'Why would we not want to keep everybody safe?' The views of family members of people who use drugs on the implementation of drug consumption rooms in Scotland.

BACKGROUND: People who use drugs in Scotland are currently experiencing disproportionately high rates of drug-related deaths. Drug consumption rooms (DCRs) are harm reduction services that offer a safe, hygienic environment where pre-obtained drugs can be consumed under supervision. The aim of this research was to explore family member perspectives on DCR implementation in Scotland in order to inform national policy. METHODS: Scotland-based family members of people who were currently or formerly using drugs were invited to take part in semi-structured interviews to share views on DCRs. An inclusive approach to 'family' was taken, and family members were recruited via local and national networks. A convenience sample of 13 family members were recruited and interviews conducted, audio-recorded, transcribed, and analysed thematically using the Structured Framework Technique. RESULTS: Family members demonstrated varying levels of understanding regarding the existence, role, and function of DCRs. While some expressed concern that DCRs would not prevent continued drug use, all participants were in favour of DCR implementation due to a belief that DCRs could reduce harm, including saving lives, and facilitate future recovery from drug use. Participants highlighted challenges faced by people who use drugs in accessing treatment/services that could meet their needs. They identified that accessible and welcoming DCRs led by trusting and non-judgemental staff could help to meet unmet needs, including signposting to other services. Family members viewed DCRs as safe environments and highlighted how the existence of DCRs could reduce the constant worry that they had of risk of harm to their loved ones. Finally, family members emphasised the challenge of stigma associated with drug use. They believed that introduction of DCRs would help to reduce stigma and provide a signal that people who use drugs deserve safety and care. CONCLUSIONS: Reporting the experience and views of family members makes a novel and valuable contribution to ongoing public debates surrounding DCRs. Their views can be used to inform the implementation of DCRs in Scotland but also relate well to the development of wider responses to drug-related harm and reduction of stigma experienced by people who use drugs in Scotland and beyond.

An Examination of the Longer-Term Impact of a Combined Classroom and Parental Intervention on Alcohol-Related Harms and Heavy Episodic Drinking.

Although fewer adolescents are consuming alcohol than was the case in previous decades, those who are consuming alcohol are still exposed to alcohol-related harms. While the evidence for the effectiveness of universal, school-based interventions is limited, a recent cluster randomised controlled trial (The STAMPP Trial) reported a significant effect at 10 months post-intervention of a combined classroom/parental intervention on heavy episodic drinking (HED) in the previous 30 days, but no significant effect on the number of self-reported alcohol-related harms (ARH) experienced in the previous 6 months. This follow-up study sought to examine intervention effects 24 months after delivery of the intervention (+ 57 months from baseline, or + 34 months post-intervention). Participants were 5029 high school students in STAMPP (38% of 12,738 pupils originally randomised into the trial), from 87 schools (82.3% of schools recruited in the original STAMPP trial). Outcomes were assessed using two-level random intercepts models (logistic regression for HED and negative binomial for number of ARH). Results of the present study show that the intervention effect for HED deteriorated over the following 2 years (OR declined from 0.60 to 0.97), and there was still no difference in ARH. This was due to an increase in the prevalence of intervention students' HED rather than a reduction in prevalence in control students. Results are discussed in the context of prevention initiatives.

Contextual factors associated with subjective effects of cannabis: A systematic review and meta-analysis.

BACKGROUND: Cannabis is consumed in various social and environmental settings, and such contexts may be important predictors of subjective effects. The aim of this systematic review and meta-analysis was to examine the relationship between contextual factors and subjective effects of cannabis. METHODS: A PRISMA-guided search of MEDLINE, Embase, PsycINFO, Global Health, and Google Scholar yielded 29 studies. RESULTS: Study type (Ecological Momentary Assessment or Experimental) was a significant predictor of intoxication effects, and experimental studies had a greater pooled effect size (z =.296,95 % CI [.132,.478], p=.004) than Ecological Momentary Assessment (EMA) studies (z =.071,95 % CI [.011,.130], p =.02). Contextual conditions (environment, social group, expectancy, time of day, day of week) were not significant predictors of cannabis effects. CONCLUSION: Findings did not point to a significant association between contextual conditions and subjective effects. However, as current literature is methodologically weak, it may be premature to conclude that subjective effects are not shaped by contextual factors. In view of policy and therapeutic implications, replications and study refinements are recommended.

Effects of media representations of drug related deaths on public stigma and support for harm reduction.

BACKGROUND: Drug related deaths (DRD) are at historically high levels in the United Kingdom (UK), but some approaches that have the potential to reduce risk of mortality remain controversial. Public support makes an important contribution to drug policy development but there are high levels of public stigma towards people who use drugs (PWUD), and this is partly shaped by media representations. We investigated whether depiction of the characteristics of decedents represented in news articles about DRD was associated with differences in stigmatising attitudes and support for harm reduction policy. METHODS: We undertook a cross-sectional online study with a randomised design, conducted with a nationally representative sample (UK). Participants (N = 1280) were randomly presented with one of eight simulated news stories that reported on a DRD that differed with respect to drug (ecstasy or heroin), and the gender (male or female) and age (younger or older) of the decedent. Data were analysed using MANOVA. RESULTS: Data were obtained for 1248 participants (51.0% female; mean age 45.7±15.4). Stigma was higher towards depictions of male, older, and heroin deaths (all p < .001). Harm reduction support was higher in those participants seeing older compared to younger subjects (p = .035), and the older ecstasy decedent compared to younger decedent (p = .029). CONCLUSION: Presentation of some types of DRD are associated with higher public stigma towards the decedent than others. Those groups developing agenda-setting activities designed to reduce stigma or foster public support for harm reduction policies should consider the different ways in which audiences may respond to the depiction and framing of DRD in news media.

Opioid prescribing and social deprivation: A retrospective analysis of prescribing for CNCP in Liverpool CCG.

BACKGROUND: Treating Chronic Non-Cancer Pain (CNCP) with long-term, high dose and more potent opioids puts patients at increased risk of harm, whilst providing limited pain relief. Socially deprived areas mapped from Index of Multiple Deprivation (IMD) scores show higher rates of high dose, strong opioid prescribing compared to more affluent areas. OBJECTIVE: To explore if opioid prescribing is higher in more deprived areas of Liverpool (UK) and assess the incidence of high dose prescribing to improve clinical pathways for opioid weaning. DESIGN AND SETTING: This retrospective observational study used primary care practice and patient level opioid prescribing data for N = 30,474 CNCP patients across Liverpool Clinical Commissioning Group (LCCG) between August 2016 and August 2018. METHOD: A Defined Daily Dose (DDD) was calculated for each patient prescribed opioids. DDD was converted into a Morphine Equivalent Dose (MED) and patients stratified according to high (≥120mg) MED cut off. The association between prescribing and deprivation was analysed by linking GP practice codes and IMD scores across LCCG. RESULTS: 3.5% of patients were prescribed an average dose above 120mg MED/day. Patients prescribed long-term, high dose, strong opioids were more likely to be female, aged 60+, prescribed three opioids and reside in the North of Liverpool where there is a higher density of areas in the IMD most deprived deciles. CONCLUSION: A small but significant proportion of CNCP patients across Liverpool are currently prescribed opioids above the recommended dose threshold of 120mg MED. Identification of fentanyl as a contributor to high dose prescribing resulted in changes to prescribing practice, and reports from NHS pain clinics that fewer patients require tapering from fentanyl. In conclusion, higher rates of high dose opioid prescribing continue to be evident in more socially deprived areas further increasing health inequalities.

The Temporal Focus Scale: factor structure and association with alcohol use in a sample of Northern Irish school children.

The Temporal Focus Scale (TFS) is a 12-item self-report measure of cognitive engagement with the temporal domains of past, present and future. Developed in college student samples, a three-factor structure with adequate reliability and validity was documented in a series of independent studies. We tested the factor structure of the scale in a sample of Northern Irish adolescents and found that our data supported a three factor structure, although there were problems with item 10. Because time perspective measures have been found to relate differentially to various health behaviours, we tested the relations between scores on the TFS and self-reported alcohol use. Results showed that scores on the TFS were not consistent statistical predictors of drinking category in a logistic regression. Results are discussed in terms of scale development, future scale use and the assessment of health-compromising behaviours such as adolescent alcohol consumption.

Drug Consumption Rooms and Public Health Policy: Perspectives of Scottish Strategic Decision-Makers.

There is widespread support for the introduction of Drug Consumption Rooms (DCRs) in Scotland as part of a policy response to record levels of drug-related harm. However, existing legal barriers are made more complex by the division of relevant powers between the UK and Scottish Governments. This paper reports on a national, qualitative study of key decision-makers in both local and national roles across Scotland. It explores views on the political barriers and enablers to the adoption of Drug Consumption Rooms and the potential role of these facilities in the wider treatment system. It also considers approaches to evidence, especially the types of evidence that are considered valuable in supporting decision-making in this area. The study found that Scottish decision-makers are strongly supportive of DCR adoption; however, they remain unclear as to the legal and political mechanisms that would make this possible. They view DCRs as part of a complex treatment and support system rather than a uniquely transformative intervention. They see the case for introduction as sufficient, on the basis of need and available evidence, thus adopting a pragmatic and iterative approach to evidence, in contrast to an appeal to traditional evidence hierarchies more commonly adopted by the UK Government.

One rule for one, and a different rule for another: The case of the Parental Rules about Alcohol Questionnaire.

BACKGROUND: The parental rules about alcohol questionnaire (Van der Vorst et al., 2005, 2006) uses 10 items to assess how strictly adolescents believe the rules set by their parents about drinking are. An increasing body of literature has attested to the importance of rule setting in the prevention of problematic alcohol use among adolescents. A recent study proposed a two-factor solution in place of the hypothesized unidimensional one, with factors assessing non-normative, and normative rules. METHODS: The present study used five waves of data to examine the structure of the scale, and how well it relates to a measure of heavy episodic drinking (HED). Participants in Waves one to four {10,954-9,383} were substantively more numerous than those at wave five (N = 2,332). RESULTS: Confirmatory Factor Analyses did not support either the ten-item hypothesized model, nor the proposed two-factor solution. Results of exploratory factor analyses all pointed to a one factor solution. Using Modification Indices, we obtained a good-fitting, five-item unidimensional model in Waves one to four. At wave five, a good fitting unidimensional model was obtained with the dropping of a further item. Scores on this shortened scale were internally consistent, correlated highly with scores on the original ten-item version, and correlated to a similar degree as the original 10-item measure, with scores on a HED measure. CONCLUSION: Further work is required in assessing the properties of this scale across cultures and samples before definitively determining that two factors best represent parental rules.

Intervention impact on alcohol use, alcohol harms, and a combination of both: A latent class, secondary analysis of results from a randomized controlled trial.

BACKGROUND: Alcohol use and alcohol-related harm (ARH) among adolescents places a substantial burden on health, and public services more generally. To date, attempts to intervene at a universal level have yielded results varying from iatrogenic to null, although some skill-enhancing universal interventions have successfully impacted drinking behaviors. One such intervention is SHAHRP. The present study is a secondary analysis of data from the STAMPP Trial, providing new, and more nuanced findings. METHODS: A total of 13,914 adolescents (41.7% female) participated in this cRCT where schools were randomly assigned to a control or intervention group. Growth mixture modelling was used to identify trajectory classes from baseline through third follow-up (+33 months) of adolescents on heavy episodic drinking (HED) and ARH. Extracted classes were related to school intervention participation using multinomial logistic regression. RESULTS: Five trajectory classes of the HED and ARH composite were identified: Low (62%), Late Onset (16%), Early Onset (13%), Delayed Onset (7%), and Unstable (3%). The intervention was most strongly related to Late Onset (OR = 0.50, 95%CI [0.25, 1.01]) and Delayed Onset (OR = 0.55, 95%CI [0.26, 1.16]), although not statistically significant. With classes constructed with ARH only, the Delayed Onset class was significantly related to the intervention (OR = 0.60, 95%CI [0.43, 0.84]). CONCLUSIONS: These results support those previously reported on the STAMPP Trial and provide a more nuanced insight into the effects of the intervention.

Use, function, and subjective experiences of gamma-hydroxybutyrate (GHB).

Self-reported use of gamma-hydroxybutyrate (GHB) among clubbers has increased over the last decade, and is often reported in the scientific literature in association with negative events such as amnesia, overdose, and use in drug facilitated sexual assault. However, there has been relatively little work investigating the phenomenology of GHB intoxication, and the reasons underlying use. In this study, 189 individuals reporting at least one lifetime use of GHB completed an online questionnaire recording GHB use behaviours, GHB use function, and subjective GHB effects. The most frequently reported primary GHB use functions were for recreation (but not in nightclubs) (18.3%); to enhance sex (18.3%); to be sociable (13.1%); and to explore altered states of consciousness (13.1%). GHB was more commonly used within the home (67%) compared to nightlife environments (26.1%) such as clubs, although this differed on the basis of respondent's sexuality. Principle components analysis of GHB user responses to the subjective questionnaire revealed six components: general intoxication effects, positive intoxication effects, negative intoxication effects, negative physiological effects, positive sexual effects and negative sexual effects. Component scores predicted function of use.

The effects of perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

Previous research has indicated that non-dependent polydrug users are willing to pay more money to buy good quality drugs as their income increased. This study sought to examine whether altering the perceived quality of controlled drugs would affect drug purchases if the monetary price remained fixed. A random sample of 80 polydrug users were recruited. All participants were administered an anonymous questionnaire consisting of the Drug Abuse Screening Test for Adolescents (DAST-A), the Severity of Dependence Scale for cannabis (SDS), the Alcohol Use Disorders Identification Test (AUDIT), the Hospital Anxiety and Depression Scale (HADS), and questions about their drug use. Participants then completed a simulation of controlled drug purchases where the price of alcohol, amphetamine, cannabis, cocaine, and ecstasy remained the same but their perceived quality changed (i.e. unit price increased as the perceived quality decreased). The demand for alcohol was quality inelastic and alcohol quality had no effects on the purchase of any other controlled drug. Demand for cannabis was quality elastic and alcohol substituted for cannabis as its unit price increased. Demand for cocaine was quality elastic and alcohol, cannabis, and ecstasy substituted for cocaine as its unit price increased. Demand for ecstasy was quality elastic and alcohol and cocaine both substituted for ecstasy as its unit price increased. These results suggest that perceived quality influences the demand for controlled drugs and that monitoring the perceived quality of controlled drugs may provide a warning of potential public health problems in the near future.

Olanzapine withdrawal/discontinuation-induced hyperthermia in rats.

In female rats olanzapine (4 mg/kg b.i.d., i.p.) induced acute hypothermia, followed by very rapid full tolerance. With more prolonged treatment (over > 10 days) the hypothermic effect of olanzapine was reinstated. Subsequent withdrawal after 18 days of treatment induced very rapid onset (within 1 day) hyperthermia, which was time limited, dissipating completely over 3-4 days. These findings are similar to previous findings with clozapine [Goudie A Smith J Robertson A Cavanagh C (1999). Clozapine as a drug of dependence. Psychopharmacology; 142: 369-374.]. Although the mechanism(s) involved in the secondary hypothermic effect of olanzapine are, at present, unclear; the withdrawal hyperthermia observed represents the first report of a clear discontinuation effect of olanzapine. Such discontinuation effects are probably observed with many antipsychotic drugs. Since they have been suggested to facilitate relapse to psychosis and to interfere with subsequent clinical responses to antipsychotics, they merit further detailed analysis in both clinical and preclinical studies.

The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy.

Previous investigations of the subjective effects of MDMA (material sold as ecstasy) have conducted interviews and surveys of various groups of ecstasy users within particular sub-populations. This study examined subjective drug effects reported by different sub-populations of ecstasy users and explored whether the function or purpose served by using ecstasy influenced the nature of the drug experience. Drawing on previous measures of alterations in consciousness, psychedelic drugs and cannabis, and informal interviews with ecstasy users and MDMA researchers, a 130-item survey assessing subjective effects of ecstasy/MDMA was developed. Principal components analysis of responses of ecstasy users revealed six components; perceptual alterations, entactogenic effects, prosocial effects, aesthetic effects, negative effects and sexual effects. The derived scale was used to predict ecstasy use behaviours, and functions and experiences of use. A variety of component scores were related to ecstasy use parameters; in particular, heavier users expected fewer negative, perceptual and aesthetic effects from taking the drug. The reasons given for using ecstasy (use function) also influenced reported drug effects. Abstainers expected greater negative, perceptual, aesthetic and sexual effects than users. These data indicate that the subjective ecstasy experience is influenced by a variety of extra-psychopharmacological factors. Drug intervention strategies may be made more effective by targeting particular user groups defined by reasons given for substance use, as it is likely that their experiences of ecstasy effects will differ. Future research into ecstasy may be improved by recognizing user diversity.

Is ecstasy perceived to be safe? A critical survey.

Recent publications claim that the recreational drug ecstasy is considered to be safe by many or most ecstasy users, or by young people or the general public. Unfortunately, there are no references that provide any support for this claim. Previous studies of various populations, including drug users and adolescents in several nations, also failed to support claims of the perceived safety of ecstasy. Epidemiological surveys from the USA and UK consistently report high proportions of young people who perceive great risk in using ecstasy. Studies in ecstasy users show that they are aware of a number of short- and long-term risks of ecstasy use, although, in the absence of actual problems, they evaluate the personal significance of these risks as low. This study further investigated the perceived harmfulness of ecstasy, drawing on an online survey of over 900 drug users. Little support for the claim was found. Seventy-three percent of the participants in the online survey viewed ecstasy as carrying at least 'some risk'. The claim of ecstasy's perceived safety is plausibly based on researchers' assumptions that the continued widespread use of the drug indicates that users are unaware of the associated risks, and that informing them about these risks would lead to a reduction in drug use. We argue that these assumptions are inadequate and that drug information and harm reduction strategies should focus on more affective and personally significant aspects of risk perception.

Self-reported depressive symptomatology in community samples of polysubstance misusers who report Ecstasy use: a meta-analysis.

National drugs information strategies convey the message that use of Ecstasy is associated with an increase in both the incidence and severity of major depressive disorder. However, very little primary research supports this. Unlike apparent deficits in higher cognitive functions, most published studies have found no difference in self-reported depressive symptomatology between Ecstasy users and controls. To investigate this further, we conducted a meta-analysis of studies investigating depressive symptomatology in recreational users of Ecstasy. According to selection criteria, we identified 25 relevant studies. A statistically significant effect size (ES) of 0.31 (95% confidence interval 0.17-0.37, p < 0.001) was calculated. Significance remained after examining the small number of studies that controlled for cannabis use (n = 9, p < 0.001) but, in general, drug histories were poorly reported. There was an association between ES and lifetime Ecstasy exposure (p < 0.001), but not for other use parameters or abstention (p > 0.05). These data indicate that there is an association between Ecstasy use and depressive symptomatology, but this is small and unlikely to be clinically relevant. In addition, the self-report scales used may be heavily confounded by the somatic effects of substance misuse. Public health strategies derived from psychopharmacological investigations should acknowledge the potential negative effects of substance misuse but qualify the difficulties in interpreting research studies.

The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine (MDMA).

3,4-Methylenedioxymethamphetamine (MDMA) is a relatively novel drug of abuse and as such little is currently known of its behavioural pharmacology. This review aims to examine whether MDMA represents a novel class of abused drug. MDMA is known as a selective serotonergic neurotoxin in a variety of animal species but acutely it is a potent releaser and/or reuptake inhibitor of presynaptic serotonin, dopamine, noradrenaline, and acetylcholine. Interaction of these effects contributes to its behavioural pharmacology, in particular its effects on body temperature. Drug discrimination studies indicate that MDMA and related drugs produce unique interoceptive effects which have led to their classification as entactogens. This is supported by results from other behavioural paradigms although there is evidence for dose dependency of MDMA-specific effects. MDMA also produces conditioned place preference but is not a potent reinforcer in self-administration studies. These unique behavioural effects probably underlie its current popularity. MDMA is found in the street drug ecstasy but it may not be appropriate to equate the two as other drugs are routinely found in ecstasy tablets

The content of ecstasy tablets: implications for the study of their long-term effects.

AIMS: To examine the variation in the content of ecstasy tablets seized in the north-west of England during 2001 and to compare it to the UK average from 1991 to 2001. MEASUREMENTS: All tablets submitted to the Forensic Science Service in the north-west of England during 2001 were analysed by high performance liquid chromatography with diode array detection (HPLC-DAD). The mean MDMA content of these tablets are reported and compared to results from all Forensic Science Service laboratories in the United Kingdom from 1991 to 2001. Multiple samples (n= 80) from a single large seizure of White Dove tablets were analysed to determine the variation due to manufacturing. FINDINGS: All tablets submitted from the north-west of England to the Forensic Science Service in 2001 were found to contain 3,4-methylenedioxymethamphetamine (MDMA) and some also contained 3,4-methylenedioxyethamphetamine (MDEA). The MDMA content of these tablets ranged from 20 to 109 mg and the mean was in the 60-69 mg range. Mitsubishi tablets were the most common type and they were found across the whole range. The low variation of MDMA content in the White Dove tablets suggests that these tablets were well manufactured. The data from the north-west of England in 2001 are in agreement with tablet analyses over the past 10 years which show that the average MDMA content is falling. CONCLUSIONS: The amount of MDMA in ecstasy tablets is axiomatic to the discussion of their long-term effects. In order for the observed differences in ecstasy users to be the result of MDMA-induced neurotoxicity it is necessary for them to have ingested one or more neurotoxic doses. These data indicate that the amount of MDMA in ecstasy tablets is dropping and that dose-effect relationships need to take this into account.