CONNECT-FX’s Higher CBD Gel Dose Was Assigned by Weight, Not Randomized Against the Lower Dose
CONNECT-FX used different CBD gel doses above and below a weight threshold. It did not independently randomize children to high versus low CBD doses.
The active-treatment rule followed body weight
Children weighing 35 kilograms or less received 250 milligrams daily, while those above 35 kilograms received 500 milligrams daily, divided into two applications. Randomization compared active gel with matching placebo and was stratified by weight, sex and region.
Weight groups are not interchangeable dose groups
A comparison between the two active-dose groups would also compare children selected by body weight. Differences in age, development or other characteristics could accompany that distinction. Stratifying active-versus-placebo allocation by weight does not remove those issues from an attempted direct high-versus-low dose comparison.
The design cannot locate a universal optimal dose
The weight rule was informed by earlier work and exposure modeling. It did not demonstrate that doubling the dose caused a particular behavioral improvement in otherwise identical children. The full-group primary efficacy comparison was nonsignificant, and favorable methylation-subgroup findings remained exploratory. Neither result supplies a stand-alone dose-response curve. The reported milligram amounts also describe this permeation-enhanced gel regimen, rather than an interchangeable swallowed dose or a dosing instruction for a commercial CBD product.
Related analysis: the trial’s main results and limitations.
