A Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Effects of Various Cannabinoids on Sleep Quality

This is a double-blind, randomized, placebo-controlled study assessing the effects of different combinations of cannabinol (CBN), cannabigerol (CBG), tetrahydrocannabinol(THC), with and without cannabidiol (CBD) and melatonin, on sleep parameters and related outcomes (i.e., depression, anxiety, irritability, and perceived stress). A total of up to 375 eligible adults (aged 21-55) will complete the study. Individuals interested in this study will provide written, informed consent to participate and complete an online screening visit. People deemed ineligible during the Screening Phase will be informed they are not eligible and thanked for their time. People who appear eligible after completing the Screening Phase will complete the full Informed Consent Form. People who meet inclusion/exclusion criteria will be enrolled into one of two arms based on their responses to the sleep disturbance questionnaire completed at screening. If they endorse difficulty falling asleep, they will be enrolled in Arm A. If they endorse difficulty staying asleep, they will be enrolled in Arm B. If they endorse both symptoms, the more frequently occurring symptom will be used to enroll them into the respective arm. They will be randomized to receive active study IP or placebo in each arm.

Inclusion criteria

Participants must meet all of the following criteria to be eligible for enrollment into the study:

• Person is between 21 and 55-years-old (inclusive).
• Person has a BMI between 18 and 39 kg/m2 (inclusive).
• Person rates past-week sleep quality on a 1 (very good) to 5 (very poor) rating scale as poor (4) or very poor (5).
• For Arm A: Person rates past-week frequency of difficulty falling asleep on a 1 (not at all) to 5 (very much) rating scale as quite a bit (4) or very much (5).
• For Arm B: Person rates past-week frequency of trouble staying asleep on a 1 (never) to 5 (always) rating scales as often (4) or always (5).
• Person is willing and able to provide informed consent.
• Person agrees to abide by all study restrictions and comply with all study procedures.

Exclusion criteria

Participants meeting any of the following criteria will not be eligible for participation in the study:

• Person has a known history of significant allergic condition or significant hypersensitivity to cannabis, cannabinoid medications, hemp products, melatonin, or excipients of the IP.
• Person has been exposed to any investigational drug or device < 30 days prior to screening or plans to use an investigational drug or device during the study.
• Person has had a change in allowable medication, tobacco, alcohol, caffeine, cannabis (including individual or combination cannabinoid products), or supplement dose or regimen within 30 days of screening or has any plans to change dose or regimen during the study.
• Person has used tetrahydrocannabinol (THC; e.g., delta-9, delta-8) or cannabinol (CBN)-containing product more than four times per week during the prior 30 days of screening or during the study.
• Person has history of use of any synthetic cannabinoid receptor agonist (e.g., spice, K2) within the past year.
• Person has used illicit substances (e.g., amphetamine, cocaine, methamphetamine, MDMA, LSD, ketamine, heroin, psilocybin, salvia, prescription medications not prescribed to the person) in the past 30 days or plans to use them during the study.
• Person is currently using products or medications that may interact or overlap with one or more of the ingredients in the IP, including the following drugs or supplements: warfarin, clobazam, valproic acid, phenobarbital, mechanistic target of rapamycin [mTOR] inhibitors, oral tacrolimus, St. John's wort, Epidiolex, sleep supplements or prescription sleep aids.
• Person has a positive screen (i.e., exceeds cut-point score) for any of the following sleep disorders on the Sleep Disorders Symptom Checklist-17 (SDS-CL-17): narcolepsy, obstructive sleep apnea, restless legs syndrome.
• Person works night or swing shift.
• Person has a personal or family history (first-degree relative) of a psychotic disorder and/or schizophrenia.
• Person has an acute or progressive disease or disorder that is likely to interfere with the objectives of the study, or the ability to adhere to protocol requirements.
• Person is currently pregnant, breastfeeding, or planning to become pregnant within 30 days of the study.
• Woman of childbearing potential, unless she has not engaged in vaginal intercourse, or she has used effective contraception when doing so (for example, double barrier), for at least 30 days prior to the study.
• Woman of childbearing potential, unless willing to ensure that she or her partner use effective contraception (for example, double barrier) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom).
• Man whose partner is of childbearing potential, unless willing to ensure that he or his partner use effective contraception (for example, double barrier) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom).
• Person has history of diagnosis related to hepatic function and/or significantly impaired hepatic function (alanine aminotransferase [ALT] >5 ⋅ upper limit of normal [ULN] or total bilirubin [TBL] >2 ⋅ ULN) OR the ALT or aspartate aminotransferase (AST) >3 ⋅ ULN and TBL >2 ⋅ ULN (or international normalized ratio [INR] >1.5).
• Person demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.