Cannabinoid and Terpenoid Doses are Associated with Adult ADHD Status of Medical Cannabis Patients
Jeffrey Y. Hergenrather, Joshua Aviram, Yelena Vysotski, Salvatore Campisi-Pinto, Gil M. Lewitus and David Meiri.
Rambam Maimonides Medical Journal, 2020, 11, (1), e0001
Doi : 10.5041/RMMJ.10384
Methods : Participants were adult patients licensed for medical cannabis (MC) treatment who also reported a diagnosis of ADHD by a physician. Data on demographics, ADHD, sleep, and anxiety were collected using self-report questionnaires. Data collected on MC treatment included administration route, cultivator, cultivar name, and monthly dose. Comparison statistics were used to evaluate differences in reported parameters between low (20–30 g, n=18) and high (40–70 g, n=35) MC monthly dose and low adult ADHD self-report scale (ASRS, 0–5) score (i.e. ≤3.17 score, n=30) or high ASRS score (i.e. ≥3.18 score, n=29) subgroups.
Results : From the 59 patients that answered the questionnaire, MC chemovar could be calculated for 27 (45%) of them. The high MC monthly dose group consumed higher levels of most phyto-cannabinoids and terpenes, but that was not the case for all of the cannabis components. The high dose consumers and the ones with lower ASRS score reported a higher occurrence of stopping all ADHD medications. Moreover, there was an association between lower ASRS score subgroup and lower anxiety scores. In addition, we found an association between lower ASRS score and consumption of high doses of cannabinol (CBN), but not with Δ-9-tetrahydrocannabinol (THC).
Conclusion : These findings reveal that the higher-dose consumption of MC components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower ASRS score. However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.
KEY WORDS : ADHD, cannabis, cannabinoids, terpenes
Attention deficit hyperactivity disorder (ADHD) is a common, heritable, neuropsychiatric disorder affecting 2.5%–5% of adults.1,2 It is described as a neuro-developmental syndrome that emerges in childhood or early adolescence; in 60%–70% of cases it per-sists into adulthood.3–5 It is characterized by symptoms of inattention or hyperactivity, and impulsivity, or both.6 These core symptoms typically manifest as restlessness, mind-wandering, emotional instability, and an inability to relax or concentrate.7 Lower educational attainment and lower levels of employment are also reported in patients with adult ADHD.8 Psychiatric conditions such as depression, anxiety, substance abuse disorder, and antisocial disorders are common psychiatric comorbidities in ADHD.9,10 The neurobiology and brain circuitry of both ADHD and other comorbid psychiatric disorders are report-ed as being similar.11 A large body of evidence re veals that untreated adult ADHD leads to various negative psychosocial consequences.6 Effective treat ment can help prevent these negative outcomes.12
The management of ADHD typically includes psychostimulant medications (methylphenidate and amphetamine derivatives),13 non-stimulant medica-tions (e.g. atomoxetine),14 and extended-release clonidine and guanfacine.15 Multiple other medications are used “off-label,” with less efficacy and tolerability.15 Nonetheless, methylphenidate remains the most prescribed, efficacious, and tolerated medication for ADHD.13,15 The non-serious adverse effects (AEs) of these medications include insomnia, de-creased appetite, anxiety, increased systolic and diastolic blood pressure,16,17 nausea, dry mouth, fatigue, headache, urinary hesitation, erectile dysfunc-tion,18 infection, and nervousness.19 A thorough review of the safety of approved ADHD medication has been conducted elsewhere.20
Increasingly, there is recognition that medical cannabis (MC) may offer an alternative treatment option for adult ADHD.21 In one case report, treat-ment with MC revealed marked improvement of ADHD symptoms.22 In addition, an uncontrolled collection of clinical case reports from 30 treatment-resistant ADHD patients reported MC to be an effec-tive and well tolerated treatment.23 In contrast, the first and only randomized controlled trial of 30 participants using nabiximols, a balanced extract of Δ-9 tetra-hydrocannabinol (THC) and cannabidiol (CBD), showed no statistically significant reduction of ADHD symptoms. Notably, no ADHD symptoms worsened.7 It is yet to be elucidated, in a controlled manner, whether other combinations of cannabinoids (and terpenoids) are capable of reducing symptoms in ADHD.
Currently there is a gap in the literature concern-ing the clinical effects of the specific cannabis plant cannabinoid and terpenoid components, best termed “chemovars” rather than utilizing “strain names,” otherwise termed “cultivars.”24 Thus far, many spe-cific phyto-cannabinoids25 and many terpenoids26 have been identified and quantified, making it pos-sible to use this information in clinical trials. How-ever, current studies on ADHD and MC disregarded MC treatment complexity, and evaluated it as if it was a single compound.21 In reality, patients con-sume combinations of cannabis cultivars, tailoring their own specific treatment by trial and error, making dosing of cannabinoid and terpenoid consti-tuents different for each patient. In Israel, ADHD is not a qualifying condition for MC treatment.27 However, of the 51,000 patients in Israel currently approved for MC treatment, a significant cohort report a comorbidity of ADHD.
Medical cannabis in Israel is governed by the Israeli Ministry of Health (IMOH) under regulations of cannabis use for medical purposes. There are spe-cific indications for which a physician can request a license for a patient; ADHD is not a qualifying con-dition for a MC license. However, it is a comorbidity of some patients with an approved indication (e.g. chronic pain, gastrointestinal disease, etc.). General-ly, a MC application is received by one of the board members of the Medical Cannabis Unit (MCU) that would reply to the physician if the request is approved or refused, and the reason for the refusal.
Physicians in Israel decide in collaboration with the patient on the route of administration that is ap-proved by the MCU, either inflorescence for smoke and vaporization, and/or oil extracts for sublingual use. The monthly dose of MC is decided by the phy-sician (starting monthly dose is generally indicated as 20 g by the MCU; any increase is also subject to MCU approval). Physicians provide consultation for the selection of specific MC cultivar or combination of cultivars. However, the final decision on the selection of MC cultivar(s) is in the hands of the patient. Hence, the consumption of cannabinoid or terpenoid doses is not controlled. Every patient goes through a personal trial-and-error process to find the cultivar or the combination of cultivars that best meets his/her therapeutic needs. Moreover, instruc-tions for titration (starting dose, doses per day, guidelines for increasing/decreasing of the dose, or maximum dose allowed) of MC treatment are made either by a nurse in some centers, but mostly by instructions provided by one of the nine licensed suppliers, eight of which are cultivators. Importantly, these guidelines are only recommendations and are not enforced.
The purpose of this cross-sectional study was to examine the differences between MC monthly dose and ADHD symptoms frequency scores subgroups of ADHD patients, their specific chemovar con-sumption, and ADHD medication use. Additionally, sleep and anxiety symptoms were evaluated as well as MC treatment AEs.