, especially in those situations involving public health and security. In addition, the miniaturization and portability of one-touch devices for the detection of specific threats is required more and more. In this study...

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 i...

Recently, synthetic opioid-related overdose fatalities, led by illicitly manufactured fentanyl and analogs, increased at an alarming rate, posing a global public health threat. New synthetic fentanyl analogs have been constantly emerging onto the drug marked for the last few years, to circumvent the laws and avoid analytical detection. Analytical m...

A fast and sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method was developed and validated for the measurement of the most common drugs of abuse and some new psychoactive substances in oral fluid. The target compounds were 6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine, amphetamine...