Children and Medical Cannabis

By Kaylee Martig

Many disorders, including Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and mood disorders have a neurological basis in the body’s endocannabinoid system. The endocannabinoid system (further discussed in each disorder’s section) is comprised of cannabinoid type I and type II receptors (CB1 and CB2, respectively) which are activated by compounds known as cannabinoids. Types of cannabinoids include endogenous cannabinoids, which are produced by the body and include neurotransmitters 2-AG and anandamide, phyto-cannabinoids, which are produced by plants, and synthetic cannabinoids, which are produced artificially. Cannabis, commonly known as marijuana, contains over 100 phyto-cannabinoids, some of which act on the body’s natural cannabinoid receptors as well as other relevant targets for therapeutic use in disorders including ASD, ADHD, and mood disorders. The two most prominent phyto-cannabinoids produced by cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC is intoxicating and is responsible for the euphoric “high” associated with cannabis use. It often causes drowsiness and increased appetite, which can sometimes be beneficial. CBD, however, is non-intoxicating, and is responsible for many of the therapeutic benefits associated with cannabis. Many studies have demonstrated CBD’s anti-inflammatory, neuroprotective, anxiolytic (anti-anxiety), and antipsychotic properties (1). One way CBD works in the brain by inhibiting the reuptake and enzymatic degradation of anandamide, increasing plasma anandamide levels, which may compensate for the low levels associated with disorders such as ASD (2). This is one mechanism by which cannabis may mediate the effects of such disorders in the brain.

Different strains of cannabis have differing ratios of THC to CBD, which can be used to target specific symptoms. For example, in ASD, the drowsiness and increased appetite associated with THC may improve symptoms of comorbid sleep and feeding disorders. Meanwhile, the anxiolytic and antipsychotic properties of CBD may improve anxiety and self-injury. In bipolar disorder, the antidepressant-like effects of THC may improve mood, while the antipsychotic properties of CBD may prevent cannabis-induced psychosis. Many treatments use a combination of CBD, THC, and other phyto-cannabinoids, which are more effective when used in combination. One study which compared five strains of CBD-rich cannabis, all with similar amounts of CBD, found different strains produced different effects, demonstrating different combinations of phyto-cannabinoids can be more effective than CBD or THC alone (3, 4). This is called the “entourage effect,” and supports the use of whole-plant products over CBD/THC extracts.

Another result of the entourage effect is a wider therapeutic window. Purified CBD extracts yield a bell-shaped dose-response, in which too-low and too-high doses are ineffective, producing a narrow therapeutic window (5). The therapeutic dose may differ depending on the desired effect (e.g., a lower dose may be effective for anxiety whereas a higher dose is effective for epilepsy), but means it may be difficult to treat multiple symptoms simultaneously. However, one study found a wider therapeutic window for a whole-plant product over a purified CBD extract, due to the entourage effect (5). Finally, the entourage effect may cause CBD to lessen the intoxicating effect of THC, permitting the administration of higher doses without a “high” and with a lower risk of cannabis-induced psychosis (4, 6).

Cannabis’ current clinical utility is limited by a relative lack of research on both efficacy and safety, particularly regarding long-term use. There is evidence that THC-rich cannabis can harm the developing brain. However, the long-term effects of CBD-rich cannabis use in children are not well known, despite promising short-term results. Adverse effects in short-term use include sleep disturbances, drowsiness, irritability, and changes in appetite (7, 8). However, most of the research on cannabis use for ASD and other disorders study only short-term use (weeks to months), meaning we do not know potential long-term effects. Some studies have shown that adolescents may be more vulnerable to adverse effects caused by cannabis, relative to adults, due to ongoing neuromaturation (9). However, these adverse effects appear to be linked primarily to THC, rather than the CBD-rich strains which are being used to treat these disorders (2).

Another factor to consider is interactions between medical cannabis and other drugs used to treat the disorders. In one study, 82% of children being treated with cannabis were receiving another drug concurrently, such as antipsychotics (72%), mood stabilizers (17%), benzodiazepines (12%) and SSRI antidepressants (7%) among others (10). One mechanism through which CBD interacts with prescription drugs is the temporary deactivation of cytochrome P450 liver enzymes, which affects the metabolism of other drugs (7, 11). Some drugs may rise to toxic levels when administered in conjunction with cannabis, because the deactivation of the P450 enzyme prevents the breakdown and removal of the drug in the body, causing it to remain more potent for longer than intended. Anti-epileptic medications, CNS depressants, SSRIs, tricyclic antidepressants, and lithium, all commonly used to treat ASD and mood disorders, are just a few drugs which fall into this category (12, 13, 14). Other drugs, however, may become less effective when administered in conjunction with cannabis, as the deactivation of the P450 enzyme can prevent the drug from being broken down and used in the body, making it less potent than intended (11). Risperidone, an antipsychotic used to treat schizophrenia, bipolar disorder, and behavioral disorders associated with autism, falls into this category (7).

More research must be conducted on interactions between cannabis and prescription drugs before they are considered safe for use, as research to date has been inconclusive (14). Some studies report no described interactions between prescription drugs and cannabis, when low to moderate doses of cannabis were used. However, doses upwards of 20mg CBD per kilogram of body weight may be used to treat disorders such as epilepsy, and could increase the risk of interactions (15). Geffrey et al. (12) emphasize the importance of monitoring drug levels in patients who are using CBD. Drug interactions can increase the risks associated with treatment using cannabis, although 24% of the children in the aforementioned study by Aran et al. (10) were able to stop taking the other prescription drugs following the cannabis treatment. Treatment with cannabis is becoming more common for a variety of disorders, but safety and efficacy are dependent on a number of factors, including strain, dose, mode of ingestion, and personal factors, and long-term outcomes are largely unknown.

References

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