Longitudinal reciprocal relationships between cannabis use, sleep, and the HPA-axis

Oregon Health & Science University, Portland OR

Investigators

Abstract

Summary Cannabis use disorder (CUD) affects at least 10% of the 193 million individuals that use cannabis worldwide. Cannabis is frequently promoted as a sleep aid despite conclusive evidence to support such benefits. Further, abrupt cessation of regular cannabis use is associated with sleep disturbances, often leading to reinitiating cannabis use. Thus, while the mechanisms by which cannabis regulates sleep remains unclear, the escalation and/or maintenance of hazardous levels of cannabis use likely involve a bidirectional (and mutually reinforcing) relationship between sleep and cannabis use. In this prospective mechanistic randomized control study, we will determine the impact of sleep restriction or extension on the amount of cannabis use and in turn the impact of this cannabis use on sleep continuity and sleep homeostasis, a pivotal component of sleep regulation. To examine this bidirectional relationship between sleep and cannabis use, as well as the hypothalamic-pituitary- adrenal (HPA) axis as a potential mediator, 60 participants (20 healthy controls, 20 with moderate cannabis use, and 20 with severe CUD) aged 21-29 years (a demographic with the highest prevalence of risky cannabis use and CUD) will complete a three-week randomized control study that includes: (1) an ecological momentary assessment, involving daily surveys delivered via phone four to five times per day to record daily sleep behaviors (time in/out of bed, napping), cannabis use (time, method, product), and motivation for cannabis use; (2) continuous actigraphy to objectively measure sleep; and (3) two 4-night in-laboratory sleep protocols to assess systematic responses to both sleep restriction and sleep extension, utilizing a randomized, counterbalanced, crossover design. Laboratory measurements will include sleep quality, quantity and dynamics (via full polysomnography; PSG), circulating cannabinoids before and after sleep (via venous blood), and cortisol (via saliva). This mixed-method approach—combining ambulatory assessments, observations of naturalistic cannabis use, and intensive laboratory measures with a controlled sleep protocol—will allow us to systematically determine the prospective relationship between sleep and cannabis use both within and between participants. This design will allow us to examine the bidirectional relationship between cannabis use and sleep (aim 1), as well as the relationship between circulating cannabinoids and sleep (aim 2). The rapid legalization of cannabis over the last decade has raised concerns about its potential negative impacts on health and safety, which are themselves influenced by sleep. Current research significantly lags behind consumers’ naturalistic cannabis use habits (e.g., the use of concentrates, which have stronger effects compared to smoked cannabis flower). The proposed study aims to address this gap.