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New psychoactive substances
... Between 2009 and 2017, 803 NPS were reported in 111 countries or territories [2,6]. In the European Union, by the end of 2017, the number of NPS was over 670, of which 632 were notified after 2004 [2,7]. ...
... There is a concerted effort to grapple with the challenges of researching NPS, as traditional methodologies are too slow and expensive to generate relevant and timely data on the effects of NPS [5]. 6. Clinicians are not usually able to identify a potential NPS user, and NPS usually produce negative results to traditional drug tests, which are designed to assess a very limited number of traditional substances [6]. On the other hand, NPS users rarely search for professional help linked exclusively to this problem, and clinicians are not trained to screen or identify NPS use. ...
BACKGROUND
During the last few years, the continuous emergence of new psychoactive substances (NPS) has become an important public health challenge. The use of NPS has been rising in two different ways: buying and consuming NPS knowingly and the presence of NPS in traditional drugs as adulterants. The rise of NPS use is increasing the number of different substances in the market to an extent impossible to study with current scientific methodologies. This has caused a remarkable absence of necessary information about newer drug effects on people who use drugs, mental health professionals, and policy makers. Current scientific methodologies have failed to provide enough data in the timeframe when critical decisions must be made, being not only too slow but also too square. Last but not least, they dramatically lack the high resolution of phenomenological details.
OBJECTIVE
This study aims to characterize a population of e-psychonauts and the subjective effects of the NPS they used during the study period using a new, internet-based, fast, and inexpensive methodology. This will allow bridging an evidence gap between online surveys, which do not provide substance confirmation, and clinical trials, which are too slow and expensive to keep up with the new substances appearing every week.
METHODS
To cover this purpose, we designed a highly personalized, observational longitudinal study methodology. Participants will be recruited from online communities of people who use NPS, and they will be followed online by means of a continuous objective and qualitative evaluation lasting for at least 1 year. In addition, participants will send samples of the substances they intend to use during that period, so they can be analyzed and matched with the effects they report on the questionnaires.
RESULTS
The research protocol was approved by the Institutional Review Board of the Hospital del Mar Research Institute on December 11, 2018. Data collection started in August 2019 and was still ongoing when the protocol was submitted (September 2020). The first data collection period of the study ended in October 2020. Data analysis began in November 2020, and it is still ongoing. The authors expect to submit the first results for publication by the end of 2021. A preliminary analysis was conducted when the manuscript was submitted and was reviewed after it was accepted in February 2021.
CONCLUSIONS
It is possible to conduct an institutional review board–approved study using this new methodology and collect the expected data. However, the meaning and usefulness of these data are still unknown.
INTERNATIONAL REGISTERED REPORT
DERR1-10.2196/24433
... Between 2009 and 2017, 803 NPS were reported in 111 countries or territories [2,6]. In the European Union, by the end of 2017, the number of NPS was over 670, of which 632 were notified after 2004 [2,7]. ...
... There is a concerted effort to grapple with the challenges of researching NPS, as traditional methodologies are too slow and expensive to generate relevant and timely data on the effects of NPS [5]. 6. Clinicians are not usually able to identify a potential NPS user, and NPS usually produce negative results to traditional drug tests, which are designed to assess a very limited number of traditional substances [6]. On the other hand, NPS users rarely search for professional help linked exclusively to this problem, and clinicians are not trained to screen or identify NPS use. ...
Background
During the last few years, the continuous emergence of new psychoactive substances (NPS) has become an important public health challenge. The use of NPS has been rising in two different ways: buying and consuming NPS knowingly and the presence of NPS in traditional drugs as adulterants. The rise of NPS use is increasing the number of different substances in the market to an extent impossible to study with current scientific methodologies. This has caused a remarkable absence of necessary information about newer drug effects on people who use drugs, mental health professionals, and policy makers. Current scientific methodologies have failed to provide enough data in the timeframe when critical decisions must be made, being not only too slow but also too square. Last but not least, they dramatically lack the high resolution of phenomenological details.
Objective
This study aims to characterize a population of e-psychonauts and the subjective effects of the NPS they used during the study period using a new, internet-based, fast, and inexpensive methodology. This will allow bridging an evidence gap between online surveys, which do not provide substance confirmation, and clinical trials, which are too slow and expensive to keep up with the new substances appearing every week.
Methods
To cover this purpose, we designed a highly personalized, observational longitudinal study methodology. Participants will be recruited from online communities of people who use NPS, and they will be followed online by means of a continuous objective and qualitative evaluation lasting for at least 1 year. In addition, participants will send samples of the substances they intend to use during that period, so they can be analyzed and matched with the effects they report on the questionnaires.
ResultsThe research protocol was approved by the Institutional Review Board of the Hospital del Mar Research Institute on December 11, 2018. Data collection started in August 2019 and was still ongoing when the protocol was submitted (September 2020). The first data collection period of the study ended in October 2020. Data analysis began in November 2020, and it is still ongoing. The authors expect to submit the first results for publication by the end of 2021. A preliminary analysis was conducted when the manuscript was submitted and was reviewed after it was accepted in February 2021.
Conclusions
It is possible to conduct an institutional review board–approved study using this new methodology and collect the expected data. However, the meaning and usefulness of these data are still unknown.
International Registered Report Identifier (IRRID)DERR1-10.2196/24433
... A variety of NPS have been designed and manufactured in laboratories and sold cheaply online or in headshops (Bruno, Poesiat, & Matthews, 2013;Cinosi et al., 2014;van Amsterdam, Nabben, Keiman, Haanschoten, & Korf, 2015). Initially, these drugs were legally sold as they were labelled 'not for human consumption' (Davidson, 2012;Musselman & Hampton, 2014). Many of these novel drugs have now been controlled or scheduled, but the arrival of new NPS is rapid. ...
... NPS tend to mimic the psychotropic effects of traditional drugs of abuse, but their acute and chronic toxicity, and side-effects are largely unknown. This has led to funneling of resources worldwide to outline the phenomenon, identify the molecules, describe effects, interpret or update existing laws, enact new regulations, and develop appropriate and effective analytical methods for their identification in biological fluids and seized materials (1)(2)(3)(4)(5)(6)(7)(8)(9). ...
Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography–tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance—either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS—the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use.
... Reported drugs in different categories were regrouped in an attempt to obtain similar groupings. s0015 11.2 THE CHALLENGE OF NPS DETECTION p0300 The misuse of NPS often leads governments to prohibit them, but once these drugs have been banned, their chemical structure is slightly altered to create legal drugs with similar properties [1]. Although many of the latest substances continue to be stimulants of the central nervous system, their chemical structures present different forms. ...
... It displays a similar structural feature chemically with 9-tetrahydrocannabinol (THC), which is the active ingredient of marijuana. Although 102 different kinds of synthetic cannabinoid substances were reported to the early warning system of European Monitoring Centre of Drugs And Drug Addiction (EMCDDA) until December 2013, more than 200 substances have been reported since 1997 (1,2). In the presentation of our cases, it was aimed to discuss the clinical courses, treatment management and the difficulties in the diagnosis of six patients who were followed up in the intensive care unit and whose blood tests were negative despite the presence of the history of bonzai use. ...
In the language of the streets, ‘bonzai’, known as ‘1-naphthalenyl of methanol’, also known as JWH-18 group, is a drug belonging to the group of synthetic cannabinoids. At the beginning of 2004, it started to be sold on the internet and it is seen that private markets. It has structurally similar chemical characteristics as delta 9-tetrahydrocannabinol (THC), the active substance in marijuana. In 2013, in a study conducted by the European Monitoring Centre of Drugs and Drug Addiction (EMCDDA), 102 varieties of synthetic cannabinoids were identified; however, more than 200 substances have been reported since 1997. In this study, we report the difficulties in the clinical course, treatment and management of six patients that had a use history of bonzai although it was not detected in blood in a short period of time in the intensive care unit.
... However, in recent years, there has been a huge upsurge in novel psychoactive substances, also known as "legal highs", "designer drugs", "herbal highs" or "research chemicals". Since 1997 more than 200 new psychoactive substances have been identified (5). In 1990s, Huffman et al. (6) synthesized naphthoylindoles, naphthoylpyrroles and related compounds with cannabinoid receptor agonist activity, which have become known as the "JWH compounds" and have become the major component of novel drugs containing synthetic cannabinoids (SCs) afterwards. ...
... In recent years, production and consumption of psychoactive drugs, namely, herbal highs and legal highs, have increased with the medical objectives to be produced by SC derivatives [7]. Use of SC is now a serious health problem. ...
Synthetic cannabinoids (SC), cannabinoid 1 and cannabinoid 2 receptors agonists, are the psychoactive substances. SC was originally produced to treat medical conditions. Compared to other narcotics, SC is easier to obtain, cheap, and highly potent and has a long half-life. In addition, routine analysis does not detect SC, which has led to widespread use. A case is presented that manic episode was developed with the use of SC. Hospitalization and admission to psychiatric units depending on SC use have been observed mostly with psychosis. Although SC-induced affective symptoms were mentioned in the literature, mania has not been reported before. We aimed to discuss the psychiatric conditions induced by widespread use of SC via our case.
... In the last few years, most forensic laboratories have been challenged worldwide with the need for detecting a variety of new psychoactive substances (NPS) in different biological specimens, including hair [5]. Since the late 1990s, more than 200 NPS of potential illegal use have been identified; 49 in 2011 alone [43]. These compounds, frequently referred to as either 'designer drugs' or 'legal highs', have little or no previous history of medicinal use. ...
Hair testing has been used in toxicological investigations for the last two decades, but only recently a remarkable extension of hair analysis to a variety of application fields was observed, besides drug abuse recognition. The dramatic improvements of LC-MS/MS instrumentation make the detection of tiny amounts of almost whatever drug in hair possible, even after single-dose intake. The progresses observed during the last 5 years in the detection of psychoactive substances in hair are reviewed herein. The literature is partitioned according to the target compounds, namely traditional drugs of abuse, new psychoactive substances and pharmaceutical psychoactive substances. The LC-MS/MS methods presented are addressed to determine a single class of drugs, with the primary aim of accurate quantitation, or to perform multiclass analysis, for rapid and effective screening protocols.
Ayahuasca (caapi, yajé), is a psychoactive brew from the Amazon Basin region of South America traditionally considered a “master plant.” It is prepared as a decoction from Banisteriopsis caapi and Psychotria viridis, which it is thought that it stimulates creative thinking and visual creativity. Native healers of the Orinoco and Amazon basins have used traditionally ayahuasca as a healing tool for multiple purposes, particularly to treat psychological disorders in the patients, with some beneficial effects experimentally and clinically validated. Recently, several syncretic religions, as the “União de Vegetal” (UDV) group in Brazil, have been spread around the world. The use of ayahuasca has been popularized by internet and smart-shops, bringing the psychoactive substance to new highs, emerging new “ayahuasqueros.” Ayahuasca has alkaloids as β-carbolines and dimethyltryptamines, which inhibit the monoamine oxidase and active the 5-HT2A (5-hydroxytryptamine) receptor, respectively, resulting in hallucinations in the users. Ayahuasca induces a psychedelic change in the anteroposterior coupling of the electrophysiological brain oscillations in humans. Traditional ayahuasca beverage is generating pharmacological, commercial and spiritual interest among the scientific community, government people, and different populations worldwide. The goal of this article is to report about the uses, chemistry and biological activities of ayahuasca.
Graphical Abstract
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This book provides for an extensive legal analysis of the international drug control system in light of the growing challenges and criticism that this system faces. In the current debate on global drug policy, the central pillars of the international drug control system - the UN Drug Conventions as well as its institutions - are portrayed as outdated, suppressive and seen as an obstacle to necessary changes. The book's objective is to provide an in-depth and positivist insight into drug control's present legal framework and thus provide for a better understanding of the normative assumptions upon which drug control is currently based. This is attained by clarifying the objectives of the international drug control system and the premises by which these objectives are to be achieved. The objective of the current global framework of international drug control is the limitation of drugs to medical and scientific purposes. The meaning of this objective and its concrete implications for States' parties as well as its problems from the perspective of other regimes of international law, most notably international human rights law, are extensively analysed. Additionally, the book focuses on how the international drug control system attempts to reach the objective of confining drugs to medical and scientific purposes, i.e. by setting up a universal system that exercises a rigid control on drug supply. The consequences of this heavy focus on the reduction of drug supply are outlined, and the book concludes by making suggestions on how the international drug control system could be reformed in the near future in order to better meet the existing challenges. The analysis occurs from a general international law perspective. It aims to map the international drug control system within a wider context of international law and to understand whether the problems that the international drug control system faces are exemplary for the difficulties that institutionalized systems of global scope face in the twenty-first century.
The detection of new psychoactive substances (NPS) in hair proved to provide insight into their current diffusion among the population and the social characteristics of these synthetic drugs' users. Therefore, a UHPLC-MS/MS method was developed in order to determine 31 stimulant and psychedelic substituted phenethylamines, and dissociative drugs in hair samples. The method proved to be simple, fast, specific, and sensitive. The absence of matrix interferents, together with excellent repeatability of both retention times and relative abundances of diagnostic transitions, allowed the correct identification of all analytes tested. The method showed optimal linearity in the interval 10-1000 pg/mg, with correlation coefficient values varying between 0.9981 and 0.9997. Quantitation limits ranged from 1.8 pg/mg for 4-methoxyphencyclidine (4-MeO-PCP) up to 35 pg/mg for 6-(2-aminopropyl)benzofuran (6-APB). The method was applied to (i) 23 real samples taken from proven MDMA and ketamine abusers and (ii) 54 real hair samples which had been previously tested negative during regular drug screening in driver's license recovery. Six samples tested positive for at least one target analyte. Methoxetamine (MXE) was found in three cases (range of concentration 7.7-27 pg/mg); mephedrone (4-MMC) was found in two cases (50-59 pg/mg) while one sample tested positive for methylone at 28 pg/mg. Other positive findings included 4-methylethcathinone (4-MEC), alpha-pyrrolidinovalerophenone (α-PVP), 4-fluoroamphetamine (4-FA), 3,4-methylenedioxypyrovalerone (MDPV), and diphenidine. The present study confirms the increasing diffusion of new designer drugs with enhanced stimulant activity among the target population of poly-abuse consumers.
Proper assessment of the harms caused by the misuse of drugs can inform policy makers in health, policing, and social care. We aimed to apply multicriteria decision analysis (MCDA) modelling to a range of drug harms in the UK.
Method Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance.
Findings MCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places.
Interpretation These findings lend support to previous work assessing drug harms, and show how the improved scoring and weighting approach of MCDA increases the differentiation between the most and least harmful drugs. However, the findings correlate poorly with present UK drug classification, which is not based simply on considerations of harm.
The aim of the study was to foster the collection and analysis of data from web pages related to information on the consumption, manufacture and sale of Spice products, a brand name for an herbal smoking blend, sold as legal substitute for cannabis. The Google search engine was used to carry out an 8-language qualitative assessment of information available on Spice products in a sample of about 200 web sites. The level of information elicited included both the users' comments on the effects of the products and the reasons behind their popularity. Users' suggestions on unusual drug combinations not found in the Medline were also identified. This is the first comprehensive and multilingual overview of the online available information on Spice products. The appeal of Spice to online customers was associated with its legal status, lack of detection in biological samples, ease of online access and cannabis-like effects. Spice product descriptions did not typically mention the presence of the powerful synthetic THC receptor agonists that seem to account for the psychoactive effects. Health professionals may need to be aware of the web being a new drug resource for both information and purchase of Spice products.
The fully synthetic 'legal high' 5,6-methylenedioxy-2-aminoindane (MDAI) is an analogue of 3,4-methylenedioxymethamphetamine. Although developed in the 1990s, it was not widely abused until 2010. However, mephedrone was banned in the UK in April 2010, and almost immediately, MDAI was widely advertised as a legal alternative. This paper provides both an overview of the current state of knowledge of MDAI and a critical analysis of online available information relating to its psychoactive effects, adverse reactions and use in combination with other drugs.
The literature on MDAI was searched in three databases: PsycInfo, PubMed and MedScape. Once the availability of information on MDAI was identified within these websites, further specific searches were carried out for narratives focusing on the nature of its effects on users, motivations behind its recreational use and possible trends of misuse, and any other relevant information.
Internet-sourced products have been shown variously to contain mephedrone, and mixed compositions of inorganic substances, while containing no MDAI. Numbers of Internet searches have been considerably higher in the UK compared with Germany and the US.
Better international collaboration levels may be needed to tackle the novel and fast growing phenomenon of novel psychoactive drug availability from the web.
The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.
Proper assessment of the harms caused by the misuse of drugs can inform policy makers in health, policing, and social care. We aimed to apply multicriteria decision analysis (MCDA) modelling to a range of drug harms in the UK.
Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance.
MCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places.
These findings lend support to previous work assessing drug harms, and show how the improved scoring and weighting approach of MCDA increases the differentiation between the most and least harmful drugs. However, the findings correlate poorly with present UK drug classification, which is not based simply on considerations of harm.
Centre for Crime and Justice Studies (UK).
Between 1997 and 2011, more than 200 new substances were notified through the early-warning system, with the record number of 49 novel molecules reported in 2011. The pattern of acute toxicity associated with the consumption of these new substances is generally similar to that seen with traditional drugs of abuse. Recently, a new class of synthetic stimulants closely related to pyrrolidine and piperidine compounds and known as pipradrol derivatives appeared in the recreational drug market. These substances, producing amphetamine-like effects, are used by people in substitution of traditional illicit drugs. The aim of this paper is to summarize the clinical, pharmacological and toxicological information currently available about this new class of synthetic drugs of abuse.
Desoxypipradrol is a methylphenidate-like drug that has been recently found in a number of 'legal highs'. Evidence from emergency room toxicology reports suggests that this drug might have led to a number of psychotic events in drug abusers in the UK and elsewhere. However, very little research has been done on the effects of this drug on the brain. Here we used rat brain slices from the nucleus accumbens core, which were exposed to either cocaine (1, 3 or 10 µM) or desoxypipradrol (1, 3 or 10 µM) for 60 min. Dopamine efflux was electrically evoked and recorded using fast cyclic voltammetry. Both drugs increased the peak dopamine efflux and also slowed dopamine re-uptake. Desoxypipradrol was more potent than cocaine causing a sevenfold increase in peak dopamine levels (versus a threefold increase for cocaine) and increasing dopamine re-uptake half-life 15-fold (versus fivefold for cocaine). These data suggest that desoxypipradrol is more potent than cocaine at dopamine terminals, and this could account for its psychotogenic effects.
To obtain damage/benefit assessments of eight commonly used addictive products and one addictive behaviour from French addiction experts and link these to overall evaluations.
Criteria-based evaluation by experts in addiction. Specific statistical modelling to estimate the relative contribution of various criteria to formulating expert general opinion on products.
Forty-eight French experts in addiction.
Twelve criteria covering the whole spectrum of damages and benefits to users and to society evaluated using visual analogue scales (VAS). Direct measure of expert overall subjective opinions on products from user and from social perspectives.
Damage scoring identified alcohol (damage score = 48.1), heroin (damage score = 44.9) and cocaine (damage score = 38.5) as the most harmful products to users and to society; gambling was considered the least harmful (score = 22.5), replicating previous results. Damage scoring correlated poorly with legal status or with overall subjective expert opinions of products. Benefit perception scores indicated alcohol as a clear outlier (benefit score = 45.5) followed by tobacco (benefit score = 34.3) and cannabis (benefit score = 31.1). Statistical modelling suggested that experts attributed 10 times more importance to benefit perception than to damages when making their subjective opinion from a user perspective and two times more importance to benefit perception than to damages in formulating their opinion from a social perspective.
The perceived benefits of addictive products appear to have a major impact on the opinion of those products expressed by a number of French addiction experts.
J. Neurochem. (2010) 114 , 1277–1290.
Abstract
Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Cytokines and chemokines are important neuroinflammatory mediators that are involved in the pathological processes resulting from brain trauma, ischemia and chronic neurodegenerative diseases. However, they are also involved in brain repair and recovery. Compelling evidence obtained, in vivo and in vitro , establish a dynamic interplay between the endocannabinoid system, the immune system and neural stem/progenitor cells (NSC) in order to promote brain self‐repair. Cross‐talk between inflammatory mediators and NSC might have important consequences for neural development and brain repair. In addition, brain immune cells (microglia) support NSC renewal, migration and lineage specification. The proliferation and differentiation of multipotent NSC must be precisely controlled during the development of the CNS, as well as for adult brain repair. Although signalling through neuroimmune networks has been implicated in many aspects of neural development, how it affects NSC remains unclear. However, recent findings have clearly demonstrated that there is bi‐directional cross‐talk between NSC, and the neuroimmune network to control the signals involved in self‐renewal and differentiation of NSC. Specifically, there is evidence emerging that neuroimmune interactions control the generation of new functional neurones from adult NSC. Here, we review the evidence that neuroimmune networks contribute to neurogenesis, focusing on the regulatory mechanisms that favour the immune system (immune cells and immune molecules) as a novel element in the coordination of the self‐renewal, migration and differentiation of NSC in the CNS. In conjunction, these data suggest a novel mode of action for the immune system in neurogenesis that may be of therapeutic interest in the emerging field of brain repair.
Mending the broken brain: neuroimmune interactions in neurogenesis
- Molinga-Holgado
Molinga-Holgado E, Molinga-Holgado F. Mending the broken brain: neuroimmune in-teractions in neurogenesis. J Neurochem 2010;114:1277–90.