Number Of Novel Psychoactive Substances Research Articles

Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects.

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know.

The rise of new psychoactive substances and psychiatric implications: A wide-ranging, multifaceted challenge that needs far-reaching common legislative strategies.

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.

Morphine drug discrimination: A behavioral model to assess novel synthetic opioid substances

A large number of novel psychoactive substances including opioid‐like compounds have appeared on the illicit market in the past decade. Several substances structurally related to fentanyl are being abused alone and in combination with other drugs (e.g., heroin and/or cocaine), resulting in overdoses at an alarming rate. There is a paucity of information about the pharmacology of these novel synthetic substances. In this study, we evaluated the opioid‐like stimulus effects of crotonyl fentanyl, thiophene fentanyl, benzodioxole fentanyl, and methoxyacetyl fentanyl, four newly identified substances structurally related to fentanyl. We compared the potencies of these new substances to schedule II opioid analgesics such as fentanyl and morphine using a preclinical abuse liability assessment model called drug discrimination. We also studied the susceptibility of the stimulus effects of these test drugs to antagonism by the opioid antagonist naltrexone, a drug used in patients to reverse the overdose effects of heroin and fentanyl. Using a two‐lever operant experimental chamber under a fixed ratio‐10 schedule for food delivery, rats (Sprague Dawley) were trained to discriminate between 3.2 mg/kg morphine and saline, subcutaneously. We evaluated saline and multiple doses of morphine, fentanyl, crotonyl fentanyl, thiophene fentanyl, benzodioxole fentanyl, and methoxyacetyl fentanyl. Crotonyl fentanyl, thiophene fentanyl, and methoxyacetyl fentanyl, similar to morphine and fentanyl, fully substituted for the morphine discriminative stimulus and decreased response rates with slightly differing potencies. Benzodioxole fentanyl failed to produce significant morphine‐like responding or rate‐decreasing effects at any dose although testing was limited by solubility issues. Crotonyl fentanyl, thiophene fentanyl, and methoxyacetyl fentanyl were blocked by naltrexone indicating that mechanisms of action of these three drugs are similar to that of morphine and fentanyl. The opioid‐like discriminative stimulus effects of crotonyl fentanyl, thiophene fentanyl, and methoxyacetyl fentanyl indicate that subjective effects and abuse liability of these three novel substances are likely to be similar to that of morphine and fentanyl.Support or Funding InformationDJD‐17‐HQ‐P‐0646This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

An early warning system for emerging drugs of concern in the emergency department: Protocol for the Western Australian Illicit Substance Evaluation (WISE) study.

An ever-increasing number of novel psychoactive substances are being detected worldwide. These emerging drugs have been demonstrated to cause toxicity in clusters, and deaths have been reported. We urgently need to learn more about their effects. We report the protocol for the Western Australian Illicit Substance Evaluation (WISE) study, a research project investigating illicit drug use in the ED. Patients can be enrolled if the treating clinician strongly suspects they are currently intoxicated with a stimulant, hallucinogenic or cannabinoid drug; and an i.v. cannula or blood tests are required for routine clinical care. Patients are enrolled under a waiver of consent. A single additional blood tube is collected, de-identified and frozen on site. A temporary link between patient identification number and study identification number is retained for up to 10 business days post-hospital discharge to allow for clinical data collection, before this is destroyed and the patients become permanently de-identified. Samples are transported for external liquid chromatography-mass spectrometry analysis in batches once de-identified. The key outcome will be identification of any psychoactive drugs present in the blood sample, together with their respective concentration. This will be linked to the clinical effects, as well as being compared with the substance the patient believed they had taken. We consider the novel approach outlined forms a template for an early warning system for emerging drugs of concern, while also providing vital and comprehensive information on current drugs of abuse, their clinical effects and their impact on the health system.

ACUTE INTOXICATION DUE TO DESIGNER DRUG TALISMAN — TREATMENT DILEMMA IN PRE-HOSPITAL SETTINGS — CASE REPORT AND REVIEW

Currently, the number of novel psychoactive substances (NPS) has significantly increased. Recent reports on the abuse of synthetic cathinones focus on serious physical and psychological risks resulting from their consumption, thereby emphasising that a growing use of these drugs might constitute an important public health. Case report: A young man presented to the emergency department with acute designer drug intox­ication complicated with severe respiratory failure. Why should an emergency physician be aware of this? We observe a growing use of NPS among young people. Further studies describing clinical manifestations of intoxication and toxicity of synthetic cathinones and treatment guidelines are still needed.

Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings.

An increasing number of novel psychoactive substances are currently available and sold as 'legal highs' or 'research chemicals' accompanied by the indication that they are 'not for human consumption'. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a 'safe' drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties. Yet, very recent preclinical data highlighted a stimulatory effect of MXE on dopamine neurotransmission within the mesolimbic pathway. The aim of this review is to provide an updated review of the behavioral and toxicological effects of MXE as well as the latest findings on its pharmacology that might explain sought effects and frequent occurrence of adverse effects. In light of the growing number of intoxications induced by MXE, knowledge of its short-term and long-term effects is urgently needed. However, the hypothetical rapid antidepressant activity of MXE suggested by its chemical analogy with ketamine and supported by recent preclinical findings deserves further investigation.

The users of Novel Psychoactive Substances: Online survey about their characteristics, attitudes and motivations

BackgroundThe increasing number of Novel Psychoactive Substances (NPS) constitutes a challenge for public health agencies and researchers worldwide. Scientific studies about NPS and their users are limited and there is a need to explore the general motivations for NPS use but also to examine if and how the motivations differ between substances from separate effect classes. The aim of the present study was to investigate the characteristics, including attitudes and motivations, of a self-selected sample of international NPS users. MethodsAn online survey containing questions about drug use history, attitudes, motivations for use, and WHO-5 Wellbeing Index was promoted at the drug discussion forum bluelight.org. The data was analysed using SPSS. ResultsThe sample consisted of 619 international NPS users with overall good emotional well-being despite extensive experience of both traditional and novel drugs. The main incentive for use of NPS in general was pleasure and enjoyment. However, going beyond the general approach to NPS revealed significant variations between drug groups. For example, the use of hallucinogens was substantially motivated by self-exploration and spiritual attainment and showed very low levels of addiction potential while the use of opioids and especially GABA activating substances was mainly motivated by coping and showed much higher levels of addiction potential. Synthetic cannabinoids were the least appreciated and least likely to be used again, and were mainly motivated by circumstances such as availability and legality. ConclusionUnderstanding the different motivations for NPS use in terms of drug groups could enable more effective prevention and consequently a reduction in harm.

The experience of using synthetic cannabinoids: A qualitative analysis of online user self-reports

IntroductionThe number of novel psychoactive substances (NPS) available is increasing. Synthetic cannabinoids (SC) are one of many NPS sold. SC aim to emulate the effects of natural cannabis by acting on cannabinoid receptors. Despite much research into pharmacology, there is limited data on the user experience of SC.AimIt is useful for psychiatrists, to understand what experiences people have whilst on illicit substances. The aim of this qualitative study is to gain an initial understanding of what characterizes the experiences of those who use SC.MethodFourty anonymously written online reports were collected from the “Erowid experience vaults” and analysed using the Empirical Phenomenological Psychological Method.ResultsThe analysis yielded 488 meaning units (MU). These were grouped into 36 categories revealing 5 broad themes: (1) physical affects; (2) sensory distortions and distortions of perception; (3) emotional and psychological effects; (4) re-dosing, addiction and comedown effects; (5) similarities to other substances.ConclusionSynthetic cannabinoids have a mixed effect on users with a myriad of experiences reported. Some experienced positive results from their usage such as euphoria and relaxation, however these were counter balanced by those who experienced some serious negative emotional and physical side effects such as anxiety, paranoia, palpitations and convulsions. SC appear to often emulate that of their natural counterpart, yet there is an unpredictability to them which can end with serious consequences. Online forum content gives us a strong base understanding of users experiences of SC. Further research is required to elucidate a more nuanced understanding.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Poisoning Casualties: Alcohol, Pharmaceuticals or “Legal Highs”? Poisoning Cases at Emergency Rooms in The Swedish County Värmland in 2007-2013

Background: The growing number of novel psychoactive substances (NPS), also labelled as “legal highs”, constitutes a challenge to public health. It is uncertain whether this trend is related to the increase in number of poising cases reported by emergency rooms. The aim of this study was to investigate the occurrence of NPS in acute cases of poisoning in the Swedish county Värmland. The numbers of NPS casualties were correlated with poisoning by other substances. Both, the gender and age distribution of the reported cases were recorded. Method: Records classified as poisoning casualties at the emergency rooms in Värmland during 2007- 2013 were collected and analyzed. Results: NPS and illicit drugs constituted only a small part (1.67% and 7.84% respectively) of the total poisoning casualties. The results also revealed that alcohol and pharmaceuticals were present in the majority of cases (91.2%), and were to a larger extent involved in polydrug abuse and suicide attempts. Furthermore, the results uncovered an alarming poisoning problem among women who had taken pharmaceuticals and for suicidal young people. Conclusions: It is unclear whether the comparatively low prevalence of NPS and illicit drug related poisoning casualties reflect the real prevalence of injury cases or a possible under-reporting. Background: The growing number of novel psychoactive substances (NPS), also labelled as “legal highs”, constitutes a challenge to public health. It is uncertain whether this trend is related to the increase in number of poising cases reported by emergency rooms. The aim of this study was to investigate the occurrence of NPS in acute cases of poisoning in the Swedish county Värmland. The numbers of NPS casualties were correlated with poisoning by other substances. Both, the gender and age distribution of the reported cases were recorded. Method: Records classified as poisoning casualties at the emergency rooms in Värmland during 2007- 2013 were collected and analyzed. Results: NPS and illicit drugs constituted only a small part (1.67% and 7.84% respectively) of the total poisoning casualties. The results also revealed that alcohol and pharmaceuticals were present in the majority of cases (91.2%), and were to a larger extent involved in polydrug abuse and suicide attempts. Furthermore, the results uncovered an alarming poisoning problem among women who had taken pharmaceuticals and for suicidal young people. Conclusions: It is unclear whether the comparatively low prevalence of NPS and illicit drug related poisoning casualties reflect the real prevalence of injury cases or a possible under-reporting.

Identifying emerging trends in recreational drug use; outcomes from the Psychonaut Web Mapping Project

This paper presents the outcomes of the 2-year European Union funded Psychonaut Web Mapping Project which aimed at developing and implementing an integrated web mapping system to promptly identify and learn about novel psychoactive substances (NPS; "legal highs") through the regular monitoring of the Internet. More than 200 discussion forums, social media, online shops, websites and other Internet resources (e.g. YouTube, eBay, Google, Google Insight) have been extensively and regularly monitored in 7 European countries (UK, Finland, Norway, Belgium, Germany, Italy and Spain) for emerging trends of NPS throughout the period of the study. Key online resources have been identified as "leading edge" which have provided accurate and timely information on novel emerging compounds. In total more than 400 substances/products have been recorded. NPS have been noted online before reaching wider audiences. Although a high number of novel psychoactive substances have been identified in the 2-year duration of the project, not all have become trends that needed public health response. Conversely, new recreational drug phenomena such as "spice drugs," mephedrone and naphyrone were all identified as emerging trends in forums and websites. In addition, it has been possible for the first time to collate detailed information on these and several more compounds even though no or limited scientific publications were available. It is therefore recommended that these monitoring activities are to be continued, that more countries, researchers and health professionals are involved, and that the findings are widely shared with all the relevant agencies, health professionals and future research projects. Implications, advantages and limitations of using the Internet as primary source for identifying emerging trends are also discussed.