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Quality Assessment of Cannabidiol Rich Cannabis Extracts Purchased on the Internet

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Research shows that cannabis has a beneficial impact on many different health issues and, as a consequence, concentrated cannabis derived products are becoming increasingly popular. Above all, high Cannabidiol (CBD) and low Tetrahydrocannabinol (THC) extracts are aggressively marketed by many vendors via internet-based shops. As with “classical” medication or food supplements, assessment of product safety is an important issue. Because many different non-standardized production methods are used and no international accepted technical verification procedures of the final products are yet available, the quality of CBD oils generally cannot be guaranteed. In this study, cannabinoid, terpene, pesticide, solvent and metal content of 24 CBD rich extracts purchased from several internet vendors were investigated. Furthermore, consumer information given on the internet site or as package insert is also discussed. Most of the samples had substandard consumer information and CBD concentrations below the proclaimed values. Terpene concentrations were highly variable, pesticides were detected in three samples and residual extraction solvents were detected in four samples. Metals were present at low, non-toxic levels in all samples. Considering the growing popularity of medical cannabis and of online shops consumer education is important and systematic quality testing for cannabis extracts should be mandatory.
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Quality Assessment of Cannabidiol Rich
Cannabis Extracts Purchased on the Internet
Anaïs Rodrigues, Carole Dauberschmidt, Claude Schummer, Georges Dahm
and Serge Schneider*
National Health Laboratory, 1 rue Louis Rech, L-3555 Dudelange, Luxembourg
Introduction
Cannabis counts among the oldest known medicines and nutrients of humanity. For
thousands of years it has been used in East and South East Asia and much later in Europe and
North America. However, with the development of chemical and pharmaceutical industries
in the 19th century and because of political and economic reasons at the beginning of the
20th
that cannabinoids in general and Cannabidiol (CBD) in particular as well as other cannabis
           
        
disease, anxiety, autism [1-4]. Additionally, CBD is generally well tolerated [5,6], it is not
psychotropic, adverse events and side effects are rare and seem to resolve on their own with
  
for medical use.
Mono, di and sesquiterpenes count among the largest group of phytochemicals and they

  
outlining potential potentiation between terpenes and cannabinoids making the “whole
plant medicine” more effective than the sum of the effects of the single compounds. Research
      
properties (…) including cancer chemopreventive effects, antimicrobial, antifungal, antiviral,
Crimson Publishers
Wings to the Research Research Article
*Corresponding author: Serge
Schneider, National Health Laboratory,
1 rue Louis Rech, L-3555 Dudelange,
Luxembourg
Submission: May 05, 2021
Published: May 21, 2021

How to cite this article: Anaïs Rodrigues,
Carole Dauberschmidt, Claude Schummer,
Georges Dahm, Serge Schneider. Quality
Assessment of Cannabidiol Rich Cannabis
    
Forensic Sci Add Res. 5(3). FSAR. 000620.
2021.
10.31031/FSAR.2021.05.000620
Copyright@ Serge Schneider, This
article is distributed under the terms of
the Creative Commons Attribution 4.0
 , which permits
unrestricted use and redistribution
provided that the original author and
source are credited.
ISSN: 2578-0042
416
Forensic Science & Addiction Research
Abstract
               
consequence, concentrated cannabis derived products are becoming increasingly popular. Above all, high
Cannabidiol (CBD) and low Tetrahydrocannabinol (THC) extracts are aggressively marketed by many
vendors via internet-based shops. As with “classical” medication or food supplements, assessment of
          
             
available, the quality of CBD oils generally cannot be guaranteed.
              
purchased from several internet vendors were investigated. Furthermore, consumer information given
on the internet site or as package insert is also discussed. Most of the samples had substandard consumer
information and CBD concentrations below the proclaimed values. Terpene concentrations were highly
variable, pesticides were detected in three samples and residual extraction solvents were detected in four
samples. Metals were present at low, non-toxic levels in all samples. Considering the growing popularity
of medical cannabis and of online shops consumer education is important and systematic quality testing
for cannabis extracts should be mandatory.
Keywords:         
vendors
Abbreviations:         


          
          
    
       

417
Forensic Sci Add Res
Copyright © Serge Schneider
FSAR.000620. 5(3).2021

    
        
cannabis extracts are generally prepared using supercritical CO2
based methods instead of the more classical solvent extraction
methods.
Meanwhile, the internet is becoming a popular source of
medical advice and an online pharmacy for standard and exotic
pharmaceuticals or food supplements [10]. Beside the ethical, legal
and regulatory aspects of this trade, major challenges are public
health issues such as manufacturing and distribution practice,
patient information and, above all, product quality [11,12].
However, often, easy ordering, and low prices are of higher priority
than product quality for buyers. Even if regulation efforts have been
made, quality control of products sold on the internet remains a

or illegal [14] making quality control efforts illusionary.
          
       
objectives were to access user/patient information provided to
purchasers and to assess the overall CBD oil quality. Cannabinoid
content, i.e. cannabidiol (CBD), Cannabidiolic Acid (CBDa),
Tetrahydrocannabinol (THC), Tetrahydrocannabinolic Acid (THCa),
Cannabinol (CBN), Cannabigerol (CBG), cannabigerolic acid (CBGa),
   -myrcene, linalool, -caryophyllene,
humulene, guaiol, limonene), solvents, pesticides and metal were
investigated.
Material and Methods
CBD oils
CBD oils were ordered from 25 online vendors. Twenty-four

an analytical laboratory. Samples were bought from Austria, France,
Germany, Great Britain, Luxembourg, Netherlands and Spain. All
samples were received in good condition in three days to two weeks
after ordering. They were all stored at 5°C in the dark, even if three
vendors recommended storing at room temperature.
Analytical methods
Cannabinoid and terpene content were determined using
     
parameters included the determination of the linearity, intraday
precision and accuracy, Limit of Detection (LOD) and Lower Limit of

equal of above three and the LLOQ as a signal to noise ratio equal
or above 10. A six-point calibration curve was established before
each series of analysis. For cannabinoid dosage, 50 to 100 mg of oil

24 pH 2.18/acetonitrile, 35/65, v/v) to
obtain concentrations in the 0.1mg/L range. 10µL of this solution
        
out on a reverse phase high performance liquid chromatography
        
      
 
x 2.4mm x 2.2µm). Detection was obtained using a photodiode
     
was 209nm for decarboxylated cannabinoids and 223nm for
carboxylated cannabinoids. Oven temperature was set at 50°C,
      
24 (eluent A) and acetonitrile (eluent
B). Chromatographic conditions were 39% eluent A/61% eluent B
for 4min followed by a linear gradient 61-90% B in 3min. Returning
to initial conditions was achieved in 0.4min. Equilibration time was
     
run.
A 6 points linear calibration curve was established before
analysis of the real case samples. Absolute amounts injected were
    
 2) was >0.99 and resolution


of the relative peak purity index <5% was considered for positive
         
analyses were performed in duplicate; the average of the two
results was retained.
For terpene determination, 100 to 150mg of oil were dissolved

    
concentration of about 10mg/L) was added as internal standard
to each sample before analysis. 1µL of the solution was injected
       
          
     

methyl siloxane) column (30m x 0.25mm x 0.25µm) with helium as

temperature was 250°C   
°C for 1min then 25°C/min to 190°C and then 10°C/min to 310°C
    
A 6 points linear calibration curve was established before analysis
of the real case samples. 1µL of solutions of 0, 20, 100, 225, 350
and 450µL of the terpenoids content in 1mL ethyl acetate (at a
concentration of about 10mg/L) with 100 µL of butyl paraben
as internal standard (at a concentration of about 10mg/L) was
injected. r2 was >0.98 and resolution was >1.5 for all terpenes.

samples, a S/N >3 was considered for positive detection and a S/N
µL.
Determination of residual solvent was carried out on a Head
Space GC/MS system (HS/GC/MC) consisting of a 6890N gas
   
       

on a DB-624 (bonded and cross-linked) column (30m x 0.32mm x
1.80µm) with helium as vector gas. Detection was done in scan mode

418
Forensic Sci Add Res
Copyright © Serge Schneider
FSAR.000620. 5(3).2021
GC/MS injector temperature was 250°C  
conditions were 40°C for 4min then 12.5°C/min to 160°C and then
100°C
over the whole run. A mass of 100 to 150mg of oil was introduced in
10mL head space vial with 100µL of a 1-butanol solution (1mL/L)
as internal standard. A 4 points linear calibration curve was
established before analysis of the real case samples. Solutions of
0 (blanc with internal standard), 1, 2.5 and 5mL/L of the solvent
in 100mL H2O with 100µL of 1-butanol as internal standard were

were dosed.
For pesticide determination, the EN 15662 method for pesticide
analysis in foods of plant origin with QuEChERS extraction was
adapted for analysis of the oils. The adaption consisted in taking
 
          
acetonitrile, and shaken for 1minute. Then, a mixture of salts was
added (4g MgSO4; 1g NaCl; 1g sodium citrate and 0.5g disodium
citrate sesquidydrate), and shaken for 1minute, centrifuged for
5minutes at 4000rpm. 1ml of the upper layer was mixed with
the internal standard (triphenyl phosphate) and injected into the
        
LC/MS/MS or GC/MS/MS. LC-MS/MS analyses of pesticides were
carried out on an Aquity ultra-performance liquid chromatography

          
1.8µm). A linear multi-step solvent gradient was applied with the
solvents A (water, 0.02% formic acid) and B (acetonitrile, 0.02%
formic acid). The gradient consisted of 0-16min 100-0% (A); 16-
          
0.4mL/min. The injection volume was 1µl. The temperature of
the sample chamber was 15°C and the temperature of the column
oven was set at 40°C. MS/MS measurements were carried out
        

detect pesticides in monitored data. Reported limit was at 0,1mg/
      
carried out in a second step with external calibration. CG/MS/MS
    

column (30m x 0.25mm x 0.25µm) in MRM mode. Screening of

reporting limit for all pesticides was 1mg/kg.
      
   
 3 (65%), 1mL of H2O2 (31%) and
1mL of H2O were added. The mixture was let to react for 5minutes
at room temperature and then heated over a 30minutes’ gradient
to 180°C using a Mars 5X press microwave. This temperature was
maintained over 30minutes. A volume of 1mL of the obtained
solution was diluted with 1mL of internal standard (10ppb of Tb,
   3). Metal analyses (expect for mercury) were
         
       
and using external calibration (0.05-100µg/L). Mercury analyses
were carried out on a Milestone DMA-80 (Milestone Srl, Sorisole,
  
     °C for 1min;
 °C    °C, 12s, measurement
time 30s. LOD for all metals was 0.01µg/g.
Results and Discussion
Consumer information
Table 1: Consumer information obtained from the vendors’ internet site or as package insert.
Oil n° Cannabinoid
Labelling
Batch
Number
Expiration
Date Storage Recommendation Dosage Recommendation Information About Side
Effects
1yes no no no yes no
2yes yes yes no yes no
3yes yes yes no yes no
4yes yes yes no yes no
5yes no no no yes yes
6yes yes yes yes no no
yes no yes yes yes no
8yes no no yes no no
9yes yes yes no yes no
10 yes no yes no yes no
11 yes yes yes no yes no
12 yes yes yes yes yes no
13 yes yes yes yes yes yes
14 yes yes yes yes yes yes
15 no yes yes no no no
419
Forensic Sci Add Res
Copyright © Serge Schneider
FSAR.000620. 5(3).2021
16 yes yes yes yes yes yes
 yes yes yes yes yes no
18 no yes no no no no
19 yes yes yes no no no
20 yes yes yes yes yes no
21 yes yes yes yes yes no
22 yes yes yes yes yes yes
23 yes no no no no no
24 yes yes yes no no no
      
product package or available on the respective internet sites are



       
dosage of CBD is highly individual and has to be adapted to each
patient, general guidelines may help healthcare professionals and
patients at the beginning of the therapy. Somnolence was mentioned
as a potential side effect by one vendor (n°. 5). Four vendors (n°. 13,
14, 16 and 22) recommended avoiding CBD for pregnant women.
All vendors who informed about the batch number also informed

about all parameters listed in Table 1. No vendor discussed possible
drug interactions. Drug-drug interactions or overdosage is generally
not considered a serious health issue for CBD, but CBD is known
  
This may result in higher levels and even toxicity of other drugs
if consumed together with CBD. CBD also reduces blood pressure
     
to be considered when simultaneously taking anti-hypertensive
        

may increase CBD levels whereas inducers may reduce CBD blood
levels. Consumers should be made attentive to these effects and be
asked to discuss the CBD intake with their doctor.
Cannabinoid and terpene content

were unknown and the results could not be compared to vendor
claims. Seven samples (29.2%) had CBD + CBDA concentrations
within 10% of claimed values (range 90-110%); eleven samples
       
     
had a CBD concentration more than 5 times below the claimed
concentration. One sample, the unlabeled one (n°. 18), had THC
concentration above 0.2 %w/w (legal limit in most European
countries). No CBN, the major THC degradation compound, was
detected in the samples. For 50% of the samples no information
about the extraction method used was available. CBDA, the
carboxylated precursor of CBD, was detected in 15 samples

(n°. 3) claiming “raw” (= low temperature) extraction, no CBDA was

2.
Table 2: Cannabinoid labelling on CBD oils and laboratory results. Data expressed as the mean in percentage of dry
starting material (w/w%).
Cannabis Oil n° Cannabinoids Labelling CBD + CBDA THC THCA CBG CBGA CBN
1  0,06 <LOD 0,02 <LOD <LOD
2  0,03 <LOD 0,01 <LOD <LOD
3 2,22 0,04 <LOD 0,02 <LOD <LOD
4 3,01 0,08 <LOD 0,03 <LOD <LOD
5 2,1 0,05 <LOD <LOD <LOD <LOD
6 2,46 0,01 0,03 <LOD <LOD <LOD
  0,12 <LOD 0,15  <LOD
8  0,13 <LOD 0,01 <LOD <LOD
9 2,26 0,05 <LOD 0,03 <LOD <LOD
10  1,19 0,04 <LOD 0,02 <LOD <LOD
11  4,65 0,13 <LOD 0,04 <LOD <LOD
12  3,58 <LOD <LOD 0,04 <LOD <LOD
13  4,14 0,06 <LOD <LOD <LOD <LOD
14  2,35  <LOD 0,03 <LOD <LOD
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15 - 3,3 0,1 <LOD 0,08 <LOD <LOD
16  3,99 0,12 <LOD 0,03 <LOD <LOD
  4,46 0,15 <LOD 0,05 <LOD <LOD
18 No labelling 8,16 0,42 0,24 0,04  <LOD
19  2,9 0,09 <LOD <LOD <LOD <LOD
20  2,43 <LOD <LOD 0,03 <LOD <LOD
21   <LOD <LOD 0,04 <LOD <LOD
22   0,15 <LOD 0,06 <LOD <LOD
23  3,2 0,05 0,04 0,02 0,09 <LOD
24  10,04 <LOD <LOD <LOD <LOD <LOD
The most prominent terpenes present in cannabis are -pinene,
-myrcene, limonene, linalool, -caryophyllene, humulene and
guaiol. -caryophyllene, also a major terpenoid in black pepper,
cinnamon and glove, was detected in 23 out of the 24 samples
(95.8%) at concentration levels ranging from 0.01-0.91w/w%.
-caryophyllene acts as an agonist of peripheral cannabinoid
receptor CB2 at levels as low as <5mg/kg [18]. Similarly to CBD, it

        

limonene and linalool in 3 samples (12.5%) and guaiol in 1 sample.

Table 3: Terpenoid content in CBD oil samples. Data expressed as the mean in percentage of dry starting material
(w/w%).
Cannabis Oil n° α-Pinene β-Myrcene Limonene Linalool β-Caryophyllene Humulene Guaiol
1 0,119 0,39 0,044 0,119 0,002 <LOD
2 <LOQ <LOQ <LOQ <LOD 0,119  <LOD
3 <LOQ <LOQ <LOQ <LOQ 0,094 <LOQ <LOD
4 <LOQ <LOQ <LOQ <LOD 0,259 0,032 <LOD
5 <LOQ <LOD <LOQ <LOD 0,043 <LOQ 0,008
6 0,322 0,161 0,52 0,053 0,604 0,006 <LOD
<LOD <LOD <LOQ <LOD 0,152 0,015 <LOD
8 0,024 0,01 <LOQ <LOD 0,909 0,053 <LOD
9 <LOQ <LOQ <LOQ <LOD  0,01 <LOQ
10 <LOD <LOD <LOQ <LOD 0,064 0,006 <LOD
11 <LOD <LOD <LOQ <LOD  0,018 <LOD
12 0,014  <LOQ <LOD 0,043 0,004 <LOD
13 <LOD <LOD <LOQ <LOD 0,153 0,022 <LOD
14 <LOQ <LOD <LOQ <LOD 0,098 <LOQ <LOD
15 <LOD <LOD <LOQ <LOD 0,03 0,005 <LOD
16 <LOQ <LOQ <LOQ <LOD  0,05 <LOD
 <LOD <LOD <LOQ <LOD 0,091 0,011 <LOD
18 0,064 0,019 <LOQ <LOD  0,033 <LOD
19 0,014 <LOD <LOQ <LOD 0,163 0,012 <LOD
20 0,014 0,029 <LOQ <LOD 0,061 <LOQ <LOD
21 0,015 0,033 <LOQ <LOD 0,045 <LOQ <LOD
22 0,005 <LOQ <LOQ <LOD  0,048 <LOD
23 <LOD <LOD <LOD <LOD 0,01 <LOQ <LOD
24 <LOD 0,1 0,13 0,02 <LOD <LOD <LOD
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Solvent content
Traditionally, extraction using ethanol with or without heating
was the method used to prepare cannabis tinctures. This method
has the advantage of being simple and cheap, but only limited
control over extraction selectivity is possible. The process results in
extracts with higher concentrations in side products (chlorophyll,
pigments and tannins) and the need of extra work-up to eliminate
the extraction solvent. Today, supercritical CO2 extraction is the
most popular preparation method. By controlling temperature
and pressure, selective components of the plant material can be
separated and collected from the bulk of the plant material. A total
of 13 vendors gave information about the extraction method used.
        
method, six indicated a CO2 extraction method and one claimed the
use of both “raw” method and CO2. Organic solvents were found
   

       
traditional solvent extraction methods but none of the vendors
         
tinctures for external use. Even if the concentrations found are low
and do not pose a health risk, 2-propanol should not be used for
the preparation of extracts intended for internal use as its major
metabolite, acetone, is a central nervous system depressants [20].
Pesticide content
        
matter of debate [21]. Because cannabis remains an illegal plant in

Europe the only notable exception is a Dutch regulation from 2002

stipulating that “All processes and procedures which may affect
the quality of the product must be recorded in the documentation
        
extensive pesticide or nutrient systems, indoor growers often use
   
insecticides and acaricides in illegal cannabis plantations [22,23].

      

is a fungicide of low toxicity, used among others against canker
 
do not pose any health risk.
Metal content

4. Cannabis is known for its easy uptake of metals from soil [24]

   
legislation (Commission regulation (EC) No 1881/2006 of 19
December 2006 setting maximum levels for certain contaminants
       
         
     
         
        
may be explained by contamination during the extraction process
using an organic solvent (ethanol) in copper containing vessles.
However, these low toxicity elements are not posing serious health
issue in this sample.
Table 4: Metal residues in medical cannabis extracts.
Cannabis Oil n° As (µg/g) Cd (µg/g) Cr (µg/g) Cu (µg/g) Hg (ng/g) Ni (µg/g) Pb (µg/g) Sn (µg/g) Zn (µg/g)
1 0,03 0,01 0,15 15,48 0,46 0,41 0,36 0,11 
2 0,41 <LOD 0,02 0,65 0,49 0,04 0,02 0,02 0,94
3 0,09 <LOD 0,01 0,24 0,52 0,02 <LOD 0,02 0,25
4 0,21 <LOD 0,06 0,22 0,38 0,05 0,02 0,05 2,84
5 0,03 <LOD 0,01 0,06 0,92 0,03 0,02 <LOD 0,52
6 0,02 <LOD 0,02  1,96 0,06 0,03 <LOD 3,19
0,04 0,01 0,08 0,26 1,43 0,06 0,15 0,01 23,12
8 0,02 <LOD 0,04 0,1 0,43 0,06 0,02 0,03 
9 0,15 <LOD 0,02 0,41 1,09 0,04 0,02 0,02 2,12
10 0,11 0,01 0,03  1,21  0,04 0,02 0,22
11 0,29 <LOD 0,05 1,03 1,38 0,1 0,04 0,03 0,45
12 0,01 <LOD 0,03 0,11 0,22 0,04 0,02 <LOD 0,22
13 0,22 <LOD 0,03 0,18 1,32 0,04 0,03 0,01 4,64
14 0,15 <LOD 0,02 0,65 1,13 0,05 0,02 0,02 
15 0,02 0,02 0,04  0,36 0,35  0,51 
16 0,48 <LOD 0,03 0,28  0,05 0,06 0,01 12,95
 0,03 0,01 0,28 0,18 1,83 0,15 0,23 0,05 2,81
18 0,02 0,01 0,04 0,21 1,42 0,06  0,03 2,45
422
Forensic Sci Add Res
Copyright © Serge Schneider
FSAR.000620. 5(3).2021
19 0,02 0,01 0,08 0,24 0,44  0,03 0,02 0,4
20 0,02 <LOD 0,05 0,11 2,15  0,05 0,01 1,6
21 0,02 <LOD 0,02 0,1 0,31 0,06 0,03 0,01 13,6
22 0,3 0,01 0,05 0,53 0,18  0,03 0,02 
23 0,32 <LOD 0,03  0,89 0,04 0,04 0,02 0,48
24 0,02 <LOD 0,02 0,14 0,35 0,05 0,03 0,01 0,5
Conclusion
A total of 24 samples containing hemp extracts have been
       
            
access user information and content control of commercial CBD
oils. Most of the samples had substandard consumer information.
Only four samples out of the 24 had overall information about
expiration date, storage and dosage conditions, residual solvent
content and possible side effects. All extracts contained CBD and/or
CBDA but less than one third of the samples had total cannabidiol
(CBD + CBDA) concentrations in the claimed concentration range.
     
were in the non-toxic range. Also, all metal concentrations were
below health concerns. There is no doubt that online commerce with
cannabis-derived products (oil, powder, capsules, suppositories,
chewing gum, soaps, skin lotions, cookies, ...) will become more
         
effects for many different ailments keeps growing. Substandard
products however, may, in the short term, be interesting for the
vendors but, in the long term, may bring discredit to a highly
    
  

and shifting somewhere between medication, herbal medicine,
food supplement or novel food. Furthermore, some countries still
     
still others have increased penalties. Considering the impact, the
         
           
 
Systematic testing of CBD extracts and all other cannabis-derived
         
health and honest CBD online retailers.
Acknowledgment

the companies included in this study.
Conict of Interest

          
interest.
References
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
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
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     
934.
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side effects of cannabidiol, a cannabis sativa constituent. Curr Drug Saf

6.             
 

         
  
1344-1364.
8. 

9. 

10. Baert B, De Spiegeleer B (2010) Quality analytics of internet

11.            
public health, patient safety and cybersecurity threats posed by illicit

12.         

13.         

14. 
 

e199.
15. 
interactions between cannabis products and conventional medications. J

16. Stout SM, Cimino NM (2014) Exogenous cannabinoids as substrates,
        

         


18.        

19. Nuutinen T (2018) Medicinal properties of terpenes found in cannabis

20. 

423
Forensic Sci Add Res
Copyright © Serge Schneider
FSAR.000620. 5(3).2021
21.           
         

22. 
The use of pesticides in Belgian illicit indoor cannabis plantations.

23. Schneider S, Bebing R, Dauberschmidt C (2014) Detection of pesticides

24.             
Cannabis sativa L
        

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Main conclusion Role of terpenes and isoprenoids has been pivotal in the survival and evolution of higher plants in various ecoregions. These products find application in the pharmaceutical, flavor fragrance, and biofuel industries. Fitness of plants in a wide range of environmental conditions entailed (i) evolution of secondary metabolic pathways enabling utilization of photosynthate for the synthesis of a variety of biomolecules, thereby facilitating diverse eco-interactive functions, and (ii) evolution of structural features for the sequestration of such compounds away from the mainstream primary metabolism to prevent autotoxicity. This review summarizes features and applications of terpene and isoprenoid compounds, comprising the largest class of secondary metabolites. Many of these terpene and isoprenoid biomolecules happen to be high-value bioproducts. They are essential components of all living organisms that are chemically highly variant. They are constituents of primary (quinones, chlorophylls, carotenoids, steroids) as well as secondary metabolism compounds with roles in signal transduction, reproduction, communication, climatic acclimation, defense mechanisms and more. They comprise single to several hundreds of repetitive five-carbon units of isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). In plants, there are two pathways that lead to the synthesis of terpene and isoprenoid precursors, the cytosolic mevalonic acid (MVA) pathway and the plastidic methylerythritol phosphate (MEP) pathway. The diversity of terpenoids can be attributed to differential enzyme and substrate specificities and to secondary modifications acquired by terpene synthases. The biological role of secondary metabolites has been recognized as pivotal in the survival and evolution of higher plants. Terpenes and isoprenoids find application in pharmaceutical, nutraceutical, synthetic chemistry, flavor fragrance, and possibly biofuel industries.
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Cannabidiol (CBD) is a highly touted product for many different disorders among the lay press. Numerous CBD products are available, ranging from a US Food and Drug Administration (FDA)‐approved product called Epidiolex to products created for medical marijuana dispensaries and products sold in smoke shops, convenience stores, and over the Internet. The legal status of the non–FDA‐approved products differs depending on the source of the CBD and the state, while the consistency and quality of the non–FDA‐approved products vary markedly. Without independent laboratory verification, it is impossible to know whether the labeled CBD dosage in non–FDA‐approved CBD products is correct, that the delta‐9‐tetrahydrocannabinol content is <0.3%, and that it is free of adulteration and contamination. On the Internet, CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence. The control of refractory seizures is a clear exception, with strong evidence of CBD's benefit. Acute CBD dosing before anxiety‐provoking events like public speaking and the chronic use of CBD in schizophrenia are promising but not proven. CBD is not risk free, with adverse events (primarily somnolence and gastrointestinal in nature) and drug interactions. CBD has been shown to increase liver function tests and needs further study to assess its impact on suicidal ideation.
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Cannabaceae plants Cannabis sativa L. and Humulus lupulus L. are rich in terpenes-both are typically comprised of terpenes as up to 3-5% of the dry-mass of the female inflorescence. Terpenes of cannabis and hops are typically simple mono-and sesquiterpenes derived from two and three isoprene units, respectively. Some terpenes are relatively well known for their potential in biomedicine and have been used in traditional medicine for centuries, while others are yet to be studied in detail. The current, comprehensive review presents terpenes found in cannabis and hops. Terpenes' medicinal properties are supported by numerous in vitro, animal and clinical trials and show anti-inflammatory, antioxidant, analgesic, anticonvulsive, antidepressant, anxiolytic, anticancer, antitumor, neuroprotective, anti-mutagenic, anti-allergic, antibiotic and anti-diabetic attributes, among others. Because of the very low toxicity, these terpenes are already widely used as food additives and in cosmetic products. Thus, they have been proven safe and well-tolerated.
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Background: Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans. Methods: Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler. Results: CBD reduced resting systolic BP (-6 mmHg; P < 0.05) and stroke volume (-8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (-5 mmHg; P < 0.05, especially before and after stress), increased HR (+10 bpm; P < 0.01), decreased stroke volume (-13 ml; P < 0.01), and a blunted forearm skin blood flow response to isometric exercise. In response to cold stress, subjects who had taken CBD had blunted BP (-6 mmHg; P < 0.01) and increased HR (+7 bpm; P < 0.05), with lower total peripheral resistance. Conclusions: This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.
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Cannabis (Cannabis spp.) use and cultivation continue to increase in many (European) countries. The illicit indoor cannabis plantations that supply Belgian and European cannabis markets create problems and concerns about health and safety of intervention staff, dismantling companies, the direct environment of cannabis plantations and, eventually, of cannabis users. Main risks may come from pesticide residues on plants, cultivation infrastructure and materials; left-over plant growth-promoting substances; mycotoxins from fungal pathogens on harvested plants; and/or high levels of cannabinoids in cannabis plant parts for consumption. In the present research, we report on pesticides found in illicit indoor cannabis plantations in Belgium. EN15662 QuEChERS extraction method and LC-MS/MS analysis were used to identify pesticides in indoor cannabis plantations and thus to evaluate the hazards associated with the use, cultivation and removal of cannabis plants in plantations as well as with dismantling activities in the cultivation rooms. We found pesticides in 64.3% of 72 cannabis plant samples and in 65.2% of 46 carbon filter cloth samples. Overall, 19 pesticides belonging to different chemical classes were identified. We found o-phenylphenol, bifenazate, cypermethrin, imidacloprid, propamocarb, propiconazole and tebuconazole, which is consistent with the commonly reported pesticides from literature. In only a few cases, pesticides found in bottles with a commercial label, were also identified in plant or stagnant water samples collected from the growth rooms where the bottles had been collected. We further revealed that, even though most pesticides have a low volatility, they could be detected from the carbon filters hanging at the ceiling of cultivation rooms. As a result, it is likely that pesticides also prevail in the plantation atmosphere during and after cultivation. The risk of inhaling the latter pesticides increases when plants sprayed with pesticides are intensively manipulated during dismantling activities. We conclude that pesticides represent an underestimated and under-documented health risk for intervention staff. The standard procedure for dismantling illicit indoor cannabis cultivation sites should be improved by including guidelines for appropriate personal protection equipment and dismantling protocols that take into account all possible hazards.
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Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ(9)-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ(9)-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of cannabidiol is also highlighted, in particular in nuerological diseases and cancer.