Cannabinoids and Side effect frequency

In a systematic review of all study designs involving 14 studies involving 682 children with developmental and epileptic encephalopathies, researchers reported an increase in adverse-event frequency across pediatric DEE studies following up to 50 mg/kg/day by the oral route over varied across included studies. The recorded comparator was varied; included nonrandomized studies. ¹

Recorded result: Adverse events were described as relatively common, including somnolence, appetite loss, diarrhea, fatigue, and elevated aminotransferases.

In a decentralized randomized double-blind placebo-controlled trial, researchers did not detect a difference in side effect frequency following 25 mg, 50 mg, or 100 mg oral CBN formulation. The recorded comparator was placebo. ²

In a randomized double-blind placebo-controlled phase 3 trial involving 171 patients aged 2-55 with treatment-resistant Lennox-Gastaut syndrome, researchers reported an increase in adverse-event frequency following 20 mg/kg/day by the oral route over 14 weeks. The recorded comparator was matched placebo. ³

Recorded result: Adverse events occurred in 86% of the CBD group and 69% of the placebo group.

In a single-centre randomized triple-blind placebo-controlled parallel trial involving 102 women with surgically confirmed endometriosis, hormonal therapy, and recurrent symptoms, researchers did not detect a difference in mean recurrent endometriosis pain intensity following escalated from 10 mg/day to 150 mg/day, then tapered by the oral route over 10 weeks. The recorded comparator was placebo. ⁴

Recorded result: End-of-treatment mean pain was 41.6 mm with CBDO and 36.8 mm with placebo; the between-group difference was not significant.

In a single-centre randomized triple-blind placebo-controlled parallel trial involving 102 women with surgically confirmed endometriosis, hormonal therapy, and recurrent symptoms, researchers did not detect a difference in rate of at least 30% endometriosis pain reduction following escalated from 10 mg/day to 150 mg/day, then tapered by the oral route over 10 weeks. The recorded comparator was placebo. ⁴

Recorded result: Approximately 60% in both groups reported at least 30% improvement; between-group differences were not significant.

In a single-centre randomized triple-blind placebo-controlled parallel trial involving 102 women with surgically confirmed endometriosis, hormonal therapy, and recurrent symptoms, researchers did not detect a difference in rate of at least 50% endometriosis pain reduction following escalated from 10 mg/day to 150 mg/day, then tapered by the oral route over 10 weeks. The recorded comparator was placebo. ⁴

Recorded result: Approximately 40% in both groups achieved at least 50% pain reduction; between-group differences were not significant.

In a single-centre randomized triple-blind placebo-controlled parallel trial involving 102 women with surgically confirmed endometriosis, hormonal therapy, and recurrent symptoms, researchers reported an increase in mild adverse-event frequency following escalated from 10 mg/day to 150 mg/day, then tapered by the oral route over 10 weeks. The recorded comparator was placebo. ⁴

Recorded result: The abstract reports more mild adverse events with CBDO, mainly gastrointestinal symptoms and perceived weight changes; counts and P values are not provided.

In a randomized double-blind placebo-controlled dose-ranging safety trial involving 34 children aged 4 to 10 years with Dravet syndrome, researchers reported an increase in adverse-event frequency following 5, 10, or 20 mg/kg/day in two daily doses by the oral route over 3-week treatment period including titration. The recorded comparator was placebo. ⁵

Recorded result: The abstract classifies the trial as Class I evidence that CBD produced more adverse events than placebo; group counts are not provided.

In a descriptive real-world multicenter study involving 551 children with treatment-resistant developmental and epileptic encephalopathies, researchers reported an increase in adverse-event frequency in a large pediatric DEE cohort following not stated in the PubMed abstract by the oral route over 12 to 32 months; median follow-up 22 months. The recorded comparator was none. ⁶

Recorded result: Adverse events occurred in 32.7% and were described as mostly mild, transient, and responsive to dose adjustment.

In a retrospective cohort study involving 29 patients aged 6 to 24 years with pediatric-onset intractable epilepsy, researchers reported an increase in adverse-event frequency in pediatric intractable epilepsy following median maintenance dose 14.2 mg/kg/day by the oral route over median follow-up 14.3 months. The recorded comparator was none. ⁷

Recorded result: Adverse events occurred in 37.9%; three patients discontinued for pneumonia, lethargy, or seizure aggravation.

In a retrospective longitudinal study involving 53 children older than 2 years with drug-resistant epileptic spasms, researchers reported an increase in adverse-event frequency in childhood epileptic spasms following not stated in the PubMed abstract by the oral route over treated from 2020 to 2024; patient-level duration not stated. The recorded comparator was none. ⁸

Recorded result: Adverse events occurred in 62.2%; 11.3% discontinued because of adverse events and 17% for lack of efficacy.

In an open-label expanded-access follow-up involving 140 patients with treatment-resistant focal epilepsies, including 33 with TSC, researchers reported an increase in adverse-event frequency in focal expanded access following started at 2-10 mg/kg/day and titrated up to 25-50 mg/kg/day by the oral route over up to 144 weeks. The recorded comparator was none. ⁹

Recorded result: Adverse events occurred in 91% of the TSC group and 96% of the non-TSC group.

In a prospective observational multicenter cohort involving 101 pediatric drug-resistant epilepsy patients across 19 Thai hospitals, researchers reported an increase in adverse-event frequency with CBD-enriched cannabis oil following median modal CBD dose 6 mg/kg/day; effective range 1-15 mg/kg/day by the oral route over median follow-up 15 months. The recorded comparator was none. ¹⁰

Recorded result: Adverse events were reported in 92%, mostly mild; 33 discontinued, including 57% of discontinuers for intolerable adverse events.

In a retrospective real-world cohort study involving 107 patients with developmental and epileptic encephalopathies, researchers reported an increase in adverse-event frequency in developmental epileptic encephalopathies following not stated in the PubMed abstract by the oral route over median follow-up 20 months. The recorded comparator was none. ¹¹

Recorded result: Adverse events occurred in 33.6%, and 9% discontinued because of side effects.