Synthetic opioids: a review and clinical update.

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.

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. METHODS: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. RESULTS: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI -0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=-0.02, 95% CI -0.43 to 0.39). CONCLUSION: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.

Endocannabinoid system alterations in Alzheimer's disease: A systematic review of human studies.

Studies investigating alterations of the endocannabinoid system (ECS) in Alzheimer's disease (AD) in humans have reported inconsistent findings so far. We performed a systematic review of studies examining alterations of the ECS specifically within humans with AD or mild cognitive impairment (MCI), including neuroimaging studies, studies of serum and cerebrospinal fluid biomarkers, and post-mortem studies. We attempted to identify reported changes in the expression and activity of: cannabinoid receptors 1 and 2; anandamide (AEA); 2-arachidonoylglycerol (2-AG); monoacylglycerol lipase (MAGL); fatty acid amide hydrolase (FAAH); and transient receptor potential cation channel V1 (TRPV1). Twenty-two studies were identified for inclusion. Mixed findings were reported for most aspects of the ECS in AD, making it difficult to identify a particular profile of ECS alterations characterising AD. The included studies tended to be small, methodologically heterogeneous, and frequently did not control for important potential confounders, such as pathological progression of AD. Eight studies correlated ECS alterations with neuropsychometric performance measures, though studies infrequently examined behavioural and neuropsychiatric correlates. PROSPERO database identifier: CRD42018096249.

Cognitive behavior therapy for comorbid dissociative seizures in patients with epilepsy.

OBJECTIVES: The main aim of this study was to assess the effectiveness of cognitive behavior therapy (CBT) for comorbid dissociative seizures (DS) in patients with epilepsy. METHODS: We conducted a retrospective case note review of 14 patients with epilepsy who underwent outpatient CBT for DS in a tertiary neuropsychiatry service. The diagnosis of DS was confirmed by neurologists clinically and/or following video-telemetry electroencephalogram (EEG). We evaluated the outcome of the CBT treatment with respect to frequency of DS, measures of depression, anxiety, and social functioning. RESULTS: Measures of depression and anxiety significantly reduced following CBT treatment. Overall, frequency of DS reduced following CBT treatment but did not reach statistical significance. SIGNIFICANCE: This study provides evidence that CBT can be effective in reducing depression and anxiety in patients with both epilepsy and DS. Anxiety and depression are likely to be associated with DS. Further research in larger samples and longitudinal studies are recommended to evaluate the long-term efficacy of CBT in this patient group.

Revising a diagnosis of functional neurological disorder-a case report.

We report a case of a 62-year-old female diagnosed with functional neurological disorder (FND), where the diagnosis was eventually revised to progressive supranuclear palsy 3 years after symptom onset. FND is a commonly encountered condition and can be diagnosed with a considerable degree of confidence in most cases. FND is associated with significant functional impairment and may occur alongside other neurological disorders, and there is now a growing evidence base for symptom-specific FND treatments. Charting clinical progression of symptoms and serial neuroimaging were useful in refining the diagnosis in this case. Alhough the diagnosis was ultimately revised to a neurodegenerative disorder, a degree of functional overlay likely remained present. The case highlights the importance of recognizing and avoiding diagnostic overshadowing in those with FND.

New psychoactive substances: a review and updates.

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.

In vivo visualization of age-related differences in the locus coeruleus.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience-an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span.

Interventions for subjective cognitive decline: systematic review and meta-analysis.

OBJECTIVES: This review provides a broad overview of the effectiveness of interventions for subjective cognitive decline (SCD) in improving psychological well-being, metacognition and objective cognitive performance. METHODS: Databases including PubMed, Web of Science and Cochrane Systematic Reviews were searched up to August 2017 to identify randomised controlled trials evaluating interventions for SCD. Interventions were categorised as psychological, cognitive, lifestyle or pharmacological. Outcomes of interest included psychological well-being, metacognitive ability and objective cognitive performance. To assess the risk of bias, three authors independently rated study validity using criteria based on the Critical Appraisal Skills Programme. Random-effects meta-analyses were undertaken where three or more studies investigated similar interventions and reported comparable outcomes. RESULTS: Twenty studies met inclusion criteria and 16 had sufficient data for inclusion in the meta-analyses. Of these, only seven were rated as being high quality. Group psychological interventions significantly improved psychological well-being (g=0.40, 95% CI 0.03 to 0.76; p=0.03) but the improvement they conferred on metacognitive ability was not statistically significant (g=0.26, 95% CI -0.22 to 0.73; p=0.28). Overall, cognitive training interventions led to a small, statistically significant improvement in objective cognitive performance (g=0.13, 95% CI 0.01 to 0.25; p=0.03). However, the pooled effect sizes of studies using active control groups (g=0.02, 95% CI -0.19 to 0.22; p=0.85) or reporting global cognitive measures (g=0.06, 95% CI -0.19 to 0.31; p=0.66) were non-significant. CONCLUSIONS: There is a lack of high-quality research in this field. Group psychological interventions improve psychological well-being and may also improve metacognition. A large, high-quality study is indicated to investigate this further. There is no evidence to suggest that cognitive interventions improve global cognitive performance and the clinical utility of small improvements in specific cognitive domains is questionable. There is a lack of research considering lifestyle interventions and poor quality evidence for pharmacological interventions. PROSPERO REGISTRATION NUMBER: CRD42017079391.