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).

Proof-of-concept trial of Goal Management Training+ to improve executive functions and treatment outcomes in methamphetamine use disorder.

BACKGROUND: Deficits in executive function are common in methamphetamine use disorder (MUD), likely contributing to difficulties in sustained treatment success. Cognitive remediation interventions are designed to treat such deficits but have not been adapted to the needs of people with MUD. This study presents a proof-of-concept trial to evaluate a new cognitive remediation program for MUD, Goal Management Training+ (GMT+). METHODS: This was a cluster-randomised crossover trial comparing GMT+ with a psychoeducation-based control (Brain Health Workshop; BHW). GMT+ is a therapist-administered group-based cognitive remediation for executive dysfunction comprising four 90-minute weekly sessions and daily journal activities. BHW is a lifestyle psychoeducation program matched to GMT+ for therapist involvement, format, and duration. Participants (n = 36; GMT n = 17; BHW n = 19) were recruited from therapeutic communities in Victoria, Australia. Primary outcomes included intervention acceptability, feasibility, and improvements in self-reported executive function. Secondary outcomes included cognitive tests of executive function, severity of methamphetamine dependence, craving, and quality of life. We performed mixed linear modelling and calculated Hedges' g effect sizes. RESULTS: GMT+ participant ratings and program retention indicated high acceptability. There was no difference between GMT+ and BHW on self-reported executive function (g = 0.06). Cognitive tasks suggested benefits of GMT+ on information gathering (g = 0.88) and delay-discounting (g = 0.80). Severity of methamphetamine dependence decreased more in GMT+ (g = 1.47). CONCLUSIONS: GMT+ was well-accepted but did not improve self-reported executive functioning. Secondary outcomes suggested GMT+ was beneficial for objective cognitive performance and severity of dependence.

Lack of longitudinal changes in cognition in individuals with methamphetamine use disorder during the first 6 weeks after commencing treatment.

Background: Methamphetamine use disorder (MUD) associates with cognitive impulsivity deficits. However, few studies have examined longitudinal changes in cognition, and it remains unclear if deficits resolve during early recovery.Objectives: To compare: (1) cognitive function of individuals with MUD at treatment onset and six-weeks later with controls tested over the same period; (2) cognitive changes in MUD-individuals who remained abstinent versus relapsed.Method: We recruited 108 participants meeting DSM-IV-TR criteria for methamphetamine dependence (81 males) and 50 demographically matched controls (38 males); 77 methamphetamine- dependent participants (59 males) and 48 controls (36 males) were retained at follow-up. We administered response inhibition, delay discounting and uncertainty-based decision-making tests at both endpoints. Relapse was defined as methamphetamine concentrations >0.4 ng/mg at follow-up in hair toxicology.Results: We found a significant time-by-group interaction on uncertainty-based decision-making (effect size: η2 = .05), although post-hoc tests to disentangle this interaction yielded inconclusive results (p-range = .14-.40; BF10-range = 0.43-1.67). There were no significant time-by-group interactions on response inhibition or delay discounting, with the former likely a null effect (η2-interaction = .003 and .02; BFincl = 0.23 and 0.71). There were no significant differences in cognitive recovery between individuals who maintained abstinence (n = 12) versus relapsed (n = 65) (η2-range = .003-.04), although evidence was inconclusive toward whether findings reflected true null effects (BFincl-range = 0.33-0.75).Conclusion: We did not find evidence that MUD-related cognitive impulsivity deficits improve beyond practice effects over 6 weeks. Findings do not support previous, albeit conflicting, evidence of early recovery of cognitive deficits in MUD.

Impulsivity predicts poorer improvement in quality of life during early treatment for people with methamphetamine dependence.

BACKGROUND AND AIMS: Methamphetamine dependence is associated with heightened impulsivity and diminished quality of life, but the link between impulsivity and changes in quality of life during treatment has not been examined. We aimed to investigate how different elements of impulsivity predict change in quality of life in the 6 weeks after engaging in treatment. DESIGN: Longitudinal, observational cohort study. SETTING: Public and private detoxification and rehabilitation facilities in metropolitan Melbourne, Australia. PARTICIPANTS: One hundred and eight individuals with methamphetamine dependence (81 male) tested within 3 weeks of commencing treatment; 80 (74%) were followed-up at 6 weeks. MEASUREMENTS: The Continuous Performance Test-2 measured impulsive action (cognitive and motor impulsivity); the Delay Discounting Task measured impulsive choice. Quality of life was measured with the World Health Organization Quality of Life Scale-Brief, which includes social, psychological, physical and environment domains. Control variables included age, gender, estimated IQ, depression severity score, methamphetamine dependence severity score, cannabis dependence severity score and treatment modality. FINDINGS: We found that all three forms of impulsivity were significant predictors of change in the social domain: motor impulsivity (ß = -0.54, P = 0.013), cognitive impulsivity (ß = -0.46, P = 0.029) and impulsive choice (ß = -0.26, P = 0.019). Change in the psychological domain was predicted significantly by motor impulsivity (ß = -0.45, P = 0.046). Control variables of age and depression were associated significantly with changes in the physical domain. CONCLUSIONS: In Australian methamphetamine-dependent individuals, elevated impulsivity predicts lower improvement of social and psychological quality of life in the first 6-9 weeks of treatment.

Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review.

BACKGROUND: There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. METHODS: We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. RESULTS: We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening in areas beyond a clinician's primary area of practice was a common strategy for facilitating referral and integrated care, as was joint care planning. CONCLUSION: Despite considerable limitations and gaps in the literature in terms of the evaluation of integrated care strategies, particularly between AOD services, our review highlights several strategies that could be useful at multiple levels. Given the interconnectedness of integrated care strategies identified, implementation of multi-level strategies rather than single strategies is likely to be preferable.

Substance use outcomes following treatment: Findings from the Australian Patient Pathways Study.

BACKGROUND AND AIMS: Our understanding of patient pathways through specialist Alcohol and Other Drug treatment and broader health/welfare systems in Australia remains limited. This study examines how treatment outcomes are influenced by continuity in specialist Alcohol and Other Drug treatment, engagement with community services and mutual aid, and explores differences between clients who present with a primary alcohol problem relative to those presenting with a primary drug issue. METHOD: In a prospective, multi-site treatment outcome study, 796 clients from 21 Alcohol and Other Drug services in Victoria and Western Australia completed a baseline interview between January 2012 and January 2013. A total of 555 (70%) completed a follow-up assessment of subsequent service use and Alcohol and Other Drug use outcomes 12-months later. RESULTS: Just over half of the participants (52.0%) showed reliable reductions in use of, or abstinence from, their primary drug of concern. This was highest among clients with meth/amphetamine (66%) as their primary drug of concern and lowest among clients with alcohol as their primary drug of concern (47%), with 31% achieving abstinence from all drugs of concern. Continuity of specialist Alcohol and Other Drug care was associated with higher rates of abstinence than fragmented Alcohol and Other Drug care. Different predictors of treatment success emerged for clients with a primary drug problem as compared to those with a primary alcohol problem; mutual aid attendance (odds ratio = 2.5) and community service engagement (odds ratio = 2.0) for clients with alcohol as the primary drug of concern, and completion of the index treatment (odds ratio = 2.8) and continuity in Alcohol and Other Drug care (odds ratio = 1.8) when drugs were the primary drugs of concern. CONCLUSION: This is the first multi-site Australian study to include treatment outcomes for alcohol and cannabis users, who represent 70% of treatment seekers in Alcohol and Other Drug services. Results suggest a substantial proportion of clients respond positively to treatment, but that clients with alcohol as their primary drug problem may require different treatment pathways, compared to those with illicit drug issues, to maximise outcomes.

A school-based health promotion programme to increase help-seeking for substance use and mental health problems: study protocol for a randomised controlled trial.

BACKGROUND: Adolescence is a high-risk time for the development of mental health and substance use problems. However, fewer than one in four 16-24 year-olds with a current disorder access health services, with those experiencing a substance use disorder being the least likely to seek professional help. Research indicates that young people are keeping their problems to themselves or alternatively, turning to peers or trusted adults in their lives for help. These help-seeking preferences highlight the need to build the mental health literacy of adolescents, to ensure that they know when and how to assist themselves and their peers to access support. The MAKINGtheLINK intervention aims to introduce these skills to adolescents within a classroom environment. METHODS/DESIGN: This is a cluster randomised controlled trial (RCT) with schools as clusters and individual students as participants from 22 secondary schools in Victoria, Australia. Schools will be randomly assigned to either the MAKINGtheLINK intervention group or the waitlist control group. All students will complete a self-report questionnaire at baseline, immediately post intervention and 6 and 12 months post baseline. The primary outcome to be assessed is increased help-seeking behaviour (from both formal and informal sources) for alcohol and mental health issues, measured at 12 months post baseline. DISCUSSION: The findings from this research will provide evidence on the effectiveness of the MAKINGtheLINK intervention for teaching school students how to overcome prominent barriers associated with seeking help, as well as how to effectively support their peers. If deemed effective, the MAKINGtheLINK programme will be the first evidence-informed resource that is able to address critical gaps in the knowledge and behaviour of adolescents in relation to help-seeking. It could, therefore, be a valuable resource that could be readily implemented by classroom teachers. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000235707 . Registered on 27 February 2013.

Decreased thalamic volumes in adolescent inhalant users from Korea and Australia.

OBJECTIVES: Research investigating the impact of inhalant misuse on brain structure suggests abnormalities in subcortical regions. We investigated the association between inhalant misuse and subcortical brain volumes in adolescents. METHODS: Based on a collaborative dataset from South Korea (inhalant users: N = 15, mean age = 16.7, SD = 1.1; controls: N = 15, mean age = 15.4, SD = 1.2) and Australia (inhalant users: N = 7, mean age = 18.2, SD = 1.4; controls: N = 7, mean age = 18.9, SD = 2.6), the volumes of caudate nucleus, putamen, pallidum, amygdala, hippocampus, and thalamus were estimated in adolescent inhalant users and healthy adolescents using FreeSurfer. RESULTS: The results revealed a significantly decreased right thalamic volume in adolescent inhalant users (P = 0.042), along with a trend-level decrease in left thalamic volume (P = 0.061). A negative correlation (r = -0.544; P = 0.036) between thalamic volume and severity of inhalant use (i.e., reduced volumes associated with greater use) was identified among Korean participants. CONCLUSIONS: These findings suggest that compared with other subcortical structures, the thalamus is particularly sensitive to damage following chronic inhalant exposure during adolescence.

"Clozapine makes me quite drowsy, so when I wake up in the morning those first cups of coffee are really handy": an exploratory qualitative study of excessive caffeine consumption among individuals with schizophrenia.

BACKGROUND: Research has shown that individuals with schizophrenia use caffeine at higher rates than the general population; however, no qualitative research has been undertaken investigating problematic caffeine use and its effects on this population. This article explores the role of caffeine consumption in the lives of people with schizophrenia through a narrative analysis of the attitudes and beliefs associated with this practice, and how these, in turn, influence caffeine consumption. METHODS: A qualitative study was undertaken with individuals who had previously scored in either a 'moderate' or 'high' risk category for caffeine use on the Alcohol, Smoking and Substance Involvement Screening Tool (ASSIST). In-depth interviews were undertaken with 20 individuals, and transcripts were analysed thematically to identify prominent perspectives. RESULTS: Consistent with previous literature, participants' caffeine consumption was driven largely by its stimulating properties; however, participants also identified 'cravings' as an important motivating factor. Participants' behaviours related to caffeine consumption seemed to be tempered by their previous experiences of consumption; if participants had experienced positive effects such as alertness or relaxation in the past, their use was maintained at a similar level or increased. Conversely, participants who anticipated negative consequences often altered their patterns of caffeine consumption; for example, by substituting caffeinated drinks that minimised or ceased their experience of negative side effects for those that directly caused such impacts. Overall, participants largely identified caffeine consumption as a highly meaningful activity, which provided structure to their day and facilitated opportunities for social interaction. CONCLUSIONS: The inconsistencies between individuals' beliefs about their health and the actual risk of harm associated with health-related behaviours present significant and ongoing challenges for the implementation of relevant and effective strategies for health promotion among individuals diagnosed with mental illness. As a starting point, it would be worthwhile for services engaging with people diagnosed with mental illness, and in particular schizophrenia, to consider implementing caffeine-related health literacy strategies to educate consumers about the risk of excessive caffeine consumption and the interactions between caffeine and antipsychotic medications.

Managing opioid dependence in pregnancy -- a general practice perspective.

BACKGROUND: Managing opioid dependence in pregnant women is a complex and potentially challenging task. Drug-dependent women may be difficult to engage in antenatal care and opioid substitution requires careful dose titration. Pregnancy, however, can be an opportune time to effect behaviour change, and supporting an opioid-dependent woman through pregnancy can be a rewarding clinical experience. OBJECTIVE: This article provides an overview of treatment principles for managing opioid dependence in pregnancy, and reviews current treatment guidelines for use of opioid-substitution therapy in pregnant women. DISCUSSION: The management of opioid dependence during pregnancy requires holistic and comprehensive assessment and referral to specialist services is often appropriate. Specific issues that may need to be addressed include decision-making regarding the choice of opioid-substitution therapy and the potential for neonatal abstinence syndrome in the newborn. General practitioners are often well placed to support and coordinate care of their opioid-dependent pregnant patients.

The role of abstinence and activity in the quality of life of drug users engaged in treatment.

There is increasing interest in understanding factors that enhance the quality of life of substance users in treatment, however limited research has been conducted to date. Measures of physical and psychological health, overall quality of life, drug use, and meaningful activity (education, training or employment) were collected at treatment entry and review in two areas of England as part of routine monitoring. Analysis was performed on an initial sample of 10,470 cases in one site and a more targeted assessment of 783 cases (with repeated measures for 528 of these) in the second site. Women reported lower satisfaction with their physical and psychological health at treatment entry compared with men, but these differences were not present at treatment review. Individuals who reported engagement in meaningful activities had significantly higher quality of life than those that did not. Clients in treatment who reported abstinence and engagement in meaningful activity demonstrated the highest quality of life. A holistic approach to supporting problematic substance users that acknowledges the importance of participation in meaningful activity is likely to be beneficial.

Cingulate biochemistry in heroin users on substitution pharmacotherapy.

OBJECTIVE: High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms. METHODS: Twenty-four heroin-dependent individuals stabilised on methadone (n=10) or buprenorphine (n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol. RESULTS: (1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner; (2) buprenorphine-treated individuals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC; and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine. CONCLUSIONS: These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.

Treatment of cannabis use among people with psychotic or depressive disorders: a systematic review.

OBJECTIVE: This article systematically reviews the evidence from randomized controlled trials (RCTs) for pharmacologic and psychological approaches to the treatment of cannabis use among individuals with psychotic or depressive disorders. DATA SOURCES: A systematic literature search was conducted using the PubMed and PsychINFO databases from inception to December 2008. Individual searches in cannabis use (search terms: marijuana, cannabis, marijuana abuse, cannabis abuse, marijuana usage, cannabis usage), mental disorders (search terms: mood disorders, affective disorders, anxiety disorders, anxiety, depressive disorder, depression, psychotic disorders, psychosis, mental disorders), and pharmacotherapy (search terms: medication, drug therapy, pharmacotherapy, psychopharmacology, clinical trials, drug trial, treatment trial) were conducted and limited to humans, adolescents and adults. STUDY SELECTION: A search combining the individual cannabis use, mental disorder and pharmacotherapy searches produced 1,713 articles (PubMed = 1,398; PsychINFO = 315). Combining the cannabis use and mental disorder searches while limiting them to English articles and RCTs produced a total of 286 articles (PubMed = 228; PsychINFO = 58). From this literature, there were 7 RCTs conducted among mental health clients that reported cannabis use outcomes using pharmacologic or psychological interventions. DATA SYNTHESIS: While few RCTs have been conducted, there is evidence that pharmacologic and psychological interventions are effective for reducing cannabis use in the short-term among people with psychotic disorders or depression. CONCLUSIONS: Although it is difficult to make evidence-based treatment recommendations due to the paucity of research in this area, available studies indicate that effectively treating the mental health disorder with standard pharmacotherapy may be associated with a reduction in cannabis use and that longer or more intensive psychological interventions rather than brief interventions may be required, particularly among heavier users of cannabis and those with more chronic mental disorders. Specific recommendations regarding the type and length of specific psychological treatments cannot be made at this time, although motivational interviewing and cognitive-behavioral therapy approaches appear most promising.

Developing integrated models of care within the youth Alcohol and Other Drug sector.

OBJECTIVE: The aim of this paper is to describe an initiative in Victoria, Australia, aimed at improving the detection and management of co-occurring mental health issues within the youth Alcohol and Other Drug (AOD) sector. CONCLUSIONS: Over the past 4 years, in partnership with local youth AOD services, we have developed a successful service model that addresses co-occurring mental health issues within the youth AOD sector. However, such capacity-building requires the full support of workers and senior management, and a cultural shift whereby the assessment and management of mental health issues are seen as a priority and core service issue. The capacity-building process was facilitated by embedding experienced mental health clinicians within each service to support and implement the initiative. This model offered learning opportunities through the modelling of relevant skills and the provision of 'on-the-job' training. Such approaches demonstrate that integrated models of care can be delivered within youth AOD services, although further research is needed to determine their effectiveness.

Inhalant misuse in youth: time for a coordinated response.

Early adolescence is associated with high rates of experimental inhalant misuse, but only a minority continue to inhale on a regular basis. Inhalant misuse is associated with a range of adverse outcomes, including reports of increased morbidity and mortality. Research into inhalant use among adolescents is lacking, with limited data available on long-term outcomes or evidence-based approaches to treatment. Legislative and supply-reduction strategies have been introduced by a number of states and territories over recent years, but direct funding for specific targeted interventions is lacking. Investment and commitment to a national research framework, as well as coordination of local services, is urgently required.