ArticlePDF Available

The Trouble with CBD Oil

  • Hazekamp Herbal Consulting

Abstract and Figures

In just a few years, cannabidiol (CBD) has become immensely popular around the world. After initially being discovered as an effective self-medication for Dravet syndrome in children, CBD is now sold and used to treat a wide range of medical conditions and lifestyle diseases. The cannabinoid CBD, a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC), is available in a growing number of administration modes, but the most commonly known is CBD oil. There are currently dozens, if not hundreds, of producers and sellers of CBD oils active in the market, and their number is increasing rapidly. Those involved vary from individuals who prepare oils on a small scale for family and (Facebook) friends to compounding pharmacies, pharmaceutical companies, and licensed cannabis producers. Despite the growing availability of CBD, many uncertainties remain about the legality, quality, and safety of this new “miracle cure.” As a result, CBD is under scrutiny on many levels, ranging from national health organizations and agricultural lobbyists to the WHO and FDA. The central question is whether CBD is simply a food supplement, an investigational new medicine, or even a narcotic. This overview paper looks into the known risks and issues related to the composition of CBD products, and makes recommendations for better regulatory control based on accurate labeling and more scientifically supported health claims. The intention of this paper is to create a better understanding of the benefits versus the risks of the current way CBD products are produced, used, and advertised.
This content is subject to copyright.
Legal and Regulatory Aspects – Commentary
Med Cannabis Cannabinoids 2018;1:65–72
The Trouble with CBD Oil
Arno Hazekamp
Hazekamp Herbal Consulting, Leiden, The Netherlands
Received: April 9, 2018
Accepted: April 11, 2018
Published online: June 12, 2018
Arno Hazekamp
Hazekamp Herbal Consulting BV
Utrechtse Veer 12b
NL–2311 NC Leiden (The Netherlands)
E-Mail Hazekamp.hc @
© 2018 The Author(s)
Published by S. Karger AG, Basel
DOI: 10.1159/000489287
Cannabidiol · CBD oil · Cannabis · Quality · Safety ·
Contaminants · Composition · Regulatory status
In just a few years, cannabidiol (CBD) has become immense-
ly popular around the world. After initially being discovered
as an effective self-medication for Dravet syndrome in chil-
dren, CBD is now sold and used to treat a wide range of med-
ical conditions and lifestyle diseases. The cannabinoid CBD,
a non-psychoactive isomer of the more infamous tetrahy-
drocannabinol (THC), is available in a growing number of ad-
ministration modes, but the most commonly known is CBD
oil. There are currently dozens, if not hundreds, of producers
and sellers of CBD oils active in the market, and their number
is increasing rapidly. Those involved vary from individuals
who prepare oils on a small scale for family and (Facebook)
friends to compounding pharmacies, pharmaceutical com-
panies, and licensed cannabis producers. Despite the grow-
ing availability of CBD, many uncertainties remain about the
legality, quality, and safety of this new “miracle cure.” As a
result, CBD is under scrutiny on many levels, ranging from
national health organizations and agricultural lobbyists to
the WHO and FDA. The central question is whether CBD is
simply a food supplement, an investigational new medicine,
or even a narcotic. This overview paper looks into the known
risks and issues related to the composition of CBD products,
and makes recommendations for better regulatory control
based on accurate labeling and more scientifically support-
ed health claims. The intention of this paper is to create a
better understanding of the benefits versus the risks of the
current way CBD products are produced, used, and adver-
tised. © 2018 The Author(s)
Published by S. Karger AG, Basel
What Is CBD Oil
Cannabidiol (CBD) oil is essentially a concentrated
solvent extract made from cannabis flowers or leaves that
is dissolved in an edible oil such as sunflower, hemp, or
olive oil. Solvents used can vary from relatively innocuous
organic solvents (ethanol, isopropyl alcohol) to more
harmful ones (petroleum-ether, naphtha), or even super-
critical fluids (butane, CO2). The exact conditions and
solvents applied have a great impact on, for example, the
taste, color, and viscosity of the final product. Because
many other plant components are co-extracted with the
desired cannabinoids present in the herbal material, these
are sometimes removed by a treatment known as “win-
terization.” By placing the extract in a freezer (–20 to
–80°C) for 24–48 h, components with a higher melting
point such as waxes and triglycerides, as well as chloro-
phyll will precipitate, so they can be removed by filtration
or centrifugation [1]. This treatment can significantly im-
prove the taste and color of the final product.
This article is licensed under the Creative Commons Attribution-
NonCommercial-NoDerivatives 4.0 International License (CC BY-
NC-ND) (
Usage and distribution for commercial purposes as well as any dis-
tribution of modified material requires written permission.
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
Cannabis oils may contain various concentrations of
CBD, tetrahydrocannabinol (THC), and minor cannabi-
noids, mainly depending on the cannabis variety used for
extraction. The most popular product currently is CBD
oil, but for example cannabigerol (CBG)-rich oil has been
spotted as well [2], and others will very likely follow soon.
The THC-rich type of cannabis oil has already been
known for some years, and is generally known under the
name “Simpson oil” [3]. Terpenes may or may not be
present in these products, depending on the preparation
method used [4]. Because they are highly volatile, elevat-
ed temperatures (such as those applied during drying of
plant materials, or during the evaporation of solvents)
may result in a significant loss of terpene components [5].
However, it is possible to capture evaporated terpenes by
condensation, and reintroduce them back into the final
oil. Additional ingredients may be added to further adjust
properties such as color, viscosity, taste, or shelf-life sta-
Oil has become a favorite mode of administration for
many medical users of cannabis and cannabinoids for
multiple reasons. First of all, concentrated extracts allow
the consumption of a large dose of cannabinoids in an
easily ingestible form. With CBD oil, there is no risk of
intoxication (getting high) [6], so much larger doses can
be consumed than would be possible for THC-rich prod-
ucts. Many users who prefer the holistic approach of us-
ing herbal cannabis worry about the stigma associated
with the typical smell caused by smoking or vaporizing it.
Cannabis oil has no smell that may identify a consumer
as a cannabis user, and it can be used discretely even in a
social setting, e.g., at work or around family. Moreover, it
can be efficiently dosed simply by counting the number
of drops consumed. These same benefits of using a con-
centrated extract were identified in a large survey among
medicinal cannabis users published in 2013 [7], perhaps
as an early indicator of the emergence of cannabis oils as
a preferred method of ingestion. Currently, the market is
developing further towards more sophisticated and pat-
entable products, including oral capsules, liposomal
products, skin creams, and chewing gums containing
Therapeutic Effects of CBD
Today, CBD is used for the treatment of a wide range
of medical conditions. This started with the somewhat
serendipitous discovery (by parents experimenting with
self-medication for their children) that CBD had a thera-
peutic effect on a serious form of epilepsy in children,
called Dravet syndrome [8]. This effect is now under
clinical investigation with the pharmaceutical CBD
product Epidiolex®, which is currently in phase 3 trials
with encouraging results [9, 10]. The media attention
generated by its effect on severely ill children gave CBD
the push needed to become a much desired medicine al-
most overnight [11]. Other medical indications that may
be treated with CBD, and are supported to some extent
by clinical proof, include Parkinson’s disease [12], schizo-
phrenia [13], and anxiety disorder [14]. However, al-
though research into the therapeutic effects of CBD is
rapidly increasing, most current uses of CBD are not
(yet) supported by clinical data. The popular use of these
products means that physicians may be confronted with
the effects of CBD oil even when they do not prescribe it
An excellent example is the use of CBD (and also THC)
products for the self-medicating of cancer, with the inten-
tion of fully curing it [15]. This is based on an increasing
body of preclinical evidence showing cannabinoids to be
capable, under some conditions, of inhibiting the devel-
opment of cancer cells in vitro or in vivo by various mech-
anisms of action, including induction of apoptosis, inhi-
bition of angiogenesis, and arresting the cell cycle [16].
This is certainly exciting news, and research is ongoing
around the world, but there is no solid clinical evidence
yet to support that cannabinoids – whether natural or
synthetic – can effectively and safely treat cancer in ac-
tual humans [17]. In fact, there are indications that cer-
tain types of cancer may even accelerate when exposed to
cannabinoids [18]. This becomes problematic when pa-
tients choose to refuse chemotherapy treatment because
they firmly believe in the rumored curative properties of
cannabinoids. As a result, recommendation of cannabi-
noids for treating cancer should be done with great care,
and with distinction as to the type of cancer being treated
Increasingly, CBD oil is also being promoted as a pro-
phylactic treatment in order to prevent certain diseases
from developing at all. The argument used is that the hu-
man endocannabinoid system is involved in basic life
functions such as appetite, immune response, reproduc-
tion, and pain management [20]. Because CBD functions
as an indirect antagonist to human CB1 and CB2 receptors
[21], it is reasoned that the presence of CBD prevents
them from being overly activated, thereby protecting the
nervous and immune systems from everyday stress. Fur-
thermore, CBD is known to be a reasonably potent anti-
oxidant, which further helps to protect against stressful
The Trouble with CBD Oil
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
influences [22]. Although this clearly increases the mar-
ket for CBD products, it also further erodes the scientific
basis for the therapeutic use of CBD. After all, it is hard
to prove scientifically that a disease was prevented by the
use of a health-promoting product.
If CBD oil was used mainly by adult, well-informed,
and reasonably healthy consumers, the impact of its wide-
spread use would perhaps be quite acceptable and limited.
However, this is not the case, as CBD is actively marketed
for use by children (e.g., for Dravet syndrome, ADHD,
autism), elderly people (Alzheimer’s disease, dementia,
Parkinson’s disease), patients suffering from complex
diseases (cancer, multiple sclerosis, chronic pain), and
even pets (anxiety, appetite, sleep). Indiscriminate use of
CBD may lead to various issues among these consumers.
For example, CBD shows an exciting potential for treat-
ing epilepsy in children, but the long-term effects of high-
dose CBD on these children’s brain functions remain un-
clear, while there are strong clues that the endocannabi-
noid system is central in the proper neuronal development
of the adolescent brain [23]. In order to halt the un-
checked advertising of CBD products, health authorities
in various countries have begun sending official warning
letters to stop producers and sellers from making un-
founded health claims [24, 25].
Legal Status of Hemp and CBD
The CBD present in oils and other products is usually
derived from fiber-type varieties of cannabis (hemp), be-
cause these are naturally higher in CBD content than
drug-type varieties (marijuana). Although cultivation of
hemp is allowed in many countries around the world, this
is usually governed by strict regulations. After being
banned for decades, hemp cultivation in the USA has only
recently been reintroduced, and is still gearing up for full
industrial production [26].
In the European Union (EU), the cultivation of cer-
tain cannabis varieties is granted provided they are reg-
istered in the EU’s Common Catalogue of Varieties of Ag-
ricultural Plant Species [27] and the THC content does
not exceed 0.2% of the dried flowers of the plant [28]. In
Canada, hemp is allowed to contain 0.3% THC [29],
while Switzerland allows up to 1% THC [30]. In most
countries, viable seeds for planting may be purchased
from certified seed companies only, in order to make
sure that the correct hemp variety is indeed being culti-
vated. Additionally, hemp may typically only be grown
in agricultural fields outdoors, while indoor cultivation
is usually forbidden. In some countries (e.g., The Neth-
erlands), growing hemp is allowed only with the intent
to produce fibers or seeds. As a result, the act of harvest-
ing fiber cannabis for its CBD is a violation of narcotics
laws [31]. New cannabis varieties (for example developed
to yield a higher content of CBD) are not (yet) registered
as approved hemp varieties, and therefore cannot be
freely cultivated, while the official registration process
takes several years to complete.
The legal status of CBD in the USA is extra compli-
cated, because many individual states have introduced
their own medicinal or even recreational cannabis laws,
while the Federal Government does not accept any con-
sumption of cannabis [32]. In the USA [33], but also in
Germany and the UK [34], CBD has been technically clas-
sified as a new medicine, requiring manufacturers to meet
much stricter safety, quality, and effectiveness standards.
The statement that CBD is simply “legal in all 50 US
states” is therefore misleading, if not untrue. It should be
noted that even in places where CBD is technically illegal,
products may still be easily available because the authori-
ties are lax about enforcing the law, or discussions are still
ongoing on how to deal with the influx of CBD. In short,
whether CBD is legal depends of how it was made, what
is in the final product, and where you are located.
An important issue in the discussion around cannabis-
derived oils is: how much THC is a legal CBD product
allowed to contain in order not to be considered a nar-
cotic? Authorities sometimes choose to deal with these
regulations in a pragmatic way, recognizing that laws
once designed to control marijuana abuse may not be ful-
ly applicable to hemp. For example, in the Netherlands, a
maximum level of 0.05% THC is allowed in CBD prod-
ucts, even though, formally, any detectable trace of THC
is illegal according to Dutch narcotics laws. This approach
is based on the fact that even hemp varieties of cannabis
produce a small amount of THC, and therefore naturally
derived CBD extracts will carry some THC in the final
The fact that the maximum CBD content in an oil is
limited by the THC present in the herbal material used
makes it attractive to add an additional amount of puri-
fied CBD to boost the percentage advertised on the label.
Unfortunately, the Novel Food Catalogue of the EU states
that “extracts of Cannabis sativa L. in which CBD levels
are higher than the CBD levels in the plant source are
novel in food” [35]. This means that enriching a natural
hemp extract with pure (often synthetic) CBD makes it a
Novel Food product, with the consequence that it must
undergo significant safety assessment prior to being mar-
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
keted. However, it is still unclear in many EU countries if
extracts with no added CBD also fall under this regime.
Given the many restrictions and conditions, it can be
difficult to set up a fully legal and functional pipeline for
the production and sale of CBD oil. Because different
countries allow different activities with regards to cultiva-
tion, processing, extracting, etc., of hemp, entrepreneurs
have often set up production pipelines that span multiple
countries, where hemp is cultivated in one country, while
extraction takes place in another, lab testing in a third,
and sales take place in yet another country. This obvi-
ously makes it harder to determine exactly where a CBD
product comes from, who is responsible for its final qual-
ity, and what standards were followed. For that reason,
thorough analytical testing of final products by certified
third-party labs is an essential tool to guarantee the safety
and composition of CBD oils.
Identifying the Real Risks
The discussion on the legal status of CBD revolves
mainly around the question: is it a medicine or a natural
food supplement? The main difference is that medicinal
drugs are considered unsafe until proven safe, whereas
food supplements are considered safe until proven other-
wise. As a result, the central question becomes whether or
not CBD is safe for consumers (children, elderly, pa-
tients) in large and unregulated quantities. Although
there is only limited knowledge about the long-term ef-
fects of chronic use, or about drug-drug interactions be-
tween CBD and other medications [36], human studies
have indicated that CBD is very well tolerated even up to
a daily dose of 1,500 mg [37]. Indeed, a recent World
Health Organization (WHO) review concluded that “to
date, there is no evidence of recreational use of CBD or
any public health-related problems associated with the
use of pure CBD” [38]. However, the risks to be assessed
about CBD products may not have much to do with the
pure compound CBD itself, but more with the unknown
composition and quality of the products offered. In par-
ticular, we should be looking into the presence of con-
taminants in these concentrated extracts, and into incor-
rect or even misleading labels for the cannabinoid con-
tent of products.
It is well known that cannabis plants obtained from
uncontrolled sources may be contaminated with various
harmful substances [39], sometimes leading to severe
health issues or hospitalization [40]. Contaminants in-
clude chemicals that were intentionally added in order to
increase yield, weight, or potency (e.g., pesticides, metal
particles [41], synthetic cannabinoids [42]) but also
agents that entered the plant unintentionally (e.g., heavy
metals, molds and bacteria [43], aflatoxins). For example,
pesticides are frequently present in cannabis sold by
Dutch coffee shops [44], but were also found in cannabis
offered under state law in California [45] as well as me-
dicinal cannabis from licensed producers in Canada [46].
If any of these contaminants were present in hemp used
for CBD extraction, they would likely end up in a concen-
trated form in the final oil. One contaminant specifically
relevant to cannabis (CBD or THC) oils is the residual
presence of toxic solvents used during the extraction pro-
cedure [3].
Although contaminants come in various shapes and
forms, most are relatively easy to detect, because many
professional analytical labs exist that routinely screen for
such contaminants in, for example, food crops, imported
medicinal plants, or edible oils. The standard lab meth-
ods, as described in Pharmacopoeia monographs (e.g.,
USP, EP) or food regulations, could simply be applied to
CBD oils, after some minor validation studies. For ex-
ample, the detection of heavy metals or pesticides present
in CBD oil does not significantly differ from the same
analysis in, say, a shipment of olive oil. The only analysis
that is not yet standard procedure in most analytical labs
is the quantification of cannabinoids. Because cannabi-
noids are only found (with few exceptions [47]) in the
cannabis plant, specific analytical methodology must be
developed to properly determine the cannabinoid com-
position of the many CBD products available.
Although a range of analytical methods have been
published in recent years [48], there is no general agree-
ment on which analytical method is most suitable and
accurate. Additionally, there are currently no generally
accepted guidelines or certifications to determine the
qualifications of cannabis labs. As a result, cannabinoid
analysis can differ significantly between labs [49], even
when the exact same sample is analyzed multiple times
[50]. This not only poses a risk to consumers (who do not
know how trust the label on their product) but may also
lead to business-to-business conflicts about the quality or
value of intermediate products. Additionally, inaccurate
analytical results may lead to legal problems if the THC
content of a CBD product unexpectedly turns out to be
higher than the maximally allowed limit. It seems clear
that a better agreement on the conditions for lab testing
of cannabinoids is urgently needed.
The Trouble with CBD Oil
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
What Studies Tell Us
Recently, an interesting study performed in the Neth-
erlands highlighted multiple issues that may be extrapo-
lated to CBD products elsewhere [51]. In this study, 46
different cannabis oil samples were collected directly
from patients and analyzed for cannabinoid content. The
obtained samples were home-made (n = 29) or purchased
from a (web) store (n = 17). For 21 of the 46 products
(46% of all samples), label information was available on
CBD/THC content, so that the claimed content could be
compared to the analyzed content as determined in the
study. Results are shown in Table 1. In many cases the
analyzed cannabinoid content strongly differed from the
claimed content on the label, while in 7 samples no can-
nabinoids (CBD or THC) were found at all. Such devia-
tions were found in home-made as well as commercially
obtained products.
Additionally, as many as 26/46 samples (57%) had a
THC content > 1%, with one sample peaking at 57.5%. In
18/46 samples (39%) the oil contained virtually only THC
(with CBD < 0.1%). Although many of the samples ana-
lyzed were purposely made to contain a high THC con-
tent, it is unclear whether oil consumers are always aware
they are consuming THC, and thereby exposing them-
selves to the adverse effects of this psychotropic com-
pound, such as intoxication, panic attacks, or disorienta-
tion. It should be noted that although the exact legal status
of CBD may be debatable, THC-rich extracts are strictly
prohibited in virtually all countries.
Another interesting observation was the presence of
high levels of non-decarboxylated cannabinoids in mul-
tiple samples. It is well known that CBD and THC are not
produced as such by the metabolism of the cannabis
plant. Instead, cannabinoids are excreted in the form of
carboxylic acids such as CBD-acid and THC-acid [52].
The physiological effects of these “acidic” cannabinoids
have been studied only to a very limited extent. Only after
proper heating (e.g., during smoking, vaporizing, or bak-
ing with cannabis) are these natural precursors rapidly
Table 1. Analysis of Dutch cannabis oil samples obtained from actual patients, comparing the claimed cannabi-
noid content on the product label with lab results measured in the study [51]
Sample ID CBD(A) THC(A)
rel. %
rel. %
127 2.3 –91.5 17 0.1 –99.4
225 0–100 35 4.6 –86.9
312 0.2 –98.3 0*
410.9 2.8 –74.3 0.1 *
510 2.2 –78 10 4–60
680.6 –92.5 40.2 –95
780.6 –92.5 40.1 –97.5
860.2 –96.7 50.1 –98
950–100 40 3.4 –91.5
10 44.7 +17.50 0.2 *
11 45.4 +35 0.3 *
12 4400*
13 44.2 +5 0*
14 33.1 +3.3 0.2 *
15 2.75 2.8 +1.8 0.1 *
16 0.1 0.1 046.3 +57.5
17 0.1 *77.9 +12.9
18 0*50.7 –86
19 0*50.9 –82
20 0.1 *20 15.8 –21
21 0*76.4 –8.6
CBD, cannabidiol; THC, tetrahydrocannabinol; CBD(A), total sum of CBD plus CBD-acid; THC(A), total
sum of THC plus THC-acid. *Not applicable because no label claim was made.
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
converted into the more well-known CBD and THC, re-
spectively. This process is called decarboxylation [52]. Al-
though decarboxylation also takes place during the pro-
duction of cannabis oils (e.g., during the evaporation of
solvents, or during a separate decarboxylation step as part
of the production process), 7/46 samples (15%) contained
> 25% of its cannabinoid content in the form of acidic can-
nabinoids, indicating poor control over the decarboxyl-
ation process. To address the issue, some producers sim-
ply add up the content of CBD and CBD-acid in order to
boast a higher “total CBD” content on the label, while
advertising this as “raw CBD.”
Various studies done on CBD oils and other cannabis
products around the world have come to similar conclu-
sions about incorrect label information [24, 53, 54] and the
presence of contaminants [54–57]. In the absence of a clear
legal status for CBD, or agreement on common safety and
quality standards, it may not be surprising that current
CBD products leave something to be desired. The time has
come for regulators to give CBD the attention it deserves
in order to ensure that affordable, safe, and reliable CBD
products are available to those who depend on them.
Almost overnight, CBD oils have become an interest-
ing combination of popular holistic medicine, miracle
cure, and a natural answer to the synthetic drugs dominat-
ing modern medicine. With CBD, patients receive the
promise of being in control of their own ailments, and no
longer feeling at the mercy of their treating physicians.
This has turned out to be a particularly powerful message.
Many patients use CBD oils freely for ailments both con-
firmed and self-diagnosed, and the rapid innovations with
CBD products have actually been quite impressive. But
while new CBD products keep entering the market virtu-
ally unchecked, effective regulatory control of these prod-
ucts has stayed far behind. As a result, unknown risks
about long-term effects remain unaddressed, especially in
vulnerable groups such as children, the elderly, and the
chronically or terminally ill. It should be noted that this
discussion goes well beyond CBD only, as new products
containing additional cannabinoids like CBG, THCV, and
acidic cannabinoids are following closely behind. We
know even less about these compounds than about CBD,
and very limited human safety data are available.
Although CBD seems destined to play an important
role as a therapeutic agent for a growing number of med-
ical indications, we should seriously ask ourselves if the
current unregulated production and sale of CBD oils is
done responsibly. Despite the fact that CBD is mainly sold
as “just” a food supplement, it is often used by severely ill
people with the intention of improving their body func-
tions in a way that their standard medication could not.
This obviously puts CBD uncomfortably close to the
realm of medicines. Interestingly, the WHO, based on a
review of available scientific data and input from interna-
tional experts, recently concluded that CBD does not im-
mediately require rescheduling as a drug [38], although a
fuller review on the risks and benefits of CBD is still being
planned. Nevertheless, perhaps the use of CBD products
should be assessed in a broader perspective, to cover all
ingredients used in the preparation, as well as any con-
taminants that are already known to be common in rec-
reational cannabis.
Determining risks and benefits through proper clinical
trials remains highly desired, but these will take consider-
able time and funds. As a result, clinical data will not ap-
pear any time soon, while patients will not simply stop
using the many CBD products to which they have become
accustomed. Taking back regulatory control over CBD
could therefore start with a more short-term and achiev-
able approach, i.e., demanding accurate and proper label-
ing, reflecting in detail what each product does and does
not contain, and how it was manufactured. For a clearer
judgment of the potential therapeutic effects, the risks,
but also the legality of a cannabis extract, it is important
to know its exact composition. After all, published data
from around the world has taught us that misleading la-
bels as well as harmful contaminants are real and actual
problems for CBD products. The analytical methodology
and the third-party labs needed for this approach largely
already exist, and could easily be optimized to quickly get
a better grip on the unrestrained cannabinoid market.
This approach would hold each producer strictly ac-
countable for the quality and safety of their own products,
as long as there are real legal consequences for those busi-
nesses that break the rules. Add to this a system for regu-
lar professional audits and inspections, and a crackdown
on unsubstantiated health claims, and we have a reason-
able system to ensure that CBD can be used responsibly
by those who need it, until much needed clinical data be-
come available.
Disclosure Statement
The author has no conflicts of interest to declare. No funding
was received for this study.
The Trouble with CBD Oil
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
1 Puri PS: Winterization of oils and fats. J Am
Oil Chem Soc 1980; 57:A848–A850.
2 Havelka J: What is CBG and what are the ben-
efits of this cannabinoid? Leafly (Internet),
101/what-is-cbg-cannabinoid (accessed April
13, 2018).
3 Romano LL, Hazekamp A: Cannabis oil:
chemical evaluation of an upcoming canna-
bis-based medicine. Cannabinoids 2013; 1: 1–
4 Sexton M, Shelton K, Haley P, West M: Evalu-
ation of cannabinoid and terpenoid content:
cannabis flower compared to supercritical
CO2 concentrate. Planta Med 2018; 84: 234–
5 Ross SA, ElSohly MA: The volatile oil compo-
sition of fresh and air-dried buds of Cannabis
sativa. J Nat Prod 1996; 59: 49–51.
6 McPartland JM, Duncan M, Di Marzo V, Per-
twee RG: Are cannabidiol and Δ9-tetra-
hydrocannabivarin negative modulators of
the endocannabinoid system? A systematic
review. Br J Pharmacol 2015; 172: 737–753.
7 Hazekamp A, Ware MA, Muller-Vahl KR,
Abrams D, Grotenhermen F: The medicinal
use of cannabis and cannabinoids – an inter-
national cross-sectional survey on adminis-
tration forms. J Psychoactive Drugs 2013; 45:
8 Devinsky O, Cross JH, Laux L, Marsh E, Mill-
er I, Nabbout R, et al: Trial of cannabidiol for
drug-resistant seizures in the Dravet syn-
drome. New Engl J Med 2017; 376: 2011–2020.
9 GW’s Epidiolex Clinical Program (Internet).
GW Pharmaceuticals, 2016.
tients (accessed April 13, 2018).
10 Devinsky O, Patel AD, Thiele EA, Wong MH,
Appleton R, Harden CL, et al; GWPCARE1
Part A Study Group: Randomized, dose-rang-
ing safety trial of cannabidiol in Dravet syn-
drome. Neurology 2018; 90:e1204–e1211.
11 Science seeks to unlock marijuana secrets (In-
ternet). National Geographic, 2015. https://
legality/ (accessed April 13, 2018).
12 Chagas MH, Zuardi AW, Tumas V, Pena-
Pereira MA, Sobreira ET, Bergamaschi MM,
et al: Effects of cannabidiol in the treatment of
patients with Parkinson’s disease: an explor-
atory double-blind trial. J Psychopharmacol
2014; 28: 1088–1098.
13 McGuire P, Robson P, Cubala WJ, Vasile D,
Morrison PD, Barron R, et al: Cannabidiol
(CBD) as an adjunctive therapy in schizo-
phrenia: a multicenter randomized controlled
trial. Am J Psychiatry 2018; 175: 225–231.
14 National Academies of Sciences, Engineering,
and Medicine: The health effects of cannabis
and cannabinoids: the current state of evi-
dence and recommendations for research.
Washington, National Academies Press,
2017, DOI: 10.17226/24625.
15 Can cannabis cure cancer? (Internet). Leafly,
can-cannabis-cure-cancer (accessed April 13,
16 Bogdanović V, Mrdjanović J, Borišev I: A re-
view of the therapeutic antitumor potential of
cannabinoids. J Altern Complement Med
2017; 23: 831–836.
17 Śledziński P, Zeyland J, Słomski R, Nowak A:
The current state and future perspectives of
cannabinoids in cancer biology. Cancer Med
2018; 7: 765–775.
18 Martínez-Martínez E, Martín-Ruiz A, Martín
P, Calvo V, Provencio M, García JM: CB2 can-
nabinoid receptor activation promotes colon
cancer progression via AKT/GSK3β signaling
pathway. Oncotarget 2016; 7: 68781–68791.
19 An open letter to Rick Simpson by Dr. Franjo
Grotenhermen (Internet). Grotenhermen,
franjo-grotenhermen/ (accessed April 13,
20 Zou S, Kumar U: Cannabinoid receptors and
the endocannabinoid system: signaling and
function in the central nervous system. Int J
Mol Sci 2018; 19:pii-E833.
21 Laprairie RB, Bagher AM, Kelly ME, Deno-
van-Wright EM: Cannabidiol is a negative al-
losteric modulator of the cannabinoid CB1 re-
ceptor. Br J Pharmacol 2015; 172: 4790–4805.
22 Hampson AJ, Grimaldi M, Axelrod, Wink D:
Cannabidiol and (–)Δ9-tetrahydrocannabinol
are neuroprotective antioxidants. Proc Natl
Acad Sci USA 1998; 95: 8268–8273.
23 Rubino T, Parolaro D: The impact of expo-
sure to cannabinoids in adolescence: insights
from animal models. Biol Psychiatry 2016; 79:
24 2015/2016 warning letters and test results for
cannabidiol-related products (Internet). US
Food and Drug Administration, 2015/2016.
chealthfocus/ucm484109.htm & https://
ucm435591.htm (accessed April 13, 2018).
25 UK Halts CBD Sales (Internet). Leafly, 2016.
ing-uk-halts-cbd-sales (accessed April 13,
26 US Hemp cultivation more than doubles in
2017 (Internet). The Leaf Online, 2017. http://
11/us-hemp-cultivation-doubles-2017/ (ac-
cessed April 13, 2018).
27 Plant variety database – European Commis-
sion (Internet). European Commission
website, 2018.
leted= (accessed April 13, 2018).
28 Commission Regulation (EC) No 2860/2000
(Internet). European Commission, 2000.
4f10-a329-b41db5b3e57c/language-en (ac-
cessed April 13, 2018).
29 Grow hemp (Internet). Canadian Hemp
Trade Alliance, 2018. http://www.hemptrade.
ca/grow-hemp (accessed April 13, 2018).
30 Ordonnance du DFI sur les tableaux des stu-
péfiants, des substances psychotropes, des
précurseurs et des adjuvants chimiques (In-
ternet). Swiss Government website, 2011.
pilation/2011/2595.pdf (accessed April 13,
31 Boeren mogen geen toppen van vezelhennep
meer oogsten (Internet).,2017.
(accessed April 13, 2018).
32 Mead AJD: The legal status of cannabis (mar-
ijuana) and cannabidiol (CBD) under US law.
Epilepsy Behav 2017; 70: 288–291.
33 FDA and marijuana: questions and answers
(Internet). US Food and Drug Administra-
tion, 2017.
supplements (accessed April 13, 2018).
34 MHRA statement on products containing
cannabidiol (CBD) (Internet). UK Govern-
ment website, 2016.
ucts-containing-cannabidiol-cbd (accessed
April 13, 2018).
35 Novel food catalogue (Internet). European
Commission, 2015.
index.cfm (accessed April 13, 2018).
36 Palleria C, Cozza G, Khengar R, Libri V, De
Sarro G: Safety profile of the newest antiepi-
leptic drugs: a curated literature review. Curr
Pharm Des 2017; 23: 5606–5624.
37 Zuardi AW, Morais SL, Guimarães FS,
Mechoulam R: Antipsychotic effect of canna-
bidiol. J Clin Psychiatry 1995; 56: 485–486.
38 Cannabidiol (CBD) pre-review report (Inter-
net). World Health Organization website,
controlled-substances/5.2_CBD.pdf (ac-
cessed April 13, 2018).
39 The Health effects of cannabis and cannabi-
noids: the current state of evidence and rec-
ommendations for research. National Acad-
emies of Sciences, Engineering, and Medi-
cine; Health and Medicine Division; Board on
Population Health and Public Health Prac-
tice; Committee on the Health Effects of Mar-
ijuana: An evidence review and research
agenda. Washington, National Academies
Press, 2017.
40 Hazekamp A: Evaluating the effects of gam-
ma-irradiation for decontamination of me-
dicinal cannabis. Front Pharmacol 2016; 7:
Med Cannabis Cannabinoids 2018;1:65–72
DOI: 10.1159/000489287
41 Busse F, Omidi L, Timper K, Leichtle A,
Windgassen M, Kluge E, et al: Lead poisoning
due to adulterated marijuana. N Engl J Med
2008; 358: 1641–1642.
42 “Fake pot” causing zombielike effects is 85
times more potent than marijuana (Inter-
net)., 2016. http://edition.cnn.
marijuana/ (accessed April 13, 2018).
43 “Medical Marijuana” riddled with mold, bac-
teria – especially bad for the sick? (Internet).
American Council on Science and Health,
%E2%80%94-especially-bad-sick-10855 (ac-
cessed April 13, 2018).
44 Cannabis contaminanten (Internet). RIVM,
ten (accessed April 13, 2018).
45 Biros AG: Steep Hill, ACCL find pesticides in
over 50% of cannabis samples (Internet).
Cannabis Industry Journal, 2016. https://
over-50-of-cannabis-samples/ (accessed
April 13, 2018).
46 Random testing, million-dollar fines: Cana-
da’s cannabis pesticide crackdown (Internet).
Leafly, 2018.
(accessed April 13, 2018).
47 Gertsch J, Pertwee RG, Di Marzo V: Phyto-
cannabinoids beyond the Cannabis plant – do
they exist? Br J Pharmacol 2010; 160: 523–529.
48 Leghissa A, Hildenbrand ZL, Schug KA: A re-
view of methods for the chemical character-
ization of cannabis natural products. J Sep Sci
2018; 41: 398–415.
49 Jikomes N, Zoorob M: The cannabinoid con-
tent of legal cannabis in Washington state var-
ies systematically across testing facilities and
popular consumer products. Sci Rep 2018; 8:
50 Hazekamp A, Gieringer D: How accurate is
potency testing? O’Shaughnessy’s Online
Autumn 2011; 17–18. https://pdfs.semantic-
51 Hazekamp A, Epifanova S: Grote variatie in
samenstelling cannabisolie noopt tot regels.
Pharmaceutisch Weekblad 2017; 152: 16–18.
52 Wang M, Wang YH, Avula B, Radwan MM,
Wanas AS, van Antwerp J, et al: Decarboxyl-
ation study of acidic cannabinoids: a novel ap-
proach using ultra-high-performance super-
critical fluid chromatography/photodiode
array-mass spectrometry. Cannabis Cannabi-
noid Res 2016; 1: 262–271.
53 Vandrey R, Raber JC, Raber ME, Douglass B,
Miller C, Bonn-Miller MO: Cannabinoid
dose and label accuracy in edible medical can-
nabis products. JAMA 2015; 313: 2491–2493.
54 Warning for consumers of CBD and cannabis
oils sold on the EU market (Internet). Inter-
national Cannabis and Cannabinoids Insti-
tute, 2017.
(accessed April 13, 2018).
55 Hazekamp A, Sijrier P, Verpoorte R, Bender
J, van Bakel N: Cannabis uit de apotheek is
beter. Pharmaceutisch Weekblad 2005; 12:
56 California has a dirty cannabis problem (In-
ternet)., 2017. http://420intel.
dirty-cannabis-problem (accessed April 13,
57 Thompson GR 3rd, Tuscano JM, Dennis M,
Singapuri A, Libertini S, Gaudino R, et al: A
microbiome assessment of medical marijua-
na. Clin Microbiol Infect 2017; 23: 269–270.
... In 2020 the FDA assessed 102 products that indicated a specific amount of CBD. 10 Only 45% of products had dosages within 20% of that specified on the label with 18% having less than 80% of the specified amount; 37% had more than 120% of the amount of CBD indicated on the label. ...
... Four were labeled correctly (less than 10% variability), two had 18% or 35% higher concentrations, and two had 74% or 98% lower CBD concentrations than the label stated, respectively. 10 ConsumerLabs is a third-party laboratory that differs from most labs. Instead of being paid to do their analysis by product manufacturers, it conducts its testing without the manufacturers consent and then charges consumers to see the results. ...
... The International Agency for Research on Cancer classifies polycyclic aromatic hydrocarbons as class IIa carcinogens and genotoxic mutagens. 10,14 Additionally, pesticide or heavy metal contamination in unregulated CBD products is possible. 10 The Florida Department of Agriculture and Consumer Services tested a random sample of a CBD product and found lead levels at 4.7 ppm. ...
Full-text available
After completing the activity, learners will be able to ● Discuss cannabidiol's known pharmacologic profile ● Identify FDA-approved indications for prescription cannabidiol and other indications in which research is promising ● Distinguish the FDA-approved cannabidiol from various nonprescription products in terms of quality and risk/benefit profile ● Maximize the pharmacist's role in helping patients who are good candidates for prescription cannabidiol or use nonprescription cannabidiol products either with or without other prescription drug therapies After completing the continuing education activity, pharmacy technicians will be able to ● Discuss the basic facts about cannabidiol products ● Acquire reputable sources for patients who have an interest in cannabidiol to find information ● Distinguish between nonprescription and prescription cannabidiols ● Infer when to refer patients to the pharmacist for recommendations or referral
... Avrupa Birliği'nde (AB), yetiştirilen ve yem için kullanılan kenevir çeşitleri, AB'nin 'Tarımsal Bitki Türlerinin Ortak Çeşitleri Kataloğu'nda listelenmektedir. (AB) 1307/20137 Sayılı Tüzüğe göre, bu çeşitlerdeki maksimum THC içeriği %0,2 (w/w) ile sınırlı (EFSA, 2015) iken bu değer Kanada"da < %0,3, İsviçre"de ise <1"dir (Hazekamp, 2018). ...
Full-text available
Cannabis has been used for different purposes since the past, and although the interest in cannabis is increasing day by day, the cannabis plant has been avoided for a while. Underlying the consumer's negative opinion of hemp is the psychoactive substance content of the plant. Contrary to popular belief, cannabis cultivated for industrial purposes is a cannabis variety with reduced psychoactive substance content and legal limits to support consumption. Although trans-Δ9-tetrahydrocannabinol (THC) in cannabis, which is responsible for the psychoactive effect, is an objectionable component that should be considered in industrial cannabis production, cannabidiol (CBD), which has the same molecular weight, has analgesic for chronic and non-chronic pain, antiepileptic, antibacterial, anti-inflammatory, anticarcinogenic, antidiabetic, antidepressant properties. THC component is not found in cannabis seeds, which are used as food for protein source purposes. In this study, the chemical properties of trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) compounds, which have the same molecular properties, were compiled by examining their effects on health, applicable legal limits, and research on compounds.
... Bertinaria", Regione Gonzole 10/1, Orbassano, Turin, Italy; Tel/Fax: +39-011-90224249, +39-011-90224242; E-mail: low content of THC, while often rich in CBD, can be legally sold and purchased in several countries [7,8]. As a consequence, the marketing of adulterated low THC-cannabis products to unaware users highlights the new and potential risk of inadvertent consumption of potent SCRAs, including MDMB-4en-PINACA. ...
Background the presence of the synthetic cannabinoid receptor agonist MDMB-4en-PINACA in adulterated low-THC cannabis products was recently highlighted in several reports. Moreover, numerous intoxication cases involving MDMB-4en-PINACA have been described. Objective In order to monitor the diffusion of cannabis products containing MDMB-4en-PINACA in our territory, a total of 358 cannabis-derived samples (213 vegetal material and 145 resins) seized in the period November 2020 – February 2021 in the western Piedmont Area (Italy) was analyzed. Methods General screening analyses for traditional and synthetic cannabinoids were performed by a GC-MS device operating in full scan mode (40-600 amu). The MDMB-4en-PINACA was quantified by means of a specific GC-SIM-MS protocol purposely developed and validated, while the quantification of THC, CBD, and CBN was carried out by a GC-SIM-MS method routinely employed in our laboratory. Results MDMB-4en-PINACA was detected in 12 out of 358 samples (3.4% of the total). Among these, the molecule was found in 11 vegetal materials and in one resin sample. Considering solely the analysis of the 213 herb products, a positive rate of 5.2% was found for the presence of MDMB-4en-PINACA in these samples. MDMB-4en-PINACA was found in the seized materials at concentration levels ranging from 0.4 up to 6.3 mg/g (mean 2.5 mg/g; median 1.7 mg/g). Concerning the traditional cannabinoids, the THC concentration was in the interval 3-43 mg/g (mean 12 mg/g; median 7 mg/g), while CBD was found at higher concentrations in all specimens, specifically in the range 47-140 mg/g (mean 87 mg/g; median 80 mg/g). Conclusions The adulteration of low-THC cannabis products with synthetic cannabinoid receptor agonists is a widespread phenomenon today. Since these substances are potentially more toxic than THC, their consumption poses a high risk of overdose for unaware users and a health-threatening situation. This study confirmed the sporadic presence on the market of CBD-prevalent cannabis products adulterated with MDMB-4en-PINACA.
Hemp is a crop that has been used since ancient times for its medicinal and textile applications, which is experiencing a resurgence today. This growing interest is due to the fact that hemp is a crop with multipurpose applications: a source of cellulosic and woody fibers, produces oil-rich seeds, is a raw material for phytochemicals and is driven by consumer demand for more natural and sustainable products. Residues recovered during the harvesting and processing of hemp fibers and/or seeds can be utilized to obtain an essential oil rich in phytochemicals with multiple applications. We review the recent progress and developments in hemp essential oil as a complex mixture of bioactive compounds with antiinflammatory, antibacterial, insecticidal and therapeutic properties, and whose exploitation can add value to hemp cultivation. Essential oils are widely used globally, and their use is constantly increasing. This could boost the utilization and market value of hemp essential oil.
Nowadays, the light hemp is promoted by different stakeholders and the customer’s preference due to the different use of crop products. The aim of this chapter was to discuss the Italian perspectives concerning the utilization of light hemp connected to customer’s preferences. It is discussed the sustainability of hemp crop to produce wellness products in Italy. It is applied as a cost model based on empirical data from hemp farmers. Customers’ preferences on light cannabis wellness products are analyzed through an online survey in Italy and other six European countries. A general misunderstanding about the differences between psychoactive hemp and nonpsychoactive hemp (light cannabis) makes the demand unstable. Light hemp business in Italy is new and there are a few studies that help entrepreneurs in assessing the attractiveness of certain investment analyzing the demand for such a product. Demand for CBD-based products indicates interest, but customers’ confusion highlights a lack of regulation and transparency about CBD-cannabis.
Background The demand and availability of commercially available cannabidiol (CBD) products has grown substantially, which is of particular interest among medically vulnerable people. Because the cannabis plant is recognized as a bioaccumulator, which is highly effective at absorbing and retaining contaminants (e.g., heavy metals) in soil, it is important to characterize the degree of contamination in CBD products and their label accuracy to better estimate potential health benefits and risks associated with consumption. Methods Levels of lead, cadmium, arsenic, mercury, four phthalates, and CBD labeling accuracy were quantified in a selection of commercially available CBD products in the US. Heavy metal concentrations were quantified by inductively coupled plasma-mass spectrometry. Phthalates were quantified by liquid chromatography-tandem mass spectrometry. CBD labeling accuracy was determined by extracting samples into a suitable organic solvent and analyzing using liquid chromatography with diode array detection. Results Lead was detected in 42 %, cadmium in 8 %, arsenic in 28 %, and mercury in 37 % of 121 edible CBD products. Four edible CBD products exceeded the California Proposition 65 threshold for daily lead consumption of 0.5μg in two servings. The percentage of edible products with detectable phthalate concentrations varied between 13 % and 80 % across the four phthalates, with DEHP being most prevalent. Among all products tested for CBD labeling accuracy (topicals, edibles, N = 516), 40 % contained <90 % of the CBD indicated on the product label, 18 % contained >110 %, and only 42 % of products fell within ±10 % of the CBD claimed on the manufacturer label. Concentrations of heavy metals and phthalates were not associated with CBD potency. Conclusions Low-level contamination of edible CBD products with heavy metals and phthalates is pervasive. There is substantial discrepancy between the product label claims for CBD potency and the amount measured in both edible and topical products, underscoring the need for tight regulations for CBD product label integrity to protect consumers.
E‐cigarette or vaping associated lung injury (EVALI) has increased in prevalence after first being noted in an outbreak among teenagers in 2019 and later became recognized as a public health crisis and unique disease entity. This article is protected by copyright. All rights reserved.
Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid and hemp derivative increasingly used in food. Illegal in food at the U.S. federal level, but legal in some states, the CBD-infused food product market has grown substantially, prompting government concerns regarding potential safety risks. CBD foods are a growing market that is driven by increasing demand from producers and consumers and that is governed by an inconsistent and evolving legal framework. This systematic review of research and regulations identified how legality relates to safety. The research also included an emphasis on dose, a key factor for determining safety in foods. Statutes and guidance documents were reviewed from a selection of jurisdictions with existing or proposed legalized CBD in food to determine what restrictions are used relative to safety, including dose and related standards for food. A search of scientific literature was conducted to evaluate what is known about safe dose in food applications and determine what information is still needed to inform a standard or regulated limit. Findings were analyzed to determine risks and what research and regulations are needed to address them. Legal jurisdictions do little to safeguard consumers against potential risks associated with CBD in food because they focus primarily on warnings and prohibiting health claims. Warning and labeling requirements lack consistency. More concerning is the absence of standards for dose in food or for the composition of the CBD used. Further, there is limited and incomplete information to inform such standards. Highlights:
Full-text available
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.
Full-text available
The majority of adults in the U.S. now have state-legal access to medical or recreational cannabis products, despite their federal prohibition. Given the wide array of pharmacologically active compounds in these products, it is essential that their biochemical profile is measured and reported to consumers, which requires accurate laboratory testing. However, no universal standards for laboratory testing protocols currently exist, and there is controversy as to whether all reported results are legitimate. To investigate these concerns, we analyzed a publicly available seed-to-sale traceability dataset from Washington state containing measurements of the cannabinoid content of legal cannabis products from state-certified laboratories. Consistent with previous work, we found that commercial Cannabis strains fall into three broad chemotypes defined by the THC:CBD ratio. Moreover, we documented systematic differences in the cannabinoid content reported by different laboratories, relative stability in cannabinoid levels of commercial flower and concentrates over time, and differences between popular commercial strains. Importantly, interlab differences in cannabinoid reporting persisted even after controlling for plausible confounds. Our results underscore the need for standardized laboratory methodologies in the legal cannabis industry and provide a framework for quantitatively assessing laboratory quality.
Full-text available
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.
Full-text available
To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.
Objective: Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia. Method: In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S). Results: After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=-0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=-0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups. Conclusions: These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.
Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit. Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug world-wide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a Schedule 1 drug in the United States. Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow.
A recent cannabis use survey revealed that 60% of cannabis users rely on smelling the flower to select their cannabis. Olfactory indicators in plants include volatile compounds, principally represented by the terpenoid fraction. Currently, medicinal- and adult-use cannabis is marketed in the United States with relatively little differentiation between products other than by a common name, association with a species type, and Δ-9 tetrahydrocannabinol/cannabidiol potency. Because of this practice, how terpenoid compositions may change during an extraction process is widely overlooked. Here we report on a comparative study of terpenoid and cannabinoid potencies of flower and supercritical fluid CO2 (SC-CO2) extract from six cannabis chemovars grown in Washington State. To enable this comparison, we employed a validated high-performance liquid chromatography/diode array detector methodology for quantification of seven cannabinoids and developed an internal gas chromatography-mass spectrometry method for quantification of 42 terpenes. The relative potencies of terpenoids and cannabinoids in flower versus concentrate were significantly different. Cannabinoid potency increased by factors of 3.2 for Δ-9 tetrahydrocannabinol and 4.0 for cannabidiol in concentrates compared to flower. Monoterpenes were lost in the extraction process; a ketone increased by 2.2; an ether by 2.7; monoterpene alcohols by 5.3, 7 and 9.4; and sesquiterpenes by 5.1, 4.2, 7.7, and 8.9. Our results demonstrate that the product of SC-CO2 extraction may have a significantly different chemotypic fingerprint from that of cannabis flower. These results highlight the need for more complete characterization of cannabis and associated products, beyond cannabinoid content, in order to further understand health-related consequences of inhaling or ingesting concentrated forms.
Background: Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. Methods: In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). Results: The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Conclusion: Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting.
Objectives: The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. Methods: A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. Results: Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of "cannabinoid sensitizers." Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness. Conclusions: A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.