BackgroundPrevalence rates for lifetime cannabis use and cannabis use disorder are much higher in people with attention deficit/hyperactivity disorder than in those without. CANreduce 2.0 is an intervention that is generally effective at reducing cannabis use in cannabis misusers. This self-guided web-based intervention (6-week duration) consists of modules grounded in motivational interviewing and cognitive behavioral therapy.ObjectiveWe aimed to evaluate whether the CANreduce 2.0 intervention affects cannabis use patterns and symptom severity in adults who screen positive for attention deficit/hyperactivity disorder more than in those who do not.MethodsWe performed a secondary analysis of data from a previous study with the inclusion criterion of cannabis use at least once weekly over the last 30 days. Adults with and without attention deficit/hyperactivity disorder (based on the Adult Attention deficit/hyperactivity disorder Self-Report screener) who were enrolled to the active intervention arms of CANreduce 2.0 were compared regarding the number of days cannabis was used in the preceding 30 days, the cannabis use disorder identification test score (CUDIT) and the severity of dependence scale score (SDS) at baseline and the 3-month follow-up. Secondary outcomes were Generalized Anxiety Disorder score, Center for Epidemiological Studies Depression scale score, retention, intervention adherence, and safety.ResultsBoth adults with (n=94) and without (n=273) positive attention-deficit/hyperactivity disorder screening reported significantly reduced frequency (reduction in consumption days: with: mean 11.53, SD 9.28, P<.001; without: mean 8.53, SD 9.4, P<.001) and severity of cannabis use (SDS: with: mean 3.57, SD 3.65, P<.001; without: mean 2.47, SD 3.39, P<.001; CUDIT: with: mean 6.38, SD 5.96, P<.001; without: mean 5.33, SD 6.05, P<.001), as well as anxiety (with: mean 4.31, SD 4.71, P<.001; without: mean 1.84, SD 4.22, P<.001) and depression (with: mean 10.25, SD 10.54; without: mean 4.39, SD 10.22, P<.001). Those who screened positive for attention deficit/hyperactivity disorder also reported significantly decreased attention deficit/hyperactivity disorder scores (mean 4.65, SD 4.44, P<.001). There were no significant differences in change in use (P=.08), dependence (P=.95), use disorder (P=.85), attention deficit/hyperactivity disorder status (P=.84), depression (P=.84), or anxiety (P=.26) between baseline and final follow-up, dependent on positive attention-deficit/hyperactivity disorder screening. Attention deficit/hyperactivity disorder symptom severity at baseline was not associated with reduced cannabis use frequency or severity but was linked to greater reductions in depression (Spearman ρ=.33) and anxiety (Spearman ρ=.28). Individuals with positive attention deficit/hyperactivity disorder screening were significantly less likely to fill out the consumption diary (P=.02), but the association between continuous attention deficit/hyperactivity disorder symptom severity and retention (Spearman ρ=−0.10, P=.13) was nonsignificant. There also was no significant intergroup difference in the number of completed modules (with: mean 2.10, SD 2.33; without: mean 2.36, SD 2.36, P=.34), and there was no association with attention deficit/hyperactivity disorder symptom severity (Spearman ρ=−0.09; P=.43). The same was true for the rate of adverse effects (P=.33).ConclusionsCannabis users screening positive for attention deficit/hyperactivity disorder may benefit from CANreduce 2.0 to decrease the frequency and severity of cannabis dependence and attenuate symptoms of depression and attention deficit/hyperactivity disorder-related symptoms. This web-based program’s advantages include its accessibility for remote users and a personalized counselling option that may contribute to increased adherence and motivation to change among program users.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 11086185; http://www.isrctn.com/ISRCTN11086185