Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized as a persistent pattern of inattention, hyperactivity, and/or impulsivity [1]. The understanding of the etiology of ADHD continues to evolve in response to research on the neurobiology, genetics, and clinical nature of ADHD. Decades of neuroimaging research have shown multiple ADHD-related abnormalities in brain structure and function, and suggests that ADHD may in part be due to delayed or disrupted neurodevelopment and maturation. These brain regions have been shown to be responsible for higher order executive functions; including executive control over behavior, attention, social cognition, and networks supporting primary sensory and motor functions [2, 3]. Childhood ADHD is associated with several functional impairments including reduced school performance and academic attainment, and social rejection [1]. In adults, ADHD is associated with poorer occupational performance and attainment, attendance, interpersonal conflicts, as well as a higher probability of unemployment and substance abuse [1]. Substance use disorder (SUD) is characterized by a problematic pattern of substance abuse regardless of short and long term consequences, leading to clinically significant impairment or distress [1]. While ADHD and SUD are different disorders, they often coexist with each other. Children with ADHD are estimated to be 2.64 times more likely to develop SUD, and individuals with ADHD are at an increased risk of substance misuse/dependence, including cannabis misuse [4–6]. A study that followed 579 children with ADHD and 258 age- and sex-matched children without ADHD, found that the ADHD group had earlier initiation- and faster escalation- of substance use in adolescence. Interestingly, the ADHD group had more weekly cannabis use (32.8% vs 21.3%), and double the rate of daily cannabis use (22.4% vs 10.9%) [7]. Cannabis use in general seems to be increasing among adults and adolescents [8].

The acute effects of cannabis on cognition has been investigated, and has been shown to impair the following; verbal memory and learning, working memory, attention (task and dose dependent), inhibition, and psychomotor function [9]. A study investigating whether these neurocognitive deficits persist, showed that heavy cannabis users (daily use) - relative to light users - had persisting deficits in verbal and visual memory, executive functioning, visuo-perception, psychomotor speed, and manual dexterity, even after 28 days of abstinence [10]. Cannabis use in youth, regardless of ADHD diagnosis, has shown that it may lead to poorer performance on tasks that require attention functioning, decreased verbal working memory, and decreased executive functioning [8, 11, 12]. A study investigating the effects of cannabis on ADHD patients’ response inhibition, showed that cannabis use was significantly associated with a slower continuous performance test (CPT) hit rate response [13]. A large (1037 participants) prospective study, which followed participants from birth to age 38, found that cannabis use was associated with more global neuropsychological impairments, including IQ, and found specific deficits in executive functioning, sustained attention, verbal list learning, and psychomotor speed. These effects were more prominent in adolescent-onset users, where more persistent use is associated with greater decline. This study is unique, as its prospective design was able to control for premorbid neuropsychological deficit and years of education, and showed that among adolescent-onset (and former persistent users), impairment was still evident even after cessation of use for 1 year or more [14]. Additionally, cannabis misuse results in negative changes in brain regions associated with response inhibition [2, 15], and these declines in neuropsychological functioning are thought to be more likely to manifest among daily (or almost daily) cannabis users [16]. Another study showed evidence which suggests that early onset of regular cannabis use may disrupt neuromaturation, especially in networks responsible for executive functions and rewards [17]. Interestingly, a meta-analysis investigating whether these brain function altercations persist on fMRI with abstinence, showed that these altercations clearly persist past 25 days abstinence in adolescent users – despite no detectable THC in urine [18]. Since the endocannabinoid system plays a role in neuroplasticity [19, 20], and neuromaturation is prevalent during adolescence [21], it is plausible that exogenous cannabinoids alters the neurodevelopmental maturation during this period – suggesting a period of vulnerability [8].

These findings are fairly consistent across reviews and meta analyses, all of which identify specific subgroups of cannabis user that are at risk of more severe neurocognitive deficits, such as early (adolescent) use onset [8, 9, 17, 21–23], and extent of exposure – including chronic use [18, 23–25], and regular (daily or almost daily) use [8, 16, 22, 24]. The concept that the neurocognitive deficits differs in severity based on specific cannabis use characteristics (age of onset, duration, frequency and quantity), is important to understand when interpreting existing literature on these topics, as not all studies control for these factors. As an example, a co-twin design study [26] (n of 856), which investigated the causal effects of cannabis on cognition, found between-family significance for measures of intelligence and executive functioning, but not after accounting for other substance use. However, only 16 participants (less then 2% of the total population sample) reported daily use, and therefor might not be generalizable to that population. It is important to note that only one effect – between age 17 cannabis frequency and executive function at age 23 - remained significant across all within-family levels and after accounting for other substance use.

Despite the overwhelming amount of studies that support the harms of cannabis use on ADHD outcomes, there are still studies that investigate the therapeutic use of cannabinoids in ADHD patients [27] and show that cannabis is perceived to be beneficial for some individuals with ADHD [28]. It is possible that the ratio of THC relative to CBD may account for some of the discrepancy of the findings among some of the studies [29]. In addition to discordance around hypotheses and research questions in current literature on cannabis use and ADHD symptoms, there are several limitations to these studies that precludes the ability to establish causation. These limitations include cross-sectional studies with modest sample sizes, and the heterogeneity in the dichotomous designation of cannabis use (i.e. Cannabis use thresholds used to allocate participants to study groups). Although cross sectional studies played a significant role in the advancement of research in this area, they do not control for confounding variables. This includes the inability to assess how changes in substance use prospectively influence ADHD-related cognitive functioning, and the inability to control for differences in baseline characteristics. Future studies should use cotwin-controlled designs or prospective designs which control for daily users and/or heavy use in adolescence, to better control for potential confounds - as these studies are rare and have low sample sizes [6, 14, 18, 30, 31]. Another challenge in this area of research is the outcome measures used, where studies that use self-report outcome measures are at risk of response bias. There is only a small amount of literature that specifically investigates SUD (and cannabis use alone) on objective cognitive testing and all-around functioning in society.

The Integrated Auditory and Visual Continuous Performance test (IVA/CPT) was the objective measure used in our study, which is a standardized test that has been validated for diagnostic accuracy in comparison to clinician diagnosed ADHD, with EEG correspondence. The IVA/CPT computes a sustained auditory and visual attention quotient (SAAQ and SVAQ, respectively), response quotient, and fine motor hyperactivity quotient. The attention quotient consists of a summary of separate audio and visual measures of vigilance (a measure of inattention based on omission of errors), focus (total variability of mental processing speed for correct responses), and speed (average reaction time for correct responses). The response control quotient is comprised of separate auditory and visual scores for prudence (a measure of impulsivity and response inhibition based on commission errors), consistency (a measure of one’s ability to stay on task by variability in response times), and stamina (a measure of sustained effort over time by comparing mean reaction times of the first 200 correct responses vs last 200 correct responses) [32].

This study is unique as it is one of the few studies that specifically focuses on both objective cognitive measures and psychosocial functioning. Our explorative study seeks to understand: 1) How do the cognitive profiles of patients who have ADHD and SUD differ from patients with ADHD without SUD, 2) Does SUD among adults in a naturalistic outpatient community setting result in more functional impairment and worse ADHD outcomes, and 3) how do the cognitive profiles of ADHD patients differ based varying cannabis use.