Clinical reviewThe effects of cannabinoid administration on sleep: a systematic review of human studies
Introduction
Cannabis is the most frequently used illicit drug around the globe and is estimated to be used by approximately 4.5% of the world's population – a prevalence which is currently increasing [1]. Cannabis use is especially prevalent among younger age groups compared to older age groups who may instead begin to embrace new roles and responsibilities [2]. This pattern of use is especially concerning as it is well established that early onset to cannabis use and frequent use are significant predictors of a range of health problems including mental health concerns [3] and reduced educational outcomes [4], as well as respiratory complaints [5] and cannabis use disorder [6]. In contrast, through the isolation of the two main active components of cannabis – the ‘cannabinoids’ tetrahydrocannabidiol (THC) and cannabidiol (CBD) among at least 60 others [7] – cannabis-based medicines (CBM) have been developed which have been used to treat a range of health problems, most notably those involving pain and muscle spasm [8].
As with any psychoactive substance there are many different motivations to use cannabis, however; it is typically used for enjoyment or fun and for promoting social cohesion [9]. A less well understood motive is use to assist with sleep problems. This motive is not uncommon and has been reported by one quarter of a large sample of cannabis using high school graduates [9]. Indeed, intoxication from cannabis use is most commonly described to involve a feeling of relaxation [10]. Interestingly, there have been few studies specifically focussed on the relationship between cannabis use and sleep. This may be surprising given the health importance of sleep. That is, insomnia, the most common sleep disorder [11], is a known risk factor for multiple impairments across quality of life domains (most notably depression and anxiety) [12], which ultimately leads to an increase in the utilisation of health care resources amongst sufferers [13].
Early investigations of cannabis use and sleep gained momentum in the 1970s. Many of these studies used objective measures (polysomnograph technology) to investigate sleep and have been reviewed by Schierenbeck and colleagues [14]. These authors noted that a reduction to rapid eye movement (REM) sleep and REM density was the most consistent finding, however; their interpretation of findings was not considered reliable due to the small sample sizes of the studies reviewed. More recent understanding has come from medicinal cannabis use trials which include a secondary measure of sleep as a gauge of positive treatment outcomes (with a primary measure relating specifically to the illness under study). A subsection of these trials involving clinical studies of Sativex (a THC and CBD based oral spray) have recently been reviewed by Russo and colleagues [15]. These authors concluded that the use of Sativex for the treatment of spasticity and pain was likely to improve subjective sleep parameters but was unlikely to result in a significant change in sleep architecture.
Unfortunately, the current understanding of the effects of cannabis use on sleep is clouded by mixed findings between studies that typically lack statistical control for confounding factors. Notably, medicinal cannabis use has recently been described to alleviate sleep problems by medicinal users [16], [17], [18], while cannabis use is a reported risk factor for sleep problems in the community [19], [20], [21], [22]. Moreover, sleeping problems are among the most commonly experienced withdrawal symptoms when abstaining from cannabis use [23], [24]. Despite this, research designed to develop a better understanding of the effects of cannabis use on sleep in humans is rarely conducted.
Recognising the effects of cannabis use on sleep is important for both the cannabis user and for health providers tasked with assisting behavioural change. If demonstrated to be harmful, this knowledge may act as a motivational tool for those deciding whether or not to use cannabis. In addition, such evidence may assist clinicians to reduce the risk of relapse to cannabis use among their clients by assessing and addressing sleep problems as necessary. In order to clarify the effects of cannabis on sleep, we conducted a systematic review of all papers which included human participants and an assessment of sleep following the administration of a measured cannabis dose. Unlike previous reviews, we include: 1) studies that used either objective or subjective measures of sleep; 2) studies that involved the administration of any cannabinoid or CBM; and 3) an assessment of the risk of bias present in each study. As participants in those trials of CBM suffered from illnesses that likely impact on their sleep, the associated articles are presented separately to isolate possible attribution bias.
Section snippets
Literature search
English language studies on human participants were located through online search of eight electronic databases (Embase, CINAHL, Cochrane Library/EBM Reviews, Medline, and PsycINFO for published studies and Project Cork, DRUG, and PsycEXTRA for grey literature). The search strategy included the keywords “cannabinoid/s, or, tetrahydrocannabinol, or THC, or cannabis/marijuana” and “sleep, or sleep onset, or sleep apnea, or sleep treatment, or sleep wake cycle, or sleep deprivation, or rapid eye
Non-medicinal cannabis use and sleep
A total of 11 studies investigated the impact of recreational cannabis use on sleep with a collective sample size of 203 participants (see Table 1). The overall quality of these studies was poor (range: 17–84%, average: 42.6%), meaning that a substantial risk of bias was introduced across the literature. This risk was most commonly due to a lack of control for confounding factors such as pre-existing sleep problems or participant gender and age. This is significant as the prevalence of insomnia
Conclusions
We have reviewed 39 manuscripts that involved the administration of cannabis and included a quantitative measure of sleep. Overwhelmingly these articles described studies that carried a substantial risk of bias, typically by failing to control for other substance use, using measures without psychometric validation and, in the case of many clinical trials, failing to blind participants. As such, conclusions from this review are tentative due to existing studies suffering a number of
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