ADHD

Atomoxetine and psychostimulants show weak recommendations for improving ADHD symptoms across various substance dependence comorbidities, but do not reduce substance use; safety is strongly recommended.

Clinical guideline (GRADE approach) on ADHD with comorbid substance disorder. Atomoxetine: weak recommendation for ADHD symptom reduction in alcohol/cannabis comorbidity. Methylphenidate: weak recommendation for ADHD symptoms in nicotine comorbidity, not recommended in cocaine comorbidity. Psychostimulants and atomoxetine appear safe in any substance disorder (strong recommendation).

Limited evidence shows differential brain activations and morphological differences with cannabis use, but no consistent negative effects on neuropsychological function in adolescents with ADHD.

Systematic review on cannabis effects on brain structure and function in adolescents/young adults with ADHD; k=11 studies (7 neuroimaging studies incl. fMRI, structural MRI, SPECT). No additive effects or ADHD×cannabis interactions identified on neuropsychological executive function tests. Two studies found negative effects of early cannabis use onset. Limited evidence does not support the hypothesis of harmful effects on neuropsychological tasks in ADHD adolescents.

The systematic review identifies mixed findings on cannabis use in ADHD patients; a conclusive assessment of benefit or harm is not made.

Systematic review on cannabis in ADHD (search period up to 2023); heterogeneous data situation with individual observational studies and case reports. Authors conclude: insufficient evidence, benefit-risk ratio unclear, RCTs lacking. No robust efficacy data for ADHD.

CANreduce 2.0 led to significant reduction of cannabis use frequency, dependence severity and symptoms of anxiety and depression in both groups (with and without ADHD screening); persons with positive ADHD screening additionally showed significantly reduced ADHD symptoms.

Secondary analysis of the CANreduce-2.0-RCT on web-based intervention for cannabis misuse, comparison of ADHD-positive (n=94) vs. ADHD-negative (n=273). Both groups showed significant reduction in use days (ADHD+: -11,53 days, SD=9,28, p<0,001; ADHD-: -8,53 days, SD=9,4, p<0,001), CUDIT score (ADHD+: -6,38, SD=5,96, p<0,001; ADHD-: -5,33, SD=6,05, p<0,001) and SDS score (ADHD+: -3,57, SD=3,65, p<0,001; ADHD-: -2,47, SD=3,39, p<0,001) after 3 months.

No significant differences in the primary outcome (cognition and activity level), but nominal improvements in secondary outcomes (hyperactivity/impulsivity, inhibition), which did not reach significance after correction for multiple testing.

n=30 adults with ADHD, randomised to Sativex oromucosal spray (n=15) vs. placebo (n=15). Primary outcome (cognitive performance/activity via QbTest): no significant ITT difference (Est=−0,17, 95% CI −0,40 to 0,07, p=0,16). Secondary outcomes: nominally significant improvement for hyperactivity/impulsivity (p=0,03) and cognitive inhibition (p=0,05), trend for inattention (p=0,10) and emotional lability (p=0,11). Effects not significant after correction for multiple testing. Per-protocol effects higher.

No significant difference in ADHD symptom reduction or cannabis abstinence, but significant reduction in weekly cannabis use days under MAS-ER versus placebo.

12-week double-blind pilot RCT of MAS-ER 80 mg vs. placebo in comorbid ADHD and cannabis use disorder (CUD), n=28. No significant difference in ≥30% ADHD symptom reduction (MAS-ER 83,3% vs. placebo 71,4%; p=0.65) or cannabis abstinence in the last 2 weeks (MAS-ER 15,4% vs. placebo 0%; p=0.27). MAS-ER showed significant reduction in weekly cannabis use days over time vs. placebo (p<0.0001). Medication well tolerated.