Difference between revisions of "Journal:Analysis of cannabidiol, delta-9-tetrahydrocannabinol, and their acids in CBD/hemp oil products"

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In the last two decades, there has been an escalation in [[wikipedia:Cannabis|cannabis]] use in the U.S., with growing public popularity and pressure, together with an inconsistent and confusing regulatory picture. In the U.S., the use and possession of marijuana is a federal crime; however, [[wikipedia:Cannabis (drug)|medical marijuana]] legislation has been adopted in the District of Columbia and in 33 states, while recreational marijuana use has been legalized in 14 states and U.S. territories.<ref name="NCSLStateMed20">{{cite web |url=https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx |title=State Medical Marijuana Laws |author=National Conference of State Legislatures |date=10 March 2020}}</ref> In addition, 13 states have now passed legislation to allow certain CBD products, restricted in [[wikipedia:Tetrahydrocannabinol|Δ9-tetrahydrocannabinol]] (Δ9-THC) content, for specific disease indications.<ref name="NCSLStateMed20" /> In the states in which medical marijuana has been legalized, recent studies have shown that 16–26% of medical cannabis users also consume other [[wikipedia:Hemp|hemp]] products.<ref name="GrellaPatterns14">{{cite journal |title=Patterns of medical marijuana use among individuals sampled from medical marijuana dispensaries in Los Angeles |journal=Journal of Psychoactive Drugs |author=Grella, C.E.; Rodriguez, L.; Kim, T. |volume=46 |issue=4 |pages=267–75 |year=2014 |doi=10.1080/02791072.2014.944960 |pmid=25188696}}</ref><ref name="WalshCanna13">{{cite journal |title=Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use |journal=International Journal on Drug Policy |author=Walsh, Z.; Callaway, R.; Belle-Isle, L. et al. |volume=24 |issue=6 |pages=511–6 |year=2013 |doi=10.1016/j.drugpo.2013.08.010 |pmid=24095000}}</ref> In December 2018, the passage of the “Farm Bill” ([[wikipedia:Agriculture Improvement Act of 2018|Agriculture Improvement Act of 2018]]) greatly accelerated the aggressive marketing of products containing [[wikipedia:Cannabidiol|cannabidiol]] (CBD), a constituent of the ''Cannabis'' plant. That legislation redefined “hemp” as ''[[wikipedia:Cannabis sativa|Cannabis sativa]]'' containing < 0.3% dry weight of the psychoactive [[wikipedia:Cannabinoid|cannabinoid]] Δ9-THC, provided it is produced under regulations and guidelines stipulated in the statute.<ref name="GPOAgric18">{{cite web |url= https://www.govinfo.gov/link/plaw/115/public/334?link-type=pdf |format=PDF |title=Public Law 115-334 - Agriculture Improvement Act of 2018 |author=U.S. Government Publishing Office |date=20 December 2018}}</ref> It also removed “hemp,” so defined, as a [[wikipedia:Controlled Substances Act#Schedules of controlled substances|Schedule I]] substance. This increasing trend of [[wikipedia:Decriminalization of non-medical cannabis in the United States|legalization]] has led to the production of hundreds of kinds of hemp and hemp oil products, commercialized in various forms, including [[wikipedia:Cannabis concentrate|oils]], balms, lotions, candies, and capsules. These products contain variable concentrations of Δ9-THC and CBD.
In the last two decades, there has been an escalation in [[wikipedia:Cannabis|cannabis]] use in the U.S., with growing public popularity and pressure, together with an inconsistent and confusing regulatory picture. In the U.S., the use and possession of marijuana is a federal crime; however, [[wikipedia:Cannabis (drug)|medical marijuana]] legislation has been adopted in the District of Columbia and in 33 states, while recreational marijuana use has been legalized in 14 states and U.S. territories.<ref name="NCSLStateMed20">{{cite web |url=https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx |title=State Medical Marijuana Laws |author=National Conference of State Legislatures |date=10 March 2020}}</ref> In addition, 13 states have now passed legislation to allow certain CBD products, restricted in [[wikipedia:Tetrahydrocannabinol|Δ9-tetrahydrocannabinol]] (Δ9-THC) content, for specific disease indications.<ref name="NCSLStateMed20" /> In the states in which medical marijuana has been legalized, recent studies have shown that 16–26% of medical cannabis users also consume other [[wikipedia:Hemp|hemp]] products.<ref name="GrellaPatterns14">{{cite journal |title=Patterns of medical marijuana use among individuals sampled from medical marijuana dispensaries in Los Angeles |journal=Journal of Psychoactive Drugs |author=Grella, C.E.; Rodriguez, L.; Kim, T. |volume=46 |issue=4 |pages=267–75 |year=2014 |doi=10.1080/02791072.2014.944960 |pmid=25188696}}</ref><ref name="WalshCanna13">{{cite journal |title=Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use |journal=International Journal on Drug Policy |author=Walsh, Z.; Callaway, R.; Belle-Isle, L. et al. |volume=24 |issue=6 |pages=511–6 |year=2013 |doi=10.1016/j.drugpo.2013.08.010 |pmid=24095000}}</ref> In December 2018, the passage of the “Farm Bill” ([[wikipedia:Agriculture Improvement Act of 2018|Agriculture Improvement Act of 2018]]) greatly accelerated the aggressive marketing of products containing [[wikipedia:Cannabidiol|cannabidiol]] (CBD), a constituent of the ''Cannabis'' plant. That legislation redefined “hemp” as ''[[wikipedia:Cannabis sativa|Cannabis sativa]]'' containing < 0.3% dry weight of the psychoactive [[wikipedia:Cannabinoid|cannabinoid]] Δ9-THC, provided it is produced under regulations and guidelines stipulated in the statute.<ref name="GPOAgric18">{{cite web |url= https://www.govinfo.gov/link/plaw/115/public/334?link-type=pdf |format=PDF |title=Public Law 115-334 - Agriculture Improvement Act of 2018 |author=U.S. Government Publishing Office |date=20 December 2018}}</ref> It also removed “hemp,” so defined, as a [[wikipedia:Controlled Substances Act#Schedules of controlled substances|Schedule I]] substance. This increasing trend of [[wikipedia:Decriminalization of non-medical cannabis in the United States|legalization]] has led to the production of hundreds of kinds of hemp and hemp oil products, commercialized in various forms, including [[wikipedia:Cannabis concentrate|oils]], balms, lotions, candies, and capsules. These products contain variable concentrations of Δ9-THC and CBD.


Δ9-THC exerts its actions through interactions with the CB1 and CB2 receptors<ref name="PertweePharm05">{{cite journal |title=Pharmacological actions of cannabinoids |journal=Handbook of Experimental Pharmacology |author=Pertwee, R.G. |issue=168 |pages=1–51 |year=2005 |doi=10.1007/3-540-26573-2_1 |pmid=16596770}}</ref>; the CB1 agonist activity is, however, responsible for giving the user a feeling of being “high” when consumed in moderation. The pharmacological effects of CBD are much less well known. It has been reported that CBD may act as an inverse agonist or antagonist on CB1 and CB2 receptors<ref name="PertweeTheDiverse09">{{cite journal |title=The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin |journal=British Journal of Pharmacology |author=Pertwee, R.G. |volume=153 |issue=2 |pages=199–215 |year=2008 |doi=10.1038/sj.bjp.0707617}}</ref>; however, this varies by cell type and the agonist ligand being studied. CBD also has activity on a number of other receptors: it antagonizes the G-protein-coupled receptor GPR55 and the transient receptor potential channel TRPM8.<ref name="PertweeIntern10">{{cite journal |title=International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂ |journal=Pharmacological Reviews |author=Pertwee, R.G.; Howlett, A.C.; Abood, M.E. et al. |volume=62 |issue=4 |pages=588–631 |year=2010 |doi=10.1124/pr.110.003004 |pmid=21079038 |pmc=PMC2993256}}</ref> When combined with Δ9-THC, it may serve to counter some of the psychotropic effects of Δ9-THC.<ref name="ColizziDoes17">{{cite journal |title=Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition |journal=Current Addiction Reports |author=Colizzi, M.; Bhattacharyya, S. |volume=4 |issue=2 |pages=62-74 |year=2017 |doi=10.1007/s40429-017-0142-2 |pmid=28580227 |pmc=PMC5435777}}</ref><ref name="SchubartCanna11">{{cite journal |title=Cannabis with high cannabidiol content is associated with fewer psychotic experiences |journal=Schizophrenia Research |author=Schubart, C.D.; Sommer, I.E.C.; van Gastel, W.A. et al. |volume=130 |issue=1–3 |pages=216-21 |year=2011 |doi=10.1016/j.schres.2011.04.017 |pmid=21592732}}</ref>


Unfortunately, the concentration levels of these two cannabinoids are often unknown in these types of products—which are widely sold on the internet—and the labels are found to omit or inaccurately list Δ9-THC and CBD concentrations. [10, 11] It is important to identify these values as the concentration is determinant of the dosage required for medical use, as well as for the determination of the legality of the possession of hemp products.
In this article, we report the development and validation of a [[gas chromatography]] coupled with [[mass spectrometry]] (GC-MS) method for the identification and quantitation of the two most principal cannabinoids, Δ9-THC and CBD (Fig. 1), in CBD oil and hemp oil products. This GC-MS method is able to analyze these cannabinoids and their acid precursors down to low concentrations, with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.1 μg (absolute) and 0.25 μg (absolute), respectively, in the products tested.
==Materials and methods==


==References==
==References==

Revision as of 19:48, 5 October 2020

Full article title Analysis of cannabidiol, Δ9-tetrahydrocannabinol, and their acids in CBD/hemp oil products
Journal Medical Cannabis and Cannabinoids
Author(s) ElSohly, M.A., Murphy, T.P.; Khan, I.; Walker, L.W.; Gul, W.
Author affiliation(s) ElSohly Laboratories, University of Mississippi
Primary contact Email: elsohly at elsohly dot com
Year published 2020
Volume and issue 3(1)
Page(s) 1–13
DOI 10.1159/000509550
ISSN 2504-3889
Distribution license Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Website https://www.karger.com/Article/FullText/509550
Download https://www.karger.com/Article/Pdf/509550 (PDF)
Emblem-important-yellow.svg This article should be considered a work in progress and incomplete. Consider this article incomplete until this notice is removed.

Abstract

Hemp products are readily available and are aggressively marketed for their health and medicinal benefits. Most consumers of these products are interested because of their cannabidiol (CBD) content, which has taken the natural products industry by storm. The CBD and Δ9-tetrahydrocannabinol (Δ9-THC) concentrations in these products are often absent, and even where labeled, the accuracy of the label amounts is often questionable. In order to gain a better understanding of the CBD content, fifty hemp products were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) for CBD, Δ9-THC, tetrahydrocannabinolic acid (Δ9-THCAA), and cannabidiolic acid (CBDA). Δ9-THCAA and CBDA are the natural precursors of Δ9-THC and CBD in the plant material. Decarboxylation to Δ9-THC and CBD is essential to get the total benefit of the neutral cannabinoids. Therefore, analysis for the neutral and acid cannabinoids is important to get a complete picture of the chemical profile of the products. The GC-MS method used for the analysis of these products was developed and validated. A 10-m × 0.18-mm DB-1 (0.4 μ film) column was used for the analysis. The majority of the hemp products were oils, while one of the products was hemp butter, one was a concentrated hemp powder capsule, and another was a hemp extract capsule. Most of the products contained less than 0.1% CBD and less than 0.01% Δ9-THC. Three products contained 0.1–1% CBD, and two products contained 0.1–0.9% Δ9-THC. All of the samples appeared to be decarboxylated since the CBDA and Δ9-THCAA results were less than 0.001%. The developed method is simple, sensitive, and reproducible for the detection of Δ9-THC, Δ9-THCAA, CBD, and CBDA in CBD/hemp oil products.

Introduction

In the last two decades, there has been an escalation in cannabis use in the U.S., with growing public popularity and pressure, together with an inconsistent and confusing regulatory picture. In the U.S., the use and possession of marijuana is a federal crime; however, medical marijuana legislation has been adopted in the District of Columbia and in 33 states, while recreational marijuana use has been legalized in 14 states and U.S. territories.[1] In addition, 13 states have now passed legislation to allow certain CBD products, restricted in Δ9-tetrahydrocannabinol (Δ9-THC) content, for specific disease indications.[1] In the states in which medical marijuana has been legalized, recent studies have shown that 16–26% of medical cannabis users also consume other hemp products.[2][3] In December 2018, the passage of the “Farm Bill” (Agriculture Improvement Act of 2018) greatly accelerated the aggressive marketing of products containing cannabidiol (CBD), a constituent of the Cannabis plant. That legislation redefined “hemp” as Cannabis sativa containing < 0.3% dry weight of the psychoactive cannabinoid Δ9-THC, provided it is produced under regulations and guidelines stipulated in the statute.[4] It also removed “hemp,” so defined, as a Schedule I substance. This increasing trend of legalization has led to the production of hundreds of kinds of hemp and hemp oil products, commercialized in various forms, including oils, balms, lotions, candies, and capsules. These products contain variable concentrations of Δ9-THC and CBD.

Δ9-THC exerts its actions through interactions with the CB1 and CB2 receptors[5]; the CB1 agonist activity is, however, responsible for giving the user a feeling of being “high” when consumed in moderation. The pharmacological effects of CBD are much less well known. It has been reported that CBD may act as an inverse agonist or antagonist on CB1 and CB2 receptors[6]; however, this varies by cell type and the agonist ligand being studied. CBD also has activity on a number of other receptors: it antagonizes the G-protein-coupled receptor GPR55 and the transient receptor potential channel TRPM8.[7] When combined with Δ9-THC, it may serve to counter some of the psychotropic effects of Δ9-THC.[8][9]

Unfortunately, the concentration levels of these two cannabinoids are often unknown in these types of products—which are widely sold on the internet—and the labels are found to omit or inaccurately list Δ9-THC and CBD concentrations. [10, 11] It is important to identify these values as the concentration is determinant of the dosage required for medical use, as well as for the determination of the legality of the possession of hemp products.

In this article, we report the development and validation of a gas chromatography coupled with mass spectrometry (GC-MS) method for the identification and quantitation of the two most principal cannabinoids, Δ9-THC and CBD (Fig. 1), in CBD oil and hemp oil products. This GC-MS method is able to analyze these cannabinoids and their acid precursors down to low concentrations, with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.1 μg (absolute) and 0.25 μg (absolute), respectively, in the products tested.

Materials and methods

References

  1. ↑ 1.0 1.1 National Conference of State Legislatures (10 March 2020). "State Medical Marijuana Laws". https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx. 
  2. ↑ Grella, C.E.; Rodriguez, L.; Kim, T. (2014). "Patterns of medical marijuana use among individuals sampled from medical marijuana dispensaries in Los Angeles". Journal of Psychoactive Drugs 46 (4): 267–75. doi:10.1080/02791072.2014.944960. PMID 25188696. 
  3. ↑ Walsh, Z.; Callaway, R.; Belle-Isle, L. et al. (2013). "Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use". International Journal on Drug Policy 24 (6): 511–6. doi:10.1016/j.drugpo.2013.08.010. PMID 24095000. 
  4. ↑ U.S. Government Publishing Office (20 December 2018). "Public Law 115-334 - Agriculture Improvement Act of 2018" (PDF). https://www.govinfo.gov/link/plaw/115/public/334?link-type=pdf. 
  5. ↑ Pertwee, R.G. (2005). "Pharmacological actions of cannabinoids". Handbook of Experimental Pharmacology (168): 1–51. doi:10.1007/3-540-26573-2_1. PMID 16596770. 
  6. ↑ Pertwee, R.G. (2008). "The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin". British Journal of Pharmacology 153 (2): 199–215. doi:10.1038/sj.bjp.0707617. 
  7. ↑ Pertwee, R.G.; Howlett, A.C.; Abood, M.E. et al. (2010). "International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂". Pharmacological Reviews 62 (4): 588–631. doi:10.1124/pr.110.003004. PMC PMC2993256. PMID 21079038. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993256. 
  8. ↑ Colizzi, M.; Bhattacharyya, S. (2017). "Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition". Current Addiction Reports 4 (2): 62-74. doi:10.1007/s40429-017-0142-2. PMC PMC5435777. PMID 28580227. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435777. 
  9. ↑ Schubart, C.D.; Sommer, I.E.C.; van Gastel, W.A. et al. (2011). "Cannabis with high cannabidiol content is associated with fewer psychotic experiences". Schizophrenia Research 130 (1–3): 216-21. doi:10.1016/j.schres.2011.04.017. PMID 21592732. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar, punctuation, and repetition was cleaned up in the title and text to improve readability. In some cases important information was missing from the references, and that information was added. Nothing else was changed in accordance with the NoDerivatives portion of the license.

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