Cannabis Discontinuation for Sleep and Circadian Rhythm

(CASCILS Trial)

Overseen By Brant P Hasler, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Benzodiazepines, Z-drugs

Disqualifiers: CNS disorders, Cardiovascular disease, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it allows certain sleep-promoting medications if you are on a stable dose and not in the acute phase of treatment. Benzodiazepines and non-benzodiazepine hypnotic drugs are not allowed.

What data supports the effectiveness of the drug Cannabis for improving sleep and circadian rhythm?

Research shows that cannabis is increasingly used by cancer survivors to manage sleep issues, suggesting it may help improve sleep quality. However, the studies focus on cancer patients, and more research is needed to confirm its effectiveness for sleep and circadian rhythm in other contexts. ^{1 2 3 4 5}

Is cannabis safe for use in humans, particularly for sleep and circadian rhythm issues?

Research on cannabis, including THC and CBD, shows mixed safety results. Some studies suggest that THC can cause increased sleepiness and mood changes, while CBD does not significantly alter sleep patterns in healthy people. More research is needed to fully understand the safety of cannabis for sleep disorders. ^{6 7 8 9 10}

How does the drug cannabis differ from other treatments for sleep and circadian rhythm issues?

Cannabis, particularly its component cannabidiol (CBD), is unique because it affects the regulation of circadian genes in microglial cells, which are involved in the brain's immune response. Unlike traditional sleep medications, CBD can influence the sleep-wake cycle by altering specific brain areas related to wakefulness, although it does not significantly change normal sleep patterns in healthy individuals. ^{7 11 12 13 14}

What is the purpose of this trial?

The goal of this study is to learn how cannabis use and discontinuation affect sleep, circadian rhythms, and sensitivity to light. The main questions it aims to answer are: 1. Does cannabis use and discontinuation impact sleep drive? 2. Does cannabis use and discontinuation impact light sensitivity and circadian phase?

Research Team

Brant P Hasler, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for young adults who regularly use cannabis and may experience issues with sleep, their body's internal clock (circadian rhythm), or sensitivity to light. Participants should be interested in stopping cannabis use temporarily for the study.

Inclusion Criteria

Provision of written informed consent

Cannabis-Using group only: Willingness to discontinue cannabis for 4 weeks

I am in good physical and mental health.

Exclusion Criteria

I do not have any severe or unstable health conditions affecting my heart, brain, liver, kidneys, stomach, or hormones.

I have an eye condition like diabetic retinopathy or glaucoma.

Past or current DSM-5 bipolar disorder or psychotic disorders

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline

Participants undergo a 1-week baseline period with at-home monitoring using sleep diaries, actigraphy, and EEG headband

1 week

At-home monitoring

Lab Assessment

Participants undergo a 2-night lab visit for circadian phase and light sensitivity assessment

2 nights

2 visits (in-person)

Cannabis Discontinuation

Cannabis-using participants undergo a 4-week cannabis discontinuation protocol

4 weeks

Post-Discontinuation Lab Assessment

Cannabis-using participants undergo a second 2-night lab visit after the discontinuation protocol

2 nights

2 visits (in-person)

Follow-up

Participants are monitored for changes in sleep, circadian rhythms, and light sensitivity after the discontinuation protocol

4 weeks

Treatment Details

Interventions

• Cannabis

Trial Overview The study is looking at how not using cannabis might change a person's sleep patterns, natural daily rhythms, and reaction to light. It will check if quitting affects how sleepy they feel or alters their sensitivity to light over time.

Participant Groups

Group I: Cannabis-Using Experimental Treatment 1 Intervention

The cannabis-using arm will consist of 60 young people reporting regular cannabis use. Participants will complete a 1-week baseline protocol followed by a 4-week cannabis discontinuation protocol (intervention).

Group II: Control Active Control 1 Intervention

The control arm will consist of 30 young people without current cannabis use. Participants will complete a 1-week baseline protocol. No intervention will be administered.

Cannabis is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy

Approved in European Union as Cannabis for:

• Spasticity associated with multiple sclerosis
• Chronic pain

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a survey of 1464 Canadian cancer survivors, 23.5% reported using cannabis as a sleep aid, experiencing benefits like improved sleep quality and reduced time to fall asleep.

Most users (68.3%) started using cannabis for sleep after their cancer diagnosis, highlighting the need for further research to evaluate the efficacy of cannabis in managing sleep issues among cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-sectional survey of the prevalence and patterns of using cannabis as a sleep aid in Canadian cancer survivors. Lee, RM., Donnan, J., Harris, N., et al.[2023]

In a study of 84 patients with advanced lung cancer, actigraphy revealed significantly disturbed sleep patterns and poorer sleep quality compared to healthy individuals, highlighting the impact of cancer on circadian rhythms.

The strong correlation between actigraphic measurements and self-reported sleep quality suggests that using actigraphy can provide objective insights into sleep issues in cancer patients, indicating that enhancing circadian function may lead to better sleep outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of actigraphy to assess circadian organization and sleep quality in patients with advanced lung cancer. Grutsch, JF., Wood, PA., Du-Quiton, J., et al.[2021]

Disruptions in sleep and circadian rhythms are common in children with cancer and can lead to negative health outcomes, including poor immune function and lower survival rates, indicating that these issues should not be dismissed as temporary side effects of treatment.

There is a need for increased research and clinical focus on sleep and circadian rhythm assessments in pediatric cancer care, as interventions that improve sleep in non-cancer populations may also be effective for children with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A call to action for expanded sleep research in pediatric oncology: A position paper on behalf of the International Psycho-Oncology Society Pediatrics Special Interest Group. Daniel, LC., van Litsenburg, RRL., Rogers, VE., et al.[2022]

Daily exposure to bright white light (BWL) significantly improved nighttime sleep and reduced sleep disturbances in women undergoing chemotherapy for breast cancer, compared to those exposed to dim red light (DRL).

The BWL group showed a healthier circadian pattern with more daytime activity and less nighttime activity by the end of the chemotherapy cycle, suggesting that morning light therapy may help maintain sleep quality during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing Sleep Disruption With Bright Light Therapy During Chemotherapy for Breast Cancer: A Phase II Randomized Controlled Trial. Rissling, M., Liu, L., Youngstedt, SD., et al.[2022]

Cancer-related fatigue may be linked to disrupted sleep and irregular sleep/wake cycles, suggesting that improving sleep quality could help alleviate daytime fatigue in cancer patients.

Inadequate or unrefreshing sleep not only contributes to fatigue but also affects the overall quality of life, treatment tolerance, and may lead to mood disorders in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between fatigue and sleep in cancer patients: a review. Ancoli-Israel, S., Moore, PJ., Jones, V.[2022]

In a study involving 20 patients aged 43-96 years, a natural compound combining melatonin (1.5 mg) and CBD (2.5 mg) showed significant improvements in sleep disorders and anxiety over a 3-month treatment period, with reductions in mood alterations and pain.

The combination of CBD and melatonin not only improved sleep quality but also provided additional benefits such as antioxidant effects and reduced chronic pain perception, suggesting it could be a viable alternative to traditional synthetic sleep medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insomnia treatment: a new multitasking natural compound based on melatonin and cannabis extracts. Palmieri, G., Vadalà, M., Corazzari, V., et al.[2022]

In a study involving 27 healthy volunteers, a single clinically anxiolytic dose of 300 mg of CBD did not significantly affect the sleep-wake cycle, indicating it does not interfere with normal sleep architecture.

Unlike traditional anxiolytic medications, CBD appears to maintain the natural sleep patterns of individuals, suggesting it may be a safer alternative for anxiety management without disrupting sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Linares, IMP., Guimaraes, FS., Eckeli, A., et al.[2020]

In a study involving 8 healthy volunteers, 15 mg of THC alone did not affect nocturnal sleep, but when combined with CBD, it decreased deep sleep (stage 3) and increased wakefulness, indicating a complex interaction between THC and CBD on sleep quality.

The study found that 15 mg of THC impaired memory and increased sleepiness the following day, while lower doses of THC combined with CBD improved reaction time on memory tasks, suggesting that CBD may counteract some of the sedative effects of THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Nicholson, AN., Turner, C., Stone, BM., et al.[2019]

A systematic review of 14 preclinical and 12 clinical studies found insufficient evidence to support the routine use of cannabinoids like THC and CBD for treating sleep disorders due to moderate-to-high risk of bias in the studies.

Despite the lack of conclusive evidence, there is promising preliminary data that suggests cannabinoids may be beneficial for specific sleep disorders, highlighting the need for more rigorous and controlled trials in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies. Suraev, AS., Marshall, NS., Vandrey, R., et al.[2021]

Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, is gaining attention for its potential to treat excessive daytime sleepiness (EDS), a common sleep disorder, as an alternative to traditional medications that often have side effects.

Experimental evidence suggests that CBD may act as a wake-inducing compound, offering a novel therapeutic approach for managing EDS and improving sleep-wake cycle regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural Cannabinoids as Templates for Sleep Disturbances Treatments. Murillo-Rodríguez, E., Machado, S., Imperatori, C., et al.[2021]

Cannabidiol (CBD) significantly deregulates circadian genes in microglial cells, affecting genes like Arntl and Clock, which are crucial for maintaining the body's internal clock, with specific P-values indicating statistical significance.

Unlike THC, CBD appears to disrupt circadian rhythms in microglial cells, which may explain its effects on sleep disorders and supports clinical observations of its use in treating insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol affects circadian clock core complex and its regulation in microglia cells. Lafaye, G., Desterke, C., Marulaz, L., et al.[2023]

Acute administration of cannabidiol (CBD) at doses of 10 mg/kg and 40 mg/kg significantly increased total sleep time in adult male Wistar rats compared to a placebo, indicating its potential efficacy in enhancing sleep.

The 40 mg/kg dose of CBD also increased REM sleep latency, suggesting that higher doses may alter sleep architecture, although further research is needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. Chagas, MH., Crippa, JA., Zuardi, AW., et al.[2022]

Cannabidiol (CBD) enhances wakefulness and reduces slow wave and REM sleep when administered directly into wake-inducing brain areas, indicating its potential as a wake-inducing compound.

The study found that CBD increases specific brain wave activity (alpha and theta) while decreasing delta power, suggesting it activates neurons in the lateral hypothalamus and dorsal raphe nuclei to promote wakefulness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent. Murillo-Rodríguez, E., Millán-Aldaco, D., Palomero-Rivero, M., et al.[2013]

A single dose of 40 mg/kg of cannabidiol (CBD) significantly increased slow-wave sleep (SWS) duration and decreased wakefulness in male Wistar rats, indicating its potential efficacy in promoting sleep.

However, after 15 days of daily injections at the same dose, the rats developed tolerance to these effects, suggesting that the benefits of CBD on sleep may diminish with prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypnoticlike effects of cannabidiol in the rat. Monti, JM.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A cross-sectional survey of the prevalence and patterns of using cannabis as a sleep aid in Canadian cancer survivors. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Validation of actigraphy to assess circadian organization and sleep quality in patients with advanced lung cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A call to action for expanded sleep research in pediatric oncology: A position paper on behalf of the International Psycho-Oncology Society Pediatrics Special Interest Group. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Preventing Sleep Disruption With Bright Light Therapy During Chemotherapy for Breast Cancer: A Phase II Randomized Controlled Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The relationship between fatigue and sleep in cancer patients: a review. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Insomnia treatment: a new multitasking natural compound based on melatonin and cannabis extracts. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Natural Cannabinoids as Templates for Sleep Disturbances Treatments. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol affects circadian clock core complex and its regulation in microglia cells. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent. [2013]

14. Germany pubmed.ncbi.nlm.nih.gov

Hypnoticlike effects of cannabidiol in the rat. [2019]