CBD consumption in children: scientific insights

CBD has become hugely popular in recent years as a 'natural' remedy for a wide range of ailments–from anxiety disorders to epilepsy. But what about the use of CBD in children? Is it safe, effective, and science-based? In this blog, we will explore what the research has to say on this subject.

CBD in children with epilepsy

CBD has been most studied in children with epilepsy, especially in severe forms like Dravet and Lennox-Gastaut syndrome. In these groups, CBD has mainly been used as complementary therapy, alongside existing antiepileptic drugs.

In a study that involved 120 children and young adults with Dravet epilepsy, patients were given CBD oil (20mg/kg/day) or a placebo in addition to their medication. After 14 weeks, seizure frequency had decreased from 12.4 to 5.9 per month with CBD, versus from 14.9 to 14.1 with the placebo. This resulted in a significantly greater reduction in seizures with CBD compared to the placebo. More parents also reported an improvement in their child's overall condition in the CBD group (62%) than in the placebo group (34%) (1).

Side effects: Patients receiving CBD experienced more frequent side effects, such as diarrhoea, vomiting, fatigue, fever and drowsiness. Moreover, increased liver enzyme levels also occurred. Five per cent of patients became seizure-free (compared to zero per cent in the placebo group).

Another study with 171 Lennox-Gastaut epilepsy patients included children, in addition to adults. CBD (20mg/kg/day) or a placebo was added to the treatment. Over 14 weeks, seizure frequency decreased by 43.9% in the CBD group vs. 21.8% in the placebo one (2).

Side effects: 86% of CBD patients experienced side effects compared to 69% of the placebo patients. Most commonly mentioned were diarrhoea, drowsiness, fever, decreased appetite and vomiting.

In tuberous sclerosis complex (TSC)–a genetic disorder that can be associated with epilepsy–a study with 224 patients (adults and children) showed that CBD in two doses (25 or 50mg/kg/day) significantly reduced the seizure rate compared to a placebo (3). After 16 weeks, the mean reduction in seizure frequency was ~48% in both CBD groups versus ~26% in the placebo one. A lower dose (25mg/kg) was found to have a more favourable safety profile than 50mg/kg.

Side effects such as diarrhoea and drowsiness were dose-dependent and more common in higher-dose groups (e.g. diarrhoea in 25% of the placebo vs. 31% of CBD-25mg vs. 56% of CBD-50mg). A reversible increase in liver enzymes also occurred in 19% of CBD users (none in placebo ones).

Summary: For various forms of epilepsy in children, studies show a positive effect of CBD as a complementary treatment. Typically, they saw 40-50% mean seizure reduction with CBD compared to 20-30% with the placebo. Also, several children achieved >50% seizure reduction and some children became completely seizure-free 

Conversely, side effects are frequent, including drowsiness, loss of appetite, diarrhoea and, in some cases, elevated liver values. In general, these side effects are described as mild to moderate, and CBD is reasonably well tolerated in children.

These results have led to purified CBD oil (Epidiolex/Epidyolex) being approved in several countries for treatment of refractory epilepsy in children (from 2 years of age) with Dravet or Lennox-Gastaut syndrome, and later TSC.

CBD in children with autism spectrum disorders (ASD)

The treatment of autism in children with CBD is still mainly in the experimental stage. Autism spectrum disorder currently has no approved medication for its core symptoms, but pilot studies have been conducted with CBD to look at behavioural problems.

In a study, 60 children with ASD and severe behavioural problems were given CBD-rich cannabis oil. The average age was 12 years (5-17 years). After several months of use, parents assessed that the outbursts of problematic behaviour had improved significantly or very significantly in 61% of the children (4).

Side effects: mild, including sleep problems (14%), irritability (9%) and decreased appetite (9%).

Barchel et al. (2019) followed 53 adolescents with ASD (aged 4-22 years) who were given CBD oil. The dose was individualised; the average CBD dose was 90mg per day. After 66 days, 75% of patients reported overall improvement in symptoms (5). Specifically, 68% of patients reduced self-injurious behaviour and outbursts of anger, and hyperactivity. Sleep improved in 71% of patients and anxiety in 47% (anxiety worsened in 24%) (5).

Side effects: usually mild; most common were drowsiness and decreased appetite.

In a larger cohort study, 188 children and young adults with ASD started medicinal cannabis (mainly oil with 30% CBD and 1.5% THC). The average age was 13 years; the average daily dose was 240mg of CBD (with 12mg of THC). After one month of use, 179 patients were still on treatment; of these, the parents of 119 children provided feedback: 49% reported significant improvement in symptoms, 31% moderate improvement and 14% no change. In particular, restlessness, tantrums and agitation decreased (6).

Side effects: relatively rare and mild, the most commonly mentioned were restlessness and drowsiness.

The first placebo-controlled study in ASD was conducted in 150 children and adolescents (5-21 years) with autism and severe behavioural problems. In this trial design, participants received either a placebo or one of two CBD-containing treatments for 12 weeks: a whole plant extract containing CBD:THC in 20:1 ratio, or pure CBD and THC in the same ratio (7). After the first 12 weeks, the treatments swapped (i.e. everyone received both a placebo and active treatment during the study). An improvement in behaviour was measured. In the group receiving the whole plant extract, 49% achieved marked improvement compared with 21% in the placebo group. The group with pure CBD/THC showed similar improvement to the plant extract. However, not all standardised tests showed significant differences, indicating that the evidence is mixed. 

Side effects: No therapy-related serious adverse events occurred. Common mild side effects were drowsiness and decreased appetite.

Summary: Due to the absence of large-scale long-term studies, CBD is not yet an established therapy for autism, but these early findings do warrant further research.

CBD in children with ADHD

For attention-deficit hyperactivity disorder (ADHD) in childhood, the scientific evidence for CBD treatment is limited. Unlike epilepsy and ASD, no randomised placebo-controlled studies have yet been published in children with ADHD (8). However, below there are relevant findings and considerations:

• Anecdotal use: There is a growing interest among parents and doctors in cannabis products (including CBD) for children with ADHD who do not respond adequately to standard medication or who have concerns about side effects of said medication. Parents report anecdotal experiences of improvements in their children's impulsivity, sleep or anxiety due to CBD oil, but this has not yet been systematically investigated (8).

• Adults with ADHD: Several studies have been published on CBD in adults with ADHD, but not many controlled trials. In a controlled study (n=30), adult patients were given an oromucosal cannabis extract (1:1 ratio CBD:THC) or a placebo for several weeks. Improvements were seen in the cannabis group in hyperactivity/impulsivity and in cognitive tasks. However, these results were no longer statistically significant after adjusting for multiple testing, probably due to the limited sample size (9).

• Current status in children: There are currently several initiatives for research into CBD in children with ADHD, but results are not yet available. For example, an observational study is being set up in Australia to monitor the effectiveness and pharmacokinetics in 12–25-year-olds with ADHD and oppositional defiant disorder who already use cannabis products (10). Despite the lack of evidence, the use of medicinal cannabis/CBD in children with ADHD is increasing in practice (8).

In summary, due to the lack of controlled research of CBD in children with ADHD, the scientific and medical community is cautious about recommendations for its use.

CBD in children and adolescents with anxiety disorders

CBD has also been mentioned as a possible treatment for anxiety disorders in adolescents, partly because of its known anxiety-inhibiting effects in adults. However, research into the paediatric population is still at an early stage. Some relevant case reports and studies are:

• Case report (PTSD): An oft-cited case is that of a 10-year-old girl with post-traumatic stress disorder (PTSD) and related anxiety and insomnia. Traditional drugs provided insufficient relief and caused side effects. She was then given CBD oil (25mg daily, sublingually and via spray) over several months. The result was steadily decreasing anxiety and improved sleep quality and duration, with no significant side effects. After five months of use, her anxiety levels remained significantly lower, and she slept better through the night. Doctors concluded that CBD proved to be a safe and effective alternative to conventional anxiety medication in a child with PTSD in this case (11). While this is of course a single case, which means it is difficult to generalise, it does illustrate the potential individual benefits.

• Open-label pilot study - youth with severe anxiety: A recent prospective study in Australia investigated CBD in treatment-resistant anxiety disorders in adolescents aged 12-25 years. In this open-label trial (without a placebo comparison), 31 adolescents received CBD as a supplement (flexibly dosed to max. 800mg daily) in addition to their standard therapy. All participants had previously shown insufficient improvement with cognitive behavioural therapy and/or antidepressants. Results: After 12 weeks, the mean severity of anxiety had decreased by 43% compared to the start. Depressive symptoms and social functioning also improved significantly (12). In 21 of the 31 young people, the anxiety score decreased to a clinically relevant degree. Side effects: 80% of participants reported at least one adverse reaction, but these were generally mild in nature. The most commonly reported side effects were fatigue, occasional gloomy mood, and sensitivity to temperature changes (hot or cold flashes). No serious or unexpected side effects occurred (12).

• Social anxiety in adolescents (double-blind RCT): A small placebo-controlled study was conducted in teenagers aged 18-19 years with social anxiety disorder (SAD) in Japan. In this study, 17 adolescents received CBD oil (300mg daily) and 20 adolescents a placebo, for 4 weeks, under double-blind conditions. Anxiety was measured with standardised questionnaires before and after the intervention. Results: After 4 weeks, the CBD group showed a significant decrease in anxiety symptoms compared to the placebo group. Scores improved with CBD (reduction in anxiety), while there was little change with the placebo (13). This provided the first evidence that CBD can relieve anxiety symptoms in teenagers with social phobia. The publication reports no serious side effects; CBD was well tolerated during the short treatment duration. 

Summary: For young patients with anxiety disorders, there is tentative evidence of an anxiolytic effect of CBD. Case descriptions show improvements in anxiety. Side effects in this context appear to be mild (e.g. fatigue, drowsiness) and CBD was well tolerated in short-term studies. However, large-scale research is still lacking. Anxiety disorders in children can have a chronic course and the long-term safety of CBD with long-term use at this developmental stage is still unknown.

Possible mechanism of action of CBD in children

CBD exerts its effects through multiple biological pathways. Unlike THC, CBD binds only very weakly to cannabinoid receptors (CB1 and CB2) and does not cause euphoria or a high. Nevertheless, CBD has broad pharmacological effects, which are relevant to the conditions mentioned. Some mechanisms described in the literature:

• Interactions with the endocannabinoid system: CBD is a modulator of the CB1 receptor, meaning that it affects the receptor indirectly and potentially modifies the effects of the body's own cannabinoids. In addition, CBD inhibits the reuptake and degradation of endocannabinoid substances (such as anandamide). This can make the endocannabinoid system more active, affecting neuronal stimulus transmission. In autism, for example, some children have been found to have lower-than-normal levels of anandamide; increasing this via CBD could theoretically improve social function (14).
  
  
• Anti-epileptic effect: CBD has shown anti-epileptic properties in animal and cell models. It appears to block certain receptors such as GPR55 and positively modulate receptors such as the GABA and glycine receptor, giving an inhibitory effect on excessive neuronal discharge. This may explain why CBD reduces seizures in various epilepsy syndromes.

• Anxiety-inhibiting and antipsychotic effects: CBD also acts on systems outside the endocannabinoid system. It is an agonist of the 5-HT-1A serotonin receptor, which is associated with anti-anxiety effects–similar to certain anxiety inhibitors and antidepressants that act on serotonin. This may explain why CBD reduces social anxiety in experimental settings. In addition, CBD has shown an antipsychotic profile in some studies in adults, possibly by affecting dopamine and glutamate signalling pathways. In children with PTSD and anxiety, these traits can help reduce re-experiencing, nightmares and hyper-excitement, as seen in the aforementioned case report.

• Inflammation inhibition and neuroprotection: Some literature suggests that CBD also has anti-inflammatory effects in the brain, via activation of PPAR-γ receptors and modulation of cytokine production. Neuroinflammation has been cited as a factor in both epilepsy and ASD; CBD's possible inhibition of this could therefore also play a role in enhancing and protecting neurons. 

In short, CBD acts on diverse receptors and pathways involved in neural excitability, mood and behaviour. This versatility could account for why CBD can be effective in a variety of central nervous system disorders (from epilepsy to anxiety disorders). At the same time, this means that CBD does not have a precisely targeted effect; it affects multiple systems simultaneously, which may explain both beneficial effects and side effects.

Specifically in children, the endocannabinoid system plays a role in brain development (e.g. in synapse formation and brain maturation). There is still limited research on the impact of CBD on the developing brain. Short-term studies in children have reported no obvious cognitive or developmental side effects, but long-term effects (with years of medication in childhood) are not yet known. Therefore, studies usually start with relatively low doses of CBD and carefully increase them, and doctors monitor growth, puberty development and cognitive functioning of children on CBD therapy.

Finally, CBD has shown a relatively high margin of safety in clinical studies in children. Nevertheless, subtle effects on alertness, appetite and liver enzyme balance can occur, so the use of CBD in children requires a very cautious approach.

References:

1. Devinsky O. et al. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal of Medicine, 376(21):2011-2020 pubmed.ncbi.nlm.nih.gov

2. Thiele EA. et al. (2018). Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet, 391(10125):1085-1096 pubmed.ncbi.nlm.nih.gov

3. Thiele EA. et al. (2021). Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurology, 78(3):285-292 pubmed.ncbi.nlm.nih.gov

4. Aran A. et al. (2019). Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems: A Retrospective Feasibility Study. Journal of Autism and Developmental Disorders, 49(3):1284-1288 pubmed.ncbi.nlm.nih.gov

5. Barchel D. et al. (2019). Medicinal Cannabis for Paediatric Developmental, Behavioural and Mental Health Disorders Neurology 90(15 Suppl) P3.318).
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9. Cooper RE. et al. (2017). Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. European Neuropsychopharmacology, 27(8):795-808 pmc.ncbi.nlm.nih.gov

10. Libzon S. et al. (2023). Safety and efficacy of medical cannabis in ADHD in children and adolescents: A retrospective analysis. pmc.ncbi.nlm.nih.gov
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12. Berger M. et al. (2022). Cannabidiol for treatment-resistant anxiety disorders in young people: an open-label trial. Journal of Clinical Psychiatry, 83(5):21m14130 pubmed.ncbi.nlm.nih.gov

13. Masataka N. (2019). Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers with Social Anxiety Disorders. Frontiers in Psychology, 10:2466 pmc.ncbi.nlm.nih.gov
14.  Hacohen, M., Stolar, O.E., Berkovitch, M. et al. Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: an open label study. Transl Psychiatry 12, 375 (2022). https://doi.org/10.1038/s41398-022-02104-8

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