Difference between revisions of "Template:Past, Present, and Future of Cannabis Laboratory Testing and Regulation in the United States/Laboratory testing of cannabis/Analytical aspects of cannabis"

From CannaQAWiki
Jump to navigationJump to search
m (Misspelled)
 
(5 intermediate revisions by the same user not shown)
Line 1: Line 1:
==3. Laboratory testing of cannabis==
[[File:Lilly96A.jpg|right|220px]]Analyzing the chemical constituents of [[Cannabis (drug)|marijuana]] is a difficult task due to its [[Matrix (chemical analysis)|matrix]], and the task becomes even more difficult when it's added to food and other matrix types, requiring established and consistent [[Scientific method|methods]] for testing.<ref name="DePalmaChallenges18">{{cite web |url=https://www.labmanager.com/insights/2018/09/challenges-of-cannabis-contaminant-testing |title=Challenges of Cannabis Contaminant Testing |author=DePalma, A. |work=Lab Manager |publisher=LabX Media Group |date=10 September 2018 |accessdate=08 January 2020}}</ref><ref name="CummingsGurus18">{{cite |journal |title=Gurus of Pesticide Residue Analysis [The Cannabis Scientist] |journal=The Analytical Scientist |author=Cummings, J. |publisher=Texere Logo Texere Publishing Ltd |issue=0218 |year=2018 |url=https://theanalyticalscientist.com/fileadmin/tas/pdf-versions/TCS_Issue4.pdf |format=PDF}}</ref> As mentioned previously, regulators, users, and the testing industry are calling for improved standardization of both the production and testing of medical and recreational marijuana. Without proper testing, several issues are bound to arise<ref name="HazekampCanna12">{{cite journal |title=Cannabis - from cultivar to chemovar |journal=Drug Testing and Analysis |author=Hazekamp, A.; Fischedick, J.T. |volume=4 |issue=7–8 |pages=660–7 |year=2012 |doi=10.1002/dta.407 |pmid=22362625}}</ref><ref name="BushWorlds15">{{cite web |url=http://www.seattletimes.com/seattle-news/worldrsquos-strongest-weed-potency-testing-challenged/ |title=World’s strongest weed? Potency testing challenged |author=Bush, E. |work=The Seattle Times |publisher=The Seattle Times Company |date=18 February 2015 |accessdate=08 January 2020}}</ref><ref name="RutschQuality15">{{cite web |url=http://www.npr.org/sections/health-shots/2015/03/24/395065699/quality-testing-legal-marijuana-strong-but-not-always-clean |title=Quality-Testing Legal Marijuana: Strong But Not Always Clean |author=Rutsch, P. |work=Shots |publisher=National Public Radio |date=24 March 2015 |accessdate=08 January 2020}}</ref><ref name="KuzdzalACloser16">{{cite web |url=https://www.ssi.shimadzu.com/sites/ssi.shimadzu.com/files/Industry/Literature/Shimadzu_Whitepaper_Emerging_Cannabis_Industry.pdf |format=PDF |title=A Closer Look at Cannabis Testing |author=Kuzdzal, S.; Clifford, R.; Winkler, P.; Bankert, W. |publisher=Shimadzu Corporation |date=December 2017 |accessdate=08 January 2020}}</ref><ref name="CassidayTheHighs16">{{cite web |url=https://www.aocs.org/stay-informed/read-inform/featured-articles/the-highs-and-lows-of-cannabis-testing-october-2016 |title=The Highs and Lows of Cannabis Testing |author=Cassiday, L. |work=INFORM |publisher=American Oil Chemists' Society |date=October 2016 |accessdate=08 January 2020}}</ref><ref name="CANORMLHow11">{{cite web |url=https://www.canorml.org/business-resources-for-cannabis-brands/how-accurate-is-cannabis-potency-testing/ |title=How Accurate Is Cannabis Potency Testing? |publisher=California NORML |date=21 September 2011 |accessdate=08 January 2020}}</ref>:
* label claims may not match actual contents;
* contaminants may linger, causing illness or even death;
* chemical properties and medicinal benefits of specific strains and their unique [[cannabinoid]]-[[terpene]] profiles can't be isolated; and
* research on potential therapeutic qualities can't be replicated, hindering scientific progress.
In 2011—a year before any U.S. state had enacted broad legalization of recreational marijuana—California [[NORML]] reported that its assessment of analytical [[cannabis]] testing [[Laboratory|laboratories]]' accuracy found that while California labs broadly reached +/- 20 percent consistency from a replicate sample, three out of 10 provided unfavorable results on at least half of their tests. Similar wide-ranging discrepancies were also found among [[Cannabis edible|edibles]], extracts, and tinctures, and NORML found that none of the labs could reach two decimal points precision of cannabinoid results despite laboratory claims stating otherwise.<ref name="CANORMLHow11" /> Another report out of the state of Washington in January 2015, not long after recreational marijuana sales to the public (requiring accredited lab testing prior) began<ref name="WLCBFAQ">{{cite web |url=http://lcb.wa.gov/mj2015/faqs_i-502 |title=FAQs on I-502 |publisher=Washington State Liquor and Cannabis Board |accessdate=03 February 2017}}</ref>, found blind tests of recreational marijuana at dispensaries could range as much as 7.5 percent in accuracy from its corresponding label.<ref name="BushWorlds15" /> Further issues in 2016 with alleged partiality by some Washington testing laboratories prompted emergency proficiency testing rules to be enacted.<ref name="YoungSome16">{{cite web |url=http://www.seattletimes.com/seattle-news/marijuana/some-pot-labs-in-state-failed-no-pot-at-all-says-scientist/ |title=Some pot labs in state failed no pot at all, says scientist |author=Young, B. |work=The Seattle Times |publisher=The Seattle Times Company |date=05 January 2016 |accessdate=03 February 2017}}</ref><ref name="Coughlin-BogueToCombat16">{{cite web |url=https://www.leafly.com/news/politics/to-combat-claims-of-inconsistency-washington-testing-labs-turn-to |title=To Combat Inconsistency, Washington Testing Labs Turn to Self-Policing |work=Leafly - Politics |author=Coughlin-Bogue, T. |publisher=Leafly Holdings, Inc |date=11 March 2016 |accessdate=03 February 2017}}</ref> ("Proficiency testing" essentially requires a laboratory in question to test a sample with known properties, and then those results are compared to those of a neutral third-party lab testing the same sample.) Additional testing problems in Alaska and Washington labs in late 2017 found high disparities between two different testing labs, as well as a laboratory that couldn't "properly perform a [[Coliform bacteria|coliform]] test that looks for bacteria."<ref name="RitchieInconsist18">{{cite web |url=https://terpenesandtesting.com/category/testing/cannabis-testing-lab-test-inconsistencies/ |title=Inconsistency in Cannabis Lab Testing |author=Ritchie, H. |work=Terpenes and Testing Magazine |date=29 April 2018 |accessdate=15 November 2018}}</ref>
These discrepancies and deficiencies highlight the growing need for homogenization of testing methods and procedures, if not nationally at least across an entire state. Such homogenization would, in theory, not only positively affect the quality of product but also provide greater consumer confidence that label and product match. As Marketing Director Scott Kuzdzal of Shimadzu pointed out during a January 2017 webinar on analytic testing of cannabis, poor [[Sample (material|sample]] preparation, lack of thorough testing, and the manual process itself—which can introduce user error, particularly when [[Laboratory quality control|good laboratory practices]] aren’t used—all can contribute to discrepancies between label and product.<ref name="KuzdzalOpp17">{{cite web |url= http://www.shimadzu.com.cn/an/news-events/news/2017/4381.html |archiveurl=http://web.archive.org/web/20170119200158/http://www.shimadzu.com.cn/an/news-events/news/2017/4381.html |title=Webinar: Opportunities & Challenges in Cannabis Analytical Testing |author=Kuzdzal, S.A. |publisher=Shimadzu Corporation |date=19 January 2017 |archivedate=19 January 2017 |accessdate=03 February 2017 |quote=Source is actual webinar.}}</ref> When dispensaries, edible manufacturers, and supplement companies perform insufficient lab testing or overstate claims on labels, it reduces consumer confidence, and both state and federal authorities—including the [[Food and Drug Administration|U.S. Food and Drug Administration]] (FDA)—have to interject.<ref name="YoungSome16" /><ref name="Coughlin-BogueToCombat16" /><ref name="FDAWarn16">{{cite web |url=http://www.fda.gov/newsevents/publichealthfocus/ucm484109.htm |title=2016 Warning Letters and Test Results for Cannabidiol-Related Products |work=Public Health Focus |publisher=U.S. Food and Drug Administration |date=31 August 2016 |accessdate=03 February 2017}}</ref>
As was mentioned at the end of the previous section on state regulation, efforts to improve testing methods and procedures, with the goal of seeing the best of them become standards, are ongoing. Where are those efforts now, and where are they going? Before we can examine that, we first need to briefly look at what aspects of cannabis are actually being analyzed.
===3.1 Analytical aspects of cannabis===
===3.1 Analytical aspects of cannabis===
====Cannabinoids====
====3.1.1 Cannabinoids====
As of mid-2015, researchers have identified 104 of the more than 750 constituents of ''[[Cannabis sativa]]'' as cannabinoids<ref name="RadwanIso15">{{cite journal |title=Isolation and pharmacological evaluation of minor cannabinoids from high-potency ''Cannabis sativa'' |journal=Journal of Natural Products |author=Radwan, M.M.; ElSohly, M.A.; El-Alfy, A.T. et al. |volume=78 |issue=6 |pages=1271-6 |year=2015 |doi=10.1021/acs.jnatprod.5b00065 |pmid=26000707 |pmc=PMC4880513}}</ref>, active chemical compounds that act in a similar way to compounds our body naturally produces, and new cannabinoids continue to be identified during cannabis research.<ref name="MudgeChemo18">{{cite journal |title=Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome |journal=Scientific Reports |author=Mudge, E.M.; Murch, S.J.; Brown, P.N. |volume=8 |page=13090 |year=2018 |doi=10.1038/s41598-018-31120-2}}</ref><ref name="CittiANovel19">{{cite journal |title=A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol |journal=Scientific Reports |author=Citti, C.; Linciano, P.; Russo, F. et al. |volume=9 |at=20335 |year=2019 |doi=10.1038/s41598-019-56785-1}}</ref> Many of our body's cells have cannabinoid receptors capable of modulating neurotransmitter release in the brain and other areas.<ref name="WHOTheHealth16">{{cite book |url=http://www.who.int/substance_abuse/publications/cannabis/en/ |title=The health and social effects of nonmedical cannabis use |author=World Health Organization |editor=Hall, W.; Renström, M.; Poznyak, V |publisher=World Health Organization |pages=95 |year=2016 |isbn=978921510240}}</ref> The plant's cannabinoids vary, with each bonding to specific receptors in our body, providing differing effects. From a theoretical and medical standpoint, crafting a strain of cannabis that has specific cannabinoids that can aid with a particular malady, while also carefully reproducing the grow conditions to consistently make that [[Cannabis strains|strain]] in the future, is a desirable but difficult goal to achieve.<ref name="RahnCannab14">{{cite web |url=https://www.leafly.com/news/cannabis-101/cannabinoids-101-what-makes-cannabis-medicine |title=Cannabinoids 101: What Makes Cannabis Medicine? |work=Leafly - Cannabis 101 |author=Rahn, B. |publisher=Leafly Holdings, Inc |date=22 January 2014 |accessdate=03 February 2017}}</ref> However, even as new strains are developed, identifying an existing strain effectively has its own set of challenges, as Mudge ''et al.'' point out: "the total &#91;[[tetrahydrocannabinol]]&#93; and &#91;[[cannabidiol]]&#93; content is not sufficient to distinguish strains &#91;though&#93; a combination of targeted and untargeted [[Chemometrics|chemometric]] approaches can be used to predict cannabinoid composition and to better understand the impact of informal breeding program and selection on the [[phytochemical]] diversity of cannabis."<ref name="MudgeChemo18" />
{{Past, Present, and Future of Cannabis Laboratory Testing and Regulation in the United States/Laboratory testing of cannabis/Analytical aspects of cannabis/Cannabinoids}}
 
Lab testing of cannabinoids is done primarily as a measure of [[Psychoactive drug|psychoactive]] "potency," though cannabinoids have many other potential therapeutic uses. Current laboratory testing looks at only a handful of cannabinoids; more research and development of analytical techniques that can quickly and accurately detect and separate the the rest is required.<ref name="KuzdzalUnrav15">{{cite journal |title=Unraveling the Cannabinome |journal=The Analytical Scientist |author=Kuzdzal, S.; Lipps, W. |issue=0915 |year=2015 |url=https://theanalyticalscientist.com/issues/0915/unraveling-the-cannabinome/ |accessdate=19 January 2017}}</ref> Some of the major cannabinoids tested for include<ref name="MudgeChemo18" /><ref name="KuzdzalUnrav15" /><ref name="APHLGuide16">{{cite web |url=https://www.aphl.org/aboutAPHL/publications/Documents/EH-Guide-State-Med-Cannabis-052016.pdf |format=PDF |title=Guidance for State Medical Cannabis Testing Programs |author=Association of Public Health Laboratories |pages=35 |date=May 2016 |accessdate=01 February 2017}}</ref><ref name="RahnUnder14">{{cite web |url=https://www.leafly.com/news/cannabis-101/understanding-cannabis-testing |title=Understanding Cannabis Testing: A Guide to Cannabinoids and Terpenes |work=Leafly - Cannabis 101 |author=Rahn, B. |publisher=Leafly Holdings, Inc |date=09 October 2014 |accessdate=03 February 2017}}</ref>:
 
* '''THC (∆9-[[Tetrahydrocannabinol]])''': This is the most commonly known cannabinoid found in cannabis, notable for its strong psychoactive effects and ability to aid with pain, sleep, and appetite issues. Included is its analogue ∆8-Tetrahydrocannabinol (which shows notably less strong psychoactive effects than ∆9<ref name="NIHDelta8">{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=485262 |title=delta-8-tetrahydrocannabinol |work=NCI Drug Dictionary |publisher=National Institutes of Health, National Cancer Institute |accessdate=08 February 2017}}</ref>) and its homologue THCV ([[Tetrahydrocannabivarin]]), which tends to appear in trace amounts and has a more pronounced psychoactive effect, but for a shorter duration. THCV shows promise in fighting anxiety, tremors from neurological disorders, appetite issues, and special cases of bone loss. Also notable is Δ9-THCA (Δ9-[[Tetrahydrocannabinolic acid]]), a non-psychoactive [[Biosynthesis|biosynthetic]] precursor to THC.
 
* '''CBC ([[Cannabichromene]])''': This non-psychoactive cannabinoid is found in trace amounts; however, it tends to be markedly more effective at treating anxiety and stress than CBD (see next). It's also notable for its anti-inflamatory properties and potential use for bone deficiencies.
 
* '''CBD ([[Cannabidiol]])''': CBD is a non-psychoactive component of cannabis, typically accounting for up to 35 to 40 percent of cannabis extracts. It acts as a counter-balance to THC, regulating its psychoactivity. It's been researched as a treatment for anxiety, sleep loss, inflammation, stress, pain, and epilepsy, among other afflictions. Included is its homologue CBDV ([[Cannabidivarin]]), which is also non-psychoactive and demonstrates promise as a treatment for epileptic seizures. Also notable is CBDA (Cannabidiolic acid), a non-psychoactive biosynthetic precursor to CBD.
 
* '''CBG ([[Cannabigerol]])''': This cannabinoid is also non-psychoactive but only appears in trace amounts of cannabis. If has potential as a sleep aid, anti-bacterial, and cell growth stimulant. Also notable is CBGA (Cannabigerolic acid), a non-psychoactive biosynthetic precursor to CBG.
 
* '''CBN ([[Cannabinol]])''': CBN is mildly psychoactive at best and appears only in trace amounts in ''Cannabis sativa'' and ''[[Cannabis indica]]''. It occurs largely as a metabolite of THC and tends to have one of the strongest sedative effects among cannabinoids. It shows promise as a treatment for insomnia, glaucoma, and certain types of pain.
 
====Terpenes====
Mandated lab testing of terpenes—volatile organic compounds that distinctly affect cannabis aroma and taste—is done primarily as a way to ensure proper labeling of cannabis and related products, including extracts and concentrates, so buyers have confidence in what they are purchasing.<ref name="HabibTesting13">{{cite web |url=http://lcb.wa.gov/publications/Marijuana/BOTEC%20reports/1c-Testing-for-Psychoactive-Agents-Final.pdf |format=PDF |title=Testing for Psychoactive Agents |author=Habib, R.; Finighan, R.; Davenport, S. |publisher=BOTEC Analysis Corp |date=24 August 2013 |accessdate=08 February 2017}}</ref><ref name="CMTLabs">{{cite web |url=http://www.cmtlaboratory.com/test-services/tests-offered/ |title=Tests Offered |publisher=CMT Laboratories |accessdate=08 February 2017}}</ref><ref name="WercShop">{{cite web |url=http://thewercshop.com/services/terpene-profiling-services/ |title=Terpene Profiling Services |publisher=The Werc Shop |accessdate=08 February 2017}}</ref> However, additional lab research goes into terpenes as they also show potentially useful pharmacological properties<ref name="HabibTesting13" /><ref name="WercShop" /><ref name="AndreCannabis16">{{cite journal |title=''Cannabis sativa'': The plant of the thousand and one molecules |journal=Frontiers in Plant Medicine |author=Andre, C.M.; Hausman, J.-F.; Guerriero, G. |volume=7 |pages=19 |year=2016 |doi=10.3389/fpls.2016.00019 |pmid=26870049 |pmc=PMC4740396}}</ref>, and they demonstrate synergies (referred to at times as the "entourage effect") with cannabinoids that largely still require further exploration.<ref name="CassidayTheHighs16" /><ref name="AndreCannabis16" /><ref name="WercShop" /><ref name="WachsbergerTerpene16">{{cite web |url=http://www.bloomcityclub.com/terpine-testing-the-future-of-cannabis-is-here/ |title=Terpene Testing: The future of Cannabis is here |author=Wachsberger, K. |work=Bloom Blog |publisher=Bloom City Club |date=02 February 2016 |accessdate=08 February 2017}}</ref> Testing for specific terpenes (discussed later) is less of a standardized practice, though it's rapidly improving.<ref name="HabibTesting13" /> Commonly tested terpenes by third-party testing labs include<ref name="WercShop" /><ref name="CMTLabs" /><ref name="AndreCannabis16" /><ref name="CassidayTheHighs16" /><ref name="RahnUnder14" /><ref name="SCLabs">{{cite web |url=http://sclabs.com/terpene-analysis/ |title=Terpene Analysis |publisher=SC Labs, Inc |accessdate=08 February 2017}}</ref>:
 
* [[Bisabolol]]
* [[Caryophyllene]]
* [[P-Cymene|Cymene]]
* [[Humulene]]
* [[Limonene]]
* [[Linalool]]
* [[Myrcene]]
* [[Phytol]]
* [[Pinene]]
* [[Terpinene|Terpinolene]]
 
====Contaminates====
Generally speaking, a [[Contamination|contaminate]] is an unwanted substance that may show up in the final product, be it recreational marijuana or a pharmaceutical company's therapeutic tincture. The following are examples of contaminates that laboratories may test for in cannabis products.
 
'''Pesticides''': [[Pesticide]]s represent the Wild West of not only growing cannabis but also performing analytical testing on it. One of the core issues, again, is the fact that on the federal level marijuana is illegal. Because it's illegal, government agencies such as the [[United States Environmental Protection Agency|Environmental Protection Agency]] (EPA) don't test and create standards or guidelines for what's safe when it comes to residual pesticides, let alone how to best test for them.<ref name="BorelTheWild15">{{cite web |url=https://www.theatlantic.com/health/archive/2015/08/pot-marijuana-pesticide-legalization/401771/ |title=The Wild West of Marijuana Pesticides |author=Borel, B. |work=The Atlantic |publisher=The Atlantic Monthly Group |date=31 August 2015 |accessdate=09 February 2017}}</ref><ref name="ZhangNobody15">{{cite web |url=https://www.wired.com/2015/08/nobody-knows-pesticides-legal-marijuana// |title=Nobody Knows What to Do About Pesticides in Legal Marijuana |author=Zhang, S. |work=Wired |publisher=Condé Nast |date=07 August 2015 |accessdate=09 February 2017}}</ref> Additionally, researchers face their fair share of difficulties obtaining product to test. The end result is we don't know much about how inhalation of pesticide-coated marijuana smoke affects long-term health<ref name="BorelTheWild15" /><ref name="ZhangNobody15" />, and we have few standard methods for pesticide application and testing.<ref name="CassidayTheHighs16" /><ref name="DeibelPesticide19">{{cite web |url=https://cannabisindustryjournal.com/feature_article/pesticide-testing-methods-strategies-sampling/ |title=Pesticide Testing: Methods, Strategies & Sampling |author=Deibel, C. |work=Cannabis Industry Journal |date=29 January 2019 |accessdate=20 February 2020}}</ref> With numerous pesticide products and little oversight on what growers apply to their plants, combined with the technical difficulty of testing for pesticides in the lab, pesticides remain one of the most difficult contaminates to test for.<ref name="CassidayTheHighs16" /><ref name="DeibelPesticide19" /> That said, several classes of of pesticides are commonly applied during cannabis cultivation and can be tested for by labs<ref name="APHLGuide16" /><ref name="KuzdzalACloser16" /><ref name="FarrerTech15">{{cite web |url=https://public.health.oregon.gov/PreventionWellness/marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf |format=PDF |title=Technical Report: Oregon Health Authority’s Process to Determine Which Types of Contaminants to Test for in Cannabis Products, and Levels for Action |author=Farrer, D.G. |publisher=Oregon Health Authority |date=December 2015 |accessdate=09 February 2017}}</ref>:
 
* '''[[avermectin]]s''': functions as an insecticide that is useful against mites, which are a common problem for cultivators
* '''[[carbamate]]s''': functions as an insecticide, similar to organophosphates, but with decreased dermal toxicity and higher degradation
* '''[[organophosphate]]s''': functions as the base of many insecticides and herbicides, valued for its easy organic bonding
* '''[[pyrethroid]]s''': functions as the base of most household insecticides and exhibits insect repellent properties
 
 
'''Solvents''': In 2003, Canadian Rick Simpson published a recipe of sorts for preparing cannabis extract via the use of [[solvent]]s such as naphtha or petroleum ether. Claiming the resulting oil helped cure his skin cancer, others hoping for a cure tried it, and the solvent method of preparation grew in popularity. Dubious healing claims aside, the solvent extraction method remains viable, though it has evolved over the years to include less harmful solvents such as [[supercritical carbon dioxide]], which has low toxicity, low environmental impact, and beneficial extraction properties.<ref name="CassidayTheHighs16" /><ref name="RomanoCannabis13">{{cite journal |url=http://www.stcm.ch/en/files/hazekamp_cann-oil_2013.pdf |format=PDF |title=Cannabis oil: Chemical evaluation of an upcoming cannabis-based medicine |journal=Cannabinoids |author=Romano, L.L.; Hazekamp, A. |volume=1 |issue=1 |pages=1–11 |year=2013}}</ref><ref name="PeachSuper14">{{cite journal |title=Supercritical carbon dioxide: A solvent like no other |journal=Journal of Organic Chemistry |author=Peach, J.; Eastoe, J. |volume=10 |pages=1878-95 |year=2014 |doi=10.3762/bjoc.10.196 |pmid=25246947 |pmc=PMC4168859}}</ref> However, chemical solvents are still used, and if not evaporated out properly, the remaining solvents can be particularly harmful to sick patients using the extract. As for what solvents should be tested for, it gets a bit trickier, though Chapter 467 of ''United States Pharmacopeia and The National Formulary'', the Oregon Health Authority's December 2015 technical report on contaminant testing of cannabis, and the Massachusetts Department of Public Health's response to public comments on cannabis testing provide helpful guidance. Listed solvents include [[benzene]], [[butane]], [[cumene]], [[dimethoxyethane]], [[hexane]], and [[pentane]], among others.<ref name="KuzdzalACloser16" /><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="FarrerTech15" /><ref name="USPNF467">{{cite web |url=https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |archiveurl=https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |format=PDF |title=<467> Residual Solvents |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=04 August 2016 |accessdate=21 June 2019}}</ref><ref name="MDPHResponse">{{cite web |url=http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf |format=PDF |title=Response to Public Comments |author=Bureau of Healthcare Safety and Quality |publisher=Massachusetts Department of Public Health |date=12 February 2016 |accessdate=14 February 2017}}</ref>
 
 
'''Heavy metals''': 2013 research on contaminant testing on the behalf of Washington State provides insights into [[heavy metals]] and why they're looked for in cannabis testing. That research, as well as other sources, tell us<ref name="KuzdzalACloser16" /><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="DaleyTesting13">{{cite web |url=http://lcb.wa.gov/publications/Marijuana/BOTEC%20reports/1a-Testing-for-Contaminants-Final-Revised.pdf |format=PDF |title=Testing ''Cannabis'' for Contaminants |author=Daley, P.; Lampach, D.; Sguerra, S. |publisher=BOTEC Analysis Corp |date=12 September 2013 |accessdate=09 February 2017}}</ref>:
 
* Heavy metals contribute to several health problems, including those of a neurological nature.
* Cannabis can "[[Hyperaccumulator|hyperaccumulate]] metals from contaminated soils."
* Research parallels can be found in tobacco research and how the FDA regulates heavy metal content in foods.
* The most prominently tested heavy metals include [[arsenic]] (As), [[cadmium]] (Cd), [[chromium]] (Cr), [[lead]] (Pb), [[Mercury (element)|mercury]] (Hg), and [[nickel]] (Ni).
 
 
'''[[Mycotoxin]]s and microorganisms''': "The ideal conditions for cannabis growth are also ideal for the growth of potentially harmful bacteria and fungi, including yeast and molds," say Shimadzu's Scott Kuzdzal and William Lipps, "therefore microbial contamination poses health risks to consumers and immunocompromised individuals."<ref name="KuzdzalUnrav15" /> In truth, these concerns have already borne out. In fact, the University of California, Davis reported in February 2017 one of its patients had contracted an incurable fungal infection from inhaling aerosolized marijuana. They later tested 20 marijuana samples from Northern California dispensaries—using specialized techniques—and found a wide variety of potentially hazardous [[microorganism]]s.<ref name="UCDavis17">{{cite web |url=http://www.ucdmc.ucdavis.edu/publish/news/newsroom/11791 |title=UC Davis study finds mold, bacterial contaminants in medical marijuana samples |publisher=UC Davis |date=07 February 2017 |accessdate=10 February 2017}}</ref>


The degree to which such contaminates commonly appear in grown and stored cannabis material and to which microbiological contaminates should be tested is not clear, however. As mentioned previously, neither the U.S. EPA or neighboring Health Canada provide any significant guidance on cannabis testing, including microbiological contaminates.<ref name="KennardYouAre16">{{cite web |url=https://populace.tantaluslabs.com/you-are-probably-smoking-mouldy-weed-why-does-quality-assurance-matter/ |title=You are Probably Smoking Mouldy Weed - Why Does Quality Assurance Matter? |work=Populace |author=Kennard, M. |publisher=Tantalus Labs |date=02 June 2014 |accessdate=21 June 2019}}</ref> Like heavy metal testing, parallels are drawn from microbial testing guidelines and standards relating to tobacco and food, where they exist.<ref name="KennardYouAre16" /> As warm, moist environments are conducive to microorganism growth, maintaining stable moisture levels during cultivation and storage is essential. Regularly measuring [[water activity]]—how moist something is—is particularly useful as a front-line preventative tool to better ensure microbial growth is limited.<ref name="FarrerTech15" /> Regardless, testing of some kind is still required by many U.S. states, including for organisms such as<ref name="KuzdzalUnrav15" /><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="FarrerTech15" /><ref name="UCDavis17" /><ref name="KennardYouAre16" /><ref name="CANNAMicro14">{{cite web |url=http://www.fundacion-canna.es/en/microbiological-study-cannabis-samples |title=Microbiological study of Cannabis samples |publisher=Fundación CANNA |date=2014 |accessdate=10 February 2017}}</ref><ref name="RussoCann13">{{cite book |url=https://books.google.com/books?id=qH-2Lj9x7L4C&pg=PT457&lpg=PT457 |chapter=Chapter 30: Contaminants and Adulterants in Herbal Cannabis |title=Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential |author=McPartland, J.M. |editor=Russo, E.B. |publisher=Routledge |year=2013 |pages=478 |isbn=9781136614934}}</ref>:
====3.1.2 Terpenes====
{{Past, Present, and Future of Cannabis Laboratory Testing and Regulation in the United States/Laboratory testing of cannabis/Analytical aspects of cannabis/Terpenes}}


* ''[[Alternaria]]''
====3.1.3 Contaminates====
* ''[[Aspergillus]]''
{{Past, Present, and Future of Cannabis Laboratory Testing and Regulation in the United States/Laboratory testing of cannabis/Analytical aspects of cannabis/Contaminants}}
* ''Cryptococcus''
* ''[[Escherichia coli|E. coli]]''
* ''Mucor''
* ''[[Penicillium]]''
* ''[[Salmonella]]''

Latest revision as of 19:42, 14 January 2021

3.1 Analytical aspects of cannabis

3.1.1 Cannabinoids

Somewhere between 104 and upwards of more than 140 of the over 750 constituents of Cannabis sativa have been identified as cannabinoids[1][2][3], active chemical compounds that act in a similar way to compounds our body naturally produces, and new cannabinoids continue to be identified during cannabis research.[3][4] Many of our body's cells have cannabinoid receptors capable of modulating neurotransmitter release in the brain and other areas.[5] The plant's cannabinoids vary, with each bonding to specific receptors in our body, providing differing effects. From a theoretical and medical standpoint, crafting a strain of cannabis that has specific cannabinoids that can aid with a particular malady, while also carefully reproducing the grow conditions to consistently make that strain in the future, is a desirable but difficult goal to achieve.[6] However, even as new strains are developed, identifying an existing strain effectively has its own set of challenges, as Mudge et al. point out: "the total [tetrahydrocannabinol] and [cannabidiol] content is not sufficient to distinguish strains [though] a combination of targeted and untargeted chemometric approaches can be used to predict cannabinoid composition and to better understand the impact of informal breeding program and selection on the phytochemical diversity of cannabis."[3]

Lab testing of cannabinoids is done primarily as a measure of psychoactive "potency," though cannabinoids have many other potential therapeutic uses. Current laboratory testing looks at only a handful of cannabinoids; more research and development of analytical techniques that can quickly and accurately detect and separate the rest is required.[7] Some of the major cannabinoids tested for include[3][8][9][10]:

  • THC (∆9-Tetrahydrocannabinol): This is the most commonly known cannabinoid found in cannabis, notable for its strong psychoactive effects and ability to aid with pain, sleep, and appetite issues. Included is its analogue ∆8-Tetrahydrocannabinol (which shows notably less strong psychoactive effects than ∆9[11]) and its homologue THCV (Tetrahydrocannabivarin), which tends to appear in trace amounts and has a more pronounced psychoactive effect, but for a shorter duration. THCV shows promise in fighting anxiety, tremors from neurological disorders, appetite issues, and special cases of bone loss. Also notable is ∆9-THCA (∆9-Tetrahydrocannabinolic acid), a non-psychoactive biosynthetic precursor to THC.
  • CBC (Cannabichromene): This non-psychoactive cannabinoid is found in trace amounts; however, it tends to be markedly more effective at treating anxiety and stress than CBD (see next). It's also notable for its anti-inflammatory properties and potential use for bone deficiencies.
  • CBD (Cannabidiol): CBD is a non-psychoactive component of cannabis, typically accounting for up to 35 to 40 percent of cannabis extracts. It acts as a counter-balance to THC, regulating its psychoactivity. It's been researched as a treatment for anxiety, sleep loss, inflammation, stress, pain, and epilepsy, among other afflictions. Included is its homologue CBDV (Cannabidivarin), which is also non-psychoactive and demonstrates promise as a treatment for epileptic seizures. Also notable is CBDA (cannabidiolic acid), a non-psychoactive biosynthetic precursor to CBD.
  • CBG (Cannabigerol): This cannabinoid is also non-psychoactive but only appears in trace amounts of cannabis. It has potential as a sleep aid, anti-bacterial, and cell growth stimulant. Also notable is CBGA (cannabigerolic acid), a non-psychoactive biosynthetic precursor to CBG.
  • CBN (Cannabinol): CBN is mildly psychoactive at best and appears only in trace amounts in Cannabis sativa and Cannabis indica. It occurs largely as a metabolite of THC and tends to have one of the strongest sedative effects among cannabinoids. It shows promise as a treatment for insomnia, glaucoma, and certain types of pain.

3.1.2 Terpenes

Mandated lab testing of terpenes—volatile organic compounds that distinctly affect cannabis aroma and taste—is done primarily as a way to ensure proper labeling of cannabis and related products, including extracts and concentrates, so buyers have confidence in what they are purchasing.[12][13][14] However, additional lab research goes into terpenes as they also show potentially useful pharmacological properties[12][14][15], and they demonstrate synergies (referred to at times as the "entourage effect") with cannabinoids, requiring further research.[16][15][14][17] Testing for specific terpenes (discussed later) has histoically been less of a standardized practice[12], though it's rapidly improving.[18] Commonly tested terpenes by third-party testing labs include[14][13][15][16][18][10][19]:

3.1.3 Contaminates

Generally speaking, a contaminant is an unwanted substance that may show up in the final product, be it recreational marijuana or a pharmaceutical company's therapeutic tincture. The following are examples of contaminants that laboratories may test for in cannabis products.

Pesticides: Pesticides represent an oft-discussed aspect not only of growing cannabis but also performing analytical testing on it. One of the core issues, again, is the fact that on the federal level marijuana is illegal. Because it's illegal, government agencies such as the Environmental Protection Agency (EPA) have historically failed to develop standards or guidelines for what's safe when it comes to residual pesticides in cannabis, let alone how to best test for them.[20][21] Additionally, researchers have faced their fair share of difficulties obtaining product to test over the years. The end result is we're only now barely understanding how inhalation of pesticide-coated marijuana smoke affects long-term health[20][21][18], and standard methods for pesticide application and testing have been slow to develop.[16][22] With numerous pesticide products and little oversight on what growers apply to their plants, combined with the technical difficulty of testing for pesticides in the lab, pesticides remain one of the most difficult contaminants to test for.[16][22] That said, several classes of of pesticides are commonly applied during cannabis cultivation and can be tested for by labs[18][9][7][23]:

  • avermectins: function as an insecticide that is useful against mites, which are a common problem for cultivators
  • carbamates: function as an insecticide, similar to organophosphates, but with decreased dermal toxicity and higher degradation
  • heterocyclics: function as a broad set of compounds with many industrial uses, including as pesticides
  • organochlorides: function as a broadly useful chemical in applications such as plastics, cleaning agents, insulators, and pesticides
  • organophosphates: function as the base of many insecticides and herbicides, valued for its easy organic bonding
  • pyrethroids: function as the base of most household insecticides and exhibits insect repellent properties

Solvents: In 2003, Canadian Rick Simpson published a recipe of sorts for preparing cannabis extract via the use of solvents such as naphtha or petroleum ether. Claiming the resulting oil helped cure his skin cancer, others hoping for a cure tried it, and the solvent method of preparation grew in popularity. Dubious healing claims aside, the solvent extraction method remains viable today, though it has evolved over the years to include less harmful solvents such as supercritical carbon dioxide, which has low toxicity, low environmental impact, and beneficial extraction properties.[16][24][25] However, chemical solvents are still used, and if not evaporated out properly, the remaining solvents can be particularly harmful to sick patients using the extract. As for what solvents should be tested for, it gets a bit trickier, though Chapter 467 of United States Pharmacopeia and The National Formulary, the Oregon Health Authority's December 2015 technical report on contaminant testing of cannabis, and the Massachusetts Department of Public Health's response to public comments on cannabis testing provide helpful guidance. Listed solvents include benzene, butane, cumene, dimethoxyethane, ethanol, hexane, pentane and propane, among others.[18][7][9][16][23][26][27]


Heavy metals: 2013 research on contaminant testing on the behalf of Washington State provides insights into heavy metals and why they're looked for in cannabis testing. That research, as well as other more recent sources, tell us[18][7][9][16][28]:

  • Heavy metals contribute to several health problems, including those of a neurological nature.
  • Cannabis can "hyperaccumulate metals from contaminated soils."
  • Research parallels can be found in tobacco research and how the FDA regulates heavy metal content in foods.
  • The most prominently tested heavy metals include arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), mercury (Hg), and nickel (Ni).


Mycotoxins and microorganisms: "The ideal conditions for cannabis growth are also ideal for the growth of potentially harmful bacteria and fungi, including yeast and molds," say Shimadzu's Scott Kuzdzal and William Lipps, "therefore microbial contamination poses health risks to consumers and immunocompromised individuals."[8] In truth, these concerns have already borne out. In fact, the University of California, Davis reported in February 2017 one of its patients had contracted an incurable fungal infection from inhaling aerosolized marijuana. They later tested 20 marijuana samples from Northern California dispensaries—using specialized techniques—and found a wide variety of potentially hazardous microorganisms.[29]

The degree to which such contaminants commonly appear in grown and stored cannabis material and to which microbiological contaminants should be tested is not clear, however. As mentioned previously, the U.S. EPA has historically had little in the way of significant guidance on cannabis testing, including microbiological contaminants.[30] Like heavy metal testing, parallels are drawn from microbial testing guidelines and standards relating to tobacco and food, where they exist.[30] As warm, moist environments are conducive to microorganism growth, maintaining stable moisture levels during cultivation and storage is essential. Regularly measuring water activity—how moist something is—is particularly useful as a front-line preventative tool to better ensure microbial growth is limited.[23] Regardless, testing of some kind is still required by many U.S. states, including for organisms such as[18][8][9][16][23][29][30][31][32]:

  1. Radwan, M.M.; ElSohly, M.A.; El-Alfy, A.T. et al. (2015). "Isolation and pharmacological evaluation of minor cannabinoids from high-potency Cannabis sativa". Journal of Natural Products 78 (6): 1271-6. doi:10.1021/acs.jnatprod.5b00065. PMC PMC4880513. PMID 26000707. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC4880513. 
  2. Solymosi, K.; Köfalvi, A. (2017). "Cannabis: A Treasure Trove or Pandora's Box?". Mini-Reviews in Medicinal Chemistry 17: 1123–91. doi:10.2174/1389557516666161004162133. 
  3. 3.0 3.1 3.2 3.3 Mudge, E.M.; Murch, S.J.; Brown, P.N. (2018). "Chemometric Analysis of Cannabinoids: Chemotaxonomy and Domestication Syndrome". Scientific Reports 8: 13090. doi:10.1038/s41598-018-31120-2. 
  4. Citti, C.; Linciano, P.; Russo, F. et al. (2019). "A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol". Scientific Reports 9: 20335. doi:10.1038/s41598-019-56785-1. 
  5. World Health Organization (2016). Hall, W.; Renström, M.; Poznyak, V. ed. The health and social effects of nonmedical cannabis use. World Health Organization. pp. 95. ISBN 978921510240. https://www.who.int/publications/i/item/9789241510240. 
  6. Stone, E. (17 February 2022). "What is a cannabinoid?". Leafly - Cannabis 101. Leafly Holdings, Inc. https://www.leafly.com/news/cannabis-101/what-is-cannabinoid. Retrieved 05 August 2022. 
  7. 7.0 7.1 7.2 7.3 Kuzdzal, S.; Clifford, R.; Winkler, P.; Bankert, W. (December 2017). "A Closer Look at Cannabis Testing" (PDF). Shimadzu Corporation. Archived from the original on 07 December 2018. https://web.archive.org/web/20181207195155/https://www.ssi.shimadzu.com/sites/ssi.shimadzu.com/files/Industry/Literature/Shimadzu_Whitepaper_Emerging_Cannabis_Industry.pdf. Retrieved 05 August 2022. 
  8. 8.0 8.1 8.2 Kuzdzal, S.; Lipps, W. (2015). "Unraveling the Cannabinome". The Analytical Scientist (0915). https://theanalyticalscientist.com/techniques-tools/unraveling-the-cannabinome. Retrieved 05 August 2022. 
  9. 9.0 9.1 9.2 9.3 9.4 Association of Public Health Laboratories (May 2016). "Guidance for State Medical Cannabis Testing Programs" (PDF). pp. 35. https://www.aphl.org/aboutAPHL/publications/Documents/EH-Guide-State-Med-Cannabis-052016.pdf. Retrieved 05 August 2022. 
  10. 10.0 10.1 Rahn, B. (9 October 2014). "Understanding Cannabis Testing: A Guide to Cannabinoids and Terpenes". Leafly - Cannabis 101. Leafly Holdings, Inc. https://www.leafly.com/news/cannabis-101/understanding-cannabis-testing. Retrieved 05 August 2022. 
  11. "delta-8-tetrahydrocannabinol". NCI Drug Dictionary. National Institutes of Health, National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/delta-8-tetrahydrocannabinol. Retrieved 05 August 2022. 
  12. 12.0 12.1 12.2 Habib, R.; Finighan, R.; Davenport, S. (24 August 2013). reports/1c-Testing-for-Psychoactive-Agents-Final.pdf "Testing for Psychoactive Agents" (PDF). BOTEC Analysis Corp. https://lcb.wa.gov/publications/Marijuana/BOTEC reports/1c-Testing-for-Psychoactive-Agents-Final.pdf. Retrieved 05 August 2022. 
  13. 13.0 13.1 "Tests Offered". CMT Laboratories. Archived from the original on 08 February 2017. https://web.archive.org/web/20170208231830/http://www.cmtlaboratory.com/test-services/tests-offered/. Retrieved 05 August 2022. 
  14. 14.0 14.1 14.2 14.3 "Terpene Profiling Services". The Werc Shop. Archived from the original on 14 September 2017. https://web.archive.org/web/20170914143702/http://thewercshop.com/services/terpene-profiling-services/. Retrieved 05 August 2022. 
  15. 15.0 15.1 15.2 Andre, C.M.; Hausman, J.-F.; Guerriero, G. (2016). "Cannabis sativa: The plant of the thousand and one molecules". Frontiers in Plant Medicine 7: 19. doi:10.3389/fpls.2016.00019. PMC PMC4740396. PMID 26870049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC4740396. 
  16. 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 Cassiday, L. (October 2016). "The Highs and Lows of Cannabis Testing". INFORM. American Oil Chemists' Society. https://www.aocs.org/stay-informed/inform-magazine/featured-articles/the-highs-and-lows-of-cannabis-testing-october-2016. Retrieved 05 August 2022. 
  17. Wachsberger, K. (2 February 2016). "Terpene Testing: The future of Cannabis is here". Bloom Blog. Bloom City Club. https://www.bloomcityclub.com/terpine-testing-the-future-of-cannabis-is-here/. Retrieved 05 August 2022. 
  18. 18.0 18.1 18.2 18.3 18.4 18.5 18.6 Goldman, Stephen; Bramante, Julia; Vrdoljak, Gordon; Guo, Weihong; Wang, Yun; Marjanovic, Olivera; Orlowicz, Sean; Di Lorenzo, Robert et al. (15 June 2021). "The analytical landscape of cannabis compliance testing" (in en). Journal of Liquid Chromatography & Related Technologies 44 (9-10): 403–420. doi:10.1080/10826076.2021.1996390. ISSN 1082-6076. https://www.tandfonline.com/doi/full/10.1080/10826076.2021.1996390. 
  19. "Terpene Analysis". SC Labs, Inc. https://www.sclabs.com/terpene-analysis/. Retrieved 05 August 2022. 
  20. 20.0 20.1 Borel, B. (31 August 2015). "The Wild West of Marijuana Pesticides". The Atlantic. The Atlantic Monthly Group. https://www.theatlantic.com/health/archive/2015/08/pot-marijuana-pesticide-legalization/401771/. Retrieved 05 August 2022. 
  21. 21.0 21.1 Zhang, S. (7 August 2015). "Nobody Knows What to Do About Pesticides in Legal Marijuana". Wired. Condé Nast. https://www.wired.com/2015/08/nobody-knows-pesticides-legal-marijuana/. Retrieved 05 August 2022. 
  22. 22.0 22.1 Deibel, C. (29 January 2019). "Pesticide Testing: Methods, Strategies & Sampling". Cannabis Industry Journal. https://cannabisindustryjournal.com/feature_article/pesticide-testing-methods-strategies-sampling/. Retrieved 05 August 2022. 
  23. 23.0 23.1 23.2 23.3 Farrer, D.G. (December 2015). "Technical Report: Oregon Health Authority’s Process to Determine Which Types of Contaminants to Test for in Cannabis Products, and Levels for Action" (PDF). Oregon Health Authority. https://www.oregon.gov/oha/ph/PreventionWellness/marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf. Retrieved 05 August 2022. 
  24. Romano, L.L.; Hazekamp, A. (2013). "Cannabis oil: Chemical evaluation of an upcoming cannabis-based medicine" (PDF). Cannabinoids 1 (1): 1–11. Archived from the original on 15 December 2017. https://web.archive.org/web/20171215021221/http://www.stcm.ch/en/files/hazekamp_cann-oil_2013.pdf. 
  25. Peach, J.; Eastoe, J. (2014). "Supercritical carbon dioxide: A solvent like no other". Journal of Organic Chemistry 10: 1878-95. doi:10.3762/bjoc.10.196. PMC PMC4168859. PMID 25246947. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC4168859. 
  26. "<467> Residual Solvents" (PDF). United States Pharmacopeia and The National Formulary. United States Pharmacopeial Convention. 1 July 2007. Archived from the original on 04 August 2016. https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf. Retrieved 05 August 2022. 
  27. Bureau of Healthcare Safety and Quality (12 February 2016). "Response to Public Comments" (PDF). Massachusetts Department of Public Health. Archived from the original on 13 October 2017. https://web.archive.org/web/20171013214634/https://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf. Retrieved 05 August 2022. 
  28. Daley, P.; Lampach, D.; Sguerra, S. (12 September 2013). "Testing Cannabis for Contaminants" (PDF). BOTEC Analysis Corp. https://lcb.wa.gov/publications/Marijuana/BOTEC%20reports/1a-Testing-for-Contaminants-Final-Revised.pdf. Retrieved 05 August 2022. 
  29. 29.0 29.1 "UC Davis study finds mold, bacterial contaminants in medical marijuana samples". UC Davis. 7 February 2017. Archived from the original on 27 September 2019. https://web.archive.org/web/20190927162134/https://health.ucdavis.edu/publish/news/newsroom/11791. Retrieved 05 August 2022. 
  30. 30.0 30.1 30.2 Kennard, M. (2 June 2014). "You are Probably Smoking Mouldy Weed - Why Does Quality Assurance Matter?". Populace. Tantalus Labs. https://populace.tantaluslabs.com/you-are-probably-smoking-mouldy-weed-why-does-quality-assurance-matter/. Retrieved 05 August 2022. 
  31. "Microbiological study of Cannabis samples". Fundación CANNA. 2014. https://www.fundacion-canna.es/en/microbiological-study-cannabis-samples. Retrieved 05 August 2022. 
  32. McPartland, J.M. (2013). "Chapter 30: Contaminants and Adulterants in Herbal Cannabis". In Russo, E.B.. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Routledge. pp. 478. ISBN 9781136614934. https://books.google.com/books?id=qH-2Lj9x7L4C&pg=PT457&lpg=PT457.