ArticlePDF Available

A cross-sectional and prospective comparison of medicinal cannabis users and controls on self-reported health

Authors:
  • Roswell Park Comprehensive Cancer Center

Abstract and Figures

Introduction: Despite widespread legalization, the impact of medicinal cannabis use on patient-level health and quality of life (QOL) has not been carefully evaluated. The objective of this study was to characterize self-reported demographics, health characteristics, QOL, and health care utilization of Cannabis Users compared with Controls. Methods: A longitudinal, cross-sectional web-based survey study was completed between April 2016 and February 2018. Study participants (n=1276) were a convenience sample of either patients with a diagnosed health condition or caregivers of a patient with a diagnosed health condition registered with the Realm of Caring Foundation (a nonprofit organization dedicated to therapeutic cannabis research and education). Participants were invited through e-mail to complete follow-up assessments every 3 months with 33% of participants completing one or more prospective follow-ups. Assessments included self-reported demographics, health care utilization, medication use, pain, anxiety, depression, sleep, and QOL. Cannabis Users (n=808) were compared with Controls (n=468) using negative binomial regression and linear mixed effects models testing the effect of initiation, cessation, and maintenance of medicinal cannabis use. Results: Cannabis Users self-reported significantly better QOL [t(1054)=−4.19, p<0.001], greater health satisfaction [t(1045)=−4.14, p<0.001], improved sleep [children: t(224)=2.90, p<0.01; adults: [t(758)=3.03, p<0.01], lower average pain severity [t(1150)=2.34, p<0.05], lower anxiety [t(1151)=4.38, p<0.001], and lower depression [t(1210)=5.77, p<0.001] compared with Controls. Cannabis Users reported using fewer prescription medications (rate ratio [RR]=0.86; 95% confidence interval [CI]: 0.77–0.96) and were less likely to have a past-month emergency department visit (RR=0.61; 95% CI: 0.44–0.84) or hospital admission (RR=0.54; 95% CI: 0.34–0.87). Controls who initiated cannabis use after baseline showed significant health improvements at follow-up, and the magnitude of improvement mirrored the between-group differences observed at baseline. Conclusions: Cannabis use was associated with improved health and QOL. Longitudinal testing suggests that group differences may be due to the medicinal use of cannabis. Although bias related to preexisting beliefs regarding the health benefits of cannabis in this sample should be considered, these findings indicate that clinical trials evaluating the efficacy of defined cannabinoid products for specific health conditions are warranted.
Content may be subject to copyright.
A Cross-Sectional and Prospective Comparison
of Medicinal Cannabis Users and Controls
on Self-Reported Health
Nicolas J. Schlienz,
1
Ryan Scalsky,
2
Erin L. Martin,
3
Heather Jackson,
4
Joel Munson,
4
Justin C. Strickland,
5
Marcel O. Bonn-Miller,
6
Mallory Loflin,
7,8
and Ryan Vandrey
5,
*
Abstract
Introduction: Despite widespread legalization, the impact of medicinal cannabis use on patient-level health and
quality of life (QOL) has not been carefully evaluated. The objective of this study was to characterize self-reported
demographics, health characteristics, QOL, and health care utilization of Cannabis Users compared with Controls.
Methods: A longitudinal, cross-sectional web-based survey study was completed between April 2016 and
February 2018. Study participants (n=1276) were a convenience sample of either patients with a diagnosed
health condition or caregivers of a patient with a diagnosed health condition registered with the Realm of Caring
Foundation (a nonprofit organization dedicated to therapeutic cannabis research and education). Participants
were invited through e-mail to complete follow-up assessments every 3 months with 33% of participants com-
pleting one or more prospective follow-ups. Assessments included self-reported demographics, health care uti-
lization, medication use, pain, anxiety, depression, sleep, and QOL. Cannabis Users (n=808) were compared with
Controls (n=468) using negative binomial regression and linear mixed effects models testing the effect of ini-
tiation, cessation, and maintenance of medicinal cannabis use.
Results: Cannabis Users self-reported significantly better QOL [t(1054) =4.19, p<0.001], greater health satisfac-
tion [t(1045) =4.14, p<0.001], improved sleep [children: t(224) =2.90, p<0.01; adults: [t(758) =3.03, p<0.01],
lower average pain severity [t(1150) =2.34, p<0.05], lower anxiety [t(1151) =4.38, p<0.001], and lower depression
[t(1210) =5.77, p<0.001] compared with Controls. Cannabis Users reported using fewer prescription medica-
tions (rate ratio [RR] =0.86; 95% confidence interval [CI]: 0.77–0.96) and were less likely to have a past-
month emergency department visit (RR =0.61; 95% CI: 0.44–0.84) or hospital admission (RR =0.54; 95% CI:
0.34–0.87). Controls who initiated cannabis use after baseline showed significant health improvements at
follow-up, and the magnitude of improvement mirrored the between-group differences observed at baseline.
Conclusions: Cannabis use was associated with improved health and QOL. Longitudinal testing suggests that
group differences may be due to the medicinal use of cannabis. Although bias related to preexisting beliefs
regarding the health benefits of cannabis in this sample should be considered, these findings indicate that clin-
ical trials evaluating the efficacy of defined cannabinoid products for specific health conditions are warranted.
Keywords: cannabinoid therapy; cannabis; health; medicinal cannabis; quality of life
1
Department of Community Health and Health Behavior, University at Buffalo, Buffalo, New York, USA.
2
University of Maryland School of Medicine, Baltimore, Maryland, USA.
3
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
4
Realm of Caring Foundation, Colorado Springs, Colorado, USA.
5
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
7
Center of Excellence for Stress and Mental Health, VA San Diego Health care System, La Jolla, California, USA.
8
Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, California, USA.
*Address correspondence to: Ryan Vandrey, PhD, Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, 5510 Nathan Shock Dr., Baltimore,
MD 21224, USA, E-mail: rvandrey@jhmi.edu
ªNicolas J. Schlienz et al. 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons
License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
Cannabis and Cannabinoid Research
Volume 6, Number 6, 2021
Mary Ann Liebert, Inc.
DOI: 10.1089/can.2019.0096
548
Introduction
The legalization of cannabis for medicinal use without
clinical trials to demonstrate safety and efficacy is un-
precedented, yet widespread, and presents significant
regulatory challenges.
1
In the United States, more
than 2.1 million individuals are registered with state
medicinal cannabis use programs and use cannabis
for over 40 different health conditions.
2,3
The canna-
bis plant consists of hundreds of distinct chemicals,
120 of which are unique to the cannabis plant (i.e.,
phytocannabinoids).
4,5
The two most prevalent phytocannabinoids are D
9
-
tetrahydrocannabinol (THC) and cannabidiol (CBD).
THC produces many of the hallmark effects associated
with cannabis intoxication (e.g., euphoria, increased ap-
petite, dry mouth, paranoia, cognitive impairment), and
is believed to drive the abuse liability of cannabis.
6
CBD,
in contrast, does not produce THC-like intoxicating ef-
fects, has low/no abuse liability, and has been associated
with relatively few acute adverse effects in human clin-
ical trials, although additional safety data in longer du-
ration trials and populations without a large number of
concomitant medications are desired.
7,8
Although specific pharmaceutical formulations of both
THC(foranorexiaassociatedwithweightlossinpatients
with AIDS, ornauseaand vomiting associated with can-
cer chemotherapy) and CBD (Dravet syndrome or
Lennox/Gastaut syndrome)havebeenapprovedby
the Food and Drug Administration (FDA), demand
for alternative cannabis products has proliferated.
Cannabis legalization has yielded a retail market of
products that vary by formulation (e.g., dried flowers,
cannabis oils/tinctures intended for oral ingestion,
cannabis-infused food and beverage products, concen-
trated extracts, and topical/transdermal products),
method of administration (e.g., smoked, vaporized,
swallowed), and chemical composition (e.g., THC-
dominant, CBD-dominant, or balanced THC/CBD).
The public health ramifications of medicinal cannabis
legalization warrant considerable attention and invest-
ment. Prior studies have documented modest increases
in cannabis use at the population level following legaliza-
tion, particularly among older adults, despite a decrease
in the rate of Cannabis Use Disorder among users.
9,10
Mixed results have been observed with respect to opioid-
sparing effects of medicinal cannabis legalization.
11–14
Epidemiological studies indicate that motor vehicle ac-
cidents and emergency department (ED) visits have in-
creased within states that have legalized cannabis,
although the relatedness of cannabis legalization to
these changes continues to be debated.
15,16
Importantly
though, the impact of medicinal cannabis legaliza-
tion at the level of individual cannabis users is poorly
understood.
Observational research methods are ideally suited to
evaluate the health effects of medicinal cannabis use
broadly, and provide a pathway for identifying specific
health conditions and/or cannabis product characteris-
tics that warrant additional study through traditional
drug development approaches (i.e., randomized, con-
trolled trials).
17,18
Prior studies have examined the health
and demographic characteristics of medicinal cannabis
users, and/or described cannabis product selection or
use behaviors among medicinal cannabis users,
19–23
but
have lacked an adequate control group. The aim of the
present study was to compare a large convenience sample
of medicinal cannabis users to a control group of individ-
uals considering medicinal cannabis use on self-reported
measures of health. Additional prospective, longitudinal
comparisons within a subsample of cannabis users and
controls evaluated the impact of initiation, cessation,
and maintenance of medicinal cannabis use on standard-
ized health measures.
Methods
Research setting
This study was conducted by the Realm of Caring
Foundation (Colorado Springs, CO), a nonprofit orga-
nization dedicated to therapeutic cannabis research
and education, in collaboration with the Johns Hopkins
University School of Medicine (Baltimore, MD). The
Realm of Caring Foundation is a resource for those
seeking information related to the use of cannabis
for therapeutic purposes. Participants were recruited
from the Realm of Caring Foundation patient registry
and social media posts made by the organization.
These participants included both those who were al-
ready using a cannabis product and those considering
initiation of medicinal cannabis product use. Partici-
pants completed assessments through web-based sur-
veys (Qualtrics, Provo, UT). The study was approved
by the Johns Hopkins University IRB and informed
consent was obtained as part of the survey.
Participants
Participants (n=1276) were enrolled between April
2016 and February 2018. Of these, 524 were adult pa-
tients who used cannabis for medicinal purposes and
284 were adult caregivers of children or dependent
adults who used cannabis for medicinal purposes
HEALTH OF MEDICINAL CANNABIS USERS VERSUS CONTROLS 549
(Cannabis Users; n=808). The control group consisted
of 271 adult patients who were considering, but had not
yet initiated therapeutic use of cannabis, and 197 adult
caregivers who were considering therapeutic use of
cannabis for a dependent child or adult patient (Con-
trols; n=468). All participants self-reported that they
or their dependent patient had a diagnosed health con-
dition at the time of the baseline assessment. Note that
we differentially refer to participants (those who com-
pleted the study assessments) and patients (individuals
with health conditions) throughout the article.
Study measures
Participants completed a web-based survey that mea-
sured several content areas. Adult patients who were
capable self-reported all information. Caregivers com-
pleted study assessments based on observations of the
dependent patient, either adult or child, under their
care. Demographic information included the age, sex,
race/ethnicity, place of residence, marital status, and
highest level of education completed (limited to pa-
tients age 18 and over) of the patient. The primary
diagnosed health condition for which the patient was
using, or considering medicinal cannabis use, was
recorded. Daily dose, frequency of use, and route of
administration were recorded, to the extent possible,
for current prescription medication, over-the-counter
(OTC) medication, and cannabis products. Partici-
pants reported past-month outpatient health care vis-
its, ED visits, and hospital admissions, as well as
past-month sick days taken from work/school. Vali-
dated assessments were used to assess past-month
quality of life (World Health Organization Quality-
of-Life assessment; score-range: 1–5 for individual items
and 4–20 for composite scores; WHOQOL-BREF
24
),
pain (Numeric Pain Rating Scale; score-range: 0–10;
NPRS
25
), anxiety and depression (Hospital Anxiety
and Depression Scale; score-range: 0–21; HADS
26
),
and sleep (Pittsburgh Sleep Quality Index
27
[PSQI])
for adults; score-range: 0–21; Children’s Sleep Habits
Questionnaire-Abbreviated
28,29
(CSHQ-A) for children;
score-range: 22–110.
a
Participants who completed the
survey each month were entered into a raffle to win
one of twenty $50 gift cards.
Following baseline survey completion, participants
were prompted through e-mail to complete follow-up
assessments at 3-month intervals. Approximately
one-third of participants completed at least one follow-
up assessment (32.6%) at an average of 284 days
following baseline. On average, these participants
completed 1.8 assessments (median =1).
Data analyses
Patients were classified as Cannabis Users or Controls
based on self- or caregiver-reported current cannabis
use at baseline. There were no differences in study
findings when controlling for self-reported versus
caregiver report, therefore results are presented with-
out categorizing by data source. Descriptive statistics
were used to summarize patient demographics, pri-
mary health condition, and cannabis use characteris-
tics. Independent-samples t-tests and chi-square tests
of independence were used to examine differences be-
tween Cannabis Users and Controls for continuous
and categorical variables, respectively. For count var-
iables (i.e., medication use, outpatient visits, ED visits,
hospital admissions, sick days from work/school), neg-
ative binomial regressions were conducted. The Benja-
mini/Hochberg procedure
30
was used to control Type
I error associated with multiple comparisons. All results
remained significant after controlling for the false dis-
covery rate. Longitudinal data (all completed follow-
up assessments) were analyzed using linear mixed
effects model parameterizing a between- and within-
person effect of medicinal cannabis use on health
symptoms
31
as well as accounting for the effect of
time independent of medicinal cannabis use status
(see Supplementary Materials for additional details
about this methodology). These models differentiated
and tested the (1) relation of the average prevalence of
medicinal cannabis use reported throughout the ana-
lyzed period (between-subject effects) and (2) the re-
lation of time-specific deviations in medicinal
cannabis use on health symptoms (e.g., initiation or
cessation of use; within-subject effects). Longitudinal
analysis of CSHQ-A scores was not conducted due
to the low number and density of follow-up assess-
ments for patients under age 18 (n=114 follow-ups
from 77 participants) as well as the infrequent report
of cannabis cessation among children in the Cannabis
User group (n=3). Inclusion of patient demographic
(age, gender, race) and assessment (self-report vs. ob-
server report) covariates in mixed effects model did
not alter the pattern of findings or their significance.
All models were conducted in Rstatistical language
using the nlme package.
32
a
Clinical cutoffs by scale: HADS score of 8 or higher is associated with clinical
diagnosis; PSQI score of 5 or higher indicates significant sleep disturbance; there
are no widely accepted clinical cutoffs for the WHOQOL-BREF, NPRS, or CSHQ-A.
550 SCHLIENZ ET AL.
Results
Patient characteristics
Cannabis Users and Controls were similar on major de-
mographic characteristics (Table 1). Patients were pre-
dominantly Caucasian (79%), female (63%), and most
patients age 18 or older had a greater than high school
education. Cannabis Users were significantly older than
Controls [t(1274) =2.31, p<0.05], with a mean age of
38 versus 35 years, respectively, and were more likely
to report a history of nontherapeutic cannabis use (e.g.,
past-month nontherapeutic cannabis use was 10% vs.
5%, respectively).
Primary health condition
The primary self-reported diagnosed health condition
for which participants used cannabis, or considered
cannabis use, was categorized into one of seven broad
health categories (Table 2) due to the incredible diver-
sity of diagnosed health conditions reported by study
participants. Cannabis Users and Controls did not sig-
nificantly differ with respect to type of primary health
condition (w
2
[6, n=1274] =7.77, p=0.35). The most
frequently endorsed health conditions were neurologi-
cal (e.g., epilepsy, multiple sclerosis), chronic pain
(e.g., fibromyalgia, chronic back pain), and psychiatric
(e.g., anxiety, depression, post-traumatic stress disor-
der) disorders.
Cannabis use characteristics: product
recommendations, type, and dose
Among Cannabis Users, 27% reported that a physician
explicitly recommended cannabis use; 45% said that a
physician did not recommend use, and 28% provided
no response. Cannabis use was reported to be a first-
line therapy for the primary health condition among
11%, a second-line therapy for 18%, an adjunctive ther-
apy for 39%, and a treatment of last resort for 29% of
Cannabis Users (3% did not answer).
Fifty-eight percent of patients used CBD-dominant
products. By comparison, THC-dominant products
were used by 13%, balanced THC/CBD products by
5%, and products in which the highest concentration
wasaminorcannabinoid,suchascannabigerol(CBG)
or cannabinol (CBN), by 3% of Cannabis Users. Many
participants (21%) did not know or did not specify the
chemotype of the cannabis products they used.
Cannabis tinctures or oils intended for oral inges-
tion were the most commonly reported cannabis for-
mulations (47%), followed by dried cannabis flowers
(9%), ‘‘edibles’’ (8%), concentrates (3%), and other for-
mulations such as topicals or suppositories (3%).
Thirty-one percent of respondents did not report the
formulation of cannabis product they most often
used. Variability in product type, formulation, method
of use, and lack of standard dose units, packaging, and
labeling made concise summarization of dosing diffi-
cult. Certificates of analysis were obtained from manu-
facturers that enabled daily CBD and THC dose
calculations for 353 patients taking specific oral canna-
bis products. Among those participants, the mean total
daily CBD dose was 79 mg (median =40 mg; range =1–
1050 mg) and the mean total daily THC dose was 3 mg
(median =1.4 mg; range =0.1–40.3 mg). Adjusted for
body weight, the mean total daily CBD dose was
1.4 mg/kg (median =0.6 mg/kg; range =0.01–15.7 mg/kg)
Table 1. Participant Demographics
Cannabis users
(n=808)
Controls
(n=468) p
Age
Mean (SD) 38 (20) 35 (21) <0.05
Range; n(%) below age 18 1–86; 175 (22) 1–82; 136 (29)
Sex, n(%)
Male 298 (37) 177 (38) 0.71
Female 510 (63) 291 (62)
Race, n(%)
Caucasian 637 (79) 372 (79) 0.48
African American 16 (2) 18 (4)
Hispanic/Latino 38 (5) 27 (6)
Other 75 (9) 43 (9)
Not reported 42 (5) 11 (2)
Education (among age 18), n(%)
High school or less 106 (17) 68 (20) 0.05
Some college 133 (21) 78 (23)
Undergraduate degree 183 (29) 87 (26)
Graduate degree 123 (19) 56 (17)
Trade/technical training 51 (8) 30 (9)
Not reported 37 (6) 13 (4)
Nontherapeutic cannabis use, n(%)
Lifetime 250 (31) 113 (24) 0.01
Past year 111 (14) 42 (9) 0.01
Past month 79 (10) 24 (5) 0.005
SD, standard deviation.
Table 2. Primary Medical Condition for Which Participants
Were or Were Not Considering Use of Cannabis
Cannabis users
(n=808)
Controls
(n=468) p
Primary medical condition 0.35
Neurological, n(%) 307 (38) 170 (36)
Chronic pain, n(%) 204 (25) 108 (23)
Neuropsychiatric, n(%) 146 (18) 94 (20)
Autoimmune, n(%) 75 (9) 46 (10)
Cancer, n(%) 59 (7) 33 (7)
Insomnia, n(%) 6 (1) 10 (2)
Other, n(%) 11 (2) 7 (1)
HEALTH OF MEDICINAL CANNABIS USERS VERSUS CONTROLS 551
and the mean total daily THC dose was 0.05 mg/kg
(median =0.02 mg/kg; range =<0.01–0.6 mg/kg).
Baseline health symptoms
Cannabis Users had significantly better symptoms on
most self-reported health assessments compared with
Controls at baseline (Table 3).
Quality of life. On the WHOQOL-BREF, Cannabis
Users reported greater quality of life (QOL) [t(1054) =
4.19, p<0.001] and perceived health satisfaction
[t(1045) =4.14, p<0.001], and had significantly higher
composite domain scores for physical health [t(1045) =
3.52, p<0.001], psychological health [t(1045) =4.87,
p<0.001], and social relationships [t(1025) =3.05,
p<0.01], but exhibited comparable environmental health
scores compared with Controls [t(1060) =1.36, p=0.18].
Pain. Compared with Controls, Cannabis Users
reported significantly lower average pain in the past
month on the NPRS [t(1150) =2.34, p<0.05], but did
not differ on ratings of worst pain in the past month
[t(11143) =1.33, p=0.18].
Anxiety and depression. Cannabis Users had signifi-
cantly lower scores on the Anxiety [t(1151) =4.38,
p<0.001] and Depression [t(1210) =5.77, p<0.001]
subscales of the HADS compared with Controls.
Sleep. As assessed by the CSHQ, caregiver reports in-
dicated that Cannabis Users under age 18 had better
overall sleep habits [t(224) =2.90, p<0.01], faster
sleep onset [t(316) =4.91, p<0.001], less frequent
night awakenings [t(293) =2.99, p<0.01], and fewer
parasomnias [t(267) =3.12, p<0.01] compared with
Controlsunderage18.AsassessedbythePSQI,adult
Cannabis Users had greater sleep quality [t(938) =3.96,
p<0.001], shorter sleep latency [t(954) =3.29, p<0.01],
longer sleep duration [t(954) =2.28, p<0.05], fewer
sleep disturbances [t(951) =2.77, p<0.01], and a
Table 3. Group Comparison on Baseline General Health Outcomes
Cannabis user mean (SD) [n] Controls mean (SD) [n]pCohen’s d
WHOQOL-BREF
a
Quality-of-life rating 3.5 (1.2) [674] 3.2 (1.2) [382] <0.001 0.25
Health satisfaction rating 2.4 (1.1) [669] 2.1 (1.0) [378] <0.001 0.29
Physical health domain 12.1 (3.8) [671] 11.2 (3.6) [376] <0.001 0.24
Psychological domain 13.3 (3.3) [670] 12.2 (3.3) [377] <0.001 0.33
Social relationships domain 13.3 (4.0) [656] 12.5 (4.3) [371] <0.01 0.19
Environment domain 15.0 (3.2) [678] 14.8 (3.0) [384] 0.18 0.06
NPRS
a
Average pain 3.9 (2.9) [742] 4.3 (3.0) [410] <0.01 0.14
Worst pain 5.8 (3.6) [738] 6.1 (3.5) [407] 0.18 0.08
HADS
a
——
Anxiety subscale 9.2 (5.2) [730] 10.5 (5.1) [423] <0.001 0.25
Depression Subscale 6.7 (4.8) [771] 8.4 (5.1) [441] <0.001 0.34
CSHQ (child sleep)
a
——
Total score 49.9 (10.6) [129] 54.3 (11.8) [97] <0.01 0.39
Bedtime resistance 11.4 (4.8) [172] 12.3 (5.1) [142] 0.08 0.18
Sleep onset delay 2.5 (1.0) [177] 3.1 (1.2) [141] <0.001 0.54
Sleep duration 2.5 (1.3) [178] 2.6 (1.4) [142] 0.73 0.07
Sleep anxiety 6.8 (3.6) [162] 7.1 (3.7) [131] 0.47 0.08
Night wakenings 7.1 (2.5) [163] 8.1 (2.9) [132] <0.01 0.37
Parasomnias 6.7 (2.2) [153] 7.7 (2.7) [116] <0.01 0.41
Sleep disordered breathing 2.0 (1.0) [177] 2.1 (1.2) [141] 0.48 0.09
Daytime sleepiness 9.4 (2.5) [178] 9.9 (3.1) [141] 0.08 0.18
PSQI (adult sleep)
a
——
Global score 8.9 (4.2) [501] 9.9 (4.2) [259] <0.01 0.24
Subjective sleep quality 1.5 (0.9) [618] 1.7 (0.9) [322] <0.001 0.22
Sleep latency 1.6 (1.1) [630] 1.8 (1.0) [326] <0.01 0.19
Sleep duration 0.9 (1.1) [630] 1.1 (1.1) [326] <0.05 0.18
Habitual sleep efficiency 1.0 (1.2) [520] 1.1 (1.3) [273] 0.29 0.08
Sleep disturbances 1.8 (0.6) [628] 1.9 (0.6) [325] <0.01 0.17
Use of sleep medication 1.1 (1.4) [624] 1.2 (1.4) [317] 0.44 0.07
Daytime dysfunction 1.2 (0.7) [613] 1.1 (0.7) [316] 0.17 0.14
a
For the WHOQOL-BREF, higher scores indicate better outcomes, for all other measures, lower scores indicate better outcomes.
CSHQ, Children’s Sleep Habits Questionnaire; HADS, Hospital Anxiety and Depression Scale; NPRS, Numeric Pain Rating Scale; PSQI, Pittsburgh Sleep
Quality Index; WHOQOL-BREF, World Health Organization Quality of Life-BREF.
552 SCHLIENZ ET AL.
significantly better PSQI Global Sleep Score compared
with adult Controls [t(758) =3.03, p<0.01].
Medications, health care utilization, and sick days.
Results for all negative binomial count data appear in
Table 4 and distribution of responses in Figure 1. Can-
nabis Users reported 14% fewer current prescription
medications (95% confidence interval [CI]: 0.77–
0.96), 39% fewer past-month ED visits (95% CI:
0.44–0.84), and 46% fewer hospital admissions (95%
CI: 0.34–0.87) than the Control group. Groups did
not significantly differ in the number of OTC medica-
tions, past-month outpatient health care visits, or past-
month sick days taken from work/school.
Longitudinal health symptoms
Raw data for primary health symptoms at baseline and
follow-up by medicinal cannabis use status are plotted
in Figure 2 (see Supplementary Materials for marginal
mean plots and sensitivity analyses evaluating alterna-
tive parameterizations). Consistent with the baseline
analyses, significant between-person effects of medici-
nal cannabis use (i.e., average prevalence of medicinal
cannabis use reported throughout the analyzed period)
were observed for QOL (b=0.35, p<0.001), perceived
health satisfaction (b=0.35, p<0.001), past-month av-
erage pain (b=0.47, p<0.05), Anxiety (b=1.58,
p<0.001), and Depression (b=1.78, p<0.001) sub-
scales of the HADS, and PSQI Global Sleep Score
(b=1.15, p<0.01). These effects reflected better
health scores (e.g., lower anxiety) for individuals
reporting medicinal cannabis use, on average, across
the reported period (i.e., averaging medicinal cannabis
exposure over time).
Significant within-person effects of medicinal cannabis
use (i.e., association of time-specific deviations in medic-
inal cannabis use such as initiation or cessation with
health symptoms) were also observed for QOL (b=0.22,
p<0.01), perceived health satisfaction (b=0.23, p<0.01),
past-month average pain (b=0.42, p<0.05), past-
month worst pain (b=0.46, p<0.05), and the Anxi-
ety (b=1.56, p<0.001) and Depression (b=1.87,
p<0.001) subscales of the HADS. These within-
person effects each reflected improved health scores
during specific assessment periods in which medicinal
cannabis was reported compared with assessment peri-
ods in which it was not reported for individual partic-
ipants (i.e., indicating that initiation of medicinal
cannabis use, on average, was associated with improved
symptoms and cessation of medicinal cannabis use, on
average, was associated with worse symptoms on these
variables).
A sensitivity analysis was conducted to determine if
missing data contributed to the observed results. No sig-
nificant differences between participants providing follow-
up data and those without were observed in age ( p=0.99),
gender ( p=0.54), race ( p=0.52), report status (self vs. ob-
server) ( p=0.58), or any of the global health measures an-
alyzed ( pvalues >0.16). Participants reporting current
medicinal cannabis use at baseline were more likely to
provide a follow-up assessment (odds ratio [OR] =1.40,
p=0.008). Sensitivity models in which only participants
with follow-up data were analyzed found between- and
within-subject associations in the same direction and sig-
nificance as the primary models are reported above.
Qualitative information was coded from 67 partici-
pants who reported discontinuation at some point
during the longitudinal period. Over half (55%) cited
financial concerns as a reason for discontinuation.
Other reasons for discontinuation included legal/
employment restrictions (16%), no benefit (13%), and
negative health consequences (13%).
Discussion
Decisions surrounding medicinal cannabis use are
challenging for both clinicians and patients due to
the diversity of products, abuse liability of cannabis,
potential product contamination or label inaccuracies,
complicated regulatory structure, and dearth of con-
trolled clinical trials on defined products for targeted
health indications.
1
In this study, Cannabis Users
reported better health and QOL, and less health care
Table 4. Group Prediction of Medication Use, Past-Month
Health Care Utilization, and Sick Days
Dependent variable, (n) Exp(B) 95% CI
Likelihood
ratio w
2
Predictor
Prescription medications, (n=774) — — 7.71
a
Group (cannabis users) 0.86
a
0.77–0.96 —
Over-the-counter medications, (n=763) — 0.74
Group (cannabis users) 1.06 0.93–1.22
Outpatient visits, (n=731) — — 0.11
Group (cannabis users) 1.03 0.89–1.19
Emergency department visits, (n=307) — 9.31
a
Group (cannabis users) 0.61
a
0.44–0.84 —
Hospital admissions, (n=180) — — 6.35
b
Group (cannabis users) 0.54
b
0.34–0.87 —
Sick days from school/work, (n=675) — 1.86
Group (cannabis users) 0.83 0.63–1.09
a
p<0.01,
b
p<0.05.
CI, confidence interval.
HEALTH OF MEDICINAL CANNABIS USERS VERSUS CONTROLS 553
utilization compared with largely comparable Controls.
The observed clinical benefit associated with medicinal
cannabis use in this study is consistent with other obser-
vational studies.
19,23,33–35
That only 27% of participants
reported that a physician explicitly recommended me-
dicinal cannabis use is somewhat concerning. Increased
physician involvement in medicinal cannabis decision
making is desirable for patient safety as well as for
monitoring, recording, and disseminating clinical out-
comes. This study extends prior research by including a
FIG. 1. Distribution of medication use and health care utilization by group assignment at baseline.
554 SCHLIENZ ET AL.
FIG. 2. Observed values for health outcomes at baseline and follow-up by medicinal cannabis use status.
Plotted are values for the Control group who initiated cannabis use in follow-up (solid circle/solid line),
Cannabis User group who continued use in follow-up (solid square/solid line), Control group who did not
initiate use in follow-up (open circle/dotted line), and Cannabis Group that discontinued use in follow-up
(open square/dotted line). For baseline groupings, individuals who did not provide follow-up data were
treated as belonging in the nonuse group for presentation purposes. Y-axis legends reflect total scale range.
Dotted line on HADS-A and HADS-D represent clinical cutoff for patient follow-up. Individual sample sizes
range from 22 to 523 depending on the time point, group, and assessment depicted. Error bars are standard
error. HADS, Hospital Anxiety and Depression Scale.
555
large sample size, both child and adult patients, only
individuals who self-reported a diagnosed health prob-
lem, assessment of multiple health domains, and a con-
trol group.
CBD-dominant products were used at a higher rate
relative to THC-dominant products, and doses of
CBD (mean 79 mg; 1.4 mg/kg) and THC (mean
3 mg; 0.5 mg/kg) used tended to be lower than what
hasbeenusedinpriorhumanlaboratorystudies
and clinical trials. For comparison, the recommended
maintenancedosage(listedonthepackageinsert)for
Epidiolex in the treatment of rare seizure disorders
is 10–20 mg/kg/day. The recommended starting dose
of dronabinol (listed on the package insert) is
5 mg/day for the treatment of anorexia in adults
with HIV/AIDS and is 20–30 mg/day for adults who
have nausea or emesis associated with chemotherapy.
Of note, most participants in this study were using
cannabis for health conditions other than the FDA-
approved uses of CBD or THC, and for which effec-
tive doses have not been determined in controlled
clinical trials.
An additional contribution of this study was the
evaluation of prospective changes in health symptoms
following initiation, cessation, or maintenance of me-
dicinal cannabis product use. These analyses indicated
significant within-person effects, in addition to the
between-person effects observed between Cannabis
Users and Controls at baseline. Within-person change
reflected the observation that initiation of medicinal
cannabis use resulted in significant increases in QOL
and health satisfaction as well as decreases in anxiety
and depression that were comparable in magnitude
to the difference between Cannabis Users and Controls
observed at baseline. Similarly, maintenance on me-
dicinal cannabis in the Cannabis User group resulted
in sustained improvements on these measures,
whereas cessation of use often resulted in a decrease
in health and QOL indicating that stopping medicinal
cannabis use was associated with a diminishing or re-
bound of effect. Notably, pain and sleep showed less
robust impacts when evaluated in this longitudinal
setting. This outcome is not entirely surprising given
that the cross-sectional comparisons for these mea-
sures made at baseline were consistent with smaller
magnitude differences. Additionally, evidence for the
opioid-sparing effects of cannabisproductsonmod-
erate or severe chronic pain have been mixed, as
noted in the introduction. It is also possible that the
magnitude (and potential direction) of these effects
will vary depending on the chronic health condition
evaluated (e.g., see evidence of specific sleep-related
motives for medicinal cannabis use among individuals
with PTSD
36
).
Several methodological limitations must be ac-
knowledged. The study was conducted with a conve-
nience sample of individuals registered with the
Realm of Caring Foundation who were willing to com-
plete a research assessment; thus, this sample may not
be representative of medicinal cannabis users broadly.
In addition, biases may be represented in both groups.
Specifically, individuals in the cannabis group likely al-
ready observed a benefit from use and continued to
use medicinal cannabis products for this reason. On
the other hand, individuals in the control group
were those seeking information regarding medicinal
cannabis products, and therefore have both unre-
solved symptomatology and at least some belief that
cannabis may improve those symptoms. High rates
of missing data were also observed during the pro-
spective portion of the study. This attrition is likely at-
tributable to study-related factors, including the
relatively modest incentives (i.e., probabilistic pay-
ments) and the exclusive use of reminder emails to en-
courage compliance. Sensitivity analyses indicated that
individuals with missing data did not significantly differ
on demographic factors or the health-related symptoms
analyzed and evaluation of longitudinal health symptoms
in a completion-only group revealed similar findings.
Nevertheless, future efforts to improve retention should
be explored (e.g., closer monitoring or an escalating incen-
tive schedule for long-term adherence). Last, the effect sizes
observed were generally small in magnitude (most Cohen’s
d0.20-to-0.30). The clinical significance of these differ-
ences are difficult to assess due to reliance on self-report
versus clinician assessment or objective measures of
health, the heterogeneity of the sample with respect to
health condition, the type of cannabis products being
used, and the manner in which products were used (dos-
ing regimen as well as physician supervision of use). It is
important that additional research on the magnitude and
clinical viability of these effects be conducted in more con-
trolled clinical settings in which known and consistent
dosing and product types are utilized.
The key finding of this study is that medicinal can-
nabis use was associated with more positive ratings of
health and QOL, assessed across multiple domains.
Prospective analyses found that Controls showed im-
provement in health and QOL if they initiated medic-
inal cannabis use, and that Cannabis Users showed
556 SCHLIENZ ET AL.
diminished health and QOL if they stopped cannabis
use. Because of this, we hypothesize that these group
differences were related to the use of medicinal canna-
bis products. That said, due to the aforementioned
limitations, the results of this study do not provide de-
finitive evidence that cannabis is an effective thera-
peutic. Rather, the results clearly indicate that additional
research should be conducted to further evaluate the ob-
served data in more targeted, representative subpopula-
tions of cannabis users. Such studies can be used to
identify specific health conditions, product types, and
doses that are appropriate for evaluation in controlled clin-
ical trials. Although the current design included a control
group to improve interpretation, future observational
studies should consider the use of Ecological Momentary
Assessment technology (i.e., repeated sampling of behavior
in real time) and/or corroboration of patient self-reports
with collateral data from additional sources such as elec-
tronic medical records or direct reporting from the physi-
cian or other health professional caring for the patient.
Acknowledgments
The authors wish to thank the study participants for
contributing their time and the staff at the Realm of
Caring Foundation and Johns Hopkins University
who contributed to this project.
Author Disclosure Statement
Dr. Bonn-Miller is an employee of Canopy Growth
Corporation, during which time he has received stock
options. He serves on the Board of Directors for Aus-
Cann Group Holdings Limited, was a prior employee
of Zynerba Pharmaceuticals, and he has received con-
sulting fees from Tilray Inc. Dr. Vandrey has received
compensation as a consultant or advisory board mem-
ber from Zynerba Pharmaceuticals, Canopy Health
Innovations Inc., and FSD Pharma.
Funding Information
This study was funded by the Realm of Caring Founda-
tion. Additional funding was provided by NIH/NIDA
Training Grant T32-DA07209 (support for Drs. Schlienz
and Strickland).
Supplementary Material
Supplementary Data
Supplementary Figure S1
Supplementary Figure S2
Supplementary Figure S3
References
1. Vandrey R. The cannabis conundrum: steering policy and medicine with
insufficient data. Int Rev Psychiatry. 2018;30:181–182.
2. ProCon. Number of legal medical marijuana patients in the U.S. as of May
2018, by state. 2018; https://www.statista.com/statistics/585154/us-legal-
medical-marijuana-patients-state/. Accessed April 3, 2019.
3. Realm of Caring. Qualifying Conditions for a Medical Marijuana Card by
State. 2019; https://rebrand.ly/roc-state-med-conditions. Accessed April
9, 2019.
4. Radwan MM, Elsohly MA, Slade D, et al. Biologically active cannabinoids
from high-potency Cannabis sativa. J Nat Prod. 2009;72:906–911.
5. Morales P, Hurst DP, Reggio PH. Molecular targets of the phytocannabi-
noids: a complex picture. Prog Chem Org Nat Prod 2017;103:103–131.
6. Mechoulam R, Gaoni Y. The absolute configuration of delta-1-
tetrahydrocannabinol, the major active constituent of hashish. Tetrahe-
dron Lett. 1967;12:1109–1111.
7. Bergamaschi MM, Queiroz RH, Zuardi AW, et al. Safety and side effects
of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6:
237–249.
8. Schoedel KA, Szeto I, Setnik B, et al. Abuse potential assessment of
cannabidiol (CBD) in recreational polydrug users: a randomized,
double-blind, controlled trial. Epilepsy Behav. 2018;88:162–171.
9. Hasin DS, Sarvet AL, Cerda M, et al. US adult illicit cannabis use, cannabis
use disorder, and medical marijuana laws: 1991–1992 to 2012–2013.
JAMA Psychiatry. 2017;74:579–588.
10. Hasin DS, Saha TD, Kerridge BT, et al. Prevalence of marijuana use
disorders in the United States between 2001–2002 and 2012–2013. JAMA
Psychiatry. 2015;72:1235–1242.
11. Shover CL, Davis CS, Gordon SC, et al. Association between medical
cannabis laws and opioid overdose mortality has reversed over time. Proc
Natl Acad Sci U S A. 2019;116:12624–12626.
12. Bachhuber MA, Saloner B, Cunningham CO, et al. Medical cannabis laws
and opioid analgesic overdose mortality in the United States, 1999–2010.
JAMA Intern Med. 2014;174:1668–1673.
13. Campbell G, Hall WD, Peacock A, et al. Effect of cannabis use in
people with chronic non-cancer pain prescribed opioids: findings
from a 4-year prospective cohort study. Lancet Public Health. 2018;3:
e341–e350.
14. Liang D, Bao Y, Wallace M, et al. Medical cannabis legalization and opioid
prescriptions: evidence on US Medicaid enrollees during 1993–2014.
Addiction. 2018;113:2060–2070.
15. Salomonsen-Sautel S, Min SJ, Sakai JT, et al. Trends in fatal motor vehicle
crashes before and after marijuana commercialization in Colorado. Drug
Alcohol Depend. 2014;140:137–144.
16. Kim HS, Hall KE, Genco EK, et al. Marijuana tourism and emergency
department visits in colorado. N Engl J Med. 2016;374:797–798.
17. Yang W, Zilov A, Soewondo P, et al. Observational studies: going beyond
the boundaries of randomized controlled trials. Diabetes Res Clin Pract.
2010;88 Suppl 1:S3–S9.
18. Dreyer NA, Tunis SR, Berger M, et al. Why observational studies should be
among the tools used in comparative effectiveness research. Health Aff.
2010;29:1818–1825.
19. Bonn-Miller MO, Boden MT, Bucossi MM, et al. Self-reported cannabis use
characteristics, patterns and helpfulness among medical cannabis users.
Am J Drug Alcohol Abuse. 2014;40:23–30.
20. Cranford JA, Arnedt JT, Conroy DA, et al. Prevalence and correlates of
sleep-related problems in adults receiving medical cannabis for chronic
pain. Drug Alcohol Depend. 2017;180:227–233.
21. Davis AK, Walton MA, Bohnert KM, et al. Factors associated with alcohol
consumption among medical cannabis patients with chronic pain. Addict
Behav. 2018;77:166–171.
22. Haug NA, Padula CB, Sottile JE, et al. Cannabis use patterns and motives: a
comparison of younger, middle-aged, and older medical cannabis dis-
pensary patients. Addict Behav. 2017;72:14–20.
23. Suraev A, Lintzeris N, Stuart J, et al. Composition and use of cannabis
extracts for childhood epilepsy in the Australian community. Sci Rep.
2018;8:10154.
24. The WHOQOL Group. Development of the World Health Organization
WHOQOL-BREF quality of life assessment. Psychol Med. 1998;28:551–558.
25. McCaffery M, Beebe A. Pain: clinical manual for nursing practice. C.V.
Mosby Company: St. Louis, MO, 1989.
HEALTH OF MEDICINAL CANNABIS USERS VERSUS CONTROLS 557
26. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta
Psychiatr Scand. 1983;67:361–370.
27. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality
Index: a new instrument for psychiatric practice and research. Psychiatry
Res. 1989;28:193–213.
28. Owens JA, Spirito A, McGuinn M. The Children’s Sleep Habits Question-
naire (CSHQ): psychometric properties of a survey instrument for school-
aged children. Sleep. 2000;23:1043–1051.
29. Hartman AG, Terhorst L, Little N, et al. Uncovering sleep in young males
with Duchenne muscular dystrophy. Eur J Paediatr Neurol. 2020;S1090-
3798(20)30043-X.DOI: 10.1016/j.ejpn.2020.02.012.
30. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical
and powerful approach to multiple testing. J Royal Statistic Soc B
(Methodological). 1995;57:289–300.
31. Wang LP, Maxwell SE. On disaggregating between-person and within-
person effects with longitudinal data using multilevel models. Psychol
Methods. 2015;20:63–83.
32. Pinheiro J, Bates D, DebRoy S, et al. Package ‘‘nlme.’’ Linear and Nonlinear
Mixed Effects Models, version, 3-1. 2017.
33. Perron BE, Bohnert K, Perone AK, et al. Use of prescription pain medica-
tions among medical cannabis patients: comparisons of pain levels,
functioning, and patterns of alcohol and other drug use. J Stud Alcohol
Drugs. 2015;76:406–413.
34. Bar-Lev Schleider L, Mechoulam R, Saban N, et al. Real life experience of
medical cannabis treatment in autism: analysis of safety and efficacy. Sci
Rep. 2019;9:200.
35. Gruber SA, Sagar KA, Dahlgren MK, et al. The grass might be greener:
medical marijuana patients exhibit altered brain activity and improved
executive function after 3 months of treatment. Front Pharmacol.
2017;8:983.
36. Bonn-Miller MO, Babson KA, Vandrey R. Using cannabis to help you sleep:
heightened frequency of medical cannabis use among those with PTSD.
Drug Alcohol Depend. 2014;136:162–165.
Cite this article as: Schlienz NJ, Scalsky R, Martin EL, Jackson H,
Munson J, Strickland JC, Bonn-Miller MO, Loflin M, Vandrey R (2021)
A cross-sectional and prospective comparison of medicinal cannabis
users and controls on self-reported health, Cannabis and Cannabinoid
Research 6:6, 548–558, DOI: 10.1089/can.2019.0096.
Abbreviations Used
CBD ¼cannabidiol
CI ¼confidence interval
CSHQ-A ¼Children’s Sleep Habits Questionnaire-Abbreviated
ED ¼emergency department
FDA ¼Food and Drug Administration
HADS ¼Hospital Anxiety and Depression Scale
NPRS ¼Numeric Pain Rating Scale
PSQI ¼Pittsburgh Sleep Quality Index
QOL ¼quality of life
RR ¼rate ratio
SD ¼standard deviation
THC ¼tetrahydrocannabinol
WHOQOL-BREF ¼World Health Organization Quality of Life-BREF
558 SCHLIENZ ET AL.
... Both THC and CBD hold promise for addressing pain and inflammation associated with dysmenorrhea 19 , endometriosis [20][21][22] , and chronic pelvic pain 23 , although clinical trial data are lacking. However, observational, longitudinal studies report that medical cannabis (MC) use is associated with improved anxiety, mood, sleep, and pain across various medical conditions [24][25][26][27][28][29][30][31] . Additionally, surveys assessing MC use for symptoms of premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) 32 , endometriosis 33,34 , chronic pelvic pain 35,36 , and menopause 37 found significantly improved self-reported pain, cramping/muscle spasms, mood, anxiety, sleep, gastrointestinal issues, and quality of life. ...
Article
Full-text available
The endocannabinoid system is involved in gynecological functions, with cannabidiol (CBD) demonstrating promise for alleviating menstrual-related symptoms. This survey-based, quasi-experimental study assessed pro re nata (PRN) use of a commercially-available, hemp-derived, broad-spectrum, high-CBD (100 mg) vaginal suppository (Foria®) for menstrual-related pain and discomfort compared to a treatment-as-usual (TAU) group (CBD n = 77, TAU n = 230), with survey assessments collected at baseline and two monthly follow-ups (~2 menstrual cycles). The CBD group demonstrated significantly reduced frequency and severity of menstrual-related symptoms, impact of symptoms on daily functioning, need for analgesics, and number of analgesics used relative to the TAU group ( ps ≤ 0.032). Correlation analyses indicated a potential dose-dependent response, with increased suppository use associated with greater reduction of symptoms ( ps ≤ 0.025). Most CBD participants reported at least moderate improvement of symptoms (follow-up 1 = 72.9%, follow-up 2 = 81.1%). Future studies (including replication in randomized clinical trials) assessing pharmacokinetics/pharmacodynamics, mechanism(s) of action, efficacy for other gynecological indications, and potential adverse events (e.g., drug-drug interactions) are indicated.
... Additionally, our results showed a significant improvement in quality-of-life scores during cannabis-based treatment, which is consistent with findings of several previous studies (Cahill et al., 2021;Doeve et al., 2020;Meng et al., 1903;Naftali et al., 2021;Peterson et al., 2021;Schlienz et al., 2021). Moreover, using EQ-5D-5L to track the impacts of medical cannabis on the quality of life of participants also presented an opportunity to assess the incremental cost per QALY for cannabis treatment (reported in Canadian Dollars). ...
Article
Full-text available
Objective: Cannabis is being used as a therapeutic option by patients around the globe, and older patients represent a rapidly growing subset of this population. This study aims to assess the patterns of medical cannabis use in patients over 50 years of age and its effect on health outcomes such as pain, sleep, quality of life, and co-medication. Method: The Medical Cannabis in Older Patients Study (MCOPS) is a multi-site, prospective observational study examining the real-world impact of medical cannabis use on patients over age 50 under the guidance of a health care provider. The study included validated instruments, with treating physicians collecting detailed data on participant characteristics, medical cannabis and co-medication use, and associated impacts on pain, sleep, quality of life, as well as adverse events. Results: Inclusion criteria were met by 299 participants. Average age of participants was 66.7 years, and 66.2% of respondents identified as female. Approximately 90% of patients used medical cannabis to treat pain-related conditions such as chronic pain and arthritis. Almost all patients reported a preference for oral cannabis products (e.g., extracts, edibles) rather than inhalation products (e.g., flower, vapes), and most preferred oral formulations high in cannabidiol and low in tetrahydrocannabinol. Over the six-month study period, significant improvements were noted in pain, sleep, and quality of life measures, with 45% experiencing a clinically meaningful improvement in pain interference and in sleep quality scores. Additionally, nearly 50% of patients taking co-medications at baseline had reduced their use by the end of the study period, and quality of life improved significantly from baseline to M3 and from baseline to M6, with an incremental cost per quality-adjusted life-year (QALY) of $25,357.20. No serious adverse events (SAEs) were reported. Conclusions: In this cohort of older patients, most of whom suffered from pain-related conditions, medical cannabis seemed to be a safe and effective treatment. Most patients experienced clinically significant improvements in pain, sleep, and quality of life and reductions in co-medication. The cost per QALY was well below the standard for traditional pharmaceuticals, and no SAEs were reported, suggesting that cannabis is a relatively safe and cost-effective therapeutic option for adults dealing with age-related health conditions.
... For some people, the costs of impairment from feeling high may outweigh the perceived benefits, rendering cannabis treatments that make a person feel high a suboptimal choice for such individuals. For chronic health conditions that are not characterized by transient states of aversive percepts, such as metabolic or cellular diseases, feeling high may present indirect detriments (e.g., cognitive and behavioral impairments) or benefits sometimes recorded in the literature as positive side effects, such as increased reported quality of life, behavioral motivations, experienced creativity, ability to accomplish personally fulfilling tasks, and/or improved social relations (Schlienz et al., 2020;Aviram et al., 2021). Among other patients, feeling high may be a direct benefit from consuming cannabis. ...
Article
Full-text available
Introduction: We measure for the first time the associations between subjective patient experiences of feeling “high” and treatment outcomes during real-time Cannabis flower consumption sessions. Methods: Our study uses data from the mobile health app, Releaf App™, through which 1,882 people tracked the effects of Cannabis flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post-administration symptom intensity levels, total dose used, and real-time side effect experiences. Results: Patients reported feeling high in 49% of cannabis treatment sessions. Using individual patient-level fixed effects regression models and controlling for plant phenotype, consumption mode, tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies, dose, and starting symptom level, our results show that, as compared to sessions in which individuals did not report feeling high, reporting feeling high was associated with a 7.7% decrease in symptom severity from a mean reduction of −3.82 on a 0 to 10 analog scale (coefficient = −0.295, p < 0.001) with evidence of a 14.4 percentage point increase (p < 0.001) in negative side effect reporting and a 4.4 percentage point (p < 0.01) increase in positive side effect reporting. Tetrahydrocannabinol (THC) levels and dose were the strongest statistical predictors of reporting feeling high, while the use of a vaporizer was the strongest inhibitor of feeling high. In symptom-specific models, the association between feeling high and symptom relief remained for people treating pain (p < 0.001), anxiety (p < 0.001), depression (p < 0.01) and fatigue (p < 0.01), but was insignificant, though still negative, for people treating insomnia. Although gender and pre-app cannabis experience did not appear to affect the relationship between high and symptom relief, the relationship was larger in magnitude and more statistically significant among patients aged 40 or less. Discussion: The study results suggest clinicians and policymakers should be aware that feeling high is associated with improved symptom relief but increased negative side effects, and factors such as mode of consumption, product potency, and dose can be used to adjust treatment outcomes for the individual patient.
... However, there is much less clinical evidence, with only a few case studies published in relation to CBD (Laczkovics et al., 2021;Shunney, 2019). In relation to THC and cannabis, there is some evidence of a positive effect in reducing depressive symptoms from cross-sectional surveys (Kosiba et al., 2019;Lintzeris et al., 2018;Sexton et al., 2016;Schlienz et al., 2021), case reports (Gruber et al., 1996), prospective observational studies (Cuttler et al., 2018;Li et al., 2020) and one RCT (though this suggested the efficacy of THC in low but not high doses where it was found to be anxiogenic) (Childs et al., 2017). The systematic review conducted by Stockings and colleagues (2018), mentioned earlier, found no difference in overall emotional functioning in patients receiving any cannabinoids compared with comparator groups, or in depressive or anxiety symptoms specifically. ...
Article
Full-text available
Background Internationally, one of the most common conditions for which people seek medicinal cannabis (MC) is chronic pain. However, relatively little is known about the effectiveness of cannabis for reducing pain in Australia. Medicinal cannabis was made legally available in Australia in 2016. Project Twenty21 Australia is an observational study that follows patients prescribed MC for chronic pain, anxiety, PTSD and multiple sclerosis for up to 12 months. It commenced recruitment in February 2022. This paper describes some preliminary findings for a cohort of patients with chronic pain. Method Participants seeking treatment for chronic pain are prescribed MC from within a Project Formulary, and complete questionnaires at baseline then three monthly for up to 12 months. Pain severity and interference are assessed using the Brief Pain Index while standardised measures of quality of life, mood and sleep quality are also applied. Results By 30 November 2022, 55 participants with chronic pain had completed the first three-month follow-up. Patients reported a low quality of life and high levels of co-morbidity. Three-month data indicate that MC use was associated with significant reductions in self-reported pain intensity and pain interference (Effect sizes = 0.66 [95% CI = 0.34–0.98] and 0.56 [0.24–0.88], respectively). Additionally, there were significant improvements in quality of life, general health, mood/depression and sleep (Effect sizes = 0.53–0.63). One adverse reaction was reported which was mild in nature. Conclusions Preliminary evidence suggests that MC may be effective in reducing both pain severity and pain interference while also improving quality of life, general health, mood and sleep in patients with chronic pain. Increasing uptake of MC coupled with growing evidence of both the effectiveness and safety of these medications indicate a need both to make MC more widely available and to reduce financial costs associated with its use.
... We did not assess quality-of-life measures such as stress levels, activity levels, or positive affect. Other studies suggest that even if symptoms themselves do not improve, cannabis may improve these quality-of-life measures (58,59). Finally, past CUD (>1 year before enrollment) was not exclusionary for this study, though we note that rates of past CUD were low (8.0% of participants) and the time between any CUD diagnosis and trial enrollment was often long (M = 23, SD = 20 years prior to study enrollment). ...
Article
Full-text available
Background Evidence for long-term effectiveness of commercial cannabis products used to treat medical symptoms is inconsistent, despite increasingly widespread use. Objective To prospectively evaluate the effects of using cannabis on self-reported symptoms of pain, insomnia, anxiety, depression, and cannabis use disorder (CUD) after 12 months of use. Methods This observational cohort study describes outcomes over 9 months following a 12-week randomized, waitlist-controlled trial (RCT: NCT03224468) in which adults (N = 163) who wished to use cannabis to alleviate insomnia, pain, depression, or anxiety symptoms were randomly assigned to obtain a medical marijuana card immediately (immediate card acquisition group) or to delay obtaining a card for 12 weeks delay (delayed card acquisition group). During the 9-month post-randomization period, all participants could use cannabis as they wished and choose their cannabis products, doses, and frequency of use. Insomnia, pain, depression, anxiety, and CUD symptoms were assessed over the 9-month post-randomization period. Results After 12 months of using cannabis for medical symptoms, 11.7% of all participants (n = 19), and 17.1% of those using cannabis daily or near-daily (n = 6) developed CUD. Frequency of cannabis use was positively correlated with pain severity and number of CUD symptoms, but not significantly associated with severity of self-reported insomnia, depression, or anxiety symptoms. Depression scores improved throughout the 9 months in all participants, regardless of cannabis use frequency. Conclusions Frequency of cannabis use was not associated with improved pain, anxiety, or depression symptoms but was associated with new-onset cannabis use disorder in a significant minority of participants. Daily or near-daily cannabis use appears to have little benefit for these symptoms after 12 months of use.
Article
Insomnia is a sleep disorder characterized by difficulty falling asleep or maintaining sleep after waking up. With the increasing pace of life and high levels of stress, there is a rising number of individuals reporting sleep disturbances. Recently, there has been a growing interest in various cannabis preparations, particularly in cannabinoids derived from Cannabis sativa plants, for the treatment of insomnia. Delta-tetrahydrocannabinol (THC) and cannabidiol (CBD) are commonly used to treat insomnia. Both of these substances have shown potential in improving sleep quality and have historically been used to induce sleep. Despite their widespread use, there is still a lack of reliable research to prove their effectiveness. Nevertheless, cannabinoids remain frequently used substances in the management of sleep disorders. While THC and CBD may enhance the sleep quality by reducing nighttime awakenings, shortening sleep onset latency, and increasing the total sleep time, their efficacy in treating insomnia lacks scientific validation. Additionally, there are safety concerns associated with cannabinoids, including potential negative impacts on the sleep quality, risk of abuse or dependence, and the development of tolerance with long-term use.This article provides a comprehensive review of literature concerning the effects and safety of cannabinoids on sleep and sleep-wake rhythms, as well as their potential benefits in treating insomnia and other sleep disorders.
Article
Full-text available
Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
Preprint
Full-text available
Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a systematic review of research studies published over the last three years. We found 156 relevant studies. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Albeit medical cannabis reduced depression in most studies, none of these were placebo controlled. In clinical studies published in the same period, placebo also ameliorated depression and in addition, the average effect size of placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
Article
Background: In 2016, California transitioned from legalized medical cannabis use to adult-use. Little is known about how this policy change affected medicinal cannabis use among young adults.Objectives: To identify longitudinal groups of medicinal cannabis users and concurrent changes in health- and cannabis use-related characteristics among young adults in Los Angeles between 2014 and 2021.Methods: Cannabis users (210 patients and 156 non-patients; 34% female; ages 18-26 at baseline) were surveyed annually across six waves. Longitudinal latent class analysis derived groups from two factors - cannabis patient status and self-reported medicinal use. Trajectories of health symptoms, cannabis use motives, and cannabis use (daily/near daily use, concentrate use, and problematic use) were estimated across groups.Results: Three longitudinal latent classes emerged: Recreational Users (39.3%) - low self-reported medicinal use and low-to-decreasing patient status; Recreational Patients (40.4%) - low self-reported medicinal use and high-to-decreasing patient status; Medicinal Patients (20.3%) - high self-reported medicinal use and high-to-decreasing patient status. At baseline, Medicinal Patients had higher levels of physical health symptoms and motives than recreational groups (p < .05); both patient groups reported higher level of daily/near daily and concentrate use (p < .01). Over time, mental health symptoms increased in recreational groups (p < .05) and problematic cannabis use increased among Recreational Patients (p < .01).Conclusions: During the transition to legalized adult-use, patterns of medicinal cannabis use varied among young adults. Clinicians should monitor increases in mental health symptoms and cannabis-related problems among young adults who report recreational - but not medicinal - cannabis use.
Article
Background: Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. Methods: Participants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate. Results: All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p < 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN. Conclusions: Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.
Article
Full-text available
Objectives Sleep health in rare disease is often overlooked due to the complex nature of the disease. For males with Duchenne muscular dystrophy, sleep assessment is typically focused on pulmonary function and identification of sleep disordered breathing. Unfortunately for young boys with Duchenne muscular dystrophy, sleep assessment is often neglected, resulting in a dearth of knowledge on sleep health in this population. This study describes sleep quantity and quality in both younger (4-9 years) and older (10-17 years) males with Duchenne muscular dystrophy (n= 19) and compares these characteristics with sleep characteristics of unaffected peers (n= 17). Methods This study was a longitudinal, observational study. Sleep measures were collected using the parent-proxy Children’s Sleep Habits Questionnaire-Abbreviated version and objective sleep measures from actigraphy (sleep efficiency, awakenings, and awakening duration) over 30 days for all participants. Means and standard deviations were examined, and effect sizes were computed to quantify the magnitude of difference between the Duchenne muscular dystrophy and unaffected groups. Results Overall, boys with Duchenne muscular dystrophy were found to experience worse sleep than their unaffected peers as measured by parent report and actigraphy. Effect sizes of both measures demonstrated moderate to large magnitudes of difference in many of the sleep variables. Parents of boys with Duchenne muscular dystrophy reported higher scores (indicating worse sleep) in all subsections and total score of the Children’s Sleep Habits Questionnaire – Abbreviated version. Actigraphy data indicated that the Duchenne muscular dystrophy group had lower percent sleep efficiency, more night awakenings and longer duration of night awakenings than their unaffected peers. Conclusion Our findings offer a novel look into sleep in young boys with Duchenne muscular dystrophy. Both parent-report and actigraphy data indicate poor sleep health in this population compared with age-matched unaffected peers. Actigraphy was found to align with parent-report of sleep in this population, supporting the use of these two different ways to measure sleep in Duchenne muscular dystrophy. Results from this study should encourage clinicians and researchers alike to further explore sleep and its impact on disease in young boys with Duchenne muscular dystrophy.
Article
Full-text available
Medical cannabis has been touted as a solution to the US opi-oid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668-1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods to extend Bachhuber et al.'s analysis through 2017. Not only did findings from the original analysis not hold over the longer period, but the association between state medical cannabis laws and opi-oid overdose mortality reversed direction from −21% to +23% and remained positive after accounting for recreational cannabis laws. We also uncovered no evidence that either broader (recre-ational) or more restrictive (low-tetrahydrocannabinol) cannabis laws were associated with changes in opioid overdose mortality. We find it unlikely that medical cannabis-used by about 2.5% of the US population-has exerted large conflicting effects on opioid overdose mortality. A more plausible interpretation is that this association is spurious. Moreover, if such relationships do exist, they cannot be rigorously discerned with aggregate data. Research into therapeutic potential of cannabis should continue, but the claim that enacting medical cannabis laws will reduce opioid overdose death should be met with skepticism.
Article
Full-text available
There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged. The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy. We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires. After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.
Article
Full-text available
Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts. This included current or previous users of cannabis extracts to treat their child's seizures (n = 41 families), and families who had never used (n = 24 families). For those using cannabis, extracts were analysed for cannabinoid content, with specific comparison of samples rated by families as "effective" versus those rated "ineffective". Results showed that children given cannabis extracts tended to have more severe epilepsy historically and had trialled more anticonvulsants than those who had never received cannabis extracts. There was high variability in the cannabinoid content and profile of cannabis extracts rated as "effective", with no clear differences between extracts perceived as "effective" and "ineffective". Contrary to family's expectations, most samples contained low concentrations of cannabidiol, while Δ9-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic value of cannabinoids in epilepsy.
Article
Full-text available
Background: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. Funding: National Health and Medical Research Council and the Australian Government.
Article
Full-text available
The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.
Article
The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
Article
Rationale: Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential. Methods: This was a single-dose, randomized, double-blind, double-dummy, placebo- and active-controlled crossover trial. The abuse potential of single oral doses of plant-derived pharmaceutical formulations of highly purified CBD (Epidiolex®; 750 mg, 1500 mg, and 4500 mg) was compared with that of single oral doses of alprazolam (2 mg), dronabinol (10 mg and 30 mg), and placebo in healthy recreational polydrug users. The primary endpoint to assess abuse potential was the maximum effect (Emax) on Drug-Liking visual analog scale (VAS). Other measurements included Emax on Overall Drug-Liking VAS, Take Drug Again VAS, positive and negative effects, other subjective effects, and Drug Similarity VAS. Cognitive and psychomotor functions were assessed using the Divided Attention Test, the Hopkins Verbal Learning Test-Revised, and the Digit-Symbol Substitution Task. Pharmacokinetic parameters were determined for CBD and its major metabolites. Standard safety measures and adverse events were assessed. Principal results: Of 95 eligible subjects, 43 qualified for the treatment phase, received at least 1 dose of investigational medicinal product, and were included in safety assessments; 35 subjects were included in the pharmacodynamic analysis. Subjects receiving alprazolam and dronabinol had significantly higher Drug-Liking Emax (P < 0.0001) compared with those receiving placebo, confirming study validity. Compared with placebo, Drug-Liking was not significantly different for subjects taking 750-mg CBD (P = 0.51). Drug-Liking Emax values for 1500-mg and 4500-mg CBD were significantly different from placebo (P = 0.04 and 0.002, respectively); however, the mean differences were <10 points on VAS compared with >18-point differences between positive controls and placebo. Alprazolam and dronabinol had significantly higher Drug-Liking, Overall-Liking, and Take Drug Again VAS Emax values compared with all doses of CBD (P ≤ 0.004). In contrast to alprazolam, CBD administration had no observable effect on cognitive/psychomotor tests. Pharmacokinetic parameters for CBD in this trial were consistent with previous studies. The majority of adverse events reported during the trial were of mild or moderate severity; no serious adverse events or deaths were reported. Conclusion: Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.
Article
Background and Aims While the US has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether statewide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees. Design Secondary data analysis of state‐level opioid prescription records from 1993‐2014 Medicaid State Drug Utilization Data. Linear time‐series regressions assessed the associations between medical cannabis legalization and opioid prescriptions, controlling for state‐level time‐varying policy covariates (such as prescription drug monitoring programs) and socioeconomic covariates (such as income). Setting United States. Participants Drug prescription records for patients enrolled in fee‐for‐service Medicaid programs that primarily provide healthcare coverage to low income and disabled people. Measurements The primary outcomes were population‐adjusted number, dosage, and Medicaid spending on opioid prescriptions. Outcomes for Schedule II opioids (e.g., Hydrocodone, Oxycodone) and Schedule III opioids (e.g., Codeine) were analyzed separately. The primary policy variable of interest was the implementation of statewide medical cannabis legalization. Findings For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% (p=0.03) reduction in number of prescriptions, 29.9% (p=0.02) reduction in dosage, and 28.8% (p=0.04) reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions. Permitting medical cannabis dispensaries was not associated with Schedule II or Schedule III opioid prescriptions after controlling for medical cannabis legalization. It was estimated that, if all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars. Conclusion Statewide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the US.