Background: There is a substantial and unmet clinical need for pharmacological treatment of cannabis use disorders. Cannabidiol (CBD) could offer a novel treatment but it is unclear which doses might be effective or safe.Methods: Participants meeting DSM-5 cannabis use disorder criteria were allocated to four-week treatment with oral CBD at 200mg, 400mg, 800mg or placebo during a cessation attempt using a double-blinded block randomisation sequence. All received a brief psychological intervention of motivational interviewing. An adaptive Bayesian dose-finding design was used to identify effective/ineffective doses at a priori interim and final analysis stages. The primary objective was to identify the Most Effective Dose (MED) of CBD for reducing cannabis use. The primary endpoint was lower urinary THC-COOH:creatinine concentrations and/or increased days per week abstinent from cannabis during treatment, evidenced by posterior probabilities exceeding Pr=0.9 for CBD versus placebo. All analyses were intention-to-treat.Outcomes: Participants were initially randomised to placebo, 200mg, 400mg and 800mg CBD (n=48; 1:1:1:1). At interim analysis 200mg CBD was eliminated from the trial as an ineffective dose.Randomisation continued to 400mg CBD, 800mg CBD, and placebo (n=34; 1:1:1). At final analysis, both 400mg CBD and 800mg CBD exceeded primary endpoint criteria (Pr=0.9) for both primary outcomes: urinary THC-COOH:creatinine (Pr(400mg=MED │Data)=0.9995; Pr(800mg=MED │Data)=0.9965), days per week abstinent from cannabis (Pr(400mg=MED │Data)=0.9966; Pr(800mg=MED │Data)=0.9247). Compared to placebo, 400mg CBD decreased THC-COOH:creatinine concentrations by -94.21 ng/ml (95% Interval ) and increased abstinence from cannabis by 0.48 days per week (95% Interval Estimate=0.15, 0.82). Compared to placebo, 800mg CBD decreased THC-COOH:creatinine concentrations by -72.02 ng/ml (95% Interval Estimate= -135.47, -19.52) and increased abstinence from cannabis by 0.27 days per week (95% Interval Estimate= -0.09, 0.64). CBD was well tolerated with no severe adverse events and 94% completed treatment.Interpretation: In the first randomised clinical trial of CBD for cannabis use disorder, 400mg and 800mg CBD were safe and more effective than placebo at reducing cannabis use.

BackgroundLike other complex psychosocial interventions, mindfulness-based treatments comprise various modality-specific components as well as nonspecific therapeutic ingredients that collectively contribute to efficacy. Consequently, the isolated effects of mindfulness strategies per se remain unclear.MethodsUsing a randomized double-blind design, we compared the isolated effects of 11-minutes of “supervised” mindfulness instruction against a closely matched active control (relaxation) on subjective, physiological, and behavioral indices of maladaptive alcohol responding in drinkers at risk of harm from alcohol use (n = 68). Simple follow-up instructions on strategy use were provided, but practice was unsupervised and not formally monitored.ResultsBoth groups showed acute reductions in craving after training, although a trend group x time interaction (P = .056) suggested that this reduction was greater in the relaxation group (d = 0.722 P < .001) compared with the mindfulness group (d = 0.317, P = .004). Furthermore, upregulation of parasympathetic activity was found after relaxation (d = 0.562; P < .001) but not mindfulness instructions (d = 0.08; P > .1; group x time interaction: P = .009). By contrast, only the mindfulness group showed a reduction in past-week alcohol consumption at 7-day follow-up (-9.31 units, d = 0.593, P < .001), whereas no significant reduction was seen in the relaxation group (-3.00 units, d = 0.268, P > .1; group x time interaction: P = .026).ConclusionVery brief mindfulness practice can significantly reduce alcohol consumption among at-risk drinkers, even with minimal encouragement to use this strategy outside of the experimental context. The effects on consumption may therefore represent a lower bound of efficacy of “ultra-brief” mindfulness instructions in hazardous drinkers, at least at short follow-up intervals.

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Mindfulness-based interventions and psychedelic-assisted therapy have been experimentally utilised in recent years as alternative treatments for various psychopathologies with moderate to great success. Both have also demonstrated significant post-acute and long-term decreases in clinical symptoms and enhancements in well-being in healthy participants. These two therapeutic interventions share various postulated salutogenic mechanisms, such as the ability to alter present-moment awareness and anti-depressive action, via corresponding neuromodulatory effects. Recent preliminary evidence has also demonstrated that psychedelic administration can enhance mindfulness capacities which has already been demonstrated robustly as a result of mindfulness-based interventions. These shared mechanisms between mindfulness-based interventions and psychedelic therapy have led to scientists theorising, and recently demonstrating, synergistic effects when both are used in combination, in the form of potentiated therapeutic benefit. These synergistic results hold great promise but require replication in bigger sample groups and better controlled methodologies, to fully delineate the effect of set and setting, before they can be extended onto clinical populations.

Background: Mindfulness-meditation has a variety of benefits on well-being. However, individuals with primary attentional impairments (e.g. attention deficit disorder) or attentional symptoms secondary to anxiety, depression or addiction, may be less likely to benefit, and require additional mindfulness-augmenting strategies. Aims: To determine whether a single dose of the cognitive enhancer, modafinil, acutely increases subjective and behavioural indices of mindfulness, and augments brief mindfulness training. Methods: A randomised, double-blind, placebo-controlled, 2 (drug: placebo, modafinil) × 2 (strategy: mindfulness, relaxation control) experiment was conducted. Seventy-nine meditation-naïve participants were assigned to: placebo–relaxation, placebo–mindfulness, modafinil–relaxation or modafinil–mindfulness. Pre-drug, post-drug and post-strategy state mindfulness, affect and autonomic activity, along with post-strategy sustained attention and mind-wandering were assessed within a single lab session. After the session, participants were instructed to practice their assigned behavioural strategy daily for one week, with no further drug administration, after which, follow-up measures were taken. Results: As predicted, modafinil acutely increased state mindfulness and improved sustained attention. Differential acute strategy effects were found following mindfulness on autonomic activity but not state mindfulness. There were no strategy or drug effects on mind-wandering. However, exploratory analyses indicated that participants receiving modafinil engaged in more strategy practice across strategy conditions during follow-up. Conclusions: Modafinil acutely mimicked the effects of brief mindfulness training on state mindfulness but did not enhance the effects of this training. Limitations of the current study, and recommendations for future research examining modafinil as an adjunct to mindfulness- (or relaxation-) based treatments are discussed.