Cannabis & ADHD

ADHD is a neurobiological disorder characterized by core symptoms of inattention or hyperactivity, impulsivity, or both, affecting more than 9% of children and over 4% of adults in the United States.1 The disorder emerges in young childhood or early adolescence, with as many as 60% of cases persisting throughout adulthood.2 Early diagnosis and treatment are essential, as inadequate management can lead to damaged relationships, impaired work and academic performance, poor self-image, substance abuse, accidents, unemployment and financial problems, and other challenges that can touch almost every aspect of an individual’s life.

Unfortunately, many adults with ADHD are undiagnosed or received a diagnosis as an adult. Complicating ADHD treatment and diagnosis is the fact that 60% to 70% of persons with ADHD have comorbid psychiatric conditions such as depression, anxiety, antisocial disorders, and substance use disorder.3

The treatment of ADHD typically includes psychostimulants (eg, amphetamines, methylphenidate) and nonstimulant medications (eg, atomoxetine) as well as behavioral therapies. These treatments are typically considered safe and effective, with 70% to 80% of those taking stimulants experiencing improved symptoms. At the same time, there’s a void in treatment options for many people with ADHD and an increase in individuals turning to cannabis as a potential treatment option. But what does the evidence say, and what are the risks?

Pathophysiology
Deficits in the neurotransmitters dopamine and norepinephrine, both of which are involved in normal cognitive and learning processes, have been implicated in the pathophysiology of ADHD.4 Dopamine plays an essential role in the regulation of emotional responses and in taking action to achieve specific rewards, and is responsible for feelings of pleasure and reward, risk taking, and impulsivity. Insufficient dopamine levels make initiating and sustaining focus nearly impossible for people with ADHD. Low norepinephrine levels cause challenges for those with ADHD, as the neurotransmitter helps modulate attention, arousal, and mood and is involved in focus, processing, and controlling impulsive behaviors.

Traditional Treatments
Psychostimulants have long been the first-line pharmacotherapy for managing ADHD symptoms in both children and adults. These medications improve ADHD symptoms by quickly increasing the level and effect of dopamine and norepinephrine in the brain. While extremely effective, psychostimulants aren’t without concerns, including challenges in adherence to treatment due to potential tolerance, stigma, and patient-specific barriers. While these medications are generally considered to be safe, there’s a potential for adverse effects including insomnia, reduced appetite, nervousness, increased blood pressure, dry mouth, difficulty urinating, nausea, drowsiness, erectile dysfunction, and headache. Long-term stimulant use is associated with growth suppression, misuse/abuse potential, and sudden cardiac arrest.

Cannabis and the Endocannabinoid System (ECS)
Similar to stimulants, cannabis may have a role in helping with ADHD symptoms by increasing levels of dopamine and norepinephrine through its cannabinoid effects within the ECS. This system comprises CB1 and CB2 receptors, which are activated by endogenous cannabinoids 2-arachidonoylglycerol and anandamide. Dopamine and the ECS are thought to have a bidirectional relationship: While dopamine has been shown to promote endocannabinoid release in the brain striatum, the ECS dampens excessive dopamine neuron release by retrogradely releasing endocannabinoids that bind to CB1 receptors.5

Perceptions/Self-Treatment
Despite there being no strong clinical evidence and no clinical recommendations supporting the beneficial effects of cannabis use for ADHD, there’s been a growing number of anecdotal reports and an increasing perception that cannabis is a safe and effective alternative therapeutic treatment option for ADHD.

An online review of 268 separate forum threads were identified to review perceptions related to cannabis for ADHD.6 Twenty percent (55) of the forum threads were randomly selected for review. Twenty-five percent of individual posts indicated the perception that cannabis is therapeutic for ADHD, as opposed to 8% that it’s harmful, 5% that it’s both therapeutic and harmful, and 2% that it has no effect on ADHD.

One study examined the association between subtypes of ADHD and self-treatment with cannabis within a sample of 2,811 current users.7 A large portion of users found cannabis improved their ADHD symptoms. Also, daily users were found to be more likely to have the ADHD subtype with hyperactive-impulsive symptoms than the inattentive subtype. For nondaily users, the proportions of users meeting symptom criteria didn’t differ by subtype. These results have implications for identifying which individuals with ADHD might be more likely to self-medicate using cannabis.

Case Reports
One 2008 case report noted that cannabis consumption by a 28-year-old male produced marked improvement of ADHD symptoms. The patient exhibited improper behavior and appeared to be very maladjusted and inattentive while sober, yet was completely inconspicuous when he had a very high blood plasma level of THC. Performance tests found improvements including enhanced driving-related performance. The authors hypothesized that the effects of cannabinoids in patients may be different from those in healthy users, suggesting an involvement of the central cannabinoid receptor systems in the pathology of the disorder.8

An uncontrolled collection of clinical case reports from 30 treatment-resistant ADHD patients reported medical cannabis to be effective and well tolerated. The study reviewed records of 30 adult patients (28 males and two females) with ADHD who had been approved to use cannabis flower. Most patients previously had been given standard treatments, such as Ritalin, with little success. The study found that when using cannabis alone, 73% reported ADHD management sufficient to enable participation in working and social life and 47% noted improvement in concentration. The mean age at the first visit was 30 years (age range 21 to 51). Sixty-three percent of the patients had been diagnosed with ADHD as adults. All patients diagnosed in childhood (between age 6 and 13) previously had been treated with methylphenidate. Other pharmacological treatments included atomoxetine, dexamphetamine, lisdexamfetamine, and amphetamine juice.9

Traditional ADHD medication was usually discontinued due to side effects and or ineffectiveness. Eight patients continued to take stimulants and combined them with cannabis, while 22 patients used cannabis alone. All patients receiving cannabis flowers experienced improved concentration and sleep and reduced impulsivity. In five cases, dronabinol (a THC-containing product) was also found to be effective. The authors concluded, “For adult patients with ADHD, who experience side effects or do not profit from standard medication, cannabis may be an effective and well-tolerated alternative.”9

In contrast, the first and only randomized controlled trial of 30 participants using Sativex (1:1 THC:CBD) produced mixed results. The study’s primary outcome measure was to determine cognitive performance and activity level, while the secondary study outcome measured ADHD and emotional lability symptoms. Over an 11-month period, participants were randomly assigned to Sativex (n=15) or placebo (n=15).10

For the primary outcome measure of cognitive performance, the Sativex group usually had better scores than did the placebo group, but these didn’t meet significance. For secondary outcomes, Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity and a cognitive measure of inhibition, and a trend toward improvement for inattention and emotional lability. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group, and one serious (cardiovascular problems) adverse event was observed in the placebo group.10

Potential Harms of THC
There are several concerns with cannabis use in adolescents and teens due to the pronounced effects of THC on brain development.11 Short-term effects of THC include an adverse influence on concentration, thinking, sensory and time perception, pleasure, and coordination. THC can also impair functions including memory and learning with effects lasting up to several days beyond the time of the actual “high.” Long-term and/or permanent effects are a significant concern, as the teenage brain isn’t fully developed until at least the early or mid-20s, and THC exposure during adolescence can negatively affect how connections are formed within the brain, cause abnormal brain shape and structural volume, and interfere with neurotransmitters. Furthermore, one study found that teens who regularly used cannabis lost an average of 5.8 IQ points by the time they reach adulthood.12

Persons with ADHD also are more likely to develop cannabis use disorder (CUD), defined as cannabis use that leads to significant impairment during a 12-month period. Persons who were diagnosed with ADHD in childhood are 1.5 times more likely to be diagnosed with CUD.13 A 2016 study estimated that as much as 45% of people seeking treatment for CUD also have ADHD.14

CBD
CBD is the second most prevalent cannabinoid in cannabis and is known to have numerous potential therapeutic properties, including as an anti-inflammatory, neuroprotective, analgesic, anticonvulsant, and antioxidant. However, to date, clinical evidence is insufficient to support the use of CBD for ADHD.15

However, one small randomized, controlled, double-blind, parallel-design pilot study evaluated the effects of CBD in patients aged 8 to 16 with intellectual disability and severe behavioral problems. Eight participants received either oral placebo or 98% CBD oil for eight weeks. Dose titration occurred over nine days to a target 20 mg/kg/day in two divided doses (max dose 500 mg). Three of four participants in the treatment arm and all of the participants in the control arm had an ADHD diagnosis. One participant in the placebo group used methylphenidate, one in the CBD group used guanfacine, and one in the control arm used clonidine.15

The study’s design wasn’t adequately powered to assess efficacy; however, results did indicate a greater reduction in baseline Aberrant Behavior Checklist Subscale hyperactivity/noncompliance score in the treatment arm compared with placebo. No dose reductions were required in response to adverse events, nor were there any study withdrawals, serious adverse effects, or clinically significant abnormal lab values. Medication and study appointment adherence were 100%, and all parents reported that they would recommend the study to families with children facing similar challenges.15

Despite the belief of many that CBD is a much safer alternative to traditional pharmaceutical drugs, there are concerns, especially related to poor understanding about the potential for harms and due to concerns that many over-the-counter CBD products have been found to contain amounts of CBD that are different from the amounts noted on their labels. More serious harms associated with CBD include hepatotoxicity, damaged male fertility (per animal studies), altered cognition and mood, and gastrointestinal distress. Pediatric CBD trials most commonly report diarrhea, somnolence, and decreased appetite as adverse effects, although these data are poorly quantified.15

Additionally, caution should be taken with concurrent administration of CBD and medications that affect (or are affected by) CYP3A4, 2C19, and 2C9 enzymes. For example, if considering CBD as an adjunctive ADHD therapy, clinicians should consider the potential drug-drug interaction with amphetamine, as in vitro data suggests one or more amphetamine metabolites act as mild CYP3A4 inhibitors.15

Cannabinol (CBN)
CBN, a lesser-known minor cannabinoid found in cannabis, may play a potential role in the treatment of ADHD symptoms.16 Fresh cannabis typically contains little CBN, but more CBN is available as the cannabis plant ages and THC is decarboxylated into CBN. This degradation process happens even faster if cannabis is exposed to light and air. Unlike THC, CBN is generally accepted as being nonintoxicating.

A recent study from Israel suggests that CBN, along with other cannabinoids, may help reduce ADHD symptoms. The researchers noted that previous studies considered cannabis as a single product in ADHD research, disregarding the inherent complexities and variability between cultivars and combinations of cultivars that lead to a unique amount of consumed cannabinoid and terpenoid constituents in each patient. In order to better understand these complexities, the researchers evaluated cultivars of all eight approved cultivators in Israel in the laboratory for their cannabinoid (by liquid chromatography–mass spectrometry) and terpenoid (by gas chromatography–mass spectrometry) presence and quantity. This enabled them to extract specificity from the data and see what cannabinoids/terpenes/strains were doing what.16

For the study, the researchers evaluated data for 53 adult patients with active medical cannabis licenses and comorbid ADHD for cannabis-related adverse effects and comorbid psychiatric conditions. The patients were asked to track several different data points including every facet of their cannabis consumption: dosages, delivery methods, strain names, manufacturer names, and additional information rating their ADHD symptoms and sleep and anxiety patterns. After four months, researchers analyzed each detailed report. Sixteen of the 53 (30%) participants used prescription stimulants as ADHD treatment. Researchers found that patients who consumed higher total monthly doses of cannabis also consumed higher doses of specific cannabis constituents.16

According to the study authors, they were able to demonstrate that patients treated with cannabis experienced improved ADHD symptoms, and many stopped their ADHD medications. This effect was most pronounced in patients who took larger amounts of cannabis and/or had fewer ADHD symptoms. In most cases, reductions in ADHD symptoms were also accompanied by reductions in anxiety. More specifically, these findings revealed that the higher-dose consumption of cannabis components (phytocannabinoids and terpenes), including CBN, is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower adult ADHD self-report score. However, the authors also noted that more studies are needed in order to fully understand whether cannabis and its constituents can be used for management of ADHD.16

Final Thoughts
It’s difficult to recommend the use of cannabis for ADHD symptoms in the absence of stronger clinical evidence for its efficacy. This is true regardless of patient age and with significant reservations for the use of cannabis in younger patients. Until adequate information is available, psychostimulants should remain the initial treatment choice.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

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