Insomnia is a common chronic sleep condition in which sufferers have trouble getting and staying asleep. While it is estimated that only a third of people in the UK are classed as “good sleepers”, according to the Mental Health Foundation, a third of people may also have chronic insomnia. Sleep conditions like insomnia are often associated with disruption to personal and professional aspects of everyday life as well as heightened levels of anxiety and stress.
Conventional treatment options for insomnia include lifestyle changes such as limiting your alcohol use, increased exercise, and other aspects of good sleep hygiene, however, if these do not work then sleep aids such as melatonin or cognitive behavioural therapy may also be considered. Current pharmacological treatment options are currently limited to ‘Z-drugs’ and benzodiazepines which are associated with the risk of dependence and abuse. However, cannabis and cannabinoids are increasingly being considered as a potential treatment option for sleep conditions, including insomnia.
There is a growing body of anecdotal evidence that cannabis may be useful in sleep conditions, including insomnia. Medical cannabis products, sometimes referred to as medical marijuana, are also increasingly being considered as an unlicensed treatment option for treatment-resistant chronic insomnia. A recent randomised, double-blind, placebo-controlled, cross-over trial aimed to assess how a cannabinoid-based medication can affect symptoms in patients with chronic insomnia disorder.
Design and Methods of the Study
A sample of 24 participants aged between 25-70 years with chronic insomnia – defined as self-reported difficulty initiating sleep and/or maintaining sleep on three or more nights per week, for three months in addition to an Insomnia Severity Index (ISV) score of more than 10 – were recruited for the study.
The cannabinoid formulation ZTL-101, which includes tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), was used as the trial medication. Prior to medical cannabis treatment, the researchers established a two-week baseline period, during which participants wore a wrist-based activity monitor. On the 14th night of the baseline period and both treatment arms of the study, a polysomnography (PSG) study was performed. Participants were also monitored for apnoeic episodes. Studies were scored according to these criteria by a single experienced scorer who was blinded to treatment.
After being screened for potential reactions to the study medication (THC 3mg; CBN 0.3mg; CBD 0.15mg + 0.15ml placebo) followed by a one-week washout period, participants were randomly allocated to either ZTL-101 or placebo for two weeks. Participants were then put through another one-week washout period before being crossed-over to the alternate study arm for a further two weeks.
Outcomes of the Study
The primary outcomes of the study were determined as the frequency, type, and severity of adverse events during each arm of the study, as well as global insomnia symptoms as assessed by the Insomnia Severity Index (ISI) on the 14th night of each two-week treatment period.
Measures of sleep quality and quantity were obtained through self-reported sleep diaries, actigraphy, and PSGs. Each of these methods were also, where possible, used to determine sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency and awakening index (number of awakenings per hour of sleep). A rating of perceived sleep quality was also taken.
Results of the Study
Of the 24 participants who proceeded to dosing, 23 completed the protocol. Of these 23, 12 (52%) were taking a double dose of ZTL-101 on the 14th night of the active arm of the study, compared with 16 (69.5%). One hundred per cent of the participants guessed that they were receiving active treatment when using ZTL-101 – 17 (81%) of these participants stated that the reason for their guess was “Improvement in sleep quality”.
Insomnia Symptoms
At the end of two weeks of treatment, ISI scores were significantly lower than scores following the placebo arm of the study (an adjusted mean difference of -5.1). According to the self-reported sleep diaries, participants perceived that they went to sleep faster, slept for longer, had improved sleep quality, and felt more rested/refreshed on waking.
The novel cannabinoid formulation used in this study was well tolerated with only one withdrawal, due to a non-serious adverse event. At least one adverse event was experienced by 17 of the remaining 23 participants, with dry mouth and dizziness being the most frequently reported. This was comparable to other trials using medicinal cannabis formulations.
The mean total time spent asleep across the two-week active treatment period was over 7 hours – the minimum amount of sleep recommended for adults, and above average for individuals of comparable age without insomnia. However, the average time spent awake during the night remained high and the time taken to fall asleep was unchanged.
Conclusions
The researchers concluded that this study “demonstrated that ZTL-1010, a novel cannabinoid therapy, is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms”.
However, it is noted that further dedicated studies are needed to confirm the findings of this trial. Nonetheless, these results are encouraging and support further investigations on the potential of cannabinoids for the treatment of insomnia and other sleep conditions.
