The effects of combined delta-9-tetrahydrocannabinol and cannabidiol on neurocognitive and behavioural function in attention-deficit/hyperactivity disorder

Purpose of the study: Substance use disorder is a common comorbidity in Attention Deficit Hyperactivity Disorder (ADHD) [1] with one of the most common drugs of abuse appearing to be cannabis [2]. Taking into account that stimulant medication is the recommended first line treatment in ADHD and, alongside cannabis, are one of the most common classes of drugs of abuse [2], may indicate that those with ADHD are more likely to use drugs that alleviate symptoms of ADHD. This suggests that those with ADHD could be 'self-medicating' with cannabis with some patients even reporting a preference for cannabis over their stimulant medication. Treatment with stimulants is not always effective or tolerated, and long term treatment may be a concern in some cases; investigation of alternative treatments is therefore vital. Methods used: We conducted, to our knowledge, the first randomised placebo-controlled trial of a cannabinoid medication in ADHD. Thirty participants were unmedicated (with stimulant or other psychoactive medications) for one week before and for the duration of the trial. Outcome measures included ADHD symptoms and associated impairments in cognition and emotional lability. Treatment effects were estimated using a repeated measures linear model with an unstructured covariance matrix. Effect sizes were classified according to Cohen's d (0.2 = small, 0.5 = medium, 0.8 = large). Summary of results: In the intention to treat analysis, Sativex treatment was associated with a nominally significant improvement in hyperactivity/impulsivity (d = 0.90, p = 0.03) and a trend for improvement in inattention (d = 0.7, p = 0.10). There were further indications for improvement in activity and cognitive performance (d = 0.59, p = 0.16) and emotional lability (d = 0.65, p = 0.11). Per protocol effects were slightly higher. Multiple imputation (under both the Missing At Random (MAR) and Missing Not At Random (MNAR) assumption) suggested that the results for activity/cognition may have been biased towards a treatment effect due to an increased drop-out rate in the placebo group. Conclusions: This pilot study provides preliminary evidence for the efficacy of Sativex in reducing hyperactiveimpulsive symptoms, and to a lesser extent inattention, activity/cognitive deficits and emotional lability, in adults with ADHD. Sativex was well tolerated in most cases, with no indication of drug induced impairments. These findings are consistent with the subjective accounts of ADHD patients who use cannabis as a form of self-medication. Given the small sample size, the moderate to large effects observed across several key outcome measures provide the basis for further studies to confirm the findings and investigate the underlying mechanisms and treatment effects. Sativex or other cannabinoid medications could be suitable as treatments for those who cannot tolerate or find current ADHD medication to be ineffective. Further investigations into the role of cannabinoids in the treatment of ADHD symptoms and associated impairments, and the underlying mechanisms, is therefore warranted on the basis of these results.