A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Drug dependence and prescribing ketamine for treatment-resistant depression in Australia and New Zealand.

Ketamine is a restricted and regulated medication in Australia and New Zealand, which has implications when considering treatment for patients with treatment-resistant depression and a history of illicit drug use, abuse or dependence. Regulations governing prescription of ketamine for treatment-resistant depression vary between jurisdictions in Australia and New Zealand, though most restrict use in those with drug dependence. There is substantial variation in definitions of drug dependence used in each jurisdiction, and between the legal and clinical definitions, with the latter specified in the current International Classification of Diseases, Eleventh Revision and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This paper reviews the literature assessing the risk of ketamine misuse and dependence in patients with a history of illicit drug use, abuse or dependence and presents recommendations for psychiatrists who prescribe ketamine in such patients with treatment-resistant depression.

Economic evaluations of alcohol pharmacotherapy: Systematic review of economic evaluations of pharmacotherapy for the treatment of alcohol use disorder.

OBJECTIVE: Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies. METHODS: A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality. RESULTS: A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%. CONCLUSION: Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.

Co-design of digital public health substance use resources: A collaboration between young people and experts.

ISSUE ADDRESSED: Substance use and mental illness remain critical issues for young Australians, however, engagement with evidence-based health resources is challenging among this age group. This study aimed to develop engaging, useful digital health resources, underpinned by neuroscience principles, to build awareness of the harms of electronic cigarettes (e-cigarettes) and concurrent alcohol and antidepressant use. METHODS: A mixed-methods approach was adopted to co-design two evidence-based videos resources. The resources were co-designed with the Matilda Centre's Youth Advisory Board Centre's Youth Advisory Board through a series focus groups and individual feedback reviews. Young people residing in New South Wales were then invited to complete a survey to evaluate the usefulness, relatability and impact on perceived harms associated with each substance pre- and post-viewing resources. RESULTS: A total of 100 participants completed the survey (mean age = 21.5 years, SD = 2.77, 42% Female, 2% Non-binary). The animated videos were well received, with the large majority (91% and 87% respectively) of participants rating them 'excellent' or 'very good'. After viewing the videos, there was a significant increase in the perception of harm associated with e-cigarette use, monthly (t(99) = 2.76, p = .003), weekly (t(99) = 4.82, p < .001) and daily (t(99) = 4.92, p < .001), and consuming alcohol whilst taking antidepressants both weekly (t(100) = 2.93, p = .004) and daily (t(100) = 3.13, p = .002). CONCLUSIONS: This study describes a successful co-design process demonstrating how meaningful involvement of young people, alongside traditional research methods, can produce substance use prevention resources that are useful, engaging and increase knowledge of harms among young people. SO WHAT?: To achieve meaningful public health impact researchers, experts and digital creators can work together to co-create substance use educational materials that are engaging, well-liked, while imparting important health knowledge.

A systematic review of the effect of ovarian sex hormones on stimulant use in females.

Stimulant use disorder is associated with significant global health burden. Despite evidence for sex differences in the development and maintenance of stimulant use disorder, few studies have focused on mechanisms underpinning distinct trajectories in females versus males, including the effect of the ovarian sex hormones estrogen and progesterone. This review aimed to identify and synthesise the existing preclinical and clinical literature on the effect of ovarian sex hormones on stimulant consumption in females. A systematic search of peer-reviewed literature identified 1593 articles, screened using the following inclusion criteria: (1) adult female humans or animals, (2) using stimulant drugs, (3) ovarian sex hormones were administered exogenously OR were measured in a validated manner and (4) with stimulant consumption as an outcome measure. A total of 50 studies (3 clinical and 47 preclinical) met inclusion criteria. High-estrogen (low progesterone) phases of the menstrual/estrus cycle were associated with increased stimulant use in preclinical studies, while there were no clinical studies examining estrogen and stimulant consumption. Consistent preclinical evidence supported progesterone use reducing stimulant consumption, which was also identified in one clinical study. The review was limited by inconsistent data reporting across studies and different protocols across preclinical laboratory paradigms. Importantly, almost all studies examined cocaine use, with impact on methamphetamine use a significant gap in the existing evidence. Given the safety and tolerability profile of progesterone, further research is urgently needed to address this gap, to explore the potential therapeutic utility of progesterone as a treatment for stimulant use disorder.

Sleep disturbance in clients attending a specialist addiction clinic.

BACKGROUND AND OBJECTIVES: Sleep problems are common among clients attending alcohol and drug services, yet the specific components of sleep disturbed by primary drug of concern (PDOC), and their relationships to affective disorder symptoms are unclear. METHODS: We examined sleep problems in clients (n = 32) attending a specialist addiction clinic. RESULTS: Global sleep quality was rated poor by >90% of participants (particularly disturbances, latency and efficiency components), with significant associations (p < .05) between poor sleep quality and depression (r = .517), anxiety (r = .571) and stress (r = .503). Sleep quality was significantly poorer among those with a nonalcohol PDOC compared with alcohol as PDOC, t(22) = 3.09, p = .005. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Poor sleep is almost ubiquitous among clients attending alcohol and drug services. However, components of sleep quality disturbed differ in terms of PDOC, highlighting the need for individualised sleep interventions.

Pregabalin misuse-related ambulance attendances in Victoria, 2012-2017: characteristics of patients and attendances.

OBJECTIVE: To compare changes in pregabalin prescribing and misuse-related ambulance attendances; to characterise the patients attended by paramedics for pregabalin misuse-related harms; to assess the association of pregabalin misuse with use of other sedatives and with suicidal ideation and self-harm; to compare the characteristics of pregabalin misuse-related harms in people who misuse pregabalin according to whether or not they also used other sedatives. DESIGN, SETTING, PARTICIPANTS: Retrospective analysis of data on ambulance attendances in Victoria, January 2012 - December 2017, for which pregabalin misuse-related harms were a contributing factor. MAIN OUTCOME MEASURES: Rates of pregabalin misuse-related ambulance attendances, pregabalin prescription rates (each 6-monthly); patient characteristics, including age, sex, history of drug misuse or psychiatric problems, concurrent use of other sedatives, and current suicidal ideation and self-harm. RESULTS: There were 1201 pregabalin misuse-related attendances during the study period; the rate increased from 0.28 cases per 100 000 population in the first half of 2012 to 3.32 cases per 100 000 in the second half of 2017. The attendance rate was strongly correlated with prescription rates in Australia (r = 0.90; P = 0.001). 593 attendances (49%) were for people with a history that may have contraindicated prescribing pregabalin. Pregabalin was frequently misused with other sedatives (812 attendances, 68%), particularly benzodiazepines (440, 37%); 472 attendances (39%) were associated with suicide attempts. People who misused pregabalin with other sedatives more frequently presented with moderate to severe impairments of consciousness, but the frequency of suicide attempts was similar whether other sedatives were concurrently used or not. CONCLUSIONS: Rates of pregabalin misuse-related ambulance attendances in Victoria have increased markedly over the past 6 years. Caution is required when prescribing pregabalin for people taking other sedatives. Limiting the dispensing of this drug may reduce the risks associated with its misuse.

Substance use and borderline personality disorder: fostering hope in the face of complexity.

OBJECTIVE: Impulsivity and emotional dysregulation are common characteristics of patients presenting with co-occurring borderline personality disorder (BPD) and substance use disorder (SUD). This article aims to provide an overview of the clinical approaches psychiatrists should consider when treating patients with these conditions. CONCLUSIONS: Co-occurring BPD and SUD can be effectively treated within a staged, transdiagnostic approach with an emphasis on the therapeutic alliance.

Synthetic cannabinoid use disorder: an update for general psychiatrists.

OBJECTIVE: Synthetic cannabinoid use disorder is emerging as a significant clinical issue. This article provides the general psychiatrist with an overview of the physical and psychiatric adverse effects of chronic synthetic cannabinoid use, as well as specific clinical responses. METHOD: We performed electronic searches of Ovid MEDLINE and Ovid Embase to identify key articles, of all methodological designs, published up to June 2018. RESULTS: The available evidence suggests that, compared to cannabis, use of synthetic cannabinoids is associated with the more rapid development of dependence, increased psychiatric risks and complex withdrawal, and serious physical adverse effects that include seizures, cardiotoxicity and death, denoting a potential need for more intensive management. CONCLUSION: When synthetic cannabinoid use is identified, along with management of acute physical and psychiatric adverse effects, psychotherapeutic strategies to reduce use and/or harm are recommended.

A systematic review of risk factors for methamphetamine-associated psychosis.

OBJECTIVE: Chronic methamphetamine use is commonly associated with the development of psychotic symptoms. The predictors and correlates of methamphetamine-associated psychosis are poorly understood. We sought to systematically review factors associated with psychotic symptoms in adults using illicit amphetamine or methamphetamine. METHODS: A systematic literature search was performed on MEDLINE (OVID), PsycINFO and EMBASE databases from inception to 8 December 2016. The search strategy combined three concept areas: methamphetamine or amphetamine, psychosis and risk factors. Included studies needed to compare adults using illicit methamphetamine or amphetamine, using a validated measure of psychosis, on a range of risk factors. Of 402 identified articles, we removed 45 duplicates, 320 articles based on abstract/title and 17 ineligible full-text articles, leaving 20 included studies that were conducted in 13 populations. Two co-authors independently extracted the following data from each study: country, setting and design; participant demographic and clinical details; sample size; measure/s used and measures of association between psychosis outcomes and risk factors. Individual study quality was assessed using a modified Newcastle-Ottawa Scale, and strength of evidence was assessed using GRADE criteria. RESULTS: Frequency of methamphetamine use and severity of methamphetamine dependence were consistently found to be associated with psychosis, and sociodemographic factors were not. There was inconsistent evidence available for all other risk factors. Individual study quality was low-moderate for the majority of studies. Heterogeneity in study outcomes precluded quantitative synthesis of outcomes across studies. CONCLUSION: The most consistent correlates of psychotic symptoms were increased frequency of methamphetamine use and dependence on methamphetamine. The findings of this review highlight the need for targeted assessment and treatment of methamphetamine use in individuals presenting with psychosis.

Managing attention deficit hyperactivity disorder in adults using illicit psychostimulants: A systematic review.

CONTEXT: Attention deficit hyperactivity disorder and stimulant use disorder commonly co-exist, and appropriate treatments have not been well established. OBJECTIVE: To provide guidance for treatment of co-existing attention deficit hyperactivity disorder and stimulant use disorder. DATA SOURCES: A systematic review of published English articles using MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane, utilising consistent search terms. STUDY SELECTION: Randomised controlled trials, comparing any treatment arm with a control group, for participants meeting Diagnostic and Statistical Manual of Mental Disorders or equivalent criteria for both attention deficit hyperactivity disorder and stimulant use disorder. RESULTS: Eight trials were identified for inclusion in this review. Four of eight studies showed improvement in attention deficit hyperactivity disorder outcome measures compared with placebo. Two of six studies that reported substance use outcomes showed improvement in treatment arms compared with placebo. Studies to show effect tended to be those with the highest treatment dosage. CONCLUSION: Evidence for the efficacy of treatment of patients with comorbid stimulant use disorder and attention deficit hyperactivity disorder is limited. Promising outcomes need replication in further studies utilising higher treatment dosage.

Key differences in treatment-seeking stimulant users attending a specialised treatment service: a means of early intervention?

OBJECTIVES: Few people who use stimulants seek clinical treatment. This study sought to describe a cohort of stimulant users who attended a stimulant-specific treatment service, Access Point, in Melbourne, Australia between 2008 and 2014. METHODS: A retrospective audit of the records of adults ( n = 175) who sought treatment for stimulant use at a stimulant-specific outpatient treatment service was conducted. RESULTS: Service users had a median age of 32 (range = 19-54). Most stimulant users were in part- or full-time employment (53.6%) and had stable accommodation (85%). There was a high rate of mental health comorbidity, with over half (52%) reporting a previous history of mental health problems, while one-third (33%) reported previous suicide attempts. There was a high rate (48%) of previous methamphetamine-associated psychosis, which was significantly correlated with frequency of use ( x2 = 13.698, p = 0.008). CONCLUSIONS: This study supports the potential of a targeted and specialised treatment service as a means of early intervention for stimulant users. The high prevalence of methamphetamine-associated psychosis history in this group suggests that frequent use of stimulants increases the risk of psychosis, even among high-functioning individuals.