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Clinicians’ Guide to Cannabidiol and Hemp Oils


Abstract and Figures

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.
Content may be subject to copyright.
CliniciansGuide to Cannabidiol and
Hemp Oils
Harrison J. VanDolah, BA; Brent A. Bauer, MD; and Karen F. Mauck, MD
Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have
become very popular over the past few years. Patients report relief for a variety of conditions,
particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the rst
CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of
rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of
preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its
potential role as another option for treating challenging chronic pain or opioid addiction. Care must be
taken when directing patients toward CBD products because there is little regulation, and studies have
found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an
overview of the scientic work on cannabinoids, CBD, and hemp oil and the distinction between
marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the
current legal status of CBD and hemp oils in the United States and provide a guide to identifying
higher-quality products so that clinicians can advise their patients on the safest and most evidence-
based formulations. This review is based on a PubMed search using the terms CBD,cannabidiol,
hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most
up-to-date information were selected for inclusion.
ª2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license ( Clin Proc. 2019;94(9):1840-1851
One of the biggest challenges facing
health care today is combatting
opioid abuse, with medical and
nonmedical overuse of opioids exacting a
huge toll on society in recent years.
Although there has been a larger focus on
reducing opioid prescriptions and prevent-
ing nonmedical use of opioids, there is an
increasing interest in nding more treatment
options for patients in pain,
and the diverse
eld of integrative medicine has been nding
an increasing role in this area.
One prom-
ising area has been use of the plant Cannabis
sativa, both in medical marijuana as well as
hemp and cannabidiol (CBD) oils, with
some evidence that access to medical mari-
juana is correlated with a decrease in opioid
use, although there has been controversy
about the risks and benets of encouraging
poorly regulated medical use of a known
substance of abuse.
Cannabidiol and
hemp oils have become especially popular
because of their low tetrahydrocannabinol
(THC) levels, resulting in attributed medical
benets without the highof marijuana.
However, clinicians have concerns about
whether these treatment options are legal,
safe, and effective and are largely unfamiliar
with these products.
Therefore, we pro-
vide an overview of the scientic work on
cannabinoids, CBD, and hemp oil and clarify
the distinction between marijuana, hemp,
and the different components of CBD and
hemp oil products so that clinicians may be
able to direct their patients to the safest
and most evidence-based products.
Cannabis sativa has long been utilized by
human populations across the world for its
therapeutic properties, from pain relief to
treatment of epilepsy.
Marijuana and
hemp are 2 strains of the same plant, C sat-
iva, with marijuana being cultivated over the
years for its THC content and hemp for its
myriad other uses including paper, clothing,
From the Creighton
University School of Medi-
cine, Omaha, NE (H.J.V.); and
Division of General Internal
Medicine (K.F.M.), Section of
Integrative Medicine and
Health (B.A.B.), Mayo Clinic,
Rochester, MN.
1840 Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n nª2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. This is an open access article
under the CC BY-NC-ND license (
and food.
Despite considerable sociopoliti-
cal obstacles, scientic understanding of C
sativa has progressed substantially in the
past 30 years as the many active ingredients
of the C sativa strains were isolated and ma-
jor discoveries were made regarding the
bodys own endogenous cannabinoids and
the endocannabinoid system (ECS).
It is now known that the ECS is globally
involved in maintaining homeostasis in the
body, connecting all of the bodys organs
and systems.
The ECS has been implicated
in a variety of disease states and important
regulatory functions, from chronic inamma-
tory conditions and regulation of immune ho-
meostasis in the gut to anxiety and
Although the body has its
own endogenous cannabinoids, most notably
anandamide and 2-arachidonylglycerol,
plant-derived cannabinoids (phytocannabi-
noids) have been researched as potential ther-
apeutic options in a variety of areas because of
their modulation of the ECS.
Figure 1
summarizes the basic molecular biology of
the ECS, as well as some of the molecular
effects of phytocannabinoids.
Although the body contains its extensive
ECS that works through endogenous cannabi-
noids, many plant-derived cannabinoids have
been discovered that act on the ECS as well.
The rst ones were discovered in the context
of C sativa research, with more than 80 phyto-
cannabinoid compounds being discovered in
the marijuana plant alone.
noids and other important C sativa compo-
nents such as terpenoids have now also been
documented in a variety of other plants and
foodstuffs, such as carrots, cloves, black pep-
per, ginseng, and Echinacea.
The most
notable and well-understood phytocannabi-
noids are THC and CBD, the most common
phytocannabinoids in marijuana and hemp
strains, respectively.
has been noted to work mostly through the
CB1 receptor as an agonist, leading to its
well-known intoxicating effects.
diol, on the other hand, has been found
to work through a variety of complex pharma-
cological actions, such as inhibition of
endocannabinoid reuptake, transient receptor
potential vanilloid 1 and G proteinecoupled
receptor 55 activation, and increasing the
activity of serotonin 5-HT
Cannabidiols minimal agonism of the CB
receptors likely accounts for its negligible
psychoactivity when compared with THC.
Figure 2 summarizes the different
endocannabinoids, phytocannabinoids, and
synthetic cannabinoids. The synthetic can-
nabinoids are laboratory-derived THC prepa-
rations that have been US Food and Drug
Administration (FDA) approved for various
usages, as well as nabiximols, which is a
nonsynthetic 1:1 THC and CBD preparation
that has been approved in the United
Kingdom for pain and spasticity related
to multiple sclerosis. Nabiximols is not
approved by the FDA.
Notably, there are
dCannabidiol (CBD) is a nonintoxicating compound extracted
from Cannabis sativa plants that has gained popularity for med-
ical uses ranging from epilepsy to pain control and addiction
treatment because of its differing mechanism of action from
marijuana and its safety prole.
dAlthough important preclinical and pilot human studies have
suggested a potential role for CBD in numerous clinical situa-
tions, thorough clinical studies have only been performed on
intractable epilepsy syndromes for which Epidiolex, a CBD drug,
was approved by the US Food and Drug Administration for use.
dThe legal landscape of CBD remains complex because of
differing state and federal laws giving access to medical hemp
and marijuana products.
dThe CBD and hemp oil product market remains a concerning
one because of noted variability in CBD and tetrahydrocan-
nabinol levels in products, as well as lack of regulation in pro-
duction and distribution.
dAlthough CBD and hemp oils remain an unproven therapeutic
option, physicians should remain open to the possible future
role these products may play in the management of a variety of
difcult to treat diseases, in particular pain and addiction
treatment in the context of the opioid crisis.
Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n 1841
many other components in hemp extracts,
and many products boast of being
full-spectrumin retaining these other
components, each with their own attributed
effects that are theorized to synergize
through what is termed the entourage
effectdessentially that the whole plant is
greater than the sum of its parts.
Since the 1970 Controlled Substances Act
outlawed growing and selling of both hemp
and marijuana, hemp continued to remain
illegal to grow in the United States until pas-
sage of the 2014 Agricultural Act, which
distinguished between hemp and marijuana
legality for the rst time. The law dened
industrial hempas Cannabis sativa L.
and any part of such plant, whether growing
or not, with a delta-9-THC content of no
more than 0.3% on dry weight basis,and
this allowed industrial hemp to be grown
for research purposes.
However, it is
technically illegal to introduce any supple-
ment or food containing CBD into interstate
commerce (as would be the case when
ordering online), so most products are im-
ported from Europe and then processed
and distributed in the United States.
tionally, 3 statesdIdaho, South Dakota, and
Nebraskadstill do not have any C sativa ac-
cess laws, and CBD and hemp oils are there-
fore illegal to sell or consume there. For all
other states, CBD and hemp oils are legal
as long as the THC content is below the
0.3% threshold. It is also important to note
that patients using CBD products may test
(GABA, glutamate)
Glutamate CB1
Release of
and 2-AG
Activation of
CB1 & CB2
©2018 MFMER 3809112-2
FIGURE 1. Modulation of the endocannabinoid system by phytocannabinoids.
Figure depicts the basic actions of the
endogenous cannabinoids anandamide (AN) and 2-arachidonylglycerol (2-AG) on the G proteinecoupled cannabinoid receptors 1
and 2 (CB1 and CB2) in presynaptic neurons in both the central and peripheral nervous system. The green-shaded compounds are
common phytocannabinoids and other herbal inclusions in hemp oils that have been found to affect the normal endocannabinoid in
some way, either through modulation of the CB receptors (eg, tetrahydrocannabinol [THC] agonism of CB1 receptors) or by other
routes not depicted, such as inhibition of enzymatic breakdown of endocannabinoids or other receptor modulation. BCP ¼b-
caryophyllene; GABA ¼g-aminobutyric acid; TRPV ¼transient receptor potential vanilloid.
1842 Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n
positive for marijuana on drug screening, as
was noted in the Epidiolex drug trials.
Figure 3 lists the current laws regarding
CBD oils and medical marijuana in the
United States available from the National
Conference of State Legislatures website,
which has helpful information on medical
marijuana and CBD laws on a state-by-state
Importantly, although many states
have allowed use of medical marijuana, phy-
sicians may only certifyor recommend
that their patients may use medical mari-
juana for a certain condition and cannot
issue a prescription for specic cannabis
products because they are not approved by
the FDA or Drug Enforcement Administra-
tion (DEA).
Notably, because CBD and
hemp oils do not contain intoxicating
amounts of THC, they do not require a cer-
tication or recommendation from a physi-
cian to be purchased and consumed.
However, there have been numerous warn-
ing letters sent by the FDA to companies
about inconsistent ingredients in their prod-
ucts, with many products containing higher
amounts of THC than legally allowed while
State cannabis programs
Vermont adult use law signed Jan. 22, 2018. Effective July 1, 2018
Limited adult possession and growing allowed, no regulated production or sales: DC, VT
Adult & medical use regulated program
Adult use only no medical regulated program
Comprehensive medical marijuana program
CBD/Low THC program
No public marijuana access program
Novermber 2018
FIGURE 3. State cannabis programs.From the National Conference of State Legislatures,
with permission.
• Anandamide (AEA)
• 2-Arachidonylglycerol (2-AG)
(brain derived)
• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC)
• Cannabichromene (CBC)
• Cannabigerol (CBG)
• Many others
(plant derived)
• Dronabinol
• Nabilone
Synthetic cannabinoids
(laboratory derived)
FIGURE 2. Important cannabinoids.
Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n 1843
also containing less CBD than labeled.
Additionally, now that CBD is the subject
of an investigational new drug authorization
for Epidiolex, it is no longer considered legal
by the FDA to use it in dietary supplement
products and foodstuffs.
Finally, although nearly all states have
passed some sort of C sativa access laws,
the federal government and the DEA still
consider CBD and hemp oils to be schedule
I substances. Although the DEA did reduce
Epidiolex, the pure CBD drug recently
approved by the FDA for intractable epilepsy
conditions, Dravet syndrome, and Lennox-
Gastaut syndrome, to a schedule V classica-
tion, they still remain concerned about the
proliferation and illegal marketing of unap-
proved CBD-containing products with un-
proven medical claims.
Because of variation in the legislation
regarding the C sativa plant as well as the
tremendous increase of new products being
marketed, there has been an accompanying
lack of clarity about the different types of
hemp and CBD oils. Depending on what
part of the plant is being extracted, there
will be different components present. The
phytocannabinoids such as THC and CBD,
as well as terpenoids like b-caryophyllene
(BCP) and limonene, collect in the owers
and leaves.
Conversely, the seeds of the C
sativa contain little to no phytocannabinoids,
instead being rich in omega-6 and omega-3
essential fatty acids, substantial amounts of
g-linolenic acid, and other nutritious antiox-
Additionally, there are cannabis
oilproducts as well, which are oils derived
from the marijuana plant that have high
levels of THC.
Table 1 summarizes these
Products may be marketed as full-spec-
trumformulas, dietary supplements, hemp
oils, or CBD-enriched products, coming in
the forms of oils, balms, sprays, capsules,
soft gels, oral applicators, foodstuffs such
as gummy bears, and even chew toys for
pets. The most popular products contain a
diverse array of phytocannabinoids from C
sativa as well as other phytocannabinoids
and terpenoids derived from other plants
and foodstuffs such as clove, hops, ashwa-
gandha, and turmeric. These products are
being marketed for a variety of uses such
as sleep aids, pain relief, or stress reduction.
Because of this inconsistency in ingredient
choices, as well as amounts and method of
administration, it is difcult to know which
ingredient accounts for a specic symptom
relief. Cannabidiol is the most well-studied
phytocannabinoid and will be the primary
focus in this article because it is also the
main ingredient in most products. Table 2
TABLE 1. Hemp Seed, CBD, and Cannabis Oils
Variable Hemp seed oils
Hemp/CBD oils
Cannabis oils
Part of plant extracted Seeds Flowers and leaves of hemp plant Flowers and leaves of marijuana plant
Main components Omega-6 and omega-3
fatty acids, g-linolenic
acid, nutritious antioxidants
Mostly CBD and BCP with other
phytocannabinoids and terpenoids
Mostly THC with some CBD and
other phytocannabinoids
and terpenoids
THC levels None <0.3% Dry weight >0.3% Dry weight (often very
high amounts such as 80%)
CBD levels Little to none More than average cannabis plants
(12%-18% CBD, often higher due
to postextraction enrichment)
Lower levels (10%-15%)
Uses Nutritional supplement,
other uses of hemp
such as clothing and bers
Medicinal uses of CBD and
full-spectrum hemp oils
Medicinal uses of THC
BCP ¼b-caryophyllene; CBD ¼cannabidiol; THC ¼tetrahydrocannabinol.
1844 Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n
TABLE 2. Common Components and Added Ingredients in CBD and Hemp Oil Products
Ingredient Chemical classication
concentration in hemp
Other sources Mechanism of action Potential therapeutic actions
Cannabidiol Phytocannabinoid Up to 40% None known Anandamide uptake inhibitor,
TRPV1 receptor activation,
GPR55 receptor activation,
Antiepileptic, antinociceptive,
anti-inammatory, anxiolytic,
antidepressive, addiction
management/treatment, inammatory
dermatologic conditions,
neuroprotective, others
Tetrahydrocannabinol Phytocannabinoid <0.3% None known Binds to CB1 receptors
Antiemetic, antinociceptive, others
b-Caryophyllene Sesquiterpenoid Less than 1% Black pepper, clove,
rosemary, hops
Binds to CB2 receptors
Anxiolytic, anti-nociceptive
Limonene Terpenoid Less than 1% Citrus fruits, rosemary Induction of glutathione Antioxidant, antitumor activity
Cannabichromene Phytocannabinoid Varies considerably
with strain
None known Anandamide uptake inhibitor
Cannabigerol Phytocannabinoid Varies considerably
with strain
None known Anandamide uptake inhibitor
Anti-inammatory, neuroprotective
Echinacea Alkylamides None Zanthoxylum
(Sichuan pepper)
Binds to CB2 receptors
antioxidant, antimicrobial
Boswellia Triterpenes None Also known
as frankincense
Inhibition of prostaglandin E
Turmeric Curcuminoids (eg,
None None known May bind to CB1 receptors
Unclear in preclinical, purported
antinociceptive and
Ashwaganda Steroidal alkaloids
and lactones
None Also known as Withania somnifera Possible mimicry of GABA
Stress reduction,
anxiolytic, immuno-modulatory
Magnolia Polyphenols None Also known as magnolia bark Binds to CB2 receptors
Antioxidant, anti-inammatory
GABA ¼g-aminobutyric acid; GPR55 ¼G proteinecoupled receptor 55; TRPV1 ¼transient receptor potential vanilloid 1.
Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n 1845
is provided for reference on the most com-
mon ingredients included in CBD and
hemp oils when looking at potential
Potential Therapeutic Actions
The chief ingredients of hemp oils are phyto-
cannabinoids such as CBD and terpenoids
such as BCP and limonene. However, there
is a paucity of clinical research conducted
on these important components because
most research focuses on THC and CB1 re-
ceptors (the primary target of THC).
Much less data are available on CBD, which
works via a variety of complex mechanisms
noted previously,
and BCP, which works
through the less-understood CB2 recep-
According to a recent systematic
review on the medical uses of cannabinoids,
there was moderate-quality evidence to
support the use of cannabinoids for chronic
pain and spasticity, and low-quality evidence
to support use for nausea and vomiting
due to chemotherapy, weight gain in HIV
infection, sleep disorders, and Tourette
However, it is important to
realize that most of the randomized
controlled trials examined in this systematic
review for each condition were of the 3 pre-
scriptible THC drugs dronabinol, nabilone,
and nabiximols; only 4 trials were found
for CBD, and none for any of the other phy-
tocannabinoids or terpenoids present in C
sativa oils,
again demonstrating the lack
of solid scientic research conducted on
In June 2018, the FDA approved Epidio-
lex, a puried CBD oral solution that was
found to provide major reductions in total
seizure frequency vs placebo for patients
with Dravet and Lennox-Gastaut syndromes.
The research on these conditions is the most
thorough clinical research that has been per-
formed on CBD and for now should be relied
on for understanding CBDs safety and
adverse effects, which will be discussed sub-
sequently in this article. Although the use of
CBD has been theorized for a variety of other
conditions from migraines and inammatory
conditions to depression and anxiety, only
preclinical and pilot studies have been
performed for any of these uses, and there-
fore there is little guidance for physicians if
their patient is interested in trying CBD or
hemp oils for these conditions.
As for CBD and hemp oilspotential for
use in the treatment of chronic pain, in the
most recent review on the topic in 2018,
Donvito et al
wrote that an overwhelming
body of convincing preclinical evidence indi-
cates that cannabinoids produce antinoci-
ceptive effects in inammatory and
neuropathic rodent pain models.Addition-
ally, it has been reported that CBD may be
able to treat addiction through reduced acti-
vation of the amygdala during negative
emotional processing and has been found
to reduce heroin-seeking behavior, likely
through its modulation of dopamine and se-
Cannabidiol therefore rep-
resents an attractive option in chronic pain
treatment, particularly in the context of
opioid abuse, not only because of its poten-
tial efcacy but also because of its limited
misuse and diversion potential as well as
safety prole.
More research will be needed
because these were pilot human studies with
small sample sizes, but they represent poten-
tial future areas of cannabinoid use in the
clinical treatment of pain relief and opioid
abuse. Additionally, more reection on the
right political and industrial means to go
about expanding access to CBD is needed
in the context of controversial evidence sup-
porting expanding access to medical mari-
juana as a pain control option.
Safety and Adverse Effects
No rigorous safety studies have been done
on full-spectrumphytocannabinoid oils
because these products are relatively new,
but the separate ingredients have been exam-
ined somewhat, generally with no major
adverse effects noted.
Cannabidiol doses
up to 300 mg/d have been used safely for up
to 6 months,
and doses of 1200 to 1500
mg/d were used in a study by Zuardi
et al
for up to 4 weeks. In the recent
larger studies on CBD treatment for epileptic
patients, CBD had associated adverse effects
of somnolence, decreased appetite, and
diarrhea noted in up to 36% of patients,
1846 Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n
although these adverse effects were less se-
vere and less frequent when compared with
the usual adverse effects of clobazam treat-
In addition, it was noted that a
considerable number of patients in these
studies had elevated liver function test
results, and the FDA recommends liver func-
tion tests before beginning Epidiolex treat-
ment, as well as 1 month and 3 months
after initiation of treatment; thus, physicians
should be cautious in patients with known
decreased hepatic function who choose to
use CBD and hemp oils. We recommend
consulting the FDA label for Epidiolex for
more information on safety, adverse effects,
and dosing that was gathered from the Epi-
diolex trials.
In the context of treating pain, one study
reported the safety of oral CBD administra-
tion (400-800 mg) alongside fentanyl admin-
istration, attributed to their different
mechanisms of action.
However, other
drug-drug interactions have been noted, or
at least hypothesized, based on the meta-
bolism of CBD by the cytochrome P450
superfamily, which includes warfarin and
various epilepsy drugs.
The other ingre-
dients in CBD and hemp oils are usually at
such small concentrations that they are un-
likely to cause severe interactions, but care
should still be taken with identifying ingre-
dients present in a product and possible
safety issues.
In addition, it is important to be aware of
the presence of synthetic cannabinoids avail-
able on the market, such as spice.These
substances have severe adverse effects and
have led to hospitalizations following inges-
As to the labeling of concentrations
in products, a 2017 survey reported that of 84
online CBD and hemp oil products examined,
only 26 were accurately labeled for CBD and
THC content, with CBD often being overla-
beled and THC underlabeled, consistent
with the statements made by the FDA.
There have also been documented cases of
pediatric THC intoxication related to CBD
product ingestion, likely due to this noted
variation in products, signaling the need for
more regulation of the market.
Finding a Quality Product
If patients and/or physicians choose to
experiment with CBD and hemp oils, it is
worthwhile to direct them toward the
highest-quality product. This issue becomes
all the more important when considering
some of the problems noted previously.
Because of the unclear regulations in the
United States as well as some of the noted
problems with online product labeling, it is
recommended that patients utilize products
imported from Europe, which actually has
even more stringent requirements for low
THC levels at less than 0.2% dry weight
compared with the US requirement of less
than 0.3% dry weight as well as a more
established regulatory system for hemp.
As with other herbal supplements, ensure
that the product has been extracted by car-
bon dioxide with no solvents, is certied
by the US Department of Agriculture as
organic, and has been tested for pesticides/
herbicides, which have been found in some
Additionally, ensure that the
product is not merely hemp seed oil, which
although containing nutritious omega-3 fatty
acids does not contain any of the phytocan-
nabinoids or terpenoids.
It is up to the
discretion of the physician whether to sug-
gest trying full-spectrumformulations
because no research is available on their
safety and efcacy outside of certain compo-
nents in separate contexts, whereas pure
CBD oils have been studied much more
rigorously in the recent seizure studies.
Table 3 provides a checklist for determining
TABLE 3. Checklist for Finding a High-Quality Cannabidiol and Hemp Oil
1. Does it meet the following quality standards?
a. Current Good Manufacturing Practices (CGMP) certication
from the US Food and Drug Administration
b. European Union (EU), Australian (AUS),or Canadian (CFIA) organic certication
c. National Science Foundation (NSF) International certication
2. Does the company have an independent adverse event reporting program?
3. Is the product certied organic or ecofarmed?
4. Have their products been laboratory tested by batch to conrm
tetrahydrocannabinol levels <0.3% and no pesticides or heavy metals?
Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 n 1847
a higher-quality product and company,
based on requirements used by Mayo Clinic
for collaboration with dietary supplement
Cannabidiol and hemp oils are nonintoxi-
cating and potentially useful phytocannabi-
noid substances that continue to grow in
popularity. With increasing patient interest
in and use of CBD and hemp oils, more
research is indicated to better understand
their potential efcacy and purported safety
prole. Careful selection of a product is
crucial for both safety and potential efcacy,
and although the products do not have FDA
approval for therapeutic use, patients
continue to use them and physicians should
inform themselves on both potential safety is-
sues and potential therapeutic benet.
Chronic pain management continues to chal-
lenge patients and physicians alike, and inves-
tigation into potential therapies such as CBD
and hemp oils is a promising area for the
future of clinical pain management for both
pain relief as well as addiction management.
We encourage physicians to not disregard pa-
tientsinterest in these therapies and instead
to retain clinical curiosity as well as healthy
skepticism when it comes to attempts to
explore new options, especially in the context
of curbing addiction and opioid overuse. Our
hope is that this article will inspire physicians
to continue to educate both patients and
themselves about alternative therapies uti-
lized by growing numbers of the public,
with the example of CBD and hemp oils in
particular as it continues to come to the fore-
front of public interest.
Abbreviations and Acronyms: BCP = b-caryophyllene;
CBD = cannabidiol; DEA = Drug Enforcement Administra-
tion; ECS = endocannabinoid system; FDA = Food and
Drug Administration; THC = tetrahydrocannabinol
Potential Competing Interests: The authors report no
competing interests.
Correspondence: Address to Harrison J. VanDolah, BA,
501 Park Ave, Apt 101, Omaha, NE 68105 (hjv72661@
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... It is crucial for individuals considering CBD as a treatment option for neurological disorders to consult with their healthcare professionals [18]. They can provide personalized advice, weigh the potential benefits and risks, and ensure that CBD does not interact with any other medications the individual may be taking [19]. In conclusion, neurological disorders can have a significant impact on individuals' lives, and there is a growing interest in exploring alternative treatment options such as CBD [13]. ...
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Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's disease, which present major healthcare concerns on a worldwide scale. Despite the lack of available therapies, CBD has been shown to possess a variety of pharmacological effects in preclinical and clinical studies, making it an intriguing competitor. This review brings together the most recent findings on the endocannabinoid and neurotransmitter systems, as well as anti-inflammatory pathways, that underlie CBD's modes of action. Synthesized efficacy and safety assessments for a range of neurological illnesses are included, covering human trials, in vitro studies, and animal models. The investigation includes how CBD could protect neurons, control neuroinflammation, fend off oxidative stress, and manage neuronal excitability. This study emphasizes existing clinical studies and future possibilities in CBD research, addressing research issues such as regulatory complications and contradicting results, and advocates for further investigation of therapeutic efficacy and ideal dose methodologies. By emphasizing CBD's potential to improve patient well-being, this investigation presents a revised viewpoint on its suitability as a therapeutic intervention for neurological illnesses.
... Patients with concurrent use of HSO and prescriptions should have regular follow-up visits to monitor their progress, assess updates and changes in drug response, and make necessary adjustments to treatment plans [99]. ...
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Hemp seed oil (HSO), esteemed for its potential health benefits and therapeutic attributes, has garnered substantial attention in recent years. However, the escalating consumption of HSO has engendered apprehensions regarding its potential interactions with pharmaceutical medications, posing the risk of adverse effects or altered drug efficacy. This comprehensive review diligently explores and elucidates the underlying mechanisms through which HSO may interact with a spectrum of drugs, accompanied by an extensive assessment of the clinical ramifications of these interactions. By assiduously unraveling these intricate dynamics, this review equips healthcare professionals and consumers with the knowledge to make judicious decisions concerning the concurrent use of HSO and prescription medications. Moreover, this comprehensive review endeavors to identify and address research gaps, charting a route for future investigations in this critical domain. This review sheds light on HSO's impact on drug-drug interactions (DDIs), delivering invaluable insights for healthcare professionals, researchers, and consumers and fostering the responsible and informed incorporation of this natural product across diverse therapeutic contexts. Keywords: Hemp seed oil; Drug-drug interactions; Mechanisms; Pharmacokinetics; Clinical implications; Therapeutics.
... The main side effects of cannabis or cannabinoid-containing products are mood swings, insomnia, heart spasms, relaxation, laughter, intense hunger, sensitivity to color perception, music, lethargy, and loss of spatial orientation (Martin-Biggers et al., 2015;Meng et al., 2018;. Genetic predisposition to mental illness and heart disease should also be considered when taking cannabinoids in various commercial forms ( Figure 5) (Levin et al., 2019). Several studies do not recommend using cannabis and cannabinoids during pregnancy and lactation (Joseph & Vettraino, 2020). ...
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There are differing views on cannabis and phytocannabinoid usage in diverse domains of application. This review explores the advantages and drawbacks of using cannabis and phytocannabinoids, including their effects on human health, in addition to highlighting the need for precise and repeatable analytical methods for quantifying controlled phytocannabinoids in consumer cannabidiol (CBD) products and foods. The composition and characteristics of the phytochemicals found in cannabis, the advantages and disadvantages of controlled and uncontrolled phytocannabinoids, and the need for regulation and standardization in the use of cannabis and products containing phytocannabinoids are all covered in this review of the pertinent literature. Cannabinoids used illegally can have negative consequences, but controlled phytocannabinoids found in consumer CBD products are relatively safe and unlikely to cause any adverse effects. It is necessary to restrict the amount of CBD in foods and consumer products in order to ensure safety. To measure the amount of restricted phytocannabinoids in these products, accurate analytical techniques are also required. In order to increase the use of cannabis among consumers, more research is needed to improve our understanding of the bioavailability and metabolic pathways of these compounds. Furthermore, consumers want clear and uniform federal rules governing the amount of CBD in food products in order to ensure correct dosing. To promote safe and responsible use, cannabis and phytocannabinoids must be carefully considered, regulated, and standardized. It is necessary for consumers to have clear, consistent standards governing the percentage of CBD in their food products. As a result, they would know the exact amount of CBD in their products.
... Complicating patients' decision making about cannabis, few trials have evaluated the safety and efficacy of cannabis use in cancer; most evidence regarding cannabis safety and efficacy in cancer comes from observational studies [12][13][14][15]. Cannabis is commonly used to treat cancer-related pain, and it may reduce nausea and anorexia [16][17][18][19][20][21]. There is also limited and conflicting evidence that cannabis has antitumor properties, carcinogenic properties, or both [20,[22][23][24][25]. Harms of cannabis include fatigue and cognitive changes, which are already common and debilitating symptoms in cancer patients [26,27]. ...
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Purpose To characterize cannabis use among cancer patients, we aimed to describe 1) patterns of cannabis use across multiple cancer sites; 2) perceived goals, benefits, harms of cannabis; and 3) communication about cannabis. Methods Patients with 9 different cancers treated at Memorial Sloan Kettering Cancer Center between March and August 2021 completed an online or phone survey eliciting cannabis use, attitudes, and communication about cannabis. Multivariable logistic regression estimated the association of cancer type and cannabis use, adjusting for sociodemographic characteristics and prior cannabis use. Results Among 1258 respondents, 31% used cannabis after diagnosis, ranging from 25% for lung cancer to 59% for testicular cancer. Characteristics associated with cannabis use included younger age, lower education level, and cancer type. In multivariable analysis, compared to lung cancer patients, gastrointestinal cancer patients were more likely to use cannabis (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.25–5.43). Cannabis use in the year prior to diagnosis was strongly associated with cannabis use after diagnosis (OR 19.13, 95% CI 11.92–30.72). Among users, reasons for use included difficulty sleeping (48%); stress, anxiety, or depression (46%); and pain (42%). Among respondents who used cannabis to improve symptoms, 70–90% reported improvement; < 5% reported that any symptom worsened. Only 25% discussed cannabis with healthcare providers. Conclusions Almost a third of cancer patients use cannabis, largely for symptom management. Oncologists may not know about their patients’ cannabis use. To improve decision making about cannabis use during cancer care, research is needed to determine benefits and harms of cannabis use.
... Introduction CBD, a cannabinoid constituent of the cannabis plant, has exponentially gained attention in both research and clinical applications as a potential treatment of several neuropsychiatric and general medical conditions. 1 Epidiolex Ò was the first FDA-approved plant-derived CBD medication. Today, many CBD-based formulations are in development aiming for FDA approval and numerous nonapproved CBD preparations are available over the counter often implying beneficial ''medicinal'' properties. 2 However, many questions raised by clinicians, researchers, and consumers of CBD products often relates to dosing and administration. ...
Background: In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of CBD and explore the impact of different factors on PK outcomes. Materials and Methods: This systematic review and meta-regression analysis was preregistered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsycInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Before-After Studies with no Control Group was used. Random-effects multivariable meta-regression analysis was conducted. Results: A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex® (n=22). For single-dose studies, CBD doses ranged between 2 and 100 mg in inhalation, 5-50 mg in oromucosal, and 0.42-6000 mg in oral administration. Sixty-six trial arms had only male participants or a higher number of male than female participants. The duration of the PK session was between 4 and 164 h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared with oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared with the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax. Conclusion: As expected, CBD dose, route of administration, and diet were major determinants of CBD PK with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Although CBD appeared to have a faster onset and longer duration in women, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
... O canabidiol (CBD) é um fitocanabinoide presente na planta Cannabis sativa que ganhou ampla atenção por seu uso em potencial na pesquisa psiquiátrica devido ao seu papel como neuromodulador em áreas do cérebro que controlam a cognição, a regulação emocional, o comportamento e as respostas fisiológicas (Kirkland et al., 2022). Os óleos de CBD são produtos se tornaram muito populares nos últimos anos, pois os pacientes relatam alívio para uma variedade de condições, particularmente da dor, sem os efeitos adversos da maconha medicinal (VanDolah et al., 2019). ...
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OBJETIVO: Apresentar as informações disponíveis sobre o canabidiol na forma de uma revisão bibliográfica narrativa, abordando sua utilização medicinal, mecanismos de ação e questões regulatórias para auxílio e embasamento técnico, a partir de informações publicadas na literatura científica. MÉTODOS: Nesta revisão bibliográfica narrativa (bases de dados, sites e periódicos especializados) foram selecionados estudos sobre a utilização de canabidiol (CBD) na terapêutica, abordando possíveis mecanismos neurobiológicos e legislação pertinente. As bases de dados avaliadas foram MEDLINE, PUBMED, SCIENCE DIRECT, SciELO e LILACS. RESULTADOS: Nos estudos selecionados sobre o tema foram descritos os mecanismos de ação do CBD, aplicações terapêuticas e questões regulatórias, sendo apresentadas as evidências descritas em literatura científica. CONCLUSÃO: A utilização clínica do CBD não se restringe somente à epilepsia pediátrica, havendo evidências consistentes sobre os benefícios de intervenções deste composto não só para doenças neurodegenerativas convencionais, mas também para condições neurodegenerativas secundárias a outras complicações do SNC isoladamente ou como adjuvante terapêutico. As suas aplicações na área de saúde mental e dor apresentam potencial terapêutico significativo, além de perfil terapêutico promissor para crianças e adolescentes com Transtornos do Espectro Autista.
Full spectrum CBD oil is widely available and touted as a safe and effective way to lower anxiety, promote restful sleep, and reduce inflammation. Given the anecdotal evidence that full spectrum CBD oil can also be used as an adjuvant to chemotherapy, an over-the-counter CBD oil product was tested to determine if it possessed cell cytotoxic properties. A “triple negative” breast cancer cell line was chosen as it represents a breast cancer subset which lacks targeted therapies and correlates with poor clinical outcomes. Cancer cells exposed to CBD oil had reduced cell viability, broad changes in gene expression, and reduced expression of a key growth factor receptor compared to control cells. Together, these data suggest that CBD oil is effective at reducing breast cancer cell viability in vitro. Future studies will focus on determining the range of cancer cell types similarly affected and on confirming mechanistic details.
Objetivo: realizar uma revisão de literatura acerca dos efeitos dos compostos presentes no fumo sobre o periodonto, e comparar a composição de ambos os produtos, analisando os malefícios na cavidade bucal causados por eles. Metodologia: foi realizada uma revisão narrativa de literatura entre janeiro de 2019 a janeiro de 2023 na base de dados eletrônica da Biblioteca Virtual de Saúde (BVS) e na base de dados internacional da PubmedMedline, utilizando os descritores de pesquisa indexados nos Descritores em Ciências da Saúde (DeCS): “Controle doTabagismo”, “Periodonto” e “Vapor doCigarro Eletrônico”, por meio da aplicação dos marcadores booleanos “AND” e “OR”. Revisão: os cigarros possuem em sua composição mais de 4500 derivados tóxicas que só em 2019 contabilizaram mais de 8 milhões de pessoas. Uma alternativa menos prejudicialà saúde gerado pelos cigarros tradicionais seria os cigarros eletrônicos, entretanto já foi demonstrado que existem inúmeras substâncias tóxicos nos aerossóis derivados desses aparelhos, entre elas as nitrosaminas, substância carcinogênica. Nos tecidos orais a utilização do tabaco tem a capacidade de diminuir a inserção epitelial e causar reabsorção do osso alveolar, redução do fluxo sanguíneo, modulando negativamente a resposta inflamatória e imunológica do hospedeiro, dificultando dessa forma a cicatrização de feridas contribuindo para o desenvolvimento de câncer oral, por exemplo. Conclusão: a utilização de cigarro está atrelada ao desenvolvimento de xerostomia, estomatite nicotínica, candidíase, língua pilosa,queilite angular e câncer oral independentemente do tipo, devendo o profissional de saúde orientar seus pacientes a cessar com o hábito.
Cannabinoid (CBD) oil is a trend in self-care management. In this digital age, patients have access to products from across the globe, and these products may not be regulated. Healthcare providers must be at the forefront of the latest trends in medicine and alternative therapies to better serve patients' needs. This article reviews various medical conditions for which CBD oil already is being used, its other medicinal uses, major adverse reactions, and what patients should know before they decide to consume CBD oil.
Nonarthroplasty knee procedures are common and may cause a wide spectrum of postoperative pain, ranging from minimal to severe, depending on the patient, pathology, and procedure. Procedures include ligament repair and reconstruction, especially anterior cruciate ligament reconstruction, meniscal débridement, repair and transplant, periarticular osteotomy, and cartilage restoration. Multimodal analgesia regimens have been implemented successfully, but notable variation characterizes current protocols. Increased public and physician awareness of the burden of opioid usage in the United States has encouraged the medical community to embrace opioid-minimizing and nonopioid techniques to mitigate the deleterious effects of these medications. Nonopioid medications; anesthesia techniques; surgical techniques; and postoperative nonmedication strategies, including physical therapy, transcutaneous electrical nerve stimulation, cryotherapy, cognitive techniques, and non-Western interventions, can form part of an effective multimodal approach. A multimodal approach can facilitate adequate analgesia without compromising patient satisfaction or outcome.
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Background and Aims Cannabidiol (CBD), a non‐intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side‐effects and research showing it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette‐related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side‐effects. Design Randomized, double‐blind crossover study with a fixed satiated session followed by two overnight abstinent sessions. Setting UK laboratory. Participants Thirty non‐treatment seeking, dependent cigarette smokers recruited from the community. Intervention and comparator 800mg oral CBD or matched placebo (PBO) in a counterbalanced order Measurements AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side‐effects, heart rate and blood pressure were assessed repeatedly. Findings When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence. Conclusions A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side‐effects.
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The therapeutic application of Cannabis is attracting substantial public and clinical interest. The Cannabis plant has been described as a veritable ‘treasure trove’, producing more than a hundred different cannabinoids, although the focus to date has been on the psychoactive molecule delta‐9‐tetraydrocannabinol (THC) and cannabidiol (CBD). Other numerous secondary metabolites of Cannabis the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesised to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’. The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardised growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source. Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC:CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of Cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.
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Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the “anti-relapse” potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.
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Objective: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. Methods: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metaboliteN-desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol). Safety assessments were clinical laboratory tests, physical examinations, vital signs, ECGs, adverse events (AEs), seizure frequency, and suicidality. Results: Thirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC0-t). CBD did not affect concomitant AED levels, apart from an increase in N-CLB (except in patients taking stiripentol). The most common AEs on CBD were pyrexia, somnolence, decreased appetite, sedation, vomiting, ataxia, and abnormal behavior. Six patients taking CBD and valproate developed elevated transaminases; none met criteria for drug-induced liver injury and all recovered. No other clinically relevant safety signals were observed. Conclusions: Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated. Classification of evidence: This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.
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The biological effects of cannabinoids, the major constituents of the ancient medicinal plantCannabis sativa(marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.
More than 50 people in Utah were sickened by synthetic or counterfeit cannabidiol (CBD) between October 2017 and January 2018, according to a study presented at CDC’s Epidemic Intelligence Service (EIS) Conference in mid-April.
Background Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy. Methods In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox–Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period. Results A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations. Conclusions Among children and adults with the Lennox–Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 number, NCT02224560.)
Background Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Methods Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4–10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks’ CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Results Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician’s global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆⁹-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Conclusion Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.
Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1, CB2or 5HT1Areceptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase - FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95). After 14 days, CBD injections (30 mg/kg) induced anxiolytic responses in stressed animals in the elevated plus-maze and novelty suppressed feeding tests, that were blocked by pre-treatment with a CB1(AM251, 0.3 mg/kg) or CB2(AM630, 0.3 mg/kg), but not by a 5HT1A(WAY100635, 0.05 mg/kg) receptor antagonist. Golgi staining and immunofluorescence revealed that these effects were associated with an increase in hippocampal neurogenesis and spine density in the dentate gyrus of the hippocampus. AM251 and AM630 abolished the effects of CBD on spines density. However, AM630 was more effective in attenuating the pro-neurogenic effects of CBD. CBD decreased FAAH and increased p-GSK3β expression in stressed animals, which was also attenuated by AM630. These results indicate that CBD prevents the behavioral effects caused by CUS probably due to a facilitation of endocannabinoid neurotransmission and consequent CB1/CB2receptors activation, which could recruit intracellular/synaptic proteins involved in neurogenesis and dendritic remodeling.
When medical marijuana was legalized in Massachusetts 5 years ago, Emma Jones, MD, was one of the first physicians on the pediatric palliative care team at the Dana-Farber Cancer Institute and Boston Children’s Hospital to register with the state so that she could provide qualifying young patients access to cannabis in the hopes of easing symptoms such as nausea and pain.