While Cannabis-based products have become more popular for symptom management among children with Cancer, evidence is lacking on the dosing, safety, and efficacy of cannabinoids in kids, according to researchers.

Of 19 Studies involving a total of 1,927 participants with cancer included in a systematic review and meta-analysis, only seven were randomized trials that reported efficacy outcomes and a lack of homogeneity among the trials precluded the pooling of efficacy data, noted Lauren E. Kelly, PhD, MSc, of the University of Manitoba in Winnipeg, Canada, and colleagues in Cancer.

“There is an urgent need to explore the real-world benefits and harms of cannabis in this vulnerable pediatric population,” the authors wrote.

Controlling nausea and vomiting was the most common indication for the use of cannabinoids in the included studies (11 of 19), and, overall, cannabinoids were reported to be superior compared with active control groups.

“[T]his leaves a knowledge gap concerning the impact of medical cannabis and cannabinoids with respect to pain, mood, sleep, anxiety, and health-related quality of life,” Kelly and colleagues observed.

As for safety, patients in the interventional studies who used cannabinoids versus control groups had higher risks of developing:

• Somnolence (risk ratio [RR] 1.51, 95% CI 1.23-1.84) in four studies
• A high (RR 9.0, 95% CI 4.38-18.48) in three studies
• Dizziness (RR 5.47, 95% CI 1.23-24.26) in three studies
• Dry mouth (RR 2.42, 95% CI 1.85-3.16) in two studies
• Increases in appetite (RR 8.0, 95% CI 1.03-61.84) in two studies

The major cannabinoid-related adverse events (AEs) reported in observational studies were drowsiness, dizziness, headache, and euphoria. Study withdrawals due to AEs were more common among participants receiving cannabinoids versus the comparator groups in two studies (RR 3.67, 95% CI 0.61-21.89).

Notably, across all included studies, no serious cannabis‐related AEs were reported.

“There is a strong need for interventional studies comparing the safety and efficacy of cannabinoids and available treatment options in children with cancer,” Kelly and team wrote. “There is also a need for cannabinoid researchers to work together on standards for reporting cannabis exposures and cannabis-related AEs to ensure that future research is optimally useful.”

“Historically, strict laws regulating cannabis have precluded undertaking studies of children in cannabis clinical trials, and this has limited the understanding of the efficacy of cannabis in children,” they noted. “Despite this, because of reports of improvements in symptoms, including pain, nausea, vomiting, sleep, mood, and appetite, with cannabis, some parents have elected to access cannabis products for their children with cancer off label.”

In an editorial accompanying the study, Holly L. Spraker-Perlman, MD, and R. Elyse Heidelberg, PsychD, both of St. Jude Children’s Research Hospital in Memphis, Tennessee, noted that several of the studies in this review and meta-analysis included both adults and children. In one study, for example, just 31 of 1,120 patients were children.

“In addition, the studies inconsistently cataloged adverse effects and medication interactions,” they wrote. “No overlapping study methods, products, and outcome data precluded a meta‐analysis. Despite ardent beliefs and clinical anecdotes, pediatric oncologists have little information on which to base cannabis treatment recommendations.”

“In sum, meticulously designed trials of standardized cannabinoid products with validated, relevant outcome metrics are imperative before medical cannabinoids for children with cancer can be universally favored,” they added.

For this systematic review and meta-analysis, Kelly and colleagues searched MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception to June 2020, with updates in June 2021 and April 2022.

Of the 19 studies included, eight were retrospective chart reviews, seven were randomized controlled trials, two were open‐label studies, and two were case reports. The studies were conducted in the U.S., Canada, Israel, Australia, and the U.K.

The median age of the participants in the observational studies ranged from 6 months to 18 years, and 3.6 months to 18 years in the interventional studies.

Most patient populations included in the observational studies had a diagnosis of a brain tumor or leukemia/lymphoma. Cancer types were not specified in most of the interventional studies.

The products studied included medical-grade cannabinoids (such as nabilone), synthetic cannabinoids, and unspecified cannabis herbal extracts.

The authors noted that the small number of studies included was a limitation. Furthermore, “as the overall quality of evidence was low, there was no uniformity in the outcomes in the included studies,” they wrote.