Medical Cannabis in Children

Abstract

The use of medical cannabis in children is rapidly growing. While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD). Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity. As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence. This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible "entourage effect" as opposed to pure cannabinoids that are more standardized and reproducible.

Figure 1

Biosynthesis, Degradation, and Receptor Binding of AEA and 2-AG. AEA is synthesized from membrane phospholipids in the postsynaptic neuron by NAPE-PLD. It crosses the synapse “against the traffic” and activates CB₁R and TRPV1 on the presynaptic neuron. Following reuptake to the presynaptic neuron by the EMT, AEA activates nuclear receptors—PPARs—and is degraded by FAAH. THC directly activates CB₁R; CBD inhibits FAAH and EMT (increasing AEA levels), the endogenous ligand of CB₁R. Like AEA, CBD activates PPARs and TRPV1. 2-AG, 2-arachidonoylglycerol (blue ellipses and related lines); AA, arachidonic acid (green ellipses); AEA, anandamide (purple ellipses and related lines); CB₁R, cannabinoid type 1 receptor; CBD, cannabidiol; DAGL, diacylglycerol lipase; EMT, endocannabinoid membrane transporter (green tubes); FAAH, fatty acid amide hydrolase; GPR55, G protein-coupled receptor 55; MAGL, monoacylglycerol lipase; NAPE-PLD, N-acylphosphatidylethanolamine-specific phospholipase D; PPARs, peroxisome proliferator-activated receptors; THC, Δ9-tetrahydrocannabinol; TRPV1, transient receptor potential channels of vanilloid type-1. Broken lines = inhibition; half ellipses ( ) = receptors; hexagons = enzymes; yellow mesh = cell membrane. Thicker lines and half ellipses are of greater importance than the thinner ones. Black lines, other pathways; red lines, phytocannabinoid pathways.