Book:LIMS Buyer’s Guide for Cannabis Testing Laboratories/Laboratory testing of cannabis and its derivative products/Cannabis testing laboratory workflow

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2.3 Cannabis testing laboratory workflow

The analytical methods of testing cannabis constituents and contaminants, as well as their associated workflows, depend on the type of laboratory conducting testing. For example, an extraction-specific lab's workflow will look a bit different from the workflow of a commercial production lab or a state-mandated, independent quality testing lab. And medical cannabis testing labs may ignore terpenes entirely, for instance.[1] Broadly speaking, however, non-extraction cannabis testing lab workflows will have some aspects in common. Those workflow similarities, from beginning to end, include[2][3][4]:

  1. reception of test orders—often through a secure web portal—and samples, as well as the start of sample tracking with RFID and barcodes for chain-of-custody purposes;
  2. assignment of tests to analysts and instruments;
  3. processing of samples—including any required quality control (QC) samples—as well as any necessary grinding, homogenization, extraction, filtration, and evaporation processes;
  4. chromatographic separation, or any other non-chromatographic preparative methods, for samples, based upon the target constituent or contaminant;
  5. actual qualitative and/or quantitative analysis, based on standards and reference materials, with appropriate notification of out-of-range or -specification results;
  6. exporting of instrument data, preferably to an information management system like a LIMS, where the data are processed and recorded with the associated existing sample data;
  7. organization and review of results by designated laboratory personnel, with results either getting approved or not approved; and
  8. reporting of approved results in a compliant format, e.g., a certificate of analysis (COA), and distributed to appropriate stakeholders (often through a secure web portal).

Of course, the specific details of the methods you choose to employ will slightly modify your workflows, as will your lab's own process and procedure (P&P) documentation. For example, your workflow for testing heavy metals may differ slightly from the U.S. FDA's ICP-MS methodology. Ultimately, your workflow will be based upon many factors, including the analyses you decided to perform, methods you choose, the equipment you use, the way your lab is laid out, the P&P you follow, and the data management systems and automation you choose. Some components of your workflow will remain the same, however, regardless of the mentioned factors. Sample tracking and accurate weight reconciliation, while maintaining complete chain-of-custody, remain vital throughout the entire process, from test ordering to after the results are reported. Additionally, any calculations performed must be steadfastly accurate for every type of workflow, at every step. These aspects are practically non-negotiable given the regulatory requirements for cannabis track-and-trace mechanisms (see the next section on reporting and certification for more).

That said, workflows can usually be optimized in any laboratory, saving time and money while increasing productivity.[5][6] Keeping P&P documents, methods, and training documentation aligned with a rapidly changing industry like cannabis testing is vital to ensuring smooth workflows. Other minor considerations for smoothing out workflow problems in the cannabis testing laboratory include adding additional automation elements[2][7][8], optimizing workspaces (e.g., well-spaced lab tables, sufficient cabinets and storage)[9], and staggering shifts (e.g., for improving social distancing success during a pandemic).[10] It's best to address these and other such issues early on to ensure the best outcomes from your workflows.

2.3.1 Differences beyond analyzing plant material

Workflows can also differ slightly based upon the substrate/matrix being tested, as well as the product's intended use. Here are a few differences to consider.

Medical vs. recreational

Medical Marijuana.jpg

Speaking in broad terms, medical cannabis tends to differ from recreational cannabis such that medical cannabis has lower THC and higher CBD than recreational cannabis, and vice versa. However, even this broad generalization isn't all that accurate. Another way to generalize this is to say that medical cannabis patients prefer a wider variety of cannabis products with varying formulated balances in THC, CBD, and other cannabinoids and terpenes, whereas recreational users may—perhaps incorrectly—put more emphasis on high-THC content, caring less about some other aspects of the product.[11][12][13][14][15][16] Some medical cannabis patients may require high amounts of THC to manage pain[13], while others may find that a much lower THC dose manages their pain better.[14] And recreational cannabis users who are knowledgeable don't always want to go for the highest THC content in their acquisitions.[15] Given these facts, it's difficult to make generalizations about the content of medical cannabis vs. recreational cannabis. Complicating the matter even further is a recent study in PLOS One that found "more than 90 percent of the legal cannabis products offered in medical dispensaries vastly exceed the THC levels recommended for chronic pain relief."[17][18] The results of that study—which showed little difference between advertised medical and recreational cannabis THC concentrations across various states—further highlight not only the lack of unified regulations across the U.S. concerning THC quantities in medical cannabis, but also the difficulty—analytically—in making assumptions about the difference in testing medical vs. recreational cannabis.

That aside, one significant workflow difference between the two is that, at least for now, terpenes testing isn't generally mandated for medical cannabis[1], unless a specific terpene type and/or amount is to be shown on a product label (as is the case in, e.g., Washington and California).[19][20] This may change at some future point as researchers learn more about the "entourage effect"[21] and the role terpenes play in medical cannabis administered to patients.

Marijuana vs. hemp

On November 29, 2018, lawmakers "struck a deal in principle" to finalize the 2018 Farm Bill, which, if passed, would remove industrial hemp from the Controlled Substance Act's definition of "marijuana" as well as strike it from Schedule I.[22][23][24] On December 20, 2018, President Trump signed the Farm Bill into law, legalizing at the federal level the cultivation and sale of hemp, defined as "the plant Cannabis sativa L. and any part of the plant with a ∆9-THC concentration of not more than 0.3 percent by dry weight."[25]

Of course, this arbitrary THC cutoff comes with its own set of challenges to growers, transporters, forensic labs, and cannabis testing labs. The 0.3% number appears to derive from a a 1976 research paper by Small and Cronquist that provided definitions of Cannabis sativa and Cannabis indica, which set 0.3% ∆9-THC as a cutoff distinction between the two. This apparently "was not intended to be a prescriptive measure of the plant’s capacity to get users high."[26] As Brian Smith of Big Sur Scientific notes in a 2019 Cannabis Science and Technology article, other problems arise as well, given that a Cannabis strain could potentially have less than 0.3% THC yet contain more than 20% THCA, the acid precursor to THC. Since THCA decarboxylates to THC when heated, a person smoking such a low-THC strain could still get high[27]:

A strict interpretation of the law means this material may be legally considered hemp and can be sold and transported throughout the U.S. Of course, when smoked, material that contains more than 20% THCA will be highly intoxicating. I doubt it was the intention of the U.S. Congress to allow high THCA marijuana to become legal nationwide.

If the intent of the U.S. Congress was to prevent people from getting high when smoking industrial hemp, total available THC should be calculated. Smith noted in 2019 that, for example, Kentucky used only THC, whereas Oregon uses total available THC for their calculations, further highlighting discrepancies between federal and state law, and as such, more testing headaches.[27][28] Add in other problems such as inconsistent cannabinoid extraction methods[27], variations in representative sampling[27], differences in agricultural variability[28], a too-short testing timeframe[28][29], insufficient USDA sampling protocol[28][30], and the time required to take accurate analyses down to the 0.3% level (as found with forensic and law enforcement labs attempting to enforce laws[31], and the end result is the whole hemp laboratory testing regime appears to be shaky. And hemp farmers only end up increasingly frustrated at the potential loss of their crops, which must be destroyed if they test above the 0.3% THC threshold.[29][32] At the end of 2020—and again in early 2021[33]—Senator Rand Paul introduced The Hemp Economic Mobilization Plan (HEMP) Act to make changes to the 2018 Farm Bill, chief among them raising the THC limit from 0.3% to 1.0%. Other aspects such as increasing the timeframe for analytical testing and making a margin of error transparent are also included.[32][29] It remains to be seen what the end result will be for laboratories testing industrial hemp.

That said, laboratory workflows for analytical testing of industrial hemp will be different from those working with cannabis-derived products with higher THC counts. On the plus side, only ∆9-THC need be analyzed in submitted samples. More challenging is the requirement that labs wanting to perform hemp compliance testing under the U.S. Domestic Hemp Production Program must be registered with the DEA by, at the latest, October 31, 2021.[34][35] This may or may not be a burdensome process for some labs. Also of consideration is whether the state where the lab is located has their own state-licensed program with its own testing guidelines, or if a state-licensed program isn't set up yet, requiring the use of USDA testing guidelines.[36][37] In many cases, those states with their own programs will utilize the USDA testing guidelines, but a few states may have slightly more stringent guidelines. Lab managers must be clear on what ∆9-THC testing guidelines must be used for their lab to better shape their workflow.

Supplements, cosmetics, and topical cannabis products

As of July 2021, the FDA still prohibits THC and CBD products from being sold as a "dietary supplement." This positions appears to largely rest on the FDA's belief that "provisions in the Food, Drug and Cosmetic Act (FDCA) related to the use of dietary supplement and food ingredients that have been previously studied as drug ingredients" forces the FDA to continue to treat CBD like a new, regulated drug.[38][39][40] Efforts were made in 2020 with proposed legislation like H.R. 8179 (Hemp and Hemp-Derived CBD Consumer Protection and Market Stabilization Act of 2020), but the FDA's input on the proposal revealed a significant gap of understanding and agreement on the topic.[40] That gap may be shrinking, with the FDA signaling some concessions in December 2020.[41] However, it would seem that laboratory testing of cannabis dietary supplements won't be more widespread until the FDA and lawmakers can formally find middle ground.

Cosmetics and topical creams or lotions containing THC and CBD are not exempt from FDA scrutiny either, though the FDA tends to be more forgiving. Cosmetics containing cannabis components are fine as long as the added cannabis components do not cause the end product to be "injurious to users under the conditions of use prescribed in the labeling, or under such conditions of use as are customary or usual."[42] The FDA adds that if a cosmetic or topical cream product "is intended to affect the structure or function of the body, or to diagnose, cure, mitigate, treat or prevent disease, it is a drug, or possibly both a cosmetic and a drug, even if it affects the appearance."[42] As such, FDA approval as a drug would be required, as occurred with GW Pharmaceuticals' Epidiolex in 2018.[43] (Note that Canada has slightly different regulations on cannabis topicals.[44])

From a workflow standpoint, lotions, creams, and balms provide their own set of challenges. Dr. Jamie York of Restek notes[45]:

These matrices contain many components such as fatty acids, plant extracts, fragrances, and esters of fatty acids. When creating a workflow, we knew it was important to develop a method that is robust, produces accurate data, and prevents instrument downtime, which was especially challenging for lotions, balms, and creams since we intended to include these three different, albeit similar, types of matrices in one method.

Restek's cannabinoid testing method appears to involve the use of liquid chromatography paired with ultraviolet detection (LC-UV), with specific sample preparation and recovery experiments.[46] This loosely aligns (fine details not given) with an LC-UV method employed by ACS Laboratory[47] and an HPLC-UV method used by analytical lab BSCG.[48]

Edibles and drinkables

Cannabis CBD chocolate edibles.jpg

Edibles can be problematic. Like the fatty components referenced by Dr. York in regards to cosmetic matrices, so too do fatty components seem to cause problems for edibles. Take for example chocolate, which is full of fat. THC is known to dissolve quite well in lipids, which can cause problems, as found by David Dawson of CW Analytical Laboratories. In 2019, he found that varying a method testing for cannabinoids in chocolate only by the sample amount caused variable values across two otherwise identical analyses.[49] Infused gummy candies and other substrates also cause problems with depositing unwanted residues in mass spectrometry instruments.[50] All of that is to say that there is a highly diverse array of food matrices out there, adding their own complications to isolating and analyzing cannabinoids and other substances; more often than not, a single method won't suffice for all edible matrices.[51]

When choosing a methodology and workflow for edibles, several questions must be asked. What are the expected challenges with sample preparation and analysis, based on the ingredients? What constitutes a serving size for the matrix? Is the edible homogenously or non-homogeneously mixed in manufacturing?[52] Ultimately, the workflow will likely be unique based upon each matrix tested. However, there is at least some growing similarity in preparation and analysis of complex matrices such as edibles. Take for example a THC analysis method described by ModernCanna Labs[53]:

...the product is frozen with dry ice or liquid nitrogen and then placed in a high speed blender with diatomaceous earth, an abrasive substance that enables solvents to draw out the THC. The solvent is then placed in a flash chromatography column that separates various chemical components. When the THC is extracted from the column, it can be tested in the usual manner, with high-pressure liquid chromatography.

ACS Laboratory and CW Analytical Laboratories describe a somewhat similar process for their edibles testing[54][49], lending credence to a slowly growing consensus on at least sample preparation methods. Millipore Sigma describes a brownie preparation and analysis method that differs slightly, using shakers, centrifuges, salts, and refrigeration for prep, and then HPLC-UV for the subsequent analysis.[55] Dr. Rob O'Brien of Supra Research and Development states that their lab has developed a preparation method for dealing with the challenges of chocolate where they "extract it hot with acetyl-nitro in an ultrasonic bath. And then when we move the cannabinoids out, we also then draw those waxes and other fats out."[56] In the end, your lab will have to do due diligence in finding a consensus standard workflow methodology for the matrix being tested. In some cases, a standardized method and workflow may not be openly established, requiring more research by your laboratorians.

On the beverage side, it's worth noting that cannabinoids are not soluble in water, requiring special formulations to stabilize the beverage over time.[57][58] This issue, as well as larger sample volume requirements, and the brewing processes not being precise in what cannabinoids are transferred into hot water, bring extra complications to testing and comparing to label claims.[57] PerkinElmer's Toby Astill notes that producers of "cannabeverages" turn to HPLC for accurate cannabinoid measurement, LC-MS/MS for pesticide residues and mycotoxins, headspace GC-MS for residual solvents, and ICP-MS for heavy metals. Flavor and aroma profiles can also be managed with headspace GC-MS.[57]

Veterinary products

The FDA currently prohibits the use of hemp and CBD in animal food, based off Association of American Feed Control Officials (AAFCO) findings.[59][60] Despite this, some manufacturers have continued to illegally produce and sell CBD- and hemp-containing pet products.[61] And like human products "intended to affect the structure or function of the body, or to diagnose, cure, mitigate, treat or prevent disease," animal products with the same claims must be treated as drugs, requiring FDA approval.[42]

Federal law, as well as many states' laws, also prohibit veterinarians "from possessing, administering, dispensing, or prescribing cannabis and related products" not approved by the FDA. Extralabel use of CBD- or THC-infused drug approved for human use is allowed with animals under specific conditions.[62][63]

What does that mean for veterinarians? The American Veterinary Medical Association (AVMA) said in early 2019[64]:

Under existing federal and state law, veterinarians who administer, dispense, prescribe, or recommend ‘hemp’ or other cannabis-derived products that are not approved for use in animals, or approved for animals or people in accord with FDA extralabel drug use regulations, face increased potential legal risk if there is an adverse event. Adverse events can include unintended effects (side effects) of a drug or it could be that the drug doesn’t deliver the intended therapeutic effect.

That said, unless something changes, laboratory testing of CBD and other cannabinoids is for now largely limited to the realm of approved research groups and manufacturers skirting largely unenforced law. Still, a handful of methods for testing pet-marketed CBD products are floating out there. In a December 2019 piece for Cannabis Science and Technology, Curtis et al. describe a study of six commercially available CBD oils marketed as pet supplements, analyzed with gas chromatography–quadrupole time-of-flight mass spectrometry (GC-QTOF) in discovery (untargeted) mode.[65] A broader study performed by Wakshlag et al. in 2020 used a cannabinoid methodology which included ultra-performance liquid chromatography (UPLC) with a diode array detector (DAD) and quadrupole mass spectrometer.[66] Like edibles, methods and workflows may vary based on the matrix being examined.

References

  1. ↑ 1.0 1.1 Kirham, E. (1 April 2015). "Testing for Terpenes in Cannabis". Lift & Co.. https://lift.co/magazine/testing-for-terpenes-in-cannabis. Retrieved 07 July 2021. 
  2. ↑ 2.0 2.1 Audino, S. (7 February 2018). "Managing Cannabis Testing Lab Workflows Using LIMS". Cannabis Industry Journal. https://cannabisindustryjournal.com/feature_article/managing-cannabis-testing-lab-workflows-using-lims/. Retrieved 07 July 2021. 
  3. ↑ emethods-5994-2242EN-agilent.pdf "Establish Your Cannabis Lab Fast". Agilent Technologies, Inc. 17 July 2020. https://www.agilent.com/cs/library/brochures/compendium-cannabis emethods-5994-2242EN-agilent.pdf. Retrieved 07 July 2021. 
  4. ↑ "Workflows and Procedures for Cannabis Testing and Analysis". Millipore Sigma. 2021. https://www.sigmaaldrich.com/technical-documents/articles/analytical/test-procedures-for-cannabis-testing-and-analysis.html. Retrieved 13 January 2021. 
  5. ↑ Grimm, E.; Schmidt, R.A. (2009). "Reengineered Workflow in the Anatomic Pathology Laboratory: Costs and Benefits". Archives of Pathology & Laboratory Medicine 133 (4): 601–4. doi:10.1043/1543-2165-133.4.601. PMID 19391659. 
  6. ↑ Hawker, C.D. (2017). "Nonanalytic Laboratory Automation: A Quarter Century of Progress". Clinical Chemistry 63 (6): 1074–82. doi:10.1373/clinchem.2017.272047. PMID 28396562. 
  7. ↑ "New Publication in the Journal of Forensic Science on Fast Discrimination of Marijuana". DPX Technologies. 28 September 2020. https://www.labtechsupplyco.com/important-advice-in-designing-your-cannabis-lab/. Retrieved 07 July 2020. 
  8. ↑ Cannalysis (8 April 2020). "Cannalysis Lab Decreases Processing Time by 94% with Lab Automation Software". Analytical Cannabis. https://www.analyticalcannabis.com/articles/cannalysis-lab-decreases-processing-time-by-94-with-lab-automation-software-312343. Retrieved 07 July 2021. 
  9. ↑ "Important Advice in Designing Your Cannabis Lab". LabTech Supply Co. 20 September 2019. https://dpxtechnologies.com/new-publication-in-the-journal-of-forensic-science-on-fast-discrimination-of-marijuana/. Retrieved 07 July 2021. 
  10. ↑ Schaneman, B. (26 March 2020). "Cannabis labs watchful of supply disruptions during coronavirus crisis as testing demand remains strong". Marijuana Business Daily. https://mjbizdaily.com/cannabis-labs-watchful-of-supply-disruptions-during-coronavirus-crisis-as-testing-demand-remains-strong/. Retrieved 07 July 2021. 
  11. ↑ Fisher, R.D.; Fisher, A.A. (12 September 2020). "Preventing Recreational Cannabis from Squeezing Out Medical". The Medical Cannabis Primer - Blog. https://medicalcannabisprimer.com/all-blogs/62-how-to-prevent-recreational-cannabis-from-squeezing-out-medical. Retrieved 07 July 2021. 
  12. ↑ Page II, R.L.; Allen, L.A.; Kloner, R.A. et al. (2020). "Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association". Circulation 142 (10): e131–52. doi:10.1161/CIR.0000000000000883. PMID 32752884. 
  13. ↑ 13.0 13.1 Smith, J. (6 March 2020). "Marijuana businesses fight state efforts to limit THC content in flower, concentrates". Marijuana Business Daily. https://mjbizdaily.com/marijuana-firms-fight-efforts-to-limit-thc-levels-in-flower/. Retrieved 07 July 2021. 
  14. ↑ 14.0 14.1 Chatterjee, R. (15 May 2019). "Highly Potent Weed Has Swept The Market, Raising Concerns About Health Risks". NPR. https://www.npr.org/sections/health-shots/2019/05/15/723656629/highly-potent-weed-has-swept-the-market-raising-concerns-about-health-risks. Retrieved 07 July 2021. 
  15. ↑ 15.0 15.1 Roberts, C. (16 June 2020). "Science Reveals The Cannabis Industry’s Greatest Lie: You’re Buying Weed Wrong (And So Is Everyone Else)". Forbes. https://www.forbes.com/sites/chrisroberts/2020/06/16/science-reveals-the-cannabis-industrys-greatest-lie-youre-buying-weed-wrong-and-so-is-everyone-else/. Retrieved 07 July 2021. 
  16. ↑ "Guide to Using Medical Cannabis". Cannabis 101. Americans For Safe Access. https://www.safeaccessnow.org/using_medical_cannabis. Retrieved 07 July 2021. 
  17. ↑ Bear-McGuinness, L. (26 March 2020). "There’s No Significant Difference Between Recreational and Medical Marijuana in the US, Study Claims". Analytical Cannabis. https://www.analyticalcannabis.com/articles/theres-no-significant-difference-between-recreational-and-medical-marijuana-in-the-us-study-claims-312318. Retrieved 07 July 2021. 
  18. ↑ Cash, M.C.; Cunnane, K.; Fan, C. et al. (2020). "Mapping cannabis potency in medical and recreational programs in the United States". PLOS One 15 (3): e0230167. doi:10.1371/journal.pone.0230167. PMC PMC7098613. PMID 32214334. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098613. 
  19. ↑ "WAC 246-70-050 Quality assurance testing". Washington State Legislature. State of Washington. https://app.leg.wa.gov/WAC/default.aspx?cite=246-70-050. Retrieved 07 July 2021. 
  20. ↑ "Bureau of Cannabis Control Text of Regulations" (PDF). State of California. 2019. https://cannabis.ca.gov/wp-content/uploads/sites/13/2019/01/Order-of-Adoption-Clean-Version-of-Text.pdf. Retrieved 07 July 2021. 
  21. ↑ James, A. (2019). "Using Gas Chromatography for Accurate Terpene Analysis in Cannabis". Cannabis Science and Technology 2 (5): 48–51. https://www.cannabissciencetech.com/view/using-gas-chromatography-accurate-terpene-analysis-cannabis. 
  22. ↑ Pamuk, H. (29 November 2018). "U.S. lawmakers seal Farm Bill agreement in principle". Reuters. https://www.reuters.com/article/us-usa-farmbill/u-s-lawmakers-seal-farm-bill-agreement-in-principle-idUSKCN1NY21M. Retrieved 07 July 2021. 
  23. ↑ Milligan, S. (4 December 2018). "Legalization of Hemp Could Be First Step for Federal Marijuana Protections". U.S. News and World Report. https://www.usnews.com/news/national-news/articles/2018-12-04/legalization-of-hemp-could-be-first-step-for-federal-marijuana-protections. Retrieved 07 July 2021. 
  24. ↑ Stewart, I.A.; Kloss, J.M.; Willner, N.M. (4 December 2018). "Will Hemp-Derived CBD Be Fully Legal with Passage of the 2018 Farm Bill? Not Quite…". The National Law Review. https://www.natlawreview.com/article/will-hemp-derived-cbd-be-fully-legal-passage-2018-farm-bill-not-quite. Retrieved 07 July 2021. 
  25. ↑ Cohen, B.; Bleicher, M.C.; Fortier, D.L. et al. (31 December 2018). "What Does the 2018 Farm Bill Mean for the Hemp and CBD Businesses?". Perkins Coie LLP. https://www.perkinscoie.com/en/news-insights/what-does-the-2018-farm-bill-mean-for-the-hemp-and-cbd-businesses.html. Retrieved 07 July 2021. 
  26. ↑ "Why is 0.3% the Legal Limit for THC in Hemp/CBD?". Bluebird Botanicals. 23 December 2020. https://bluebirdbotanicals.com/blogs/announcements/why-is-0-3-thc-legal-limit. Retrieved 07 July 2021. 
  27. ↑ 27.0 27.1 27.2 27.3 Smith, B.C. (2019). "Hemp Testing Insanity". Cannabis Science and Technology 2 (5): 10–13. https://www.cannabissciencetech.com/view/hemp-testing-insanity. 
  28. ↑ 28.0 28.1 28.2 28.3 Erickson, B.E. (2020). "Hemp Growing Pains". Chemical & Engineering News 98 (8). https://cen.acs.org/food/agriculture/Hemp-growing-pains/98/i8. 
  29. ↑ 29.0 29.1 29.2 Paul, R. (December 2020). "The Hemp Economic Mobilization Plan (HEMP) Act" (PDF). U.S. Senate. https://www.paul.senate.gov/sites/default/files/page-attachments/HEMPActOnePager.pdf. Retrieved 07 July 2021. 
  30. ↑ "New Hemp Testing Guidelines Make Meeting 0.3% THC Limit Difficult". Medical Genomics. 5 November 2019. https://www.medicinalgenomics.com/new-hemp-sampling-guidelines-make-meeting-0-3-thc-limit-difficult/. Retrieved 07 July 2021. 
  31. ↑ Horne, M.; Mastrianni, K.R.; Amick, G. et al. (2020). "Fast Discrimination of Marijuana using Automated High‐throughput Cannabis Sample Preparation and Analysis by Gas Chromatography–Mass Spectrometry". Journal of Forensic Sciences 65 (5): 1709–15. doi:10.1111/1556-4029.14525. 
  32. ↑ 32.0 32.1 Long, J. (17 December 2020). "Sen. Paul introduces bill to raise THC limit for hemp". Natural Products Insider. https://www.naturalproductsinsider.com/regulatory/sen-paul-introduces-bill-raise-thc-limit-hemp. Retrieved 07 July 2021. 
  33. ↑ Senate Office of Dr. Rand Paul (30 March 2021). "Dr. Rand Paul Reintroduces HEMP Act to Relieve Unnecessary Constraints on Hemp Industry, Provide Transparency and Certainty". Rand Paul, U.S. Senator for Kentucky. https://www.paul.senate.gov/news/dr-rand-paul-reintroduces-hemp-act-relieve-unnecessary-constraints-hemp-industry-provide. Retrieved 07 July 2021. 
  34. ↑ Agricultural Marketing Service. "Hemp Analytical Testing Laboratories". U.S. Department of Agriculture. https://www.ams.usda.gov/rules-regulations/hemp/dea-laboratories. Retrieved 07 July 2021. 
  35. ↑ Agricultural Marketing Service. "Enforcement Discretion - Interim Final Rule". U.S. Department of Agriculture. https://www.ams.usda.gov/rules-regulations/hemp/enforcement. Retrieved 07 July 2021. 
  36. ↑ "Testing guidelines for Identifying Delta-9 Tetrahydrocannabinol (THC) Concentration in Hemp" (PDF). U.S. Department of Agriculture. https://www.ams.usda.gov/sites/default/files/media/TestingGuidelinesforHemp.pdf. Retrieved 07 July 2021. 
  37. ↑ "State Industrial Hemp Statutes". National Conference of State Legislatures. 16 April 2020. https://www.ncsl.org/research/agriculture-and-rural-development/state-industrial-hemp-statutes.aspx. Retrieved 07 July 2021. 
  38. ↑ "Questions and Answers: 9. Can THC or CBD products be sold as dietary supplements?". FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). U.S. Food and Drug Administration. 1 October 2020. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#dietarysupplements. Retrieved 07 July 2021. 
  39. ↑ "Frequently Asked Questions: Cannabidiol (CBD) Use in Dietary Supplements". Council for Responsible Nutrition. November 2019. https://www.crnusa.org/resources/frequently-asked-questions-cannabidiol-cbd-use-dietary-supplements. Retrieved 07 July 2021. 
  40. ↑ 40.0 40.1 Long, J. (24 November 2020). "FDA, Congress differ on how CBD should be regulated in supplements". Natural Products Insider. https://www.naturalproductsinsider.com/regulatory/fda-congress-differ-how-cbd-should-be-regulated-supplements. Retrieved 07 July 2021. 
  41. ↑ Bennett, T. (18 December 2020). "Bill to Legalize CBD in Dietary Supplements Gains More Congressional Support". HempGrower. https://www.hempgrower.com/article/hb-8179-cbd-dietary-supplements-gains-congressional-support-update/. Retrieved 07 July 2021. 
  42. ↑ 42.0 42.1 42.2 "Questions and Answers: 13. What is FDA’s position on cannabis and cannabis-derived ingredients in cosmetics?". FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). U.S. Food and Drug Administration. 1 October 2020. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#cosmetics. Retrieved 07 July 2021. 
  43. ↑ Barrett, J. (15 June 2018). "FDA Approves Groundbreaking Drug for Treating Rare, Severe Forms of Epilepsy". Pharmacy Times. https://www.pharmacytimes.com/view/fda-approves-groundbreaking-drug-for-treating-rare-severe-forms-of-epilepsy. Retrieved 07 July 2021. 
  44. ↑ "Is it legal to sell cannabis topicals?". Legal Line. https://www.legalline.ca/legal-answers/is-it-legal-to-sell-cannabis-topicals/. Retrieved 07 July 2021. 
  45. ↑ Smith, C.; York, J. (17 December 2020). "Editorial Article: Cannabis-infused lotions, creams, and balms: Achieving standardization and quality assurance". Select Science. https://www.selectscience.net/editorial-articles/cannabis-infused-lotions,-creams,-and-balms-achieving-standardization-and-quality-assurance/?artID=53412. Retrieved 07 July 2021. 
  46. ↑ York, J. (2020). "Quantitative LC-UV Method for CBD in Topicals with Simplified Extraction of Lotions, Balms, and Creams" (PDF). Restek Corporation. https://www.selectscience.net/downloads/articles/4671_Restek_-_balms,_lotions_and_creams_testing.pdf. Retrieved 07 July 2021. 
  47. ↑ "Topicals Testing". American Clinical Solutions, LLC. 2020. https://acslabcannabis.com/services/lab-testing/topical-creams/. Retrieved 07 July 2021. 
  48. ↑ "BSCG Batch Certification: Certified CBD - Elixicure" (PDF). Banned Substances Control Group. 17 August 2020. https://www.bscg.org/wp-content/uploads/2020/08/BSCG-Certified-CBD-Batch-Certification-Honest-Globe-Elixicure-Wintergreen-32010-August-17-2020.pdf. Retrieved 07 July 2021. 
  49. ↑ 49.0 49.1 Adlin, B. (27 August 2019). "Chocolate Edibles Are Vexing Cannabis Labs. Here’s Why". Leafly. https://www.leafly.com/news/science-tech/chocolate-edibles-are-vexing-cannabis-labs-heres-why. Retrieved 07 July 2021. 
  50. ↑ Kahen, K.; Astill, T. (23 October 2019). "Taking the guess work out of analysing cannabis edibles". New Food. https://www.newfoodmagazine.com/article/96931/taking-the-guess-work-out-of-analysing-cannabis-edibles/. Retrieved 07 July 2021. 
  51. ↑ Wolf, C. (12 June 2020). "Determining Cannabinoids in Marijuana-Infused Edibles". News Medical. https://www.news-medical.net/news/20200612/Determining-Cannabinoids-in-Marijuana-Infused-Edibles.aspx. Retrieved 07 July 2021. 
  52. ↑ "Edibles". Iron Laboratories. https://www.ironlaboratories.com/edibles. Retrieved 07 July 2021. 
  53. ↑ "Testing THC Levels in Edibles". ModernCanna Labs. 2020. https://www.moderncanna.com/testing-thc-levels/edibles/. Retrieved 07 July 2021. 
  54. ↑ "Edibles Testing". American Clinical Solutions, LLC. 2020. https://acslabcannabis.com/services/lab-testing/edibles/. Retrieved 07 July 2021. 
  55. ↑ Stenerson, K.K.; Claus, J.E.; Shimelis, O.I. (August 2018). Literature/MilliporeSigma/MPS An Easy Approach for the Analysis of Active Cannabis Compounds in Edible Food ProductsGummy Bears and Brownies.pdf "An Easy Approach for the Analysis of Active Cannabis Compounds in Edible Food Products: Gummy Bears and Brownies" (PDF). Millipore Sigma. https://emeraldscientific.com/content/Product Literature/MilliporeSigma/MPS An Easy Approach for the Analysis of Active Cannabis Compounds in Edible Food ProductsGummy Bears and Brownies.pdf. Retrieved 07 July 2021. 
  56. ↑ O'Brien, R. (7 February 2020). "Overcoming challenges in edibles analysis for the Canadian market". SelectScience. https://www.selectscience.net/SelectScience-TV/Videos/overcoming-challenges-in-edibles-analysis-for-the-canadian-market/?videoID=4925. Retrieved 07 July 2021. 
  57. ↑ 57.0 57.1 57.2 Astill, T. (16 September 2020). "The (Analytical) Problem With “Cannabeverages”". The Cannabis Scientist. https://thecannabisscientist.com/testing-processing/the-analytical-problem-with-cannabeverages. Retrieved 07 July 2021. 
  58. ↑ "Testing THC edibles: The Importance of stability testing in the cannabis field". Formulaction. 28 August 2019. https://www.formulaction.com/en/about-us/news/blog/testing-thc-edibles. Retrieved 07 July 2021. 
  59. ↑ "Questions and Answers: 25. Can hemp be added to animal food?". FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). U.S. Food and Drug Administration. 1 October 2020. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#hempanimal. Retrieved 07 July 2021. 
  60. ↑ "AAFCO Issues Guidelines on Hemp in Animal Food". Shook, Hardy and Bacon. 17 May 2019. https://www.shb.com/intelligence/newsletters/fblu/fblu-2019/fblu-713/fblu-713. Retrieved 07 July 2021. 
  61. ↑ Gray, J.L. (10 December 2019). "FDA Cracks Down on Pet Products Containing CBD After USDA Clears Path for Hemp Production". JD Supra. https://www.jdsupra.com/legalnews/fda-cracks-down-on-pet-products-98779/. Retrieved 07 July 2021. 
  62. ↑ "Questions and Answers: 26. Can approved human drugs containing CBD or synthetic THC be used extralabel in animals?". FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). U.S. Food and Drug Administration. 1 October 2020. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#extralabelanimalsl. Retrieved 07 July 2021. 
  63. ↑ "Cannabis & Pets". County of Los Angeles Public Health. 18 November 2019. http://publichealth.lacounty.gov/vet/CannabisAndPets.htm. Retrieved 07 July 2021. 
  64. ↑ "Cannabis as Drug, Food, or Supplement in Veterinary Medicine" (PDF). American Veterinary Medical Association. 15 February 2019. https://www.avma.org/sites/default/files/resources/About-Cannabis-as-Veterinary-Drug-or-Food.pdf. Retrieved 07 July 2021. 
  65. ↑ Curtis, M.; D'Antonio, S.; Macherone, A. (2019). "GC-TOF Discovery-Based Profiling of CBD Oil Pet Supplements". Cannabis Science and Technology 2 (6): 61–65. https://www.cannabissciencetech.com/view/gc-tof-discovery-based-profiling-cbd-oil-pet-supplements. 
  66. ↑ Wakshlag, J.J.; Cital, S.; Eaton, S.J.; Prussin, R.; Hudalla, C. (2020). "Cannabinoid, terpene, and heavy metal analysis of 29 over-the-counter commercial veterinary hemp supplements". Veterinary Medicine: Research and Reports 11: 45–55. doi:10.2147/VMRR.S248712. PMC PMC7169471. PMID 32346530. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169471. 
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