cbd rem sleepDecember 15, 2021
The concern here is that the concentration and absorption of CBD will vary among these different formulations—and this will ultimately affect CBD's therapeutic effect.
A 2017 study found that only 31% of 84 CBD products bought online were labeled accurately for concentration, with 43% having less CBD than stated and 26% having more. In addition, over 21% had detectable THC.
Once extracted, CBD oil can be taken by itself or infused into other forms, including:
Getting better sleep is a challenge for many people, and researchers are exploring whether cannabidiol (CBD) can help. Over 80 different chemicals, called cannabinoids, can be found in the Cannabis sativa plant. The most abundant cannabinoid found is tetrahydrocannabinol (THC), while the second most abundant is CBD.
Another factor in dosing is that there is only one CBD medication available by prescription—Epidolex—which is FDA-approved for some forms of epilepsy. Its CBD concentration and purity are standardized. CBD products bought without prescription lack standardization.
Arno Kroner, DAOM, LAc, is a board-certified acupuncturist, as well as an herbalist and integrative medicine doctor. He operates a private practice in Santa Monica, California.
Genetics, environmental factors (such as travel, a crying baby, a loud bedroom), medications, or substance abuse may also contribute to poor sleep.
In addition, some people may experience a worsening of their sleep quality after taking CBD. This paradoxical effect warrants further investigation.
For instance, in one of the studies mentioned above, the average adult dose used was 25 milligrams per day, whereas in another study, the participants used 300 milligrams per day.
The idea of finding a natural therapy for sleeping problems is certainly appealing. However, sleep is a complex phenomenon. In fact, there is an array of reasons why a person may suffer from sleeping difficulties.
While it's true there is scientific evidence that CBD can help with sleep, many of the human studies examining this association are small, and/or they lack a control group.
Hemp-derived CBD is legal in all 50 states. However, state laws vary with regard to the legality of marijuana. CBD oil that still contains THC or other cannabinoids may only be sold in states that have legalized marijuana use.
CBD oil extracted from industrial hemp, which must contain less than 0.3% THC, is federally legal. Marijuana, however, remains illegal under federal law in the United States.
While not an exhaustive list, some potential reasons include:
Dosing is another consideration. Unfortunately, it's not yet clear exactly what dose of CBD is needed to give a person a restful night's sleep.
CBD oil is extracted from the marijuana or hemp plant, which are both strains derived from the Cannabis sativa plant.
Factors that may affect dosing include:
That said, here are examples of research studies supporting the use of CBD for improving sleep:
The research, while emerging and evolving, is promising, suggesting that CBD may improve both sleep quality and quantity.
If you or a loved one is dealing with sleep problems, it's important to see your healthcare provider or a sleep specialist. In some instances, treatment of the underlying problem (e.g., an overactive thyroid or changing a medication) will resolve the problem. Other diagnoses may require a more comprehensive approach.
It's likely that the dose required needs to be individualized and perhaps, titrated, based on its effect.
Research suggests that, in the short-term, CBD is largely safe and well-tolerated. Some people, however, do experience side effects, such as:
In addition, some studies have examined the combined role of THC and CBD for sleep, which we are not addressing here.
Lastly, there is the legal issue of CBD to consider. Here is a brief summary of the laws encompassing CBD:
Besides addressing the cause behind you or your loved one's sleep issues, there are other problems to consider regarding the use of CBD.
A retrospective case study published in the Permanente Journal revealed that out of 72 adults who took CBD on a regular basis in a psychiatric clinic, 48 (66.7%) of them had improved sleep scores and 57 (79.2%) had reduced anxiety scores, both after the first month. The results fluctuated over time and the benefits diminished once supplementation was stopped. 5.
Overall, the data behind the use of CBD and sleep are new and in the beginning stages of development. Small studies over a short period of time do not provide conclusive evidence for the recommendation of CBD for sleep, though larger studies do seem to indicate there may be benefit for patients with insomnia.
In a more robust literature review of studies exploring sleep and CBD published in Experimental and Clinical Psychopharmacology , the authors found that in the studies they assessed, sleep was often a secondary outcome, the study sample sizes were small, and many of the studies were short-term in nature. The authors of the review concluded that drawing any conclusions from these studies would be difficult. 4.
Additionally, patients should be urged to take only one kind of product, to start taking it on its own so that adverse events (AEs) can be more easily identified, and to stop taking it and seek medical attention if AEs do develop, such as excessive somnolence, diarrhea, fatigue, and vomiting.
The Hemp Farming Act of 2018 removed hemp, which is defined as cannabis with less than 0.3% tetrahydrocannabinol (THC), from Schedule I controlled substances and made it an ordinary agricultural commodity. 1 Since then, a plethora of new research and CBD products have come on the market in a very short period of time.
However, more research is needed regarding the specific ways that CBD can affect sleep, the implications of long-term use, and interactions it may have with other medications. Finally, with CBD being a health and dietary supplement, several brands have entered the market, and so the gold standard product or brand has not yet been identified.
For this reason, pharmacists will come across more patients who use CBD and CBD-related products, yet many pharmacists may remain uncertain of how to manage their patients’ medication regimen along with CBD. The research and data on CBD are new and more is coming out over time, making this a dynamic medicinal agent on which to stay informed.
The endocannabinoid system (ECS) is an extensive, endogenous signaling system with many elements that are still being discovered as research progresses. In consideration of the fact that the ECS is modulated by diet, sleep, exercise, and stress, researchers believe that the modulation of ECS may hold therapeutic promise for a diverse scope of diseases, one of which is insomnia. 2.
At the moment, pharmacists should recommend to their patients to choose a brand of CBD that is reputable. A search on the Better Business Bureau and the FDA’s CFSAN Adverse Event Reporting System can provide information on the product’s reliability.
Specifically, a study published in Current Psychiatry Reports demonstrated that CBD may hold promise for rapid-eye movement (REM) sleep behavior disorder, but there are mixed results and the research is still in its infancy. 3.
The Evidence Behind CBD’s Use for Sleep.
This supports a larger study, published in Medicines , which followed 409 patients taking cannabis (not CBD) and found a 4.5-point reduction on a 0 to 10 visual analog scale of their sleep symptoms. 6.
More patients may start taking or seeking CBD in their desire to achieve their optimal health. Pharmacists are the ideal health care practitioners to educate patients on these products and provide up-to-date information as it becomes available.
Although no previous study on sleep and CBD applied these specific measures, our findings are consistent with a study on multiple sclerosis that used the digits test to assess possible changes in disease status following the administration of CBD associated with THC, in which no significant change was recorded (Vaney et al., 2004).
Likewise, selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) may interfere with sleep architecture and decrease restorative sleep, leading to increased awakenings, reduced REM sleep, increased REM latency, as well as increased periodic limb movement during sleep (Feige et al., 2002). In addition, SSRIs and SNRIs have been associated with REM sleep without atonia, characterized by increased tonic or phasic motor activity in electromyographic channels during REM sleep (Schenck et al., 1992; American Academy of Sleep Medicine, 2014; Lee et al., 2016).
Schematic representation of the participants selection and of the protocol – this was a four period crossover study. CBD, cannabidiol; ESS, Epworth Sleepiness Scale; PSQI, Pittsburgh Sleep Quality Index; PSG, polysomnography; PVT, Psychomotor Vigilance Test; STAI, State-Trait Anxiety Inventory; TCLE, written informed consent form; VAMS, Visual Analog Mood Scale; WAIS, Wechsler Adult Intelligence Scale.
Polysomnographic parameters measured after the administration of CBD and placebo.
Cannabidiol (CBD), one of the major compounds of Cannabis sativa , has been shown to have several therapeutic effects including antipsychotic (Zuardi et al., 1991; Leweke et al., 2000; Moreira et al., 2006), antidepressant (Zanelati et al., 2010), anti-epileptic (Devinsky et al., 2016) anti-inflammatory (Esposito et al., 2013), and analgesic properties (Boychuk et al., 2015), besides improving Parkinson’s disease symptoms (Chagas et al., 2014c).
Cannabidiol’s anti-anxiety (Zuardi et al., 1993, 2017; Crippa et al., 2009; Bergamaschi et al., 2011b) and antidepressant (Saito et al., 2010; Zanelati et al., 2010) potential seems to differ from other drugs with effects on the central nervous system, since we found no alterations in sleep architecture. Additionally, studies on the anxiolytic, antipsychotic and antiparkinson effects of CBD described no sedation or drowsiness side effects in their volunteers (Zuardi et al., 1993; Crippa et al., 2004; Fusar-Poli et al., 2009; Chagas et al., 2014a). These findings complement the literature on the few significant side effects resulting from the administration of CBD to humans in a wide range of doses, administered chronically or acutely (Bergamaschi et al., 2011b; Kerstin and Grotenhermen, 2017). It seems, therefore, that CBD has an adequate safety profile with good tolerability and does not affect psychomotricity or cognition (Hayakawa et al., 2007; Crippa et al., 2010; Bergamaschi et al., 2011b; Kerstin and Grotenhermen, 2017). This is particularly important in Parkinson’s disease, where motor and cognitive symptoms play a central role.
Despite these limitations, this is the first controlled study to evaluate the effects of CBD on sleep architecture using polysomnography. Although the absence of interference with the sleep cycle is not sufficient for concluding that sleep is not affected, the results obtained contribute for the understanding of the effects of CBD in the modulation of sleep in humans.
We found no differences between CBD and placebo in respect to polysomnographic findings or cognitive and subjective measures in a sample of healthy subjects. Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of CBD does not appear to interfere with the sleep cycle of healthy volunteers. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as evaluate the chronic effects of CBD in larger samples of patients with sleep and neuropsychiatric disorders.
The main polysomnographic results of the administration of CBD and placebo are described in Table Table3 3 . The comparative analyses between CBD and placebo indicate that none of the parameters evaluated presented statistically significant changes.
Cannabidiol may play a therapeutic role in sleep regulation (Monti, 1977; Chagas et al., 2014b). In healthy volunteers with regular sleep cycle, 600 mg of CBD induced sedative effects (Zuardi et al., 1993), whereas in subjects with insomnia, acute use of CBD (160 mg/day) was associated with an increase in total sleep time and less frequent awakenings (Carlini and Cunha, 1981). Daily CBD doses of 40, 80, or 160 mg were shown to reduce dream recall and did not cause ‘hangover’ effects compared to placebo (Carlini and Cunha, 1981).
Participants were recruited through advertisements in the local media of the city of Ribeirão Preto, São Paulo, Brazil. Initially, 335 individuals who were interested in participating were evaluated, 265 of whom were excluded in the recruitment interview (which contained questions about clinical data, demographics, psychiatric symptoms, sleep patterns, among others). The remaining 70 participants were asked to keep a sleep log and completed the rating scales on sleep patterns (ESS, Epworth Sleepiness Scale ; PSQI, Pittsburgh Sleep Quality Index). After these procedures, 27 participants were considered eligible for the study ( Figure Figure1 1 ) and were randomized into two groups (group 1: placebo – CBD, group 2: CBD – placebo) matched in terms of sex, age, and years of education. To ensure the adequacy of the matching procedure, one participant of each pair had his treatment blindly chosen between the two treatment options available and the other participant (matched to the first one) was assigned to the remaining option.
Subjects were instructed to abstain from alcohol for 24 h and caffeine for at least 24 h before each visit to the laboratory. Subjects who reported having less than 6 h of sleep the previous night were excluded from the trial. After at least 8 h of fasting, subjects were instructed to have a light, standardized meal 2 h before the experiment. For the present study, a randomized, double blind, and crossover model was used. Once one volunteer gave up participating the study, the 26 participants were assessed on two different occasions, in a 2-week interval, with identical procedures except for the substance that was administered. In each visit, participants were first submitted to a cognitive and subjective evaluation, then an oral dose of CBD (300 mg) or placebo was administered 30 min before the polysomnographic recordings began.
Cannabidiol (300 mg), 99.9% purity without THC (kindly supplied by STI-Pharm, Brentwood, United Kingdom) was dissolved in corn oil (Zuardi et al., 1993, 2017; Crippa et al., 2004). The same amount of corn oil was used as placebo. The drug and placebo were packed in identical gelatin capsules. The 300 mg dose was chosen based on previous studies that detected the acute anxiolytic effect of this dose (Zuardi et al., 1993, 2017) and the studies by Chagas et al. (2014b) and Chagas et al. (2014c), in which this dose caused a reduction in the frequency of REM sleep behavioral events and improving quality of life (including sleep) in patients with Parkinson’s disease, respectively. The time of drug delivery was based on previous studies that showed that the peak plasma concentration of an oral dose of CBD normally occurs 1–2 h after ingestion (Agurell et al., 1981; Crippa et al., 2004, 2010; Borgwardt et al., 2008; Fusar-Poli et al., 2009; Zuardi et al., 2017).
At lower doses, CDB (15 mg/day) co-administered with tetrahydrocannabinol (THC, 15 mg/day) increased wakefulness (Nicholson et al., 2004). More recently, Chagas et al. (2014b) investigated the effects of chronically administered CBD (75–300 mg per day for 6 weeks) in patients with Parkinson’s disease and found a reduction in symptoms of REM sleep behavior disorder. After discontinuation of the drug, the frequency of symptoms returned to baseline levels, prior to treatment with CBD. Finally, CBD-enriched extract was described as a safe treatment for reducing anxiety and improving sleep in a young girl with post-traumatic stress disorder (Shannon and Opila-Lehman, 2016).
Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg) or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study). In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect ( p > 0.05). Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune.
AZ, JH, FG, and JC are co-inventors (Mechoulam R, JC, FG, AZ, JH, and Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296; 29/07/2015; INPI on 19/08/2015 (BR1120150164927). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic cannabidiol and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JH and JC have received travel support from and are medical advisors of BSPG-Pharm. AZ is medical advisor of BSPG-Pharm. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We found no significant differences in polysomnography results following the administration of CBD and placebo to healthy volunteers. Likewise, there were no statistically significant changes in the subjective and cognitive measures collected during the two nights of polysomnographic exams.
It is known that a major problem of several medications used in the treatment of clinical anxiety and depression is their effect on sleep architecture. Benzodiazepines are an example, since despite the rapid onset of their anxiolytic action, these drugs may produce undesirable side effects such as the increase in non-REM stage 2 sleep and reduction of SWS (Borbély et al., 1985). Long-term use of benzodiazepines may also cause reduction of SWS, loss of efficacy in the treatment of insomnia, alterations in electroencephalogram results during sleep (Poyares et al., 2004) and cognitive dysfunction, even after drug discontinuation (Stewart, 2005).
The following instruments were used: (a) Visual Analog Mood Scale – VAMS (Norris, 1971); (b) State-Trait Anxiety Inventory – STAI (Spielberger et al., 1970), translated and adapted to Brazilian Portuguese by Gorenstein and Andrade (1996); (c) Epworth Sleepiness Scale – ESS (Johns, 1991); (d) Pittsburgh Sleep Quality Index – PSQI (Buysse et al., 1989); (e) digit symbol substitution and symbol copying tests of the Wechsler (1955) Adult Intelligence Scale – WAIS; and (f) Psychomotor Vigilance Test – PVT (Graw et al., 2004; as made available by the National Center on Sleep Disorders Research).
The apparatus used for the polysomnography exams consisted of different devices including electroencephalogram with the international 10–20 system (to rule out the occurrence of epileptic seizures), electrooculogram, electromyogram of chin muscles and upper and lower limbs, nasal pressure cannula, oral thermistor, thoracic and abdominal respiratory inductive plethysmography straps, pulse oximetry, electrocardiogram, and snoring and body position sensors. Video and sound were also recorded during the exam.
Average scores in the seven components of the PSQI.
The exclusion criteria for the trial were: (i) presence of organic brain syndromes; (ii) use of psychoactive drugs, including nicotine; (iii) presence of general medical conditions, assessed by the patient’s report during the interview and/or through physical examination; (iv) presence of psychiatric disorders (assessed with the SCID-IV); (v) pregnancy; (vi) previous history of any sleep disorder (based on the Pittsburgh Sleep Quality Index – PSQI); and (vii) recent changes in sleep time (variation of more than 2 h in the last 7 days, measured through the sleep log). Thus, the volunteers were all non-smokers and had not taken any medications for at least 3 months before the study. Moreover, none of them had used marijuana more than five times in their lives (no use in the last year) and none had ever used any other illegal drug. All subjects gave their written consent to participate after being fully informed about the research procedures, which were approved by the Hospital das Clínicas de Ribeirão Preto of University of São Paulo ethics committee (HCRP No. 17912/2013).
Screening Procedure and Clinical Assessment.
Polysomnography recordings were obtained through a computerized system (BrainNet BNT; LYNX Tecnologia Eletrônica , Rio de Janeiro, Brazil). Sleep stages were recorded in periods of 30 s, according to the criteria established by Rechtschaffen and Kales (1968). The following polysomnographic parameters were evaluated: total sleep time (TST, min), sleep onset latency (min), rapid eye movement (REM) onset latency (min), wake after sleep onset (min), wake after sleep onset index (h), apnea index (h), hypopnea index (h), respiratory disturbance index (RDI, h), sleep efficiency (%), stage 1 sleep (%), stage 2 sleep (%), stage 3 sleep (%), REM (%), lowest saturation (%), and baseline saturation (%).
Several parameters were recorded during polysomnography, considering that the essential tests for sleep staging are electroencephalogram, electrooculogram, and electromyogram. Given the lack of studies on the effect of CBD on human polysomnography-monitored sleep, other parameters were selected based on studies that tested the effect of other drugs in healthy volunteers (Orr et al., 2012; Yadollahi et al., 2014). When comparing our polysomnographic data with results from other studies that used placebo in healthy volunteers, similar findings were observed (Buysse et al., 1989; Sabbatini et al., 2005; Fidan et al., 2011; Feld et al., 2013; Wilson et al., 2015).
The data obtained in the seven components and the total PSQI score are indicative of good sleep quality. Total PSQI scores greater than five suggest difficulties in at least two components or moderate difficulties in more than three components (Buysse et al., 1989).
Earlier preclinical studies have suggested that the therapeutic effects of CBD might depend on the presence of specific clinical conditions. As an example, Campos et al. (2013) showed that the chronic use of CBD for 2 weeks, while not directly increasing hippocampal neurogenesis, prevented its decrease by unpredictable chronic stress. Thus, the absence of changes in the sleep of healthy volunteers treated with CDB in our study should not be considered as a final indication that CBD could not have positive effects in patients with sleep disorders.
Clinical and demographic data were analyzed with descriptive statistics and expressed in terms of mean ± standard error of the mean. The Kolmogorov-Smirnov test was used to check for normality. Non-parametric Wilcoxon or Friedman tests analyzed results that failed this test. The remained data was analyzed by two-way repeated-measures ANOVA. A preliminary analysis indicated no gender effect; thus, the factors analyzed were drug, order of drug administration (placebo-CBD versus CBD-placebo), and the interaction between drug and phase. A three-way repeated-measures ANOVA was employed to analyze data throughout the three phases of each exam. In case of significant interactions, paired Student’s t -tests were performed at each phase and/or order to compare the differences between groups. In case of significant time effect, the Bonferroni’s post hoc test was used for multiple comparisons. In cases where sphericity conditions were not reached, the degrees of freedom of the repeated factor were corrected with the Huynh-Feldt epsilon. All the analyses were performed with the Statistical Package for the Social Sciences (SPSS) v.20.0.
JC, JH, FG, AZ, and AE: conception or design of the work. IL, JS, and AE: data collection. AE, FG, IL, AZ, and AC: data analysis and interpretation. JC, IL, AZ, JH, and FG: drafting the article. JC, JH, FG, AZ, AE, AC, JS, and IL: critical revision of the article. JC, JH, FG, AZ, AE, AC, JS, and IL: final approval of the version to be published.
It is known that lack of sleep can interfere with certain aspects of cognitive functioning, such as attentional levels (Goel et al., 2009) and PVT, which has a high sensitivity to measure responses that require selective attention (Basner and Dinges, 2011). However, the results of the present study did not show any significant impairment in either the reaction time or number of errors measured by the PVT, suggesting that the attention levels of the volunteers were preserved in the morning after the sleep assessment, regardless of the administration of CBD or placebo. Not having administered the PVT test before CBD and placebo administration does not significantly affect the conclusions once the study does not intend to assess the effect of CBD on baseline vigilance (which would require comparison with baseline PVT results), but to rather evaluate if CBD may be safely administered to patients without affecting their vigilance state overall, such that the patients may safely conduct every-day tasks, like for example driving.
No statistically significant differences were found between groups in the VAMS, STAI, Digit Symbol Substitution and Symbol Copying Tests, and PVT. In the analysis of the WAIS, the results in the Symbol Copying Tests showed no effects of drug ( F 1,24 = 2.46; p > 0.05) or order of administration ( F 1,24 = 0.44; p > 0.05), but the interaction between drug and order was significant ( F 1,24 = 4.9, p < 0.05). To check if this interaction could have potentially interfered with the results, we split the subjects, comparing the placebo and CBD groups separately in the two orders (first placebo or CBD). Again, there was no difference between groups in the two situations.