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The term ‘opioids’ refers to both the natural compounds (‘opiates’) which are extracted from the opium poppy plant ( Papaver somniferum ) and their semi-synthetic and synthetic derivatives. They all possess relatively similar biochemical profiles and interact with the opioid receptors within the human body to produce a wide range of physiological effects. They have historically been used for medicinal purposes, their analgesic and sedative effects, and in the management of chronic and severe pain. They have also been used for non-medicinal and recreational purposes to produce feelings of relaxation, euphoria and well-being. Over the last decade, the emergence of an illegal market in new synthetic opioids has become a major global public health issue, associated with a substantial increase in unintentional overdoses and drug-related deaths. Synthetic opioids include fentanyl, its analogues and emerging non-fentanyl opioids. Their popularity relates to changes in criminal markets, pricing, potency, availability compared to classic opioids, ease of transport and use, rapid effect and lack of detection by conventional testing technologies. This article expands on our previous review on new psychoactive substances. We now provide a more in-depth review on synthetic opioids and explore the current challenges faced by people who use drugs, healthcare professionals, and global public health systems.

Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome. Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis. Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient’s clinical symptoms and functional status. Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations. Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement.

New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.

Objective: A bibliometric study was undertaken of peer-reviewed publications on atypical antipsychotic drugs (AADs) from the United Kingdom and the findings are presented herein. Methods: We selected the documents from the Scopus database. We applied several production and dispersion bibliometric indicators, including Price’s law on the growth of the scientific literature, and Bradford’s law. We also calculated a so-called ‘participation index’ across different countries. The bibliometric data were thereafter correlated with social and health data from the UK, including total per capita expenditure on health and gross domestic expenditure. Results: A total of 4156 original manuscripts were published within the timeframe 1967–2015. Our results are in accord with Price’s law, with scientific output demonstrating exponential growth ( r = 0.9227, as against an r = 0.8766 after adjustment). The drugs most widely evaluated were clozapine (465 documents), olanzapine (263) and risperidone (248). Stratification into Bradford zones produced a nucleus represented by the Journal of Psychopharmacology (168 articles) and British Journal of Psychiatry (159 articles). A total of 1250 different journals were evaluated. Conclusions: Publications on AADs in the UK have shown exponential growth across the studied period, which is in line with the progressively burgeoning novel AAD releases. No evidence of a saturation point was observed.