Key findings
In a randomized, double-blind, placebo-controlled trial of 1,020 adults, nightly TruCBN™ softgels at 25, 50 and 100 mg of cannabinol (CBN) each improved sleep more than placebo over the six-week study. To the authors’ knowledge, it is the first study of its size to show that highly purified CBN isolate formulations are effective.
Every TruCBN™ dose improved sleep more than placebo. PROMIS Sleep Disturbance scores fell faster with 25 mg (p = 0.030), 50 mg (p = 0.018) and 100 mg CBN (p = 0.023) than with placebo.
50 mg had the largest effect of any arm. Sleep disturbance fell 0.60 points per study week faster than placebo with 50 mg, slightly ahead of 4 mg melatonin at 0.56. The differences between the active arms were small.
CBN performed on par with melatonin. No CBN dose differed significantly from 4 mg melatonin on sleep quality.
Side effects were no more common than with placebo. None were serious or needed medical care. The most common was grogginess or drowsiness, reported by 22 participants across all five arms.
The design was large, balanced and blinded. About 200 adults per arm were randomized 1:1:1:1:1, and participants, data collectors and analysts did not know assignments until the end. An independent lab tested every product for potency and contaminants.
Peer-reviewed and registered. The trial was registered on ClinicalTrials.gov (NCT05511818), approved by Sterling Institutional Review Board and published in Pharmaceuticals in 2024.
How the trial worked
Adults across the United States who wanted better sleep were randomly assigned to one of five softgels: TruCBN™ at 25, 50 or 100 mg of CBN, 4 mg melatonin as an active comparator, or placebo. Assignment was 1:1:1:1:1 and stratified by sex at birth.
The trial was fully decentralized. Participants enrolled online, received their product at home and completed every survey on a phone or computer. They took one softgel 1–2 hours before bed and were asked to confirm the ID code printed on their product.
Blinding. Participants and the people who collected and analyzed the data did not know who received which product until the study ended.
Who could join. Adults 21 or older living in the US who wanted better sleep and ranked it as a main reason for taking a supplement. People who were pregnant or breastfeeding, or taking medications that could interact with the study ingredients, were excluded.
Five arms, about 200 adults each
All five products were softgels. Samples from each arm were sent to an independent lab and tested for potency, the active ingredient and contaminants.
Six assessments over six weeks
Baseline
Sleep and health surveys before any product
One softgel nightly for 4 weeks
Weekly sleep and health surveys with side-effect reporting; the fifth came one week after the last softgel
Unblinding
Participants learned which product they took only after the study ended
Measures
| Measure | What it assesses | Scoring | Role |
|---|---|---|---|
| PROMIS Sleep Disturbance 8a | Sleep quality and disturbance over the past 7 days; 8 items | 8–40; higher means worse sleep | Primary outcome |
| PROMIS Anxiety 4a and Stress 4a | How often anxiety or stress symptoms occurred in the past 7 days | 4–20; higher is worse | Exploratory |
| PEG scale | Pain intensity and interference with enjoyment and activity | 0–10; higher is worse | Exploratory |
| WHO-5 Well-Being Index | Overall well-being in the past 7 days | Higher is better | Exploratory |
| Side-effect reports | Any unwanted effect, graded for severity | Type and severity | Safety |
Who participated
Participants were adults in their early 40s on average, slightly more women than men, and all wanted to sleep better. The five groups were closely matched before treatment began.
| At baseline | 25 mg CBN | 50 mg CBN | 100 mg CBN | Melatonin | Placebo |
|---|---|---|---|---|---|
| Randomized | 206 | 205 | 203 | 202 | 204 |
| Age, mean (years) | 43.2 | 44.0 | 43.1 | 43.3 | 42.7 |
| Female | 54% | 54% | 54% | 54% | 54% |
| BMI, mean | 29.9 | 30.2 | 30.1 | 31.1 | 31.3 |
| Sleep disturbance score, mean (8–40) | 29.9 | 30.0 | 30.5 | 29.4 | 29.3 |
From Table 1 of the published paper. None of these characteristics differed significantly between arms. Overall, 80% of participants were White and about 9% Hispanic or Latino.
Follow-up. About 74% of participants completed at least one follow-up survey. Dropout was well below the 45% the researchers planned for when they set the sample size, which was sized to give 85% power to detect a medium effect against placebo.
Every TruCBN™ dose improved sleep more than placebo
The primary outcome was the PROMIS Sleep Disturbance 8a score, measured weekly. Sleep disturbance fell faster in all three CBN arms and the melatonin arm than in the placebo arm.
How much faster sleep disturbance fell than with placebo
Points per study week by which the sleep-disturbance score (8–40 scale) fell faster than in the placebo arm. These are the treatment-by-week coefficients from the paper’s mixed-effects model, adjusted for sex, age, race, ethnicity, BMI and education.
| Arm vs placebo | Coefficient (β) | Standard error | p-value |
|---|---|---|---|
| TruCBN™ 25 mg | −0.544 | 0.250 | 0.030 |
| TruCBN™ 50 mg | −0.603 | 0.254 | 0.018 |
| TruCBN™ 100 mg | −0.566 | 0.249 | 0.023 |
| Melatonin 4 mg | −0.564 | 0.258 | 0.029 |
A negative coefficient means sleep disturbance fell faster than with placebo. Source: Table 2 of the published paper.
CBN performed on par with melatonin
Melatonin is one of the most widely used sleep supplements, so the trial included 4 mg melatonin as an active comparator. After correcting for multiple comparisons, no TruCBN™ dose differed significantly from melatonin on sleep.
Head-to-head comparisons on sleep disturbance
Post hoc pairwise comparisons with Bonferroni correction, as reported in the published paper.
Side effects were no more common than with placebo
Participants reported any unwanted effects each week. Across the five arms, the frequency of side effects did not differ significantly between placebo and the active products (χ² = 8.58, p = 0.073).
Most-reported side effects
Number of participants reporting each effect, across all five arms including placebo. Every other side effect was reported by three or fewer people.
A safe, effective option for better sleep
In this randomized, double-blind, placebo-controlled trial of 1,020 adults, TruCBN™ softgels containing 25, 50 or 100 mg of CBN each improved sleep more than placebo over the six-week study, with no significant difference from 4 mg melatonin.
Side effects were uncommon, none were serious, and their frequency did not differ from placebo. The authors concluded that oral CBN at these doses may be a safe and effective option for improving sleep.
A later real-world study of TruCBN™ 50 mg in 417 adults found sleep improvements in line with this trial. See the real-world study.
Questions about the trial
What did the TruCBN™ randomized controlled trial find?
In a randomized, double-blind, placebo-controlled trial of 1,020 adults, TruCBN™ softgels containing 25, 50 or 100 mg of cannabinol (CBN) each improved sleep more than placebo on the PROMIS Sleep Disturbance 8a scale (p = 0.030, 0.018 and 0.023). No CBN dose differed significantly from 4 mg melatonin, and side effects were no more common than with placebo.
How was the trial designed?
It was a five-arm, randomized, double-blind, placebo-controlled, decentralized trial. Adults were assigned 1:1:1:1:1, stratified by sex at birth, to TruCBN™ 25 mg, 50 mg or 100 mg CBN, 4 mg melatonin or placebo. They took one softgel 1–2 hours before bed and completed a baseline survey and five weekly surveys online. Participants and the people who collected and analyzed the data were blinded until the study ended.
How many people took part?
1,020 adults were randomized: 206 to 25 mg CBN, 205 to 50 mg CBN, 203 to 100 mg CBN, 202 to 4 mg melatonin and 204 to placebo. Participants averaged about 43 years old, 54% were female, and the five groups were closely matched at baseline.
Which TruCBN™ dose worked best?
All three doses improved sleep more than placebo. The 50 mg dose had the largest effect of any arm, with sleep disturbance falling 0.60 points per study week faster than placebo (p = 0.018), compared with 0.54 for 25 mg, 0.57 for 100 mg and 0.56 for melatonin. Differences between the active arms were small.
How did CBN compare with melatonin?
The trial included 4 mg melatonin as an active comparator. After correcting for multiple comparisons, none of the three TruCBN™ CBN doses differed significantly from melatonin on sleep quality.
Was TruCBN™ well tolerated?
Yes. Side-effect frequency did not differ significantly between placebo and the active products (χ² = 8.58, p = 0.073). No side effects were serious or required medical care. The most common, counted across all five arms, were grogginess or drowsiness (22 participants), trouble falling or staying asleep (10) and headache (10).
Where was the trial published?
The trial was published in the peer-reviewed journal Pharmaceuticals in July 2024 (volume 17, issue 8, article 977; doi:10.3390/ph17080977). It was registered on ClinicalTrials.gov as NCT05511818 and approved by Sterling Institutional Review Board.
Who funded and ran the trial?
FloraWorks, the maker of TruCBN™, funded data collection. Radicle Science conducted the trial. The authors are from Radicle Science, the University of California, Los Angeles, the University of Maryland School of Medicine and the University of Pittsburgh.
Is there real-world evidence for TruCBN™ as well?
Yes. In a separate real-world study, 417 adults took TruCBN™ 50 mg nightly for 28 days. Insomnia severity fell by 5.8 points on average, and the rate of improvement on PROMIS Sleep Disturbance was in line with the TruCBN™ arms of this randomized trial.
References
- Kolobaric A, Saleska J, Hewlings SJ, Bryant C, Colwell CS, D’Adamo CR, Chen J, Pauli EK. A randomized, double-blind, placebo-controlled trial to assess the effectiveness and safety of melatonin and three formulations of Floraworks proprietary TruCBN™ for improving sleep. Pharmaceuticals (Basel). 2024;17(8):977. doi:10.3390/ph17080977
- ClinicalTrials.gov identifier NCT05511818. View the registration
- Buysse DJ, Yu L, Moul DE, et al. Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments. Sleep. 2010;33(6):781–792.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. Anyone who is pregnant, nursing or taking medication should consult a physician before use.