Attention-deficit/hyperactivity disorder (ADHD) is one of the most common mental health conditions in children, with an estimated worldwide prevalence of 7.2% [1]. This chronic neurobehavioral disorder is characterized by inattention and hyperactivity-impulsivity and affects both children and teens, with up to 60% of those affected exhibiting symptoms into adulthood [2]. Treatment of ADHD typically involves nonpharmacologic strategies (eg, healthy diet, education, and cognitive and behavioral interventions), and pharmacologic therapy with a psychostimulant (eg, methylphenidate) [3]. While stimulant pharmacotherapy is effective for treating the core symptoms of ADHD, in approximately 70%-90% of cases, symptoms of aggression are less likely to respond. Approximately 35%-65% of children with ADHD exhibit comorbid disruptive behavior disorders (DBDs; oppositional defiant disorder [ODD], or conduct disorder) [4,5], and a substantial number continue to exhibit aggressive and disruptive behaviors even after stimulant treatment [4-6]. The consequences of inadequately treated aggressive and disruptive behaviors are significant; these children are more likely to have encounters with the justice system, deficits in academic achievement, behavioral and disciplinary problems, and substance use challenges [7].

The growing perception that cannabis may be useful for alleviating ADHD symptoms has motivated individuals to use cannabis without the necessary evidence to support its use and without clear guidance on appropriate dosing [8,9]. A recent study of internet-based discussions about the effects of cannabis on ADHD found at least 3 times as many comments advocating for cannabis’ therapeutic benefits, compared to comments regarding harm or lack of efficacy [10]. Moreover, several parents of children with ADHD have admitted to administering cannabis to their children for symptom management [8,11].

Some adults with ADHD have reported benefits from using cannabis. These benefits include feeling calmer, improved sleep, and the ability to sustain focus [12]. Patients with ADHD typically use cannabis “to improve their mood and sleep” rather than “to get high” [13]. Cannabinoids act on the endocannabinoid system, which is a signaling system consisting of 2 receptor subtypes (CB1 and CB2). ADHD involves a dysregulation of dopamine, and stimulant pharmacotherapy works by blocking the reuptake of dopamine as a result of the inhibition of noradrenergic areas in the prefrontal cortex [14]. CB1 receptors also interact with the dopaminergic system, and it is hypothesized that the modulation of endocannabinoids in the medial prefrontal cortex and the ventral tegmental area may lead to regulation of the impulsive action and restraint [15,16]. Several other neurotransmitters, such as glutamate, γ-aminobutyric acid, and N-methyl-D-aspartate, as well as CB2 receptors can interact with endocannabinoids and may contribute to the modulation of impulsivity [15-17].

Co-occurring substance use is one of the most common problems associated with ADHD. Children with ADHD are at an increased risk for both using cannabis and having a cannabis use disorder, and these youth are nearly 3 times more likely to report cannabis later in life compared to the general population [10,18]. Whether or not potential harms associated with substance use are worse for youth with ADHD is currently unknown.

The self-medication theory is one possible theory to explain the increased risk of substance misuse in some patients [19,20]. This hypothesis, which is a theory about addiction, originally focused on why and how individuals were drawn to heroin and cocaine [19]. In 1997, it was updated to consider a variety of other applications [20]. Based on decades of clinical observation, it proposes that patients consume drugs in an effort to cope with the illness or treatment side effects [19,20]. In the case of ADHD, individuals may self-medicate to alleviate negative emotionality, such as anger, sadness, anxiety, and inadequate emotional regulation [21]. In medicine, the decision to initiate a medication or other treatment is based on the theoretical gains in therapeutic benefits weighed against the potential harms [22]. Observational studies indicate that cannabis may improve symptom management and decrease side effects associated with prescription medication, or as a substitute for alcohol and illicit drugs [16,23,24]. Nonmedical cannabis use has also helped to decrease cocaine dependence in a study of patients with ADHD [25]. In this capacity, cannabis substitution could be considered a harm reduction strategy [22]. Some psychiatrists within our institution have now resorted to prescribing medicinal cannabis for patients with ADHD and ODD who were using unregulated cannabis recreationally, or “self-medicating,” or among those who continue to experience symptoms after exhausting all other treatment options. The dearth of evidence regarding cannabis use for ADHD bespeaks an urgent need to determine whether cannabis use is safe and effective in these individuals.

The goal of this pilot study is to examine the real-world effectiveness by comparing changes in their disease-related symptoms before and after beginning treatment with medical cannabis, using validated assessment scales for ADHD, ODD, depression, and anxiety. We will characterize their experiences with using medical cannabis by way of a semistructured interview and cannabis side effects survey. Furthermore, blood levels of commonly found cannabinoids in cannabis in children and young adults who are currently taking medical cannabis for the treatment of their ADHD and ODD under the care of a pediatric psychiatrist will be correlated with symptom scores and demographic variables (age, weight, and ethnicity). Finally, a sample of the participant’s cannabis will be analyzed through liquid chromatography–tandem mass spectrometry (LC–MS/MS) to confirm its chemical composition.

An observational, mixed methods, proof-of-concept study will be undertaken at 1 center in Saskatchewan. The protocol was designed to minimize face-to-face contact, so the study can be performed during the COVID-19 pandemic. Patients with ADHD and ODD who are currently taking cannabis herbal extract (at a THC:CBD ratio of 1:20) as a treatment adjunct to stimulant pharmacotherapy are eligible to participate. Participants are between the ages of 12 and 25 years; have a diagnosis of ADHD in accordance with Diagnostic and Statistical Manual of Mental Disorders (5th edition) with features of ODD; are stabilized on medical cannabis herbal extract (at a THC:CBD ratio of 1:20); and have been deemed safe to participate by the study physician. Participants under the age of 18 years must also have the permission of a guardian to participate. We acknowledge that some patients with ADHD may have comorbid mental health disorders, such as autism spectrum disorder. For the purpose of this study, though, we will only enroll participants who are functionally able and willing to provide assent. We will aim to enroll at between 10 and 20 participants in this pilot study.

Potential participants and their caregivers will be identified and initially contacted by the study physician (DQ) through his childhood and adolescent psychiatry practice at the Saskatchewan Health Authority (SHA) in Saskatoon (Saskatchewan, Canada). If the family is interested in learning more, their contact information will be forwarded to a research team member who will follow up with the family. Potential participants (and guardians, if applicable) who express interest will be provided with a copy of the consent form and the study information reviewed. If the participant (and caregiver, if applicable) opts to participate, logistics will be arranged and informed consent taken.

Legalization of recreational cannabis occurred in Canada in October 2018. The increased public accessibility, coupled with perceptions that cannabis is “natural” and perhaps “safer” than some of the other available pharmacotherapeutic agents [8,9], has increased the probability of cannabis use in this population, despite an absence of evidence on efficacy or safety in youth or young adults.

At the time this study was designed, only 1 controlled clinical trial was published on the use of cannabis in ADHD. Cooper et al [37] performed a (pilot) randomized controlled trial using Sativex Oromucosal Spray (1:1 THC:CBD) or placebo, in 30 adults with ADHD. Participants in the Sativex group demonstrated a pattern of improved cognitive performance as measured by the QbTest, nominally significant improvements in symptoms of hyperactivity/impulsivity (P=.03), and trends toward improvement for inattention and emotional lability. All trends were strengthened when the per-protocol analysis was performed [37]. Case reports have also described the beneficial effects of cannabis on ADHD symptoms [16,38].

Controlled clinical trials are clearly needed to determine the impact of cannabis use on ADHD symptoms in youth and young adults. Understanding the impact of pharmacotherapy is of particular importance in the pediatric population, where development may be adversely and unpredictably impacted by drug therapy [39]. However, pilot studies need to precede interventional studies to understand feasibility and to glean important information about the pharmacokinetics of cannabis in the pediatric patient population to guide dosing strategies.

While the small sample size of this pilot study will preclude treatment recommendations, the importance of this study should not be understated. Exploring the real-world effectiveness and pharmacokinetics of cannabis in a cohort that is already taking cannabis is the most ethical way to gather the necessary information for initiating a research program in this area. If the results from this pilot study are positive, our future work will include a single dose pharmacokinetic study and eventually a randomized controlled trial.

Novel treatment strategies are needed for patients who experience symptoms of ADHD and ODD despite stimulant pharmacotherapy. Some desperate families have resorted to using cannabis, despite the lack of safety or efficacy data. This pilot study will be the first to explore the real-world effectiveness, perceptions, and pharmacokinetics of cannabis in children and young adults, and the results will guide future study in this area.