The safety and relative effectiveness of non-psychoactive cannabinoid formulations for the improvement of sleep: a double-blinded, randomized controlled trial

Abstract

The objective of this randomized, double-blinded controlled trial was to evaluate the safety and relative effects of different formulations containing Cannabidiol (CBD) and melatonin, with and without the addition of minor cannabinoids, on sleep. Participants (N=1,793 adults experiencing symptoms of sleep disturbance) were assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15mg CBD or 5mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance SF 8A, administered via weekly online surveys. All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p<0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15mg CBD isolate and formulations containing 15mg CBD and 15mg Cannabinol (CBN), alone or in combination with 5 mg Cannabichromene (CBC). There were also no significant differences in effect between 15mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15mg CBD and 15mg CBN. Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.

Cannabidiol usage, efficacy, and side effects: analyzing the impact of health conditions, medications, and cannabis use in a cross-sectional online pilot study

“…The exact mechanisms underlying the impact of CBD on the body remain unclear; however, they interact with serotonin receptors and modulate CB1 receptor activation, potentially influencing anxiety-related brain structures ( 4 , 24 ). The results regarding the effects of CBD on sleep are inconsistent, with studies showing varied outcomes ( 25 , 26 , preprint; 27 , 28 ). Notably, lower CBD doses (18–25 mg) demonstrated positive effects on anxiety and sleep in retrospective studies and individual patient case reports ( 29 , 30 ).…”

The effects of a brand-specific, hemp-derived cannabidiol product on physiological, biochemical, and psychometric outcomes in healthy adults: a double-blind, randomized clinical trial

“…Further, there appears to be a dose-response effect of CBD supplementation on sleep, with higher doses inducing a sedative effect and lower doses promoting alertness [ 23 ]. In a study investigating the impact of CBD on sleep among adults with sleep disturbances, more than half of the 1,793 participants improved sleep quality following the administration of 15 mg CBD over five weeks [ 24 ]. Several studies have demonstrated the sedative effects of CBD in clinical populations, however, more evidence is needed in healthy populations.…”