Clinicians’ Guide to Cannabidiol and Hemp Oils

Abstract

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.

Full text

Clinicians’Guide to Cannabidiol and
Hemp Oils
Harrison J. VanDolah, BA; Brent A. Bauer, MD; and Karen F. Mauck, MD
Abstract
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.
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 (http://creativecommons.org/licenses/by-nc-nd/4.0/)nMayo 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.
1
Although there has been a larger focus on
reducing opioid prescriptions and prevent-
ing nonmedical use of opioids, there is an
increasing interest in finding more treatment
options for patients in pain,
2
and the diverse
field of integrative medicine has been finding
an increasing role in this area.
3,4
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 benefits of encouraging
poorly regulated medical use of a known
substance of abuse.
5,6
Cannabidiol and
hemp oils have become especially popular
because of their low tetrahydrocannabinol
(THC) levels, resulting in attributed medical
benefits without the “high”of marijuana.
7
However, clinicians have concerns about
whether these treatment options are legal,
safe, and effective and are largely unfamiliar
with these products.
8,9
Therefore, we pro-
vide an overview of the scientific 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.
10
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.
REVIEW
1840 Mayo Clin Proc. nSeptember 2019;94(9):1840-1851 nhttps://doi.org/10.1016/j.mayocp.2019.01.003
www.mayoclinicproceedings.org 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

and food.
11
Despite considerable sociopoliti-
cal obstacles, scientific 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
body’s own endogenous cannabinoids and
the endocannabinoid system (ECS).
12
THE ENDOCANNABINOID SYSTEM
It is now known that the ECS is globally
involved in maintaining homeostasis in the
body, connecting all of the body’s organs
and systems.
13
The ECS has been implicated
in a variety of disease states and important
regulatory functions, from chronic inflamma-
tory conditions and regulation of immune ho-
meostasis in the gut to anxiety and
migraines.
14-17
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.
18-20
Figure 1
summarizes the basic molecular biology of
the ECS, as well as some of the molecular
effects of phytocannabinoids.
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 first ones were discovered in the context
of C sativa research, with more than 80 phyto-
cannabinoid compounds being discovered in
the marijuana plant alone.
21
Phytocannabi-
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.
22,23
The most
notable and well-understood phytocannabi-
noids are THC and CBD, the most common
phytocannabinoids in marijuana and hemp
strains, respectively.
21
Tetrahydrocannabinol
has been noted to work mostly through the
CB1 receptor as an agonist, leading to its
well-known intoxicating effects.
24
Cannabi-
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
1A
receptors.
25-28
Cannabidiol’s minimal agonism of the CB
receptors likely accounts for its negligible
psychoactivity when compared with THC.
29
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.
30
Notably, there are
ARTICLE HIGHLIGHTS
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 profile.
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
difficult to treat diseases, in particular pain and addiction
treatment in the context of the opioid crisis.
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many other components in hemp extracts,
and many products boast of being
“full-spectrum”in 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.
22
LEGAL AND REGULATORY
CONSIDERATIONS
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 first time. The law defined
“industrial hemp”as “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.”
32
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.
33
Addi-
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
Normal
neurotransmitter
release
(GABA, glutamate)
1
Presynaptic
neuron
Postsynaptic
neuron
GABA
Glutamate CB1
GABA
receptors
TRPV
Release of
anandamide
and 2-AG
Activation of
CB1 & CB2
receptors
CB2
2
3
BCP,
Echinacea
+
THC
AN
©2018 MFMER 3809112-2
I
+
FIGURE 1. Modulation of the endocannabinoid system by phytocannabinoids.
19,20,31
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.
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positive for marijuana on drug screening, as
was noted in the Epidiolex drug trials.
34
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
basis.
35
Importantly, although many states
have allowed use of medical marijuana, phy-
sicians may only “certify”or “recommend”
that their patients may use medical mari-
juana for a certain condition and cannot
issue a prescription for specific cannabis
products because they are not approved by
the FDA or Drug Enforcement Administra-
tion (DEA).
33
Notably, because CBD and
hemp oils do not contain intoxicating
amounts of THC, they do not require a cer-
tification 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
AS GU
AK
WA
OR
CA
NV
ID
MT ND MN
SD
NE
KS MO
IL
OH
WV
NY
PA
MI
AR
OK
LA
FL
CO
NM
AZ
TX
UT
WY
IA
WI
IN
KY VA
NC
SC
TN
MS AL GA
MP VI PR
MA
NH
ME
VT
RI
CT
NJ
DE
ND
DC
HI
FIGURE 3. State cannabis programs.From the National Conference of State Legislatures,
35
with permission.
Cannabinoids
• Anandamide (AEA)
• 2-Arachidonylglycerol (2-AG)
Endocannabinoids
(brain derived)
• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC)
• Cannabichromene (CBC)
• Cannabigerol (CBG)
• Many others
Phytocannabinoids
(plant derived)
• Dronabinol
• Nabilone
Synthetic cannabinoids
(laboratory derived)
FIGURE 2. Important cannabinoids.
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also containing less CBD than labeled.
36
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.
37
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 classifica-
tion, they still remain “concerned about the
proliferation and illegal marketing of unap-
proved CBD-containing products with un-
proven medical claims.”
38
CBD AND HEMP OILS
Definitions
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 flowers
and leaves.
39
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-
idants.
40
Additionally, there are “cannabis
oil”products as well, which are oils derived
from the marijuana plant that have high
levels of THC.
41
Table 1 summarizes these
differences.
Products may be marketed as “full-spec-
trum”formulas, 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 difficult to know which
ingredient accounts for a specific 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
40
Hemp/CBD oils
22
Cannabis oils
22,41
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
smaller-quantity
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 fibers
Medicinal uses of CBD and
full-spectrum hemp oils
Medicinal uses of THC
BCP ¼b-caryophyllene; CBD ¼cannabidiol; THC ¼tetrahydrocannabinol.
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TABLE 2. Common Components and Added Ingredients in CBD and Hemp Oil Products
Ingredient Chemical classification
Approximate
concentration in hemp
39
Other sources Mechanism of action Potential therapeutic actions
Cannabidiol Phytocannabinoid Up to 40% None known Anandamide uptake inhibitor,
TRPV1 receptor activation,
GPR55 receptor activation,
5-HT
1A
activation
27,28,31
Antiepileptic, antinociceptive,
anti-inflammatory, anxiolytic,
antidepressive, addiction
management/treatment, inflammatory
dermatologic conditions,
neuroprotective, others
42-62
Tetrahydrocannabinol Phytocannabinoid <0.3% None known Binds to CB1 receptors
31
Antiemetic, antinociceptive, others
31
b-Caryophyllene Sesquiterpenoid Less than 1% Black pepper, clove,
rosemary, hops
Binds to CB2 receptors
63
Anxiolytic, anti-nociceptive
64-67
Limonene Terpenoid Less than 1% Citrus fruits, rosemary Induction of glutathione Antioxidant, antitumor activity
68
Cannabichromene Phytocannabinoid Varies considerably
with strain
None known Anandamide uptake inhibitor
69
Antinociceptive
70
Cannabigerol Phytocannabinoid Varies considerably
with strain
None known Anandamide uptake inhibitor
70
Anti-inflammatory, neuroprotective
71,72
Echinacea Alkylamides None Zanthoxylum
(Sichuan pepper)
Binds to CB2 receptors
73-75
Anti-inflammatory,
antioxidant, antimicrobial
75-78
Boswellia Triterpenes None Also known
as frankincense
Inhibition of prostaglandin E
2
synthase
79
Anti-inflammatory
79
Turmeric Curcuminoids (eg,
diferuloylmethane,
demethoxycurcumin)
None None known May bind to CB1 receptors
80
Unclear in preclinical, purported
antinociceptive and
anti-inflammatory
properties
81
Ashwaganda Steroidal alkaloids
and lactones
None Also known as Withania somnifera Possible mimicry of GABA
82
Stress reduction,
anxiolytic, immuno-modulatory
82
Magnolia Polyphenols None Also known as magnolia bark Binds to CB2 receptors
83
Antioxidant, anti-inflammatory
84
GABA ¼g-aminobutyric acid; GPR55 ¼G proteinecoupled receptor 55; TRPV1 ¼transient receptor potential vanilloid 1.
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is provided for reference on the most com-
mon ingredients included in CBD and
hemp oils when looking at potential
products.
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).
24
Much less data are available on CBD, which
works via a variety of complex mechanisms
noted previously,
31
and BCP, which works
through the less-understood CB2 recep-
tors.
64
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
syndrome.
30
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,
30
again demonstrating the lack
of solid scientific research conducted on
them.
In June 2018, the FDA approved Epidio-
lex, a purified 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 CBD’s 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 inflammatory
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 oils’potential for
use in the treatment of chronic pain, in the
most recent review on the topic in 2018,
Donvito et al
42
wrote that “an overwhelming
body of convincing preclinical evidence indi-
cates that cannabinoids produce antinoci-
ceptive effects in inflammatory 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-
rotonin.
43,44,85,86
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 efficacy but also because of its limited
misuse and diversion potential as well as
safety profile.
86
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 reflection 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.
6,86
Safety and Adverse Effects
No rigorous safety studies have been done
on “full-spectrum”phytocannabinoid oils
because these products are relatively new,
but the separate ingredients have been exam-
ined somewhat, generally with no major
adverse effects noted.
87,88
Cannabidiol doses
up to 300 mg/d have been used safely for up
to 6 months,
89,90
and doses of 1200 to 1500
mg/d were used in a study by Zuardi
et al
91,92
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,
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although these adverse effects were less se-
vere and less frequent when compared with
the usual adverse effects of clobazam treat-
ment.
45-49
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.
34
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.
93
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.
94-97
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-
tion.
98,99
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.
36,100
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.
101
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.
11
As with other herbal supplements, ensure
that the product has been extracted by car-
bon dioxide with no solvents, is certified
by the US Department of Agriculture as
organic, and has been tested for pesticides/
herbicides, which have been found in some
products.
102
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.
40
It is up to the
discretion of the physician whether to sug-
gest trying “full-spectrum”formulations
because no research is available on their
safety and efficacy 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
Product
1. Does it meet the following quality standards?
a. Current Good Manufacturing Practices (CGMP) certification
from the US Food and Drug Administration
b. European Union (EU), Australian (AUS),or Canadian (CFIA) organic certification
c. National Science Foundation (NSF) International certification
2. Does the company have an independent adverse event reporting program?
3. Is the product certified organic or ecofarmed?
4. Have their products been laboratory tested by batch to confirm
tetrahydrocannabinol levels <0.3% and no pesticides or heavy metals?
CLINICIANS’GUIDE TO CBD AND HEMP OILS
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a higher-quality product and company,
based on requirements used by Mayo Clinic
for collaboration with dietary supplement
manufacturers.
CONCLUSIONS AND FUTURE RESEARCH
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 efficacy and purported safety
profile. Careful selection of a product is
crucial for both safety and potential efficacy,
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 benefit.
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-
tients’interest 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@
creighton.edu).
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