Overview

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?

Eligibility

List the inclusion criteria:

• Age 18-25 years
• Physically and psychiatrically healthy, as determined by instruments described below
• Cannabis-Using group only: Regular cannabis use, defined as "frequent" (6-29 days/month) or "daily" (daily) use over the past 3 months
• Cannabis-Using group only: Willingness to discontinue cannabis for 4 weeks.
• Control group only: No cannabis use in the past 3 months. Deny engaging in daily or near-daily cannabis use during the past year. No history of alcohol and/or substance use disorders. No current sleep disorders (including insomnia and delayed sleep phase disorder).
• Provision of written informed consent

List the exclusion criteria:

• Significant or unstable acute or chronic medical conditions. Examples of such conditions include, but are not limited to, central nervous system disorders (e.g., head injury, seizure disorder, multiple sclerosis, tumor), cardiovascular or hemodynamically significant cardiac disease, liver disease (e.g., acute or chronic hepatitis, hepatic insufficiency), migraine or chronic headaches, active peptic ulcer disease, inflammatory bowel disease, renal failure, arthritis, and diabetes and other endocrine disorders. Seizure disorder in particular will be exclusionary due to the increased risk it confers for cannabis withdrawal symptoms. Eye/retinal conditions such as diabetic retinopathy or glaucoma will be exclusionary, although should be very rare in this population. Individuals with well-controlled health conditions that do not affect sleep, retinal function, and/or well-being (e.g., well-controlled thyroid disorders, asthma, or ulcer) will not be excluded. To evaluate these criteria, potential participants will complete a locally-developed Medical History Questionnaire.
• Past or current DSM-5 bipolar disorder or psychotic disorders. Psychiatric disorders will be evaluated using the Mini International Neuropsychiatric Interview (MINI) and the WHO-DAS 2.0, supplemented by clinical interview. We will not exclude participants for subsyndromal symptoms or disorders in these domains. We will not exclude participants for other psychiatric disorders, particularly given the high comorbidity between cannabis use disorder and major depression and anxiety disorder, as long as severity is in the moderate range or lower based on the WHO-DAS 2.0 (average score <4).
• Daily use of alcohol; regular use of illicit substances. Regular use (as defined above) of illicit substances other than cannabis over the past 3 months will be exclusionary. Substance use will be assessed using the Timeline Follow Back method, as well as a urine drug screen.
• Past or current substance use disorders other than cannabis use disorder and nicotine use disorder.
• Current syndromal sleep disorders other than insomnia and delayed sleep phase disorder, including narcolepsy, restless legs syndrome, obstructive sleep apnea, and current night shift work (i.e., any work occurring between the hours of midnight and 6:00 a.m.). We will not exclude for subsyndromal symptoms or disorders in these domains. We will not exclude Cannabis-using participants for insomnia and delayed sleep phase disorder because of their conceptual overlap and high co-occurrence with sleep phenotypes of interest. Sleep disorders will be diagnosed according to criteria in the DSM-5 and the International Classification of Sleep Disorders, 3rd Edition, 2014. These disorders will be evaluated using clinical interview and the locally-developed Structured Clinical Interview for Sleep Disorders. Control participants will be excluded for any current sleep disorders, including insomnia and delayed sleep phase disorder.
• Travel across 2+ time zones in the past 60 days.
• Benzodiazepines and non-benzodiazepine hypnotic drugs ("Z-drugs"). Other sleep-promoting medications will be permitted, including SSRIs/SNRIs, will be permitted if on stable dose and not in the acute phase of treatment. In order to evaluate medications, participants will complete a listing of current medications, including prescription and over the counter medications, "natural" preparations, and nutritional supplements.
• Individuals with a Pennsylvania Medical Marijuana Card using dispensary-obtained marijuana or other THC products for documented Qualifying Medical Conditions other than those of a mental health nature will be excluded. However, individuals who have been issued a Pennsylvania Medical Marijuana ID card for a mental health condition will not be excluded from the study.

There will not be any Medical Record review. For most individuals, the Medical History Questionnaire, including medical conditions and medications, will be sufficient for identifying exclusionary medical criteria. For instances where an individual is uncertain about exclusionary or current medical conditions or medications, medical records, prescription records or labeled prescription pill bottles, or a Release of Information to contact the individual's Primary Care Practitioner [PCP] to clarify the individual's medical status will be obtained.