scholarly journals Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) for chronic insomnia disorder (‘CANSLEEP’ trial): protocol for a randomised, placebo-controlled, double-blinded, proof-of-concept trial

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e034421 ◽  
Author(s):  
Anastasia Suraev ◽  
Ronald R Grunstein ◽  
Nathaniel S Marshall ◽  
Angela L D'Rozario ◽  
Christopher J Gordon ◽  
...  
Keyword(s):  
Single Dose ◽  
Brain Mri ◽  
Sleep Onset ◽  
Healthcare Utilisation ◽  
Open Access Journal ◽  
Chronic Insomnia ◽  
Proof Of Concept ◽  
Single Dose Study ◽  
Insomnia Disorder ◽  
Daytime Function

IntroductionInsomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.Methods and analysisA randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.Ethics and disseminationEthics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.Trial registration numberANZCTRN12619000714189.

scholarly journals Insomnia – A Heterogenic Disorder Often Comorbid With Psychological and Somatic Disorders and Diseases: A Narrative Review With Focus on Diagnostic and Treatment Challenges

2021 ◽  
Vol 12 ◽  
Author(s):  
Bjørn Bjorvatn ◽  
Susanna Jernelöv ◽  
Ståle Pallesen
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Sleep Disorder ◽  
Sleep Onset ◽  
Chronic Insomnia ◽  
Diagnostic Challenge ◽  
Insomnia Disorder ◽  
Obstructive Sleep ◽  
Somatic Disorders ◽  
Insomnia Symptoms

Patients with insomnia complain of problems with sleep onset or sleep maintenance or early morning awakenings, or a combination of these, despite adequate opportunity and circumstances for sleep. In addition, to fulfill the diagnostic criteria for insomnia the complaints need to be associated with negative daytime consequences. For chronic insomnia, the symptoms are required to be present at least 3 days per week for a duration of at least 3 months. Lastly, for insomnia to be defined as a disorder, the sleep complaints and daytime symptoms should not be better explained by another sleep disorder. This criterion represents a diagnostic challenge, since patients suffering from other sleep disorders often complain of insomnia symptoms. For instance, insomnia symptoms are common in e.g., obstructive sleep apnea and circadian rhythm sleep-wake disorders. It may sometimes be difficult to disentangle whether the patient suffers from insomnia disorder or whether the insomnia symptoms are purely due to another sleep disorder. Furthermore, insomnia disorder may be comorbid with other sleep disorders in some patients, e.g., comorbid insomnia and sleep apnea (COMISA). In addition, insomnia disorder is often comorbid with psychological or somatic disorders and diseases. Thus, a thorough assessment is necessary for correct diagnostics. For chronic insomnia disorder, treatment-of-choice is cognitive behavioral therapy, and such treatment is also effective when the insomnia disorder appears comorbid with other diagnoses. Furthermore, studies suggest that insomnia is a heterogenic disorder with many different phenotypes or subtypes. Different insomnia subtypes may respond differently to treatment, but more research on this issue is warranted. Also, the role of comorbidity on treatment outcome is understudied. This review is part of a Research Topic on insomnia launched by Frontiers and focuses on diagnostic and treatment challenges of the disorder. The review aims to stimulate to more research into the bidirectional associations and interactions between insomnia disorder and other sleep, psychological, and somatic disorders/diseases.

A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women

SLEEP ◽  
2022 ◽  
Author(s):  
Shadab A Rahman ◽  
Margo D Nathan ◽  
Aleta Wiley ◽  
Sybil Crawford ◽  
Aviva Y Cohn ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Controlled Trial ◽  
Sleep Onset ◽  
Estrogen Therapy ◽  
Severity Index ◽  
Vasomotor Symptom ◽  
Midlife Women ◽  
Chronic Insomnia ◽  
Double Blind ◽  
Insomnia Disorder

Abstract Study Objectives The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. Methods In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 minutes of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n=27) or placebo (n=29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. Results Mean baseline ISI scores were 18.1 (95% CI, 16.8-19.4) and 18.3 (95% CI, 17.2-19.5) in the suvorexant and placebo groups, respectively (p=0.81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant [-8.1 (95% CI, -10.2 to -6.0)] compared to placebo [-5.6 (95% CI, -7.4 to -3.9), p=0.04]. Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p<0.01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparison. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. Conclusion These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia.

Toxicological evaluation of xanthan gum based hydrogel formulation in Wistar rats using single dose study

2020 ◽  
Vol 77 (2) ◽  
pp. 353-360
Author(s):  
Nadia Malik ◽  
Mahmood Ahmad ◽  
Muhammad Minhas ◽  
Ruqia Tulain ◽  
Ikrima Khalid ◽  
...  
Keyword(s):  
Single Dose ◽  
Xanthan Gum ◽  
Wistar Rats ◽  
Toxicological Evaluation ◽  
Single Dose Study ◽  
Dose Study ◽  
Hydrogel Formulation

scholarly journals A phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover, single-dose clinical trial of a new class of bronchodilator for acute asthma

Trials ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Veronica Swystun ◽  
Francis H. Y. Green ◽  
John H. Dennis ◽  
Emmanouil Rampakakis ◽  
Gurkeet Lalli ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Single Dose ◽  
Acute Asthma ◽  
Proof Of Concept ◽  
Double Blind ◽  
New Class

324 Naturalistic Characterization of Sleep in Chronic Insomnia Using a Non-Contact Sleep Measurement Device

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A130-A130
Author(s):  
Devon Hansen ◽  
Mary Peterson ◽  
Roy Raymann ◽  
Hans Van Dongen ◽  
Nathaniel Watson
Keyword(s):  
Sleep Onset ◽  
Contact Device ◽  
Chronic Insomnia ◽  
Poor Sleep ◽  
Measurement Device ◽  
Home Setting ◽  
Time In Bed ◽  
Sleep Measurement ◽  
Measurement Devices

Abstract Introduction Individuals with insomnia report poor sleep quality and non-restorative sleep, and often exhibit irregular sleep patterns over days and weeks. First night effects and logistical challenges make it difficult to measure these sleep characteristics in the laboratory. Also, sensitivity to sleep disruption from obtrusive measurement devices confounds sleep measurements in people with insomnia in their naturalistic setting. Non-contact sleep measurement devices have the potential to address these issues and enable ecologically valid, longitudinal characterization of sleep in individuals with insomnia. Here we use a non-contact device – the SleepScore Max (SleepScore Labs) – to assess the sleep of individuals with chronic insomnia, compared to healthy sleeper controls, in their home setting. Methods As part of a larger study, 13 individuals with chronic insomnia (ages 25-60y, 7 males) and 8 healthy sleeper controls (ages 21-46y, 6 females) participated in an at-home sleep monitoring study. Enrollment criteria included an age range of 18-65y and, for the insomnia group, ICSD-3 criteria for chronic insomnia with no other clinically relevant illness. Participants used the non-contact sleep measurement device to record their sleep periods each night for 8 weeks. Sleep measurements were analyzed for group differences in both means (characterizing sleep overall) and within-subject standard deviations (characterizing sleep variability across nights), using mixed-effects regression controlling for systematic between-subject differences. Results Based on the non-contact sleep measurements, individuals with chronic insomnia exhibited greater variability in bedtime, time in bed, total sleep time, sleep latency, total wake time across time in bed, wakefulness after sleep onset, sleep interruptions, and estimated light sleep, compared to healthy sleeper controls (all F>5.7, P<0.05). No significant differences were found for group averages and for variability in estimated deep and REM sleep. Conclusion In this group of individuals with chronic insomnia, a non-contact device used to characterize sleep naturalistically captured enhanced variability across nights in multiple aspects of sleep stereotypical of sleep disturbances in chronic insomnia, differentiating the sample statistically significantly from healthy sleeper controls. Support (if any) NIH grant KL2TR002317; research devices provided by SleepScore Labs.

818 A Ghost from the Past: Unmasked Insomnia Affecting Hypoglossal Nerve Stimulation Therapy Adherence

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A319-A320
Author(s):  
Elena Stuewe ◽  
Aarti Grover ◽  
Peter Ostrow ◽  
Greg Schumaker ◽  
Joel Oster ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Hypoglossal Nerve ◽  
Sleep Onset ◽  
Chronic Insomnia ◽  
Apnea Hypopnea Index ◽  
Therapy Adherence ◽  
Hypoglossal Nerve Stimulation ◽  
Obstructive Sleep ◽  
Patient Reported ◽  
History Of

Abstract Introduction Hypoglossal nerve stimulation (HNS) is an efficacious option for treating moderate to severe obstructive sleep apnea (OSA). However, there is sparse evidence regarding tolerance and adherence to HNS therapy in patients with a diagnosis of insomnia. Report of case(s) A 57-year-old man with well-controlled depression presented for evaluation for HNS therapy. He had been diagnosed with moderate OSA with an apnea-hypopnea index of 22/hour, intolerant of continuous positive airway pressure and mandibular advancement device. He underwent uvulopalatopharyngoplasty without significant improvement. At the time of initial evaluation, he denied history of insomnia and prior sleep aid use. He subsequently underwent successful HNS device implantation and activation. One week after HNS initiation, the patient reported new symptoms of significant difficulty with sleep onset and inability to fall back asleep, which was worse than his untreated OSA symptoms. Device interrogation did not reveal any hardware problems. Adjustments to start delay, pause time and device configuration with awake endoscopy did not improve tolerance. Subsequently, the patient disclosed a remote history of insomnia, which was treated with multiple hypnotics in addition to cognitive-behavioral therapy for insomnia (CBTi) and had resolved. He was diagnosed with recurrent chronic insomnia, for which eszopiclone was initiated without significant improvement. He eventually agreed to CBTi, with partial improvement in device tolerance and improvement in insomnia symptoms. Conclusion This case highlights that HNS therapy adherence can be affected by prior history of, or a current diagnosis of insomnia. Our patient had a predisposition for insomnia that was well controlled prior to HNS therapy initiation. The onset of recurrent insomnia with HNS activation suggests that HNS was a precipitating factor for his now chronic insomnia. Although there is insufficient evidence to suggest whether history of insomnia should affect the decision to initiate HNS therapy, this case illustrates the importance of screening for insomnia at pre-implant evaluation. Our center is now routinely screening for a history of insomnia to identify patients who may benefit from treatment prior to HNS implantation. Larger studies are needed to explore a possible relationship between insomnia and HNS adherence. Support (if any):

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