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).

Meditation attenuates default-mode activity: A pilot study using ultra-high field 7 Tesla MRI.

OBJECTIVES: Mapping the neurobiology of meditation has been bolstered by functional MRI (fMRI) research, with advancements in ultra-high field 7 Tesla fMRI further enhancing signal quality and neuroanatomical resolution. Here, we utilize 7 Tesla fMRI to examine the neural substrates of meditation and replicate existing widespread findings, after accounting for relevant physiological confounds. METHODS: In this feasibility study, we scanned 10 beginner meditators (N = 10) while they either attended to breathing (focused attention meditation) or engaged in restful thinking (non-focused rest). We also measured and adjusted the fMRI signal for key physiological differences between meditation and rest. Finally, we explored changes in state mindfulness, state anxiety and focused attention attributes for up to 2 weeks following the single fMRI meditation session. RESULTS: Group-level task fMRI analyses revealed significant reductions in activity during meditation relative to rest in default-mode network hubs, i.e., antero-medial prefrontal and posterior cingulate cortices, precuneus, as well as visual and thalamic regions. These findings survived stringent statistical corrections for fluctuations in physiological responses which demonstrated significant differences (p < 0.05/n, Bonferroni controlled) between meditation and rest. Compared to baseline, State Mindfulness Scale (SMS) scores were significantly elevated (F(3,9) = 8.16, p < 0.05/n, Bonferroni controlled) following the fMRI meditation session, and were closely maintained at 2-week follow up. CONCLUSIONS: This pilot study establishes the feasibility and utility of investigating focused attention meditation using ultra-high field (7 Tesla) fMRI, by supporting widespread evidence that focused attention meditation attenuates default-mode activity responsible for self-referential processing. Future functional neuroimaging studies of meditation should control for physiological confounds and include behavioural assessments.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Focused attention meditation in healthy adults: A systematic review and meta-analysis of cross-sectional functional MRI studies.

Meditation trains the mind to focus attention towards an object or experience. Among different meditation techniques, focused attention meditation is considered foundational for more advanced practices. Despite renewed interest in its functional neural correlates, there is no unified neurocognitive model of focused attention meditation developed via quantitative synthesis of contemporary literature. Hence, we performed a quantitative systematic review and meta-analysis of all functional MRI studies examining focussed attention meditation. Following PRISMA guidelines, 28 studies were included in this review, of which 10 studies (200 participants) were amenable to activation likelihood estimation meta-analysis. We found that regions comprising three key functional brain networks i.e., Default-mode, Salience, and Executive Control, were consistently implicated in focused attention meditation. Furthermore, meditation expertise, mindfulness levels and attentional skills were found to significantly influence the magnitude, but not regional extent, of activation and functional connectivity in these networks. Aggregating all evidence, we present a unified neurocognitive brain-network model of focused attention meditation.