Accurate Education – Marijuana (Cannabis): Cannabis and Sleep

Sleep Cycles and Stages of Sleep

Ideally, one engages four to six cycles of sleep every 24 hours to feel fresh and rested. Each sleep cycle contains four individual stages: three that encompass non-rapid eye movement (NREM) sleep and one rapid eye movement (REM) sleep. Stages 1 through 3 are NREM sleep (N1, N2, and N3) and the 4th stage is REM sleep. In a sleep cycle, each NREM stage leads to progressively deeper sleep and an average sleep cycle lasts about 90 minutes.

NREM Sleep
Approximately 75% of sleep is spent in the three NREM stages, with the majority spent in the Stage 2 NREM sleep stage. The third stage of NREM is known as Slow-Wave Sleep (SWS) because brain activity during N3 is characterized by slow delta waves on an EEG.

Stage 1 NREM sleep is the lightest stage of sleep. Ones enter stage 1 right after falling asleep. This stage usually lasts only a few minutes, making up about 5% of one’s sleep time. After that, as sleep gets deeper, one moves into stage 2 NREM sleep.

Stage 2 NREM sleep is still light sleep, but deeper than stage 1. During this stage, brain waves slow down and there are noticeable pauses between short, powerful bursts of electrical activity. During  these bursts the brain  is organizing memories and information from the previous wakeful state. This stage accounts for about 45% of sleep time (the most of any stage). One passes through multiple rounds of stage 2 NREM sleep, with each round usually longer than the last. After stage 2, one usually moves deeper into stage 3 NREM sleep.

Stage 3 NREM sleep is also known as Slow-Wave Sleep (SWS) because brain activity during this stage is characterized by slow delta waves on an EEG. Stage 3 NREM is associated with moderate muscle tone and slow or absent eye movement. This stage is when it is most difficult to awaken someone from sleep, so Stage 3 NREM is often referred to as deep sleep. Because stage 3 NREM sleep is so deep, if one is awakened during this stage, they may experience a state of confusion or “brain fog” that may lasts up to 30 minutes.

Stage 3 NREM sleep is important for memory consolidation of learning material experienced during previous wake period including the conscious recall of facts and the ability to store and retrieve personal information and events. Stage 3 NREM is considered to be critical for restorative functions and maintenance of sleep. Without enough stage 3 NREM sleep, one feels tired and drained even if they slept for a long time. That’s why during sleep, if there has been sleep deprivation, the cycle automatically engages as much stage 3 sleep into the sleeping period as early as possible. The SWS stage determines sleep quality and is vital for waking up feeling revitalized.

Stage 3 NREM sleep usually lasts between 70 and 90 minutes, and the majority of slow-wave sleep happens early in the night. Most adults spend around 10% to 20% of their sleep in slow-wave sleep.

Drugs Known to Increase Slow Wave Sleep:

• • Gabapentin (Neurontin)
  • Pregabalin (Lyrica)
    
  • THC

Cannabis for Insomnia

Cannabis may impact insomnia but research is limited regarding which constituents in cannabis provide specific benefits for insomnia. Most research at this time has been focused on the cannabinoids, especially THC and CBD. It is likely that various terpenes also play a role but less is known about them. While some studies show that cannabis use decreases insomnia severity, most research has shown mixed results.

Cannabinoids

The effect of cannabinoids (THC and CBD) on sleep and insomnia is dose dependent but also influenced by which cannabinoid and what combinations as well as their dose and frequency of use.

THC

Acute exposure/short-term use of THC:
With short-term use, THC may reduce the time it takes to fall asleep (sleep onset latency – SOL), increase total sleep time (TST), and decrease waking up after sleep onset (WASO). Short-term use of THC decreases REM sleep and increases slow wave sleep (SWS). However, these effects on slow wave sleep and total sleep time do not tend to persist over time.

Long-term use of THC:
In contrast to short-term use, chronic use of of THC may increase sleep disruption by increasing time needed to fall asleep and increasing waking during sleep resulting in decreased overall sleep time.

In one study, the majority of participants with long-term use show decreased overall sleep time (78%), with increased time it takes to fall asleep (>30 min), poor sleep efficiency, the percentage of time spent asleep while in bed (<85%), and increased waking up after sleep (54.7%). Additionally the study suggested chronic THC use increases sleep time prior to starting REM stage – average 114.5 min) as well as decreased percentage of REM sleep (17.7%).


Effects of THC Withdrawal:

THC/cannabis withdrawal, is associated with sleep disturbances and vivid dreams.as well as lower total sleep time, decreased slow wave sleep needed to feel revitalized and decreased sleep time prior to starting REM stage. One study also showed longer sleep onset and worse sleep efficiency. Another study also showed an increase in periodic limb movements (PLMs) after abrupt discontinuation of heavy marijuana use. Withdrawal-related sleep disturbances is worse among heavy users with onset in about 24–72 hours after discontinuation use and can persist up to 6– 7 weeks. Given these duration-dependent variable effects on sleep architecture, the role of cannabinoids in sleep disorders remains under investigation.

CBD

A 2022 systematic review based on very limited research on the therapeutic benefits of CBD in the management of insomnia concluded that CBD alone or with equal quantities of THC may be beneficial in alleviating the symptoms of insomnia.

Research regarding effects of CBD on sleep stages are limited. Animal studies show an increase in total percentage of sleep, with a decrease in REM latency at lower doses and an increase in REM latency at higher doses. At this time, there are a lack of human studies collaborating these findings. One recent controlled trial did show increased sleepiness based on subjective assessment in subjects who used CBD- dominant cannabis, but it is unclear if this was due to the small amount of THC in it. Animal studies suggest that its effectiveness depends on the dose. CBD at a variety of doses helps sleep, but lower doses may allow for falling asleep faster.

Chronic effects of CBD are yet to be studied. Thus, studies on the isolated effects of CBD on sleep architecture are limited and mostly have mixed results. CBD use has been shown to increase total sleep with mid to high doses in animal studies. There is a dose- dependent effect on REM sleep latency—with higher doses causing an increase in latency while mid-range doses yield a decrease. Another study found that CBD had a positive effect on anxiety-related REM sleep suppression but no effect in the NREM phase.

A 2024 study  explored the effectiveness of 150 mg CBD compared with placebo as a sleep aid in primary insomnia. Insomnia severity, self-reported sleep-onset latency, sleep efficiency, and wake after sleep onset did not differ between treatments throughout the trial . Compared with placebo, the CBD group reported greater well-being scores throughout the trial and had superior objective sleep efficiency after 2 weeks of treatment but no other significant treatment effects were observed. It was concluded that nightly supplementation of 150 mg CBD was similar to placebo regarding most sleep outcomes except sustaining greater well-being. Unfortunately this study did not evaluate higher doses of CBD that are often required for successful treatment of anxiety with CBD.

There is growing evidence of improvement in insomnia symptoms secondary to chronic conditions such as fibromyalgia.

CBN

CBN is a minor cannabinoid promoted for its sedative effects which are thought to be enhanced when combined with THC. Research that suggests it may promote healthy sleep is limited.

Combined THC and CBD
Studies of CBD in combination with THC have shown that CBD has more alerting effects and tends to counteract the sedative effects of THC especially at higher doses. However, definitive findings are inconclusive because most of the studies evaluating effects of cannabis and cannabinoids are limited by differences in study designs, sample sizes, and procedures, as well as the ratios of THC to CBD used.

A 2023 crossover study  evaluating a medicinal cannabis oil on sleep in adults with insomnia.  A total of 29 participants received placebo or active oil containing 10 mg/ml THC) and 15 mg/ml cannabidiol (CBD) over 2-weeks titrated 0.2-1.5 ml/day (2 – 15 mg THC with 3 – 22.5 mg CBD), followed by a 1-week wash-out period before crossover. The cannabis oil was well tolerated, and effective in improving sleep, with 60% of participants no longer having clinical insomnia at the end of the 2-week intervention period. Midnight salivary melatonin levels significantly improved in the active group by 30% compared to a 20% decline in the placebo group. The cannabis oil improved both time and quality of sleep improved overall by up to 80% in the active group, including higher daily functioning. The study concluded that cannabis oil was well tolerated and effective in improving sleep in adults with insomnia.

Combined THC, CBD and CBN

Another crossover, placebo controlled study published in 2021 assessed the use of a multi-cannabinoid medication  containing THC, CBD and CBN. The test medication contained THC 20 mg/mL, CBN 2 mg/mL, CBD 1 mg/ mL and naturally occurring terpenes, extracted from a cannabis plant.  The placebo contained the same terpenes, but no cannabinoids, extracted from the same cannabis plant. Participants were given 0.5-1 ml sublingually for the study  (up to 20 mg THC, 2 mg CBN and 1 mg CBD).

The average total time spent asleep each night increased by 33.5 minutes and sleep efficiency increased by 2.9%–84.8%. The mean total time spent asleep across the 2-week period was over 7 hours while taking the medication (the recommended minimum sleep duration for adults, and above average for individuals of comparable age without insomnia).

Their data also suggested that for patients with sleep onset insomnia dosing 2–4 hours before desired bedtime might be optimal, while those with sleep maintenance insomnia should dose 1 hour before desired bedtime. It was concluded that nightly sublingual use of this cannabinoid formulation for 2 weeks improved insomnia symptoms without significant adverse events.

Terpenes

While the cannabinoids THC, CBD and CBN may play dominant roles in how cannabis impacts insomnia, some strains do appear to offer more benefits than others outside of their cannabinoid profiles, suggesting the likelihood that the terpene profile of a cannabis strain is important but research is lacking for definitive answers. A number of terpenes are promoted to help sleep, including linalool, myrcene and caryiphyllene as well as possibly pinene, limonene, terpineol, terpinolene, and phytol.

The following terpenes are likely the most important for insomnia:

• • Linalool
  • Myrcene
  • Caryophyllene

Linalool

Linalool is the dominant terpene found in lavender oil and is present in many cannabis strains known for their benefit for sleep and anxiety. It is postulated that that linalool improves the impairments caused by memory loss following REM-sleep deprivation. It is likely that linalool has the ability to improve the behavioral impairments of REM-sleep deprivation via serotonin which is related to the inhibition of sleep and the promotion of wakefulness.

Myrcene

Myrcene is generally considered the most important terpene to facilitate sleep so selecting a myrcene-dominant strain appears to be a reasonable choice at this time.

Cannabis Strains

In a 2018 study referenced above regarding cannabis strain preferences, the following 15 cannabis strains were preferred by patients using cannabis for insomnia:

Insomnia Associated with Fibromyalgia (FM)

How cannabinoids and terpenes may enhance sleep

To begin with, a substance than can induce calm and relaxation or reduce anxiety will indirectly promote sleep. However, research is investigating the mechanisms by which these compounds may directly interact with sleep mechanisms and impact various stages of sleep such as SWS and REM sleep.

One mechanism by which terpenes may facilitate sleep is by activating the body’s GABA system. GABA is an amino acid produced in the brain that functions as a neurotransmitter to facilitate communication between brain cells.
It is the body’s most important inhibitory neurotransmitter, in that it reduces activity of nerves in the brain and spinal cord.  By inhibiting nerve activity, GABA helps initiate sleep, decrease stress and reduce anxiety.  Some terpenes that have sedative and anti-anxiety effects, including phytol and alpha-pinene, have been shown to work at least in part by activating the brain’s GABA system.

Restless Leg Syndrome (RLS)

Restless leg syndrome (RLS) is a sleep-related movement disorder characterized by an unpleasant urge to move the legs and sometimes arms, worsened by inactivity and relieved by movement. This condition is often associated with a sleep-related movement disorder—periodic limb movement of sleep (PLMS).

There is limited evidence for cannabinoids use to treat RLS. Two small case series, one including 6 patients and another with 12 patients who continued previously prescribed medications for RLS while adding marijuana showed near total remission in RLS with recreational marijuana smoking.

RLS is thought to be related to several central neurotransmitters, especially dopamine but also including glutamate, gamma-aminobutyric acid (GABA), and endogenous opioid. Dopamine agonists have been a mainstay of treatment in addition to anticonvulsants and opiates.