The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial

Saleska, Jessica Londeree; Bryant, Corey; Kolobaric, Antonija; D’Adamo, Christopher R.; Colwell, Christopher S.; Loewy, Derek; Chen, Jeff; Pauli, Emily K.

doi:10.1080/27697061.2023.2203221

Cited by 7 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 We recently published the results of a similar sleep study on 1793 adults. 23 Participants were randomly assigned to take 1 of 6 products, containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids, including CBN. Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality though not statistically better than the active control group that took 5 mg of melatonin alone.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Kolobaric,

Saleska,

Hewlings

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Introduction: Prescription sleep aids often have side effects, making alternative solutions necessary. Melatonin is an efficacious sleep aid and is often the comparator for alternatives. The phytocannabinoid cannabinol (CBN), has a potential mechanism of action but minimal evidence to support its effectiveness. Methods: TruCBN™ is a hemp-derived cannabinol (CBN) sleep aid. The primary aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of TruCBN™ [25 mg (n=206), 50 mg (n=205), 100 mg (n=203)], on sleep quality measured by PROMIS Sleep Disturbance 8A scale, relative to placebo (n=204). As a secondary aim, the effectiveness and safety of these formulations relative to a 4 mg melatonin (n=202) were assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG) and well-being (WHO 5). Results: All treatment groups (25, 50 and 100 mg TruCBN™) and the 4 mg melatonin group experienced significant improvement in sleep quality relative to placebo. There were no significant differences between any of the TruCBN™ groups and melatonin for improving sleep. Participants taking 100 mg TruCBN™ showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being or frequency of side effects between any TruCBN™ group and placebo. There was no significant difference in improvements in sleep quality between any of the treatment groups and 4mg melatonin. Discussion: Orally ingested TruCBN™, 25 mg, 50 mg and 100 mg, is a safe and effective alternative for the improvement of sleep.Sterling Institutional Review Board (SIRB) approved the study [10147-EKPauli]. The study was registered onClinicalTrials.gov[NCT05511818] on August 21, 2023.

show abstract

Section: Discussionmentioning

confidence: 99%

“…This research process has been successfully implemented for several other dietary supplement clinical trials. 22,23…”

Section: Methodsmentioning

confidence: 99%

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

Kolobaric,

Saleska,

Hewlings

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, subjects receiving a tablet containing 10 mg THC and 5 mg CBN nightly experienced significantly improved sleep quality and slept significantly longer, with a 5% increase in sleep duration [12]. We recently published the results of a similar sleep study on 1793 adults [37]. Participants were randomly assigned to take 1 of 6 products, containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids, including CBN.…”

Section: Discussionmentioning

confidence: 99%

A randomized, double-blind, placebo-controlled decentralized trial to assess sleep, health outcomes, and overall well-being in healthy adults reporting disturbed sleep, taking a melatonin-free supplement

Kolobaric,

Hewlings,

Bryant

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Objectives: Inadequate sleep increases the risk for health complications and has become a global health concern. Sleep is multidimensional and complex; sedative hypnotic drugs are commonly used, but not always tolerated. New treatments are needed and multi-ingredient agents, targeting different systems, may be a potential solution. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Methods: Adults (N=620) with a primary health concern for better sleep were randomly assigned to receive 1 of 3 study products (Sleep A, Sleep B or placebo) for 4 weeks. Both active products contained federally legal hemp-derived cannabinoids, botanical oils, GABA and L-theanine. Sleep disturbance (primary outcome) was assessed at baseline and weekly using NIH’s Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Other health outcomes (anxiety, stress, pain, and well-being) were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in each health outcome score between each active product group and the placebo. Results: There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. Conclusions: A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.

show abstract

“…Unfortunately, given that CBN represented a small fraction of the cannabinoids present in the formulation, its contribution with respect to any of the observed effects is unknown. Saleska et al (2023) conducted a six-arm randomized doubleblind study of multiple cannabinoid combinations with and without melatonin on a sample of individuals reporting symptoms of sleep disturbance. Participants were randomized 1:1:1:1:1:1 to receive capsules containing either (a) 15 mg CBD + 15 mg CBN + 5 mg melatonin; (b) 15 mg CBD + 15 mg CBN; (c) 15 mg CBD; (d) 5 mg melatonin; (e) 15 mg full-spectrum CBD + 15 mg CBN; or (f) 15 mg full-spectrum CBD + 15 mg CBN + 5 mg cannabichromene.…”

mentioning

confidence: 99%

“…Four studies have examined the impact of CBN on human sleep (Gannon et al, 2021; Kaufmann, 2021; Saleska et al, 2023; Walsh et al, 2021). Of the four studies that have been conducted, three tested proprietary formulations, only one of which was placebo controlled.…”

mentioning

confidence: 99%

A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality.

Bonn-Miller,

Feldner,

Bynion

et al. 2024

Experimental and Clinical Psychopharmacology

View full text Add to dashboard Cite

The present study sought to determine the effects of cannabinol (CBN) alone and in combination with cannabidiol (CBD) on sleep quality. This was a double-blind, randomized, placebo-controlled study conducted between May and November 2022. Participants were randomized to receive either (a) placebo, (b) 20 mg CBN, (c) 20 mg CBN + 10 mg CBD, (d) 20 mg CBN + 20 mg CBD, or (e) 20 mg CBN + 100 mg CBD for seven consecutive nights. Participants were 18-55 years of age who self-rated sleep quality as "very poor" or "poor." The primary endpoint was sleep quality, while secondary endpoints included sleep onset latency, number of awakenings, wake after sleep onset (WASO), overall sleep disturbance, and daytime fatigue. In a modified intent-to-treat analyses (N = 293), compared to placebo, 20 mg CBN demonstrated a nonsignificant but potentially meaningful effect on sleep quality (OR [95% CI] = 2.26 [0.93, 5.52], p = .082) and significantly reduced number of awakenings (95% CI [−0.96, −0.05], p = .025) and overall sleep disturbance (95% CI [−2.59, −0.14], p = .023). There was no difference from placebo among any group for sleep onset latency, WASO, or daytime fatigue (all p > .05). Individuals receiving 20 mg CBN demonstrated reduced nighttime awakenings and overall sleep disturbance relative to placebo, with no impact on daytime fatigue. The addition of CBD did not positively augment CBN treatment effects. No differences were observed for latency to sleep onset or WASO. Findings suggest 20 mg of CBN taken nightly may be helpful for improving overall sleep disturbance, including the number of times one wakes up throughout the night, without impacting daytime fatigue. Public Health SignificanceThe present study serves as the first placebo-controlled study of CBN for sleep. This study demonstrated that 20 mg CBN was effective in improving several aspects of sleep, including nighttime awakenings and overall sleep disturbance, without impacting daytime fatigue. Adding CBD to CBN did not appear to positively augment the effects of CBN alone.

show abstract

The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial

Cited by 7 publications

References 42 publications

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

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

A randomized, double-blind, placebo-controlled decentralized trial to assess sleep, health outcomes, and overall well-being in healthy adults reporting disturbed sleep, taking a melatonin-free supplement

A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality.

Contact Info

Product

Resources

About