Abstract

Introduction

Public acceptance of medical cannabis for the treatment of chronic conditions has increased despite a lack of scientific evidence for safety and efficacy [1, 2]. In Canada, access to both medical and recreational cannabis is now legal, and self-medication with cannabis for a variety of symptoms has become more prevalent. Evidence-based information has not kept pace with the legislation, and many clinicians remain reluctant to authorize cannabis until robust evidence is available to guide treatment [3]. Unfortunately, the limited evidence base may persist due to key challenges such as the difficulty in conducting randomized and placebo-controlled trials with cannabis [4] and the significant variability in cultivars. With >489 distinct compounds in the leaves and flowering tops of cannabis plants, which include at least 120 different phytocannabinoids and other entities such as flavonoids and terpenes [5, 6], cultivars demonstrate important differences in therapeutic effect. Even within a given cultivar, soil and climate conditions and various cultivation techniques can influence its constituent bioactive components. The method of consumption or route of administration further impacts the pharmacokinetics and therapeutic effects of cannabis [7].

Attention deficit hyperactivity disorder (ADHD) is one such condition where few clinicians authorize cannabis, but interest in self-medication is high. ADHD is a chronic neurobehavioral disorder characterized by inattention and/or hyperactivity-impulsivity with a prevalence of approximately 7% in children and 2.5% in adults [8, 9]. Over half of the children and adults with ADHD have comorbid psychiatric conditions, such as sleep disorders, mood and anxiety disorders, and oppositional defiant disorder [10, 11]. In addition to the first-line pharmacotherapy with stimulants, internet discussions frequently indicate and advocate use of cannabis for relief of ADHD symptoms [12, 13, 14]. In one study, at least 3 times as many online comments attested for its therapeutic benefits in comparison with harm or lack of efficacy [14]. Despite the public interest and anecdotal reports, we only found one study on the use of cannabis in ADHD which compared Sativex Oromucosal Spray to placebo in a pilot study of 30 adults, where participants in the intervention group showed no difference in the primary outcome (cognitive performance as measured by the QbTest), but improved symptoms of hyperactivity/impulsivity (secondary outcome, p = 0.03) [15]. While this study investigated a commercially available product (containing 1:1 cannabidiol [CBD]:Δ⁹-tetrahydrocannabinol [THC]), a product available in some countries by prescription, many patients are self-medicating with unlicensed products in a variety of formulations [12, 13, 14].

In the absence of scientific data, case reports are valuable for presenting new observations, generating hypotheses, and providing in-depth examinations of a subject of study as well as its related contextual conditions [16]. In this case report, we identified patients from a psychiatry practice who were prescribed ADHD medications but also self-medicated with cannabis. We explored treatment efficacy and patient perceptions of cannabis use. Since no literature exists to provide guidance for cannabis dosing in patients with ADHD, we also collected patient blood samples to determine plasma concentrations of the cannabinoids and relevant metabolites.

Methods

Three patients who were taking cannabis for symptomatic relief of their ADHD participated in telephone interviews conducted by one of the authors (H.M.). The patients were previously diagnosed using the DSM-V criteria. The interviews lasted between 39 and 59 min. To characterize the patient’s experiences of taking cannabis and its perceived efficacy, a semistructured interview guide facilitated a discussion about the patient’s life prior to initiating cannabis, the decision/reasons for starting it, how (if at all) things have changed since initiating cannabis, logistics on consumption and access, and what (if any) concerns they might have about cannabis. A cannabis side effect survey [17] inquired about potential cannabis side effects experienced by the patients, using the time frame of the previous week.

Self-report symptom rating scales, including the Swanson Nolan and Pelham (SNAP-IV) (90-item) [18], the Screen for Child Anxiety Related Emotional Disorders (SCARED) [19], and Patient Health Questionnaire (PHQ-9) [20], were performed during the interviews as a measure for treatment efficacy. The SNAP-IV rating scale contains 90 items from the DSM-IV criteria which assess inattention, hyperactivity/impulsivity, and oppositional defiant disorder, as well as items representing a general index of childhood problems. This tool, which is a modified version of the original SNAP questionnaire [18, 21], consists of Likert scale questions that measure the frequency/severity of a symptom or behavior. The items are scaled from 0 to 3 (0 = “not at all,” and 3 = “very much”), and the tool has had good reliability and validity in different study samples [22]. The SCARED rating scale and PHQ-9 assessed symptoms of anxiety and depression, respectively. The 3 rating scales were summed according to standardized methods [18, 19, 20] to achieve a composite score, with higher scores equating to higher levels of debility. Baseline symptom scores obtained before cannabis was initiated were collected from the patient’s medical chart and subtracted from the totals, producing an indicator of symptom change. ADHD inattentive symptoms were measured using items 1–9 of the SNAP-IV, while emotional regulation and irritability were measured using the Clinical Evaluation of Emotional Regulation-9 (CEER-9) method, whereby items 21, 23, 25, 26, 28, 34, 38, 39, and 54 from the SNAP-IV questionnaire were converted to a binary score (1 = not at all; 2 = very much) [23].

Two blood samples were obtained from each patient by the mobile laboratory to allow quantification of plasma concentrations of cannabinoids and relevant metabolites (THC, CBD, 11-hydroxy-THC, 7-hydroxy-CBD, cannabichromene, and 11-nor-9-carboxy-tertrahydrocannabinol). The samples were collected in BD Vacutainer® Barricor^TM tubes [24], centrifuged to separate plasma, transferred to Eppendorf^TM Protein LoBind microcentrifuge tubes, and stored in a −80°C freezer until they were analyzed by liquid chromatography-tandem mass spectrometry. The method was previously developed and validated within our institution [25] according to FDA guidelines [26]. Written informed consent was obtained from patients for publication of the details of their medical case, and ethical approval for data collection was approved by the Biomedical Research Ethics Boards at the University of Saskatchewan (#1726).

Discussion/Conclusion

We describe 3 patients with ADHD who added cannabis to their treatment regimen and experienced positive therapeutic effects. The improvements in their symptoms and quality of life were substantial, such as the ability to keep emotions in check (3 patients) or to obtain and excel at a new job with more responsibility (2 patients). Objective measures accompanied these narratives with all 3 patients experiencing improvements in validated rating scales for measures of mental health. Scores on the PHQ-9, which measure depression, improved by 8–22 points (30–81%). Improvements on the SCARED, which measure anxiety, ranged from 0 to 27 (up to 33%), and the CEER-9 scale, which indicates emotional regulation, ranged from 2 to 7 (22–78%). Finally, the 9-item SNAP scale measuring inattention showed improvements ranging from 2 to 8 points on the raw scale, which equated to 7–30%.

Notably, all 3 patients used cannabis as an adjunct to their other medications (e.g., stimulants, antidepressants, or mood stabilizers). Patient 1 described cannabis as “a really good helping hand” to compliment his other medications. Patient 3 was able to discontinue his stimulant pharmacotherapy, but acknowledged that the “cannabis, in addition to a change in prescription medications to lithium, helped to change his life.” Plasma levels of the cannabinoids were not detectable at trough levels suggesting that the effects of the cannabis may not be sustained throughout the day; however, the patients perceived the effects of the cannabis to last throughout the day. This bespeaks to the importance of the other medications to ensure treatment success.

All 3 patients discussed the use of cannabis with their psychiatrist and were authorized oral cannabidiol oil CBD:THC (20:1) from a medical source. Our patient interviews and accompanying blood levels, however, indicated that this route and formulation was not consistent, and that the patients sought out a product and regimen that worked for them. Two patients reported taking cannabis once daily, whereas the other patient preferred a twice daily regimen. Two patients preferred smoking cannabis (as opposed to an edible oil). With respect to chemical composition, 1 patient preferred a product high in THC and low in CBD (CBD:THC 0:18–19). Another patient reported using CBD:THC 20:1, but high amounts of THC and no CBD were detected in the post-dose sample, which brings into question the contents of product used by the patient. The use of cannabis is also complicated by the dual supply streams in Canada. Two patients obtained their cannabis from a recreational cannabis store, versus a medical source due to significant cost differences (double the price for medical cannabis). Unlike other medications, patients are freely available to choose their cannabis product and source. Even within the same source, batch to batch variation is expected, which contributes to significant inter- and intrapatient variability with cannabis-based medicine.

An increasing number of patients are self-medicating with cannabis for the treatment of ADHD. Yet, a dearth of literature exists on this topic, and only 2 other published case reports of patients receiving benefits from cannabis were found in the literature. One publication from 2008 reported improvement in performance tests (ART2020 and TAP) in an adult male smoking cannabis, suggesting that THC may have atypical effects in patients with ADHD [27]. A second case report in 2018 described improved symptoms in an ADHD patient who was taking a product high in THC [28]. Although the potential mechanism of cannabis remains to be determined, cannabinoids, such as THC, may mediate their effects through induction of dopamine release in the human striatum [28, 29]. Elucidating such mechanisms will be particularly challenging since the biochemical composition of cannabis (e.g., phytocannabinoids, terpenes, and flavonoids) varies from strain to strain. Plasma cannabinoid concentrations of 2 of the patients in the present discussion were high in THC (with no CBD), while the other patient had higher CBD concentrations, but THC was still present. In the previous literature, products high in THC or containing both THC and CBD ameliorated ADHD symptoms [15, 27, 28]. While we cannot draw any conclusions on the optimal ratio of CBD:THC, we suggest that future studies involve a product consisting of some amount of THC (instead of a product consisting only of CBD).

An important limitation of case reports is their inability to generalize to a wider population given the selection bias, and there is limited information that can be gleaned from these reports of a few selected patients. While randomized controlled trials are urgently needed to provide insight on the efficacy of cannabis in the treatment of ADHD, such studies will never be performed with smoked cannabis flower, and we are left to rely on observational data for these exposures. This report adds to the literature by providing detailed personal accounts from 3 patients and objective evidence of improvement on validated measures for ADHD symptoms. Clinicians who care for patients who self-medicate with cannabis should aim to objectively monitor symptoms, using validated scales for ADHD and other comorbidities. The patients presented in this case report were also taking concurrent medications; therefore, the added benefits of cannabis on ADHD symptoms are unclear. Significant variation noted amongst these 3 individuals (e.g., product, chemical composition, dose, route of administration, and supplier) highlights the challenges with cannabis-based medicine development and research.

Statement of Ethics

Written informed consent was obtained from patients for publication of the details of their medical case, and ethical approval for data collection was approved by the Biomedical Research Ethics Boards at the University of Saskatchewan (#1726).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was funded by an internal College of Pharmacy and Nutrition Seed Fund Grant.

Author Contributions

H.M. contributed to the research design, data collection, and manuscript writing. D.Q., L.E.K., and J.A. contributed to the research design and reviewed and revised the manuscript.

Data Availability Statement

The data that support the findings of this case report are not publicly available to protect the individual’s anonymity.

Acknowledgments

References