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Use of Cannabidiol in the Management of Insomnia:
A Systematic Review
Rylea M. Ranum,
1
Mary O. Whipple,
2
Ivana Croghan,
3
Brent Bauer,
3
Loren L. Toussaint,
1
and Ann Vincent
3,
*
Abstract
Background: Cannabidiol (CBD), one of the major cannabinoids derived from the cannabis plant, is available
over the counter. CBD is often used by patients for the management of insomnia, yet research supporting
CBDs effectiveness as a treatment for insomnia is inadequate.
Objective: The objective of this review was to critically evaluate the literature regarding the therapeutic benefits
of CBD in the management of insomnia.
Methods: A comprehensive search of the following databases from inception to December 29, 2021, was con-
ducted: Ovid MEDLINE
and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid
Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews,
and Scopus. The search included randomized controlled trials, nonrandomized experimental studies, cross-
sectional studies, cohort studies, case series, and case reports. Risk of bias was assessed with the Agency for
Healthcare Research and Quality design-specific recommended criteria.
Results: Thirty-four studies were eligible for inclusion. All studies reported improvement in the insomnia
symptoms of at least a portion of their participants. Of the 34 studies, 19 studies used CBD predominant ther-
apy and 21 studies used nearly equal ratios of CBD to D
9
-tetrahydrocannabinol (THC). Of the studies that per-
formed hypothesis testing, 4 of 7 studies with a CBD predominant arm and 12 of 16 studies with a nearly equal
ratio of CBD to THC arm reported significant improvement in insomnia outcomes. However, only 2 of the 34
studies focused on patients with insomnia, of which 1 study was a case report. Additionally, several studies
used nonvalidated subjective measures, and most studies failed to include objective measures for symptom
assessment.
Conclusions: The results of our systematic review suggest that CBD alone or with equal quantities of THC may
be beneficial in alleviating the symptoms of insomnia. Nevertheless, future research assessing CBDs effective-
ness in population of patients specifically with insomnia utilizing validated subjective and objective measures
is necessary before definitive inferences can be made.
Keywords: insomnia; sleep; cannabidiol; cannabinoids
Introduction
Insomnia, a sleep disorder characterized by poor sleep
quality and quantity, affects more than 10% of the
population.
1
To meet the diagnostic criteria for insom-
nia, an individual must report difficulty with sleep ini-
tiation and maintenance at least three times a week for
3 months or longer.
2
Insomnia significantly impacts
physical and mental health, social functioning, and
quality of life and frequently coexists with multiple
medical and psychiatric disorders.
3
Common medical
disorders comorbid with insomnia include chronic
pulmonary disorders, hypertension, diabetes, cancer,
chronic pain, heart failure, rheumatologic disorders
(such as osteoarthritis and rheumatoid arthritis), and
1
Department of Psychology, Luther College, Decorah, Iowa, USA.
2
Department of Adult and Gerontological Health Cooperative, School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA.
3
Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
*Address correspondence to: Ann Vincent, MD, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, E-mail: vincent.ann@mayo.edu
Cannabis and Cannabinoid Research
Volume X, Number X, 2022
ªMary Ann Liebert, Inc.
DOI: 10.1089/can.2022.0122
1
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neurological disorders (such as Parkinson’s and
dementia).
4–8
Comorbid psychiatric disorders include
depression, anxiety, substance use disorders, and post-
traumatic stress disorder (PTSD).
9–12
In addition,
insomnia is also frequently comorbid with other sleep
disorders such as sleep apnea, limb movement disor-
ders of sleep, and circadian sleep disorders.
13
Despite the pervasive negative effects of insomnia
on health and quality of life, currently available man-
agement modalities for insomnia have several limi-
tations. Cognitive behavioral therapy (CBT) is the
recommended first-line management for insomnia.
14
Although CBT has clinically meaningful effect sizes,
compliance to CBT remains a challenge.
15
Reasons
for this include the patient’s time commitment to
engage in the CBT strategies and changes in behaviors
to improve sleep (sleep hygiene), which is challenging
for individuals who are already chronically sleep
deprived. For patients who have suboptimal clinical
responses with CBT, a limited number of medications
have been approved for the management of insomnia
and include eszopiclone, zaleplon, zolpidem, lemborex-
ant, suvorexant, ramelteon, and low-dose doxepin.
16
While these medications can at least partially alle-
viate insomnia symptoms, they all share the risk for
common side effects such as central nervous system
depression (impaired alertness and motor coordina-
tion), abnormal thinking and behavior changes, com-
plex sleep-related behaviors, and a risk of worsening
depression. These side effects along with concerns
regarding dependence to these medications impact
patient willingness to consider pharmacotherapy.
15
Therefore, despite limited evidence of efficacy and
safety, patients frequently resort to over-the-counter
medications such as diphenhydramine, dietary sup-
plements such as melatonin, and botanicals such as
valerian, chamomile, kava, passion flower, hops, and
cannabis.
17,18
In the United States, the 2018 farm bill legalized
the production of hemp and hemp-derived products
as agricultural products, removing them from their
prior designation of controlled substances.
19
This made
cannabidiol (CBD) legally available over the counter
across the United States. CBD is one of the canna-
binoids derived from the cannabis plant, and it is one
of two major cannabinoids in therapeutic use today,
the other being D
9
-tetrahydrocannabinol (THC).
20
CBD differs from THC in its lack of psychoactive
effects, making it less controversial for therapeutic use
than THC. The increased availability of CBD over the
counter has resulted in heightened marketing of CBD
for a wide variety of symptoms, including pain, anxi-
ety, cancer treatment side effects, and insomnia. The
majority of these indications are, however, not suppor-
ted by rigorous clinical studies.
Observational studies report that sleep difficulties
are one of the primary reasons for cannabis/CBD
use.
21,22
However, research on CBDs effectiveness as
a treatment for insomnia is scant and varying in
results.
23
The majority of studies evaluating cannabi-
noids and sleep have focused on the effects of THC;
very few studies have specifically examined CBD.
24–26
For example, a recent systematic review by Kuhathasan
et al
27
examining cannabinoids and sleep reported 13
studies on nabiximols (1:1 ratio of CBD to THC), but
only 1 study that examined the effectiveness of CBD
alone. Another systematic review on cannabinoids and
sleep that included at least three studies with CBD
reported improvements in several sleep outcomes but
concluded that there was insufficient evidence for
their use in clinical practice.
25
Although it appears
that cannabinoids may be beneficial in the manage-
ment of insomnia and sleep disorders, more research
is needed to determine if CBD specifically is beneficial
in the management of insomnia.
The aim of this systematic review was to evaluate
the possible benefits of CBD in the management of
insomnia. While past reviews on this topic have focu-
sed broadly on cannabinoids in the treatment of sleep
disorders, this review specifically examines the effects
of CBD on insomnia.
Methods
The protocol for this review was registered with
the PROSPERO International Prospective Register
of Systematic Reviews (ID: CRD42021257197). This
review followed the 2020 Preferred Reporting Items
for Systematic Review and Meta-Analyses (PRISMA)
guidelines.
28
Search strategies
A comprehensive search of the following databases
from inception to December 29, 2021, was conducted:
Ovid MEDLINE
and Epub Ahead of Print, In-Process
& Other Non-Indexed Citations and Daily, Ovid
Embase, Ovid Cochrane Central Register of Controlled
Trials, Ovid Cochrane Database of Systematic Reviews,
and Scopus. One reviewer also searched the reference
lists of previous reviews for relevant publications. The
specific inclusion criteria were as follows: (1) human
2 RANUM ET AL.
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participants, (2) age 18 years or older, (3) written in
English, (4) measured CBD use, and (5) at least some
participants took CBD in an equal or higher concen-
tration compared with other cannabinoids taken simul-
taneously by the individual. Studies of any design were
eligible for inclusion. Review articles, conference pro-
ceedings, book chapters, and study protocols were
excluded. The complete search strategy for each data-
base can be found in Table 1.
Article screening and data extraction
Covidence systematic review software (Veritas Health
Innovation, Melbourne, Australia) was utilized for
the article screening process. Two reviewers inde-
pendently screened each article against the eligibility
criteria by abstract and title. Articles that met the eligi-
bility criteria were then moved to the full-text screening
stage and screened by two reviewers independently.
Two reviewers then independently extracted data
from all eligible articles. Disagreements at each step
of the screening and data extraction process were set-
tled via discussion with a third reviewer.
During data extraction, only measures pertaining to
insomnia (subjective or objective difficulty in falling
asleep, staying asleep, or early awakening; restful or
refreshing sleep; sleep quality; sleep duration) or pla-
cebo were included. For these measures, data for each
time point (means and standard deviations or medians
and ranges) and intervention details were extracted.
Specific data extracted included country in which the
study was conducted, sample size, participant demo-
graphic information (sex, age, race, ethnicity, body
mass index, comorbidities, experience with canna-
bis), primary and secondary outcomes, intervention
Table 1. Search Strategies for All Databases
No.
Searches for the following databases: Embase 19881, Ovid MEDLINE
and Epub Ahead of Print, In-Process,
In-Data-Review & Other Non-Indexed Citations 19961, APA PsycInfo 19871, EBM Reviews—Cochrane Central Register
of Controlled Trials 19911, EBM Reviews—Cochrane Database of Systematic Reviews 20051
1 exp ‘‘Sleep Initiation and Maintenance Disorders’’/
2 *insomnia/
3 insomnia.ti,ab.
4 (sleep adj3 (initiat* or maintenance or maintain*) adj3 (disorder* or dysfunction)).ti,ab,hw,kw.
5 (‘‘subwakefullness syndrome*’’ or dyssomnia* or ‘‘sleep initiation dysfunction’’ or ‘‘early awakening’’ or sleeplessness or ‘‘sleep-wake transition
disorder’’).ti,ab.
6 (sleep* adj1 (disturb* or disrupt* or restrict* or duration or fragment* or hygiene or interrupt* or efficien* or continuity)).ti,ab,hw,kw.
7 or/1-6
8 (cannabidiol or epidyolex or nabidiolex or sativex).ti,ab,hw,kw. or (‘‘gwp 42003p’’ or ‘‘gwp-42003-p’’ or gwp42003p).ti,ab.
9 exp cannabidiol/
10 or/8-9
11 7 and 10
12 (conference abstract or conference review or editorial or erratum or note or addresses or autobiography or bibliography or biography or
blogs or comment or dictionary or directory or interactive tutorial or interview or lectures or legal cases or legislation or news or newspaper
article or patient education handout or periodical index or portraits or published erratum or video-audio media or webcasts).mp. or
conference abstract.st.
13 11 not 12
14 (children or child or youth or young or adolescent* or adolescence or pediatri*).ti.
15 13 not 14
16 15 not ((exp animals/or exp nonhuman/) not exp humans/)
17 limit 16 to English language
18 limit 16 to no language specified
19 17 or 18
20 remove duplicates from 19
Searches for the following database: SCOPUS
1 (TITLE-ABS-KEY (sleep W/3 (initiat* OR maintenance OR maintain*) W/3 (disorder* OR dysfunction))) OR (TITLE-ABS-KEY (sleep* W/1 (disturb*
OR disrupt* OR restrict* OR duration OR fragment* OR hygiene OR interrupt* OR efficien* OR continuity))) OR (TITLE-ABS-KEY
(‘‘subwakefullness syndrome*’’ OR dyssomnia* OR ‘‘sleep initiation dysfunction’’ OR ‘‘early awakening’’ OR sleeplessness OR ‘‘sleep-wake
transition disorder’’))
2 TITLE-ABS-KEY (cannabidiol OR epidyolex OR nabidiolex OR sativex OR ‘‘gwp 42003p’’ OR ‘‘gwp-42003-p’’ OR gwp42003p)
3 1 and 2
4 INDEX(embase) OR INDEX(medline) OR PMID(0* OR 1* OR 2* OR 3* OR 4* OR 5* OR 6* OR 7* OR 8* OR 9*)
5 3 not 4
6 DOCTYPE(ed) OR DOCTYPE(bk) OR DOCTYPE(er) OR DOCTYPE(no) OR DOCTYPE(sh) OR DOCTYPE(ch)
7 5 not 6
8 LANGUAGE(english)
9 7 and 8
CANNABIDIOL AND INSOMNIA 3
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characteristics (types of cannabinoids studied, dose
route of administration, frequency, and type of canna-
binoid strain or product), and funding sources.
Risk of bias assessment
Two reviewers independently assessed the risk of
bias utilizing the Agency for Healthcare Research and
Quality design-specific criteria.
29
The questions used
to assess the risk of bias are included in Table 2. Dis-
agreements were settled via discussion with a third
reviewer.
Data synthesis
Data were synthesized via summary tables. Study
author, year, sample demographic information,
intervention/study description, and results of CBD-
dominant/equal CBD:THC preparations on insomnia
symptoms are reported. The results of all cannabi-
noid preparations compared with placebo or baseline
for clinical trials are also summarized, along with the
risk of bias results.
Results
Study identification, screening, and inclusion
Details of the identification, screening, and inclusion of
studies are reported in Figure 1. Our primary search
identified a total of 286 studies. After duplicates
were removed, 209 studies remained for screening.
Of the 209 studies, 47 were eligible for full-text review.
Following the full-text review, 15 studies were eligible
for inclusion. An additional 19 eligible studies were
identified through citation searching, resulting in 34
studies
22,30–62
eligible for inclusion in this systematic
review.
Characteristics of included studies
Details of the included studies can be found in Table 3,
and results of clinical trials are included in Table 4.
Of the 34 studies included in this systematic review,
18 studies were clinical trials (randomized controlled
trials [n=16]
31,32,39,43,46,47,50–53,55–58,60,61
and nonran-
domized experimental studies [n=2]
34,42
), 7 were
cross-sectional studies,
22,33,35,37,44,48,49
5 were cohort
studies,
36,38,41,45,62
3 were case series,
40,54,59
and 1 was
Table 2. Agency for Healthcare Research and Quality Design-Specific Recommended Criteria Questions
and Types of Biases
Type of bias,
question number AHRQ questions
Selection bias
Q1 Was treatment adequately randomized (e.g., random number table, computer-generated randomization)?
Q2 Was the allocation of treatment adequately concealed (e.g., pharmacy-controlled randomization or use of sequentially
numbered sealed envelopes)?
Q3 Any attempt to balance the allocation between the groups?
Q4 Did the study apply inclusion/exclusion criteria uniformly to all comparison groups?
Q5 Is the selection of the comparison group appropriate?
Q6 Did the strategy for recruiting participants into the study differ across study groups?
Q7 Are baseline characteristics similar between groups? If not, did the analysis control for differences?
Q8 Does the design or analysis control account for important confounding and modifying variables?
Performance bias
Q9 Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?
Q10 Did variation from the study protocol compromise the conclusions of the study?
Attrition bias
Q11 In cohort studies, is the length of follow-up different between the groups, or in case–control studies, is the time period
between the intervention/exposure and outcome the same for cases and controls?
Q12 Was there a high rate of differential or overall attrition?
Q13 Did attrition result in a difference in group characteristics between baseline (or randomization) and follow-up?
Q14 Is the analysis conducted on an intention-to-treat basis?
Detection bias
Q15 Were the outcome assessors blinded to the intervention or exposure status of participants?
Q16 Are the inclusion/exclusion criteria measured using valid and reliable measures, implemented consistently across all study
participants?
Q17 Are interventions/exposures assessed using valid and reliable measures, implemented consistently across all study
participants?
Q18 Are primary outcomes assessed using valid and reliable measures, implemented consistently across all study participants?
Q19 Are confounding variables assessed using valid and reliable measures, implemented consistently across all study participants?
Reporting bias
Q20 Are the potential outcomes prespecified by the researchers? Are all prespecified outcomes reported?
AHRQ, Agency for Healthcare Research and Quality; Q, question.
4 RANUM ET AL.
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a case report
30
(Table 3). Only two studies
30,45
(includ-
ing one case report) focused specifically on patients
with insomnia.
The remainder of the 32 studies evaluated insomnia
symptoms in patients with cancer,
43,55,57
multiple scle-
rosis and other neurological diagnoses,
34,35,39,42,46,52,56,60,61
psychiatric disorders,
40,59
chronic pain,
36,37,51,53,58
autoimmune hepatitis,
49
brachial plexus injury,
31
rheu-
matoid arthritis,
32
fibromyalgia,
33
cannabis/CBD
users,
22,38,41,62
and healthy adults.
44,47,50,54
Insomnia
was the primary outcome in 10 studies
30,32,35,45,47,49,50,
54,59,62
and a secondary outcome for the remaining 24
studies. Other primary outcomes included pain,
31,32,
36–38,41,43,46,53,55,56,58,60,61
spasticity,
39,52,60,61
mobility,
41
anxiety and other psychiatric disorders,
30,38,40,41,54,62
fatigue/sleepiness,
49,50
urinary tract symptoms,
34,39
safety/tolerability of CBD/cannabis use,
33,42,51
and
reasons for CBD/cannabis use.
22,33,44,48
Sleep measures and outcomes
Studies utilized a variety of sleep outcomes related to
insomnia, including number of sleep disturbances per
night,
30,31,35,42,52,53,55,56
sleep quality,
31,32,36,39,40,43,44,
46,57–61
ability to fall asleep or stay asleep,
22,35,47,50
and total sleep duration
47,50,61
(Table 3). All but two
studies
47,50
used subjective self-report questionnaires
such as numeric rating scales,
31,32,35,38,39,42,43,46,52,55,
56,58
Likert scales,
33
visual analog scales,
34,60,61
purpose-
developed survey questions,
44,49
the Pittsburgh Sleep
Quality Index,
36,59
or specific questions within ques-
tionnaires such as the European Organization for the
Research and Treatment of Cancer Quality of Life
Questionnaire.
35,40,43,57
Two studies
47,50
utilized poly-
somnography to objectively measure CBDs impact
on sleep outcomes. However, the participants in both
studies were healthy adults with no preexisting insom-
nia symptoms.
CBD preparations and usage
Nineteen studies investigated the effects of CBD
monotherapy/predominant therapy on insomnia symp-
toms (seven cross-sectional studies,
22,33,35,37,44,48,49
four cohort studies,
36,38,41,45
four clinical trials,
42,47,51,60
three case series,
40,54,59
and one case report
30
)
(Table 3). Twenty-one studies investigated the effects
of products with nearly equal ratios of CBD to THC
(17 clinical trials,
31,32,34,39,42,43,46,50–53,55–58,60,61
2
cross-sectional studies,
35,37
and 2 cohort studies
38,62
).
FIG. 1. PRISMA flow diagram of identified, included, and excluded articles. PRISMA, Preferred Reporting
Items for Systematic Review and Meta-Analyses.
CANNABIDIOL AND INSOMNIA 5
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Table 3. Details of the Included Studies Examining the Use of Cannabidiol for the Management of Insomnia Symptoms
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Berger (2020)
30
Case report
Age: 20
Sex: 1 (100) M
Patients with longstanding and severe
social anxiety, depression, chronic
insomnia, and subthreshold
psychotic experiences
CBD administered for 6 months, escalated
from 200 to 800 mg/day over an 8-week
period
Chronic insomnia/sleep
disturbances—self-report
Self-reported improvement in sleep
Berman (2004)
31
Randomized crossover trial
Age: 39 (range 23–63)
Sex: 46 (95.8) M, 2 (4.2) F
Patients with brachial plexus injury
treated at the Royal National
Orthopedic Hospital
Three groups: 2.5 mg CBD +2.7 mg THC,
2.7 THC, placebo
Oromucosal spray; maximum dose of 8
sprays per 3 h interval and a maximum of
48 sprays per 24 h; baseline period of 2
weeks, followed by three 2-week
treatment periods during each of which
patients received one of three
oromucosal spray preparations
Sleep quality—NRS
Sleep disturbance—number of
times woken due to pain
Sleep quality in the THC group improved
significantly from a mean score of 4.8 at
baseline to 6.0 compared with placebo
(95% CI: 0.33 to 1.24; p<0.001), and
sleep disturbances improved
significantly from a mean score of 1.3 at
baseline to 1 compared with placebo
(95% CI: 0.49 to 0.16; p<0.001). Sleep
quality in the CBD:THC group improved
significantly from a mean score of 4.8 at
baseline to 5.9 compared with placebo
(95% CI: 0.09 to 1.01; p=0.019), and sleep
disturbances improved significantly from
a mean score of 1.3 at baseline to 1.1
compared with placebo (95% CI 0.37 to
0.04; p=0.017).
Blake (2006)
32
Randomized controlled trial
Age: 62.8 (9.8)
Sex: 12 (21) M, 46 (79) F
Patients with rheumatoid arthritis
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; Starting dose was one
actuation, increased by one actuation
every 2 days to a maximum of six
actuations, stable dosing was then
maintained for a further 3 weeks; 5-week
treatment duration
Sleep quality—single-item NRS Sleep quality improved significantly from
baseline with a difference of 1.17
relative to placebo (95% CI: 2.20 to
0.14; p=0.027).
Boehnke
(2021)
33
Cross sectional
Age: 56.6 (12)
Sex: 135 (4.3) M, 2566 (95) F
Patients with fibromyalgia
Varying/unknown routes of CBD
administration, dosages, duration, and
frequency of use
Insomnia/sleep problems—
7-point Likert scale
40.1% of participants with insomnia/sleep
problems reported ‘‘much’’ or ‘‘very
much’’ improvement following CBD use.
Brady (2004)
34
Nonrandomized experimental
Age: 48 (range 31–64)
Sex: 4 (19) M, 17 (81) F
Patients with advanced MS and
troublesome lower urinary tract
symptoms refractory to maximal
conventional treatment
Two groups: 2.5 mg THC +2.5 mg CBD,
2.5 mg THC
Oral spray; THC +CBD or THC once per day
the first 2 weeks of treatment, then a
maximum permitted daily dose was
120 mg each for CBD +THC or 120 mg
THC (48 sprays)
Difficulty sleeping—VAS (0–100) No significant differences ( p<0.05) were
found for sleep difficulties between
baseline (mean =49.78, SD =26.05) and
follow-up (mean =32.00, SD =25.95) in
the THC:CBD group.
(continued)
6
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Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Braley (2020)
35
Cross sectional
Age: 51.2 (12.3)
Sex: 239 (19.6) M, 978 (80.4) F
Patients with MS
Preferred THC:CBD ratio: low THC +low
CBD, high THC +high CBD, CBD
monotherapy or predominant therapy,
THC monotherapy or predominant
therapy
Varying/unknown routes of administration,
dosages, and frequency of use
Ability to fall asleep—NRS
(0–10)
Ability to stay asleep—NRS
(0–10)
More restful/refreshing sleep—
NRS (0–10)
Relieves pain that interferes with
sleep—NRS (0–10)
Sleep disturbance—PROMIS
Sleep Disturbance—8b
(normed T scores [range
0–100, mean =50, SD =10])
In the low THC +low CBD group, 43%
reported improved ability to fall asleep,
14% improved ability to stay asleep, 29%
more restful/refreshing sleep, 29%
relieves pain that interferes with sleep.
In the high THC +high CBD group, 75%
reported improved ability to stay asleep,
53% improved ability to stay asleep, 33%
more restful/refreshing sleep, 69%
relieves pain that interferes with sleep. In
the CBD monotherapy or predominant
therapy group, 42% reported improved
ability to stay asleep, 36% improved
ability to stay asleep, 22% more restful/
refreshing sleep, 38% relieves pain that
interferes with sleep.
Capano (2020)
36
Cohort
Age: 56.1 (range 39–70)
Sex: 31 (32) M, 66 (68) F
Patients with chronic pain who have
been on opioids for at least 1 year
Oral soft gels; *30 mg CBD-rich extract
daily for 8 weeks
Sleep quality—PSQI (0–21) Sleep quality significantly improved from
12.09 at baseline (95% CI 11.37 to 12.80)
to 10.7 at 4 weeks (95% CI 9.99 to 11.44)
to 10.3 at 8 weeks (95% CI 9.48 to 11.20;
p=0.03).
Carrubba (2021)
37
Cross sectional
Age: 44.1 (13.9)
Sex: 96 (100) F
Patients with diagnosis of pelvic and
perineal pain, dyspareunia, or
endometriosis
Three groups: CBD-dominant, THC-
dominant, THC +CBD
Varying/unknown routes of administration,
dosages, and frequency of use
Sleeplessness and insomnia—
self-reported
50% (n=3) of participants taking CBD
reported improvement in sleep. 100%
(n=3) of participants taking THC
reported improvement. 73.3% (n=11) of
participants taking THC +CBD reported
improvement.
Casarett (2019)
38
Cohort
Age: (of those with insomnia) 34 (range
18–76)
Sex: (of those with insomnia) 375
(43.2%) M, 494 (56.8%) F
Patients who self-reported cannabis use
for a variety of symptoms
Continuum: high and low CBD
concentration compared with THC
Vaporizer; varied/unknown dosage and
duration of use
Insomnia—self-ratings of
efficacy of cannabis, defined
as a 3-point reduction in
insomnia (0–10 NRS)
For participants taking 100% CBD, slightly
less than 45% reported a 3-point
improvement in their insomnia. More
participants taking roughly equal
CBD:THC concentrations reported a
3-point improvement in their insomnia
than participants taking 100% CBD.
Collin (2010)
39
Randomized controlled trial
Age: 47.5 (9.61)
Sex: 130 (39) M, 207 (61) F
Patients with MS with spasticity and not
relieved with current therapy
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; maximum dose of
8 sprays per 3 h interval and a maximum
of 48 sprays per 24 h; 14-week treatment
duration
Sleep quality—NRS (0–10) Sleep quality did not improve significantly
from baseline compared with placebo
(mean =0.07; p=0.764).
Elms (2019)
40
Case series
Age: 39.9 (17.4)
Sex: 3 (27.3) M, 8 (72.7) F
Patients with PTSD
Liquid, capsular, or both; mean total
starting dose of CBD per day was
33.18 mg (SD =23.34). Mean total dose
of CBD at the 8-week follow-up
appointment at the conclusion of the
study period was 48.64 mg (range:
2–100)
Sleep quality—PCL-5 (asks
about ‘‘trouble falling or
staying asleep’’)
38% (n=8) of participants reported
subjective improvement in the quality of
their sleep.
(continued)
7
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Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Gulbransen
(2020)
41
Cohort
Age: 51.48 (19.1)
Sex: 183 (46.1) M, 214 (53.9) F
Patients seen in Cannabis Care, a
primary care clinic (either referred by
their primary care provider or self-
referred to the service) prescribed
CBD
Oral dropper; 40–300 mg/day of CBD
(clinician-recommended dosing to at
least 100 mg/day)
‘‘Improved sleep’’—assessed as
part of positive side effect
profile of study
12.3% (n=31) of participants reported
improved sleep as a side effect.
Gustavsen
(2021)
42
Nonrandomized experimental
Age: 50 (range 27–74)
Sex: 7 (25) M, 21 (75) F
Patients with MS and refractory
neuropathic pain and/or spasticity
Four groups: THC-dominant, CBD-
dominant, high THC +low CBD, equal
THC:CBD
Sublingual drops; measured at baseline and
4-week follow-up
Sleep disturbances—NRS (1–11) Sleep disturbances significantly decreased
in patients taking THC-containing
preparations from a median score of 7.0
(range: 0.0–9.0) to 3.0 (range: 0.0–10;
p<0.01), and sleep disturbances also
decreased in patients taking CBD-
dominant products from a median score
of 8.0 (range: 3.0–10) to 0.0 (range
0.0–1.0; p=0.07).
Johnson (2010)
43
Randomized controlled trial
Age: 60.2 (12.3)
Sex: 95 (54) M, 85 (46) F
Patients previously using strong opioids
for at least 1 week to relieve pain
associated with advanced cancer
Three groups: 2.7 mg THC +2.5 mg CBD,
2.7 mg THC, placebo
Oromucosal spray; maximum permitted
dose was 8 actuations in any 3-h period
and 48 actuations in any 24-h period;
2 weeks
Sleep quality—NRS (0–10)
Insomnia—EORCT QLQ-C30
No significant group differences were
found for sleep quality (mean
difference =0.31, p=0.346) or insomnia
(mean difference =1.05, p=0.833)
between the THC:CBD and placebo
group (placebo statistics not reported).
Kasper (2020)
44
Cross sectional
Age: 25 (5)
Sex: 517 (100) M
Professional United Kingdom rugby
players
Oils or capsules; varying/unknown dosages
and concentrations of CBD
Purpose-developed survey—
‘‘for what reasons do/did you
use CBD—improve sleep
quality’’
78% of respondents who reported using
CBD cited sleep difficulties as their
reason for CBD use. Of those who
reported sleep difficulties as their reason
for taking CBD, 41% endorsed ‘‘improved
sleep’’ as a perceived benefit.
Kuhathasan
(2021)
45
Cohort study
Age: 36.32 (11.65)
Sex: 42.6% (422/991) self-identified M,
56.1% (556/991) self-identified F
Canadian medicinal cannabis users with
insomnia who used the medicinal
cannabis tracking app ‘‘Strainprint’’ to
monitor changes in insomnia
symptoms
Varying/unknown routes of cannabinoid
(CBD, balanced hybrid, indica, indica
hybrid, sativa, sativa hybrid) strains
administration, dosages, duration, and
frequency of use
Insomnia symptom severity
rating—self-reported
Insomnia symptoms improved significantly
(p<0.001) from baseline for cannabinoid
strains of CBD with a change score of
3.074027 (0.114947), balanced hybrid
with a change score of 3.461359
(0.112701), indica with a change score of
3.661426 (0.094507), indica hybrid with a
change score of 3.589259 (0.097939),
sativa with a change score of 2.916945
(0.163117), and sativa hybrid with a
change score of 3.470149 (0.171074).
Langford (2013)
46
Randomized controlled trial
Age: A: 48.97 (10.47), B: 48.01 (10.12)
Sex: A: 109 (32) M, B:17 (40) M; A: 230
(68) F, B: 230 (68) F
Patients with MS and chronic
neuropathic pain
Two (and two phases): 2.5 mg CBD
+2.7 mg THC, placebo
Oromucosal spray; Patients were restricted
to a maximum of 12 sprays per 24-h
period (Phase B escalated dose to
12 daily sprays); A: 14 weeks, B: 18 weeks
Sleep quality—NRS (0–10) Sleep quality did not improve significantly
from baseline in phase A with a
difference of 1.96 relative to placebo
(p=0.833). Sleep quality improved
significantly from baseline in phase B
with a difference of 0.07 relative to
placebo ( p=0.015)
(continued)
8
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Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Linares (2018)
47
Randomized crossover trial
Age: 29.3 (8.5)
Sex: 12 (46) M, 14 (54) F
Healthy volunteers with no sleep
problems
Two groups: 300 mg CBD, placebo
Oral gelatin; CBD or placebo was
administered 30 min before the
polysomnographic recordings began
Sleep onset latency—
polysomnography (minutes)
Sleep efficiency—
polysomnography (%)
Total sleep time—
polysomnography (minutes)
No significant differences ( p>0.05) were
found between the administration of CBD
compared with placebo for sleep onset
latency (mean =9.8, SD =8.4; mean =13.4,
SD =12.8), sleep efficiency (mean =87.1,
SD =10.2; mean =85.3, SD =13.2), or total
sleep time (mean =388.1, SD =51.4;
mean =389.3, SD =66.2).
Lovecchio
(2021)
48
Cross sectional
Age: 58.0 (14.5)
Sex: 123 (58%) M, 91 (42%) F
Patients presenting for evaluation by
one of nine spine surgeons at a single
center in New York, New York, during
October 2019
Varying/unknown routes of CBD
administration, dosages, duration, and
frequency of use
Use of CBD for insomnia (yes/
no) and if improved sleep was
a benefit experienced from
CBD (yes/no)—self-reported
25.9% (n=14) of participants used CBD for
insomnia and 33.3% (n=18) of
participants reported improved sleep as
a benefit experienced from CBD.
Mathur (2020)
49
Cross sectional
Age: median 49 (range 38–59)
Sex: 32 (8.6) M, 339 (91.4) F
Adults with AIH
Sublingual drops, oral capsule, inhalation,
topically; varying/unknown dosages,
duration, and frequency of CBD use
Purpose-developed survey—
questions about reasons for
CBD use and if symptoms
improved with CBD use
93% (54/59) of participants who endorsed
CBD use reported improvement in sleep.
Moltke (2021)
22
Cross sectional
Age: 3.9%, 18–24; 23.9%, 25–34; 24.9%,
35–44; 23.4%, 45–54; 14.3%, 55–64;
9.4%, 65 +
Sex: 150 (38.8) M, 237 (61.2) F
Current/past CBD users identified via
email databases of CBD brands/
retailers and social media
Varying/unknown routes of CBD
administration, dosages, duration, and
frequency of use
Time to fall asleep—Self-
reported
48.2% (73/124) reported CBD helped them
fall asleep faster (23.4% reported CBD
did not make a difference and they still
had a hard time falling asleep).
Nicholson
(2004)
50
Randomized crossover trial
Age: M 28.8 (range 24–34), F 21.8
(21–22)
Sex: 4 (50) M, 4 (50) F
Healthy young adults without
significant medical or psychiatric
conditions
Four groups: 15 mg THC, 5 mg THC +5mg
CBD, 15 mg THC +15 mg CBD, placebo
Oromucosal spray; doses given via six
actuations over the course of 30 min
beginning at 10 pm
Sleep onset latency—
polysomnography (minutes)
Sleep efficiency index—
polysomnography (log)
Total sleep time—
polysomnography (minutes)
Number of awakenings
No significant differences ( p>0.05) were
found between the administration of
5 mg THC +5 mg CBD (mean =22.56) or
15 mg THC +15 mg CBD (mean =23.5)
compared with placebo (mean =24.63)
for sleep onset latency. No significant
differences ( p>0.05) were found
between the administration of 5 mg THC
+5 mg CBD (mean =0.92) or 15 mg THC
+15 mg CBD (mean =0.84) compared
with placebo (mean =0.89) for sleep
efficiency. No significant differences
(p>0.05) were found between the
administration of 5 mg THC +5 mg CBD
(mean =443.83) or 15 mg THC +15 mg
CBD (mean =404.56) compared with
placebo (mean =429.13) for total sleep
time. No significant differences ( p>0.05)
were found between the administration
of 5 mg THC +5 mg CBD (mean =12.5) or
15 mg THC +15 mg CBD (mean =14.25)
compared with placebo (mean =13.63)
for number of awakenings.
(continued)
9
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Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Notcutt (2004)
51
Randomized crossover trial (34 N of 1)
Age: 46.7 (10.1)
Sex: 11 (32.4) M, 23 (67.6) F
Patients with chronic stable pain, poorly
responsive to other modalities of
control
Four groups: 2.5 mg CBD, 2.5 mg of THC,
2.5 mg THC +2.5 mg CBD, placebo
Sublingual spray; individually titrated, in
each group for two separate 1-week
periods
Duration of sleep (hours)—self-
reported
Quality of sleep—self-reported
(Good, Fair, Poor)
Participants reported significantly better
sleep quality when taking 2.5 mg CBD
(IQR =36.9, range =47.9–28.6), 2.5 mg of
THC (IQR =42.9, range =57.2–35.7), or
2.5 mg THC +2.5 mg CBD (IQR =55.4,
range =78–34.5) compared with placebo
(IQR =17, range =35.7–3.6); p<0.05).
There were no mean differences
between the CBD (mean =6.4, SD =1.4),
THC (mean =6.7, SD =1.3), or THC +CBD
(mean =6.8, SD =1.3), and placebo
(mean =6.3, SD =1.6) in their effect on
sleep duration.
Novotna (2011)
52
Randomized controlled trial
Age: 48.6 (9.33)
Sex: 96 (40) M, 145 (60) F
Patients with MS spasticity not fully
relieved with current antispasticity
therapy
(Phase B) Two groups: 2.5 mg CBD +2.7 mg
THC, placebo
Oromucosal spray; maximum of 12 sprays
in any 24-h period, 12-week study
duration
Sleep disturbance—NRS Participant scores in the CBD +THC group
differed by a mean of 0.13 from
baseline compared with placebo scores,
which differed by a mean of 0.75. The
group mean scores were significantly
different with a mean difference
between groups of 0.88 ( p<0.0001).
Nurmikko
(2007)
53
Randomized controlled trial
Age: Sativex: 52.4 (15.8), placebo: 54.3
(15.2)
Sex: 51 (40.8) M, 74 (59.2) F
Patients with unilateral peripheral
neuropathic pain and allodynia
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; maximum dose of
8 sprays per 3-h interval and a maximum
of 48 sprays per 24 h; 5-week treatment
duration
Sleep disturbance—single item
rating the number of times
they woke in the previous
night due to symptoms
Sleep disturbances improved significantly
from baseline with a mean difference of
0.43 relative to placebo (95% CI 0.67
to 0.19; p=0.001).
Pacheco
(2021)
54
Case series
Age: 32.5 (6.9)
Sex: 6 (46.1) M, 7 (53.8) F
Non-frontline hospital employees
(individuals in administration,
teaching, research) during the
COVID-19 pandemic
Oral dose; 165 mg CBD twice a day; 3-week
treatment duration
Insomnia—7-item Insomnia
Severity Index
CBD was associated with significant
improvements in insomnia ( p<0.05).
Portenoy
(2012)
55
Randomized controlled trial
Age: 58 (12.2)
Sex: 186 (51.7) M, 174 (48.3) F
Opioid-treated cancer patients with
poorly controlled chronic pain
Four groups: (all 2.5 mg CBD +2.7 mg THC
per spray) 1–4 sprays per day, 6–10
sprays per day, 11–16 sprays per day,
placebo
Oromucosal spray; 35-day study duration
Sleep disturbance—NRS (0–10) Participant scores in the low-dose group
differed by a mean of 0.88 from
baseline, the medium-dose group
differed by 0.33, and the high-dose
group differed by 0.08. The mean
change scores were significantly
different from placebo for only the low-
dose group ( p=0.003).
(continued)
10
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Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Rog (2005)
56
Randomized controlled trial
Age: 49.2 (8.3)
Sex: 14 (21.2) M, 52 (78.8) F
Patients with central neuropathic pain
syndromes due to MS
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; Patients were advised to
increase the number of sprays stepwise
on consecutive days up to 48 sprays in
24 h, patients were advised to take no
more than 8 sprays within any 3 h
interval and refrain from up-titrating the
daily dose by more than 50% from the
previous day; 4-week treatment duration
Sleep disturbance due to pain—
NRS-11
Sleep disturbances improved significantly
from baseline with a difference of 1.39
relative to placebo (95% CI 2.27 to
0.50; p=0.003).
Schloss (2021)
57
Randomized controlled trial
Age: 53.3 (12.6)
Sex: 42 (50.6) M, 41 (49.4) F
Patients with high-grade gliomas
Two groups: 4.8 mg CBD +4.6 mg THC,
3.8 CBD +15 mg THC
Single dose at night before bed that was
titrated up to tolerance starting at
0.20 mL (maximum 5 mL in one dose);
12-week treatment duration
Sleep quality—Functional
Assessment of Cancer
Therapy for Brain Cancer
Sleep improved in both groups (statistical
significance for each group separately is
unknown).
Serpell (2014)
58
Randomized controlled trial
Age: 57.3 (14.2)
Sex: 96 (39) M, 150 (61) F
Patients with peripheral neuropathic
pain and associated allodynia
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; maximum of 8 sprays in
a 3-h period up to a maximum of
24 sprays per 24-h period; 14-week
treatment duration
Sleep quality—NRS (0–10) Sleep quality improved significantly from
baseline with a mean difference of
0.83 relative to placebo (mean =0.306;
p=0.007).
Shannon
(2019)
59
Case series
Age: anxiety: 34 (range: 18–70), sleep:
36.5 (range: 18–72)
Sex: M with anxiety: 28 (59.6), with sleep
disorders: 9 (36.0); F with anxiety: 19
(40.4), with sleep disorders: 16 (64.0)
Consecutive adult patients treated with
CBD at an outpatient psychiatry
practice
Most oral capsule; patients received
25 CBD mg/day; measured at baseline
and monthly for 3 months
Sleep quality—PSQI (0–21) On average, sleep improved for most
patients, and these improvements were
sustained over time. For patients with
anxiety, sleep quality scores changed
from a mean of 10.98 (3.43) at baseline
to 9.25 (2.46) at the 3-month follow-up.
For patients with sleep disorders,
scores changed from 13.08 (3.03) at
baseline to 9.33 (4.63) at the 3-month
follow-up.
Wade (2003)
60
Randomized crossover trial
Age: 48
Sex: 10 (50) M, 10 (50) F
Patients with a neurological diagnosis
and troublesome symptoms
(neuropathic pain, spasticity, muscle
spasms, impaired bladder control,
and tremor), which were stable and
unresponsive to standard treatments
Four groups: 2.5 mg CBD, 2.5 mg THC,
2.5 mg THC +2.5 mg CBD, placebo
Sublingual spray; max dose of 120 mg/24 h,
2 weeks per preparation
Sleep quality—VAS (1–10) Participants reported significantly better
sleep quality when taking 2.5 mg THC
+2.5 mg CBD (mean =65.3, SD =22.6)
compared with placebo (mean =59,
SD =24.4; p<0.05), but no differences
between the placebo and 2.5 mg CBD
(mean =57.9, SD =25.2) or 2.5 mg THC
(mean =61.7, SD =25.4; p>0.05).
(continued)
11
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CBD-containing products were administered through
various routes, including oromucosal or sublingual
sprays/drops,
31,32,34,39–41,43,44,46,49–56,58,60,61
oral capsules/
gelatine,
40,44,47,49,59
inhalation,
38,49
or topical applica-
tion
49
with varying dose and frequency. For studies
that reported the quantity of CBD used, doses ranged
from 2.5 mg of CBD to 330 mg daily.
Effects of CBD on insomnia symptoms
All the 34 studies reported some level of improve-
ment in the insomnia symptoms of at least a portion
of their participants following the administration of
CBD-containing products (Table 3). Of the 19 studies
that investigated the effects of CBD monotherapy/
predominant therapy on insomnia symptoms, 7 stud-
ies
36,42,45,47,51,54,60
tested for significant versus insignif-
icant improvement compared with baseline or placebo.
Four of these studies reported statistically significant
improvements in insomnia symptoms (two cohort
studies,
36,45
one case series,
54
and one clinical trial
51
).
Of the 21 studies that investigated the effects of
products with nearly equal ratios of CBD to THC, 16
studies
31,32,34,39,42,43,46,50–53,55,56,58,60,61
tested for signif-
icant versus insignificant improvement compared with
baseline or placebo. Twelve of these studies reported
statistically significant improvements in insomnia
symptoms (12 clinical trials
31,32,42,46,51–53,55,56,58,60,61
).
Risk of bias
A similar number of studies had low versus high risk
of bias (Table 5). Overall, 16 studies had a low risk of
bias (15 clinical trials
31,32,39,43,46,47,50,52,53,55–58,60,61
and 1 cross-sectional study
33
), 4 studies had a moder-
ate risk of bias (2 case series/case reports,
30,59
1 cohort
study,
45
and 1 clinical trial
51
), and 14 studies had a
high risk of bias (6 cross-sectional studies,
22,35,37,44,48,49
4 cohort studies,
36,38,41,62
2 case series/case reports,
40,54
and 2 clinical trials
34,42
). Common problems among
studies with cohort designs included not attempting
to balance the allocation between the groups, not
selecting an appropriate comparison group, and not
having similar baseline characteristics between the
groups.
Additionally, only clinical trials addressed the
impact from concurrent interventions or unintended
exposure that might bias results. Thirteen studies
22,30,
35–38,40,41,44,48,54,59,62
did not assess confounding vari-
ables using valid and reliable measures. Seventeen
studies
22,30,34–38,40–42,44,48–50,54,59,62
did not have out-
come assessors blinded to the intervention or exposure
Table 3. Continued
First author
(year)
Study design and sample
characteristics (age [years]*;
sex, M, F, n(%);
population description)
Intervention (cannabinoid type,
dose, and timing)
Insomnia measure
(insomnia outcome,
measure utilized)
Findings related to CBD
and insomnia
Wade (2004)
61
Randomized controlled trial
Age: Active group: 51.0 (9.4); 27–74
Placebo: 50.4 (9.3); 27–74
Sex: 61 (38.1) M, 99 (61.9) F
Patients with MS
Two groups: 2.5 mg CBD +2.7 mg THC,
placebo
Oromucosal spray; maximum of 120 mg
THC and 120 mg CBD per day with no
more than 20 mg of each in any 3-h
period; 6-week treatment duration
Sleep quality—VAS
Sleep duration
Sleep quality improved significantly from
baseline with a difference of 7.1
compared with placebo ( p=0.047).
Sleep disturbances did not improve
significantly from baseline with a
difference of 9.4 compared with
placebo ( p=0.198).
Wan (2017)
62
Cohort
Age: 44.9 (range 1–80)
Sex: M 575 (68.8), F 259 (30.9)
Online survey of patients using medical
cannabis from one Canadian licensed
provider
Of 15 cannabis strains reported, the 2 that
included CBD were Midnight (11–14%
CBD +8–11% THC) and Avidekel
(15–18% CBD +15–18% THC)
Varying/unknown routes of administration
and dosage, 4-month study duration
Sleep disorder—self-reported
severity
Sleep problems—self-reported
severity
Sleep—self-reported severity
Of the cannabis strains, Midnight was
ranked third for improving sleep
disorders. Midnight was ranked second
and Avidekel was ranked third for
improving sleep problems. Midnight was
ranked first and Avidekel was ranked
third for improving sleep.
*Mean (SD) unless otherwise noted.
AIH, autoimmune hepatitis; CBD, cannabidiol; CI, confidence interval; EORCT QLQ-C30, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire; F, female;
IQR, interquartile range; M, male; MS, multiple sclerosis; NRS, numerical rating scale; PCL-5, Post-traumatic Stress Disorder Checklist; PROMIS, Patient-Reported Outcomes Measurement Information
System; PSQI, Pittsburgh Sleep Quality Index; PTSD, post-traumatic stress disorder; SD, standard deviation; THC, D
9
-tetrahydrocannabinol; VAS, visual analog scale.
12 RANUM ET AL.
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status of participants. Attrition was also a potential
problem for 19 studies.
32,34,36,38–43,45,47,51–53,55,57,60–62
Discussion
The results of this systematic review suggest that CBD,
either alone or in combination with equal amounts of
THC, may be beneficial in the management of comor-
bid insomnia in patients with cancer, multiple sclero-
sis, psychiatric disorders, chronic pain, and PTSD.
However, because only two included studies focused
on patients with insomnia (including one case report),
these results cannot be generalized to patients with
primary insomnia.
Our results are consistent with previous reviews
examining the effects of CBD on sleep outcomes. For
example, a systematic review by Khan et al
63
examined
the therapeutic benefits of CBD in psychiatric disorders
and reported that CBD may be beneficial in patients
with insomnia related to seasonal affective disorder
and PTSD. However, based on the level of evidence,
the authors graded their recommendation for the use
of CBD for insomnia as weak. The results of another
systematic review that evaluated the use of THC
alone or THC in combination with CBD for sleep out-
comes in patients with multiple sclerosis, PTSD, and
chronic pain also concurred with the results of our
study.
27
However, the authors reported several short-
comings, including a dearth of studies in which sleep
was the primary outcome and the use of nonvalidated
questionnaires to measure sleep outcomes.
Although the initial goal of this review was to exclu-
sively evaluate CBD (and not THC) for insomnia, it
became clear following our literature searches that
there were few clinical studies with CBD alone that
included sleep as an outcome. Consequently, we elected
to include all studies that had a treatment arm with
Table 4. Insomnia Outcome Results of All Cannabinoid Preparations in Clinical Trials
First author (year)
CBD:THC ratio
100%
CBD/CBD-
dominant
Equal
CBD/THC
100%
THC/THC-
dominant
Berman (2004)31
—
Blake (2006)32
—
—
Brady (2004)34
—
Collin (2010)39
—
—
Gustavsen (2021)42,a
Johnson (2010)43
—
Langford (2013)46
—
—
Linares (2018)47
—
—
Nicholson (2004)50
—
Notcutt (2004)51
Novotna (2011)52
—
—
Nurmikko (2007)53
—
—
Portenoy (2012)55
—
—
Rog (2005)56
—
—
Schloss (2021)57,b
Serpell (2014)58
—
—
Wade (2003)60
Wade (2004)61
—
—
— Signifies no preparation in that category identified; vertical lines signify significant benefits in at least one insomnia outcome compared with
placebo (or baseline if no placebo was included); diagonal lines signify benefits (although insignificant) in at least one insomnia outcome compared
with placebo (or baseline if no placebo was included); solid fill signifies no benefits in any insomnia outcome compared with placebo (or baseline if no
placebo was included).
a
All THC-containing products were analyzed for significance together.
b
No statistical comparisons by group were reported.
CANNABIDIOL AND INSOMNIA 13
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Table 5. Risk of Bias of Individual Studies Using the Agency for Healthcare Research and Quality Design-Specific Recommended Criteria
Study design,
first author (year) Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 Q16 Q17 Q18 Q19 Q20 Total Percent Risk of bias
Clinical trials
Berman (2004)
31
11———11—11—1111111—114100 Low
Blake (2006)
32
11———01—11—1011111—112 85.7 Low
Collin (2010)
39
00———11—01—0111111—110 71.4 Low
Johnson (2010)
43
10———11—11—0111111 112 85.7 Low
Langford (2013)
46
11———11—11—1111111—114100 Low
Linares (2018)
47
11———11 11—1101111 113 92.9 Low
Nicholson (2004)
50
00———11 11—1110111—111 78.6 Low
Novotna (2011)
52
11———11—11—0101111—112 85.7 Low
Nurmikko (2007)
53
11———11—10—0011111—111 78.6 Low
Portenoy (2012)
55
11———11 11—0011110—111 78.6 Low
Rog (2005)
56
11———11—10—1111111—113 92.9 Low
Schloss (2021)
57
11 11—01—0011111—111 78.6 Low
Serpell (2014)
58
11———11—11—1111111—114100 Low
Wade (2003)
60
11———11—11—1101111—113 92.9 Low
Wade (2004)
61
11———11—11—1101111—113 92.9 Low
Notcutt (2004)
51
11———11—00—1101010—1 9 64.3 Moderate
Brady (2004)
34
00———11—01—0000111—0 6 42.9 High
Gustavsen (2021)
42
00———10—00—0000110—1 4 28.6 High
Cross sectional
Boehnke (2021)
33
——————— 0 0 — — — 1 — 1 1 1 1 1 1 7 77.8 Low
Braley (2020)
35
——————— 0 0 — — — 1 — 0 1 1 1 0 1 5 55.6 High
Carrubba (2021)
37
——————— 0 0 — — — 1 — 0 1 1 1 0 1 5 55.6 High
Kasper (2020)
44
——————— 0 0 — — — 1 — 0 1 0 0 0 1 3 33.3 High
Lovecchio (2021)
48
——————— 0 0 — — — 1 — 0 1 0 0 0 1 3 33.3 High
Mathur (2020)
49
——————— 0 0 — — — 1 — 0 1 1 0 1 0 4 44.4 High
Moltke (2021)
22
——————— 1 0 — — — 1 — 0 0 0 0 0 1 3 33.3 High
Cohort
Kuhathasan (2021)
45
——01010001111011111112 66.7 Moderate
Capano (2020)
36
——010100011000011101 8 44.4 High
Casarett (2019)
38
——011100001110001101 9 50 High
Gulbransen (2020)
41
——010100001000011101 7 38.9 High
Wan (2017)
62
——000100001000000001 3 16.7 High
Case series/case report
Shannon (2019)
59
——————— 0 0 1 — — 1 — 0 1 1 1 0 1 6 60 Moderate
Berger (2020)
30
——————— 0 0 1 — — 1 — 0 1 1 1 0 1 6 60 Moderate
Elms (2019)
40
——————— 0 0 1 — — 0 — 0 1 1 1 0 1 5 50 High
Pacheco (2021)
54
——————— 0 0 0 — — 1 — 0 1 1 1 0 1 5 50 High
Articles with a score less than 60% of the highest possible score are designated as high risk of bias; articles with a score 60%–69.9% of the highest possible score are designated as moderate risk
of bias; articles with a score greater than or equal to 70% of the highest possible score are designated as low risk of bias.
—Signifies that question is not relevant to the study design; 1 signifies desirable, low risk of bias answer to question; 0 signifies undesirable, high risk of bias answer to question (including
‘‘unsure’’). Questions can be found in Table 2.
14
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CBD in equal or higher concentration compared with
other cannabinoids. This decision resulted in the inclu-
sion of studies with nabiximols (which have a nearly
equal ratio of THC to CBD). In these studies, it is dif-
ficult to differentiate the specific effects of CBD versus
THC, and nabiximols require further study.
For example, high doses of CBD have been shown
to be sedative while also being nonintoxicating and
having a low addiction risk.
64
THC, however, is psy-
choactive and with chronic use may decrease sleep
latency, interfere with the circadian sleep–wake cycle,
reduce somnolence (while increasing daytime sleepi-
ness and delaying sleep onset the next night), and
decrease slow-wave sleep.
24,64,65
However, given that
the 12 studies using nearly equal ratios of CBD to
THC found significant improvements in insomnia out-
comes, it is possible that CBD balances the effects of
THC on sleep and the combination of the 2 cannabi-
noids may be synergistic for insomnia.
Study limitations
Our study had several limitations. First, only three
clinical trials in this systematic review investigated
CBD monotherapy/predominant therapy, and none
of these three studies were conducted in patients
with insomnia (one focused on healthy adults, one on
patients with neurological diagnoses, and one on pati-
ents with chronic pain). Second, only 1 study
50
of the
34 studies reported being specifically powered to detect
insomnia-related outcomes. Third, the majority of the
studies lacked objective measures of insomnia, and sev-
eral studies used nonvalidated instruments to measure
insomnia symptoms. Fourth, there was a high degree
of variability in outcomes and treatments. Finally,
nearly half of our included studies had a high risk of
bias.
Conclusions
Despite these limitations, the results of our systematic
review suggest that CBD (alone or in combination
with THC) may be helpful in managing insomnia
symptoms. Additional studies examining the effects
of CBD in patients with insomnia are needed, particu-
larly studies that use validated subjective and objec-
tive measures to assess insomnia, before CBD can be
strongly recommended in clinical practice.
Availability of Data and Material
The data supporting the conclusions of this article are
available from the corresponding author upon request.
Acknowledgments
The authors would like to acknowledge Mayo Clinic
Librarians Leslie Hassett, MLS, and Julie Taylor,
MLS, for their valuable help in conducting literature
searches for this systematic review.
Authors’ Contributions
R.M.R., M.O.W., L.L.T., and A.V. were responsible
for the conception and design of the work. R.M.R.,
M.O.W., and A.V. were responsible for the acquisition
and interpretation of data. All authors were involved in
drafting the article, critically revised it for intellectual
content, and approved the final version of the article.
Author Disclosure Statement
No competing interests have been declared by the
authors.
Funding Information
No funding was received for this systematic review.
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Cite this article as: Ranum RM, Whipple MO, Croghan I, Bauer B,
Toussaint LL, Vincent A (2022) Use of cannabidiol in the management
of insomnia: a systematic review, Cannabis and Cannabinoid Research
X:X, 1–17, DOI: 10.1089/can.2022.0122.
Abbreviations Used
AHRQ ¼Agency for Healthcare Research and Quality
AIH ¼autoimmune hepatitis
CBD ¼cannabidiol
CBT ¼cognitive behavioral therapy
CI ¼confidence interval
EORCT QLQ-C30 ¼European Organization for the Research
and Treatment of Cancer Quality of Life
Questionnaire
F¼female
IQR ¼interquartile range
M¼male
MS ¼multiple sclerosis
NRS ¼Numerical Rating Scale
PCL-5 ¼Post-traumatic Stress Disorder Checklist
PRISMA ¼Preferred Reporting Items for Systematic
Review and Meta-Analyses
PROMIS ¼Patient-Reported Outcomes Measurement
Information System
PSQI ¼Pittsburgh Sleep Quality Index
PTSD ¼post-traumatic stress disorder
Q¼question
SD ¼standard deviation
THC ¼D
9
-tetrahydrocannabinol
VAS ¼visual analog scale
CANNABIDIOL AND INSOMNIA 17
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