Δ9-tetrahydrocannabinol and 11-hydroxy-Δ9-tetrahydrocannabinol as markers of cannabis use in urinary drug testing.

With some exceptions, California Assembly Bill 2188 will preclude the use of ∆9-tetrahydrocannabinol-9-carboxylic acid (Δ9-THC-COOH) as a marker of cannabis use in urinary workplace drug testing. The bill allows for the use of psychoactive cannabis markers, which include Δ9-tetrahydrocannabinol (Δ9-THC) and the metabolite 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC). Both analytes are present in urine mainly as conjugated metabolites and will require hydrolysis prior to analysis, but very little is known about expected concentrations in urine. The aim of this study was to report concentrations from two large data sets comprising 1,411 workplace drug testing urine specimens positive by immunoassay (50 ng/mL cutoff) and discuss strategies for using 11-OH-Δ9-THC and/or Δ9-THC to detect cannabis use. Median 11-OH-Δ9-THC and Δ9-THC concentrations were 28-35% and 1.1-1.6% of those of Δ9-THC-COOH and correlations between analytes were observed. To avoid the risk of positives from passive exposure, laboratories could use a cutoff with equivalent sensitivity to cannabis exposure. A 5 ng/mL cutoff for 11-OH-Δ9-THC showed 92% agreement with a 15 ng/mL cutoff for Δ9-THC-COOH, with only 0.9% of specimens being positive only for 11-OH-Δ9-THC. It was not possible to propose an estimated cutoff for Δ9-THC, due to the constraints of the limit of detection used in this study.

Cannabinoid Content and Label Accuracy of Various Hemp-Derived Haircare, Cosmetic, and Edible Products Available at Retail Stores and Online in the United States.

Aim: To evaluate the label accuracy and content of various hemp-derived cannabidiol (CBD) products (cannabinoid products with ≤0.3% Δ9-tetrahydrocannabinol [THC]), as well as evaluate advertised claims on product labels. Methods: Hemp haircare, cosmetics, and food/drink products that were advertised to contain CBD were purchased from retail stores in the Baltimore, Maryland area (purchased in July 2020) and online (purchased in August 2020). Cannabinoid concentrations were measured using gas chromatography-mass spectrometry. Percent deviations between labeled and actual CBD concentrations were determined. Label information such as references to the Food and Drug Administration (FDA), external testing claims, and other claims (i.e., cosmetic or beauty, therapeutic, health halo effect, or "other") were quantified. Results: Ninety-seven products were purchased (35 in-store, 62 online). Of the 71 products with a specific total CBD amount on the label, 35 (49%) were underlabeled (>10% more CBD than advertised), 27 (38%) were overlabeled (>10% less CBD than advertised), and 9 (12.7%) were accurately labeled (within ±10% of labeled CBD). The median (range) percentage deviations were -53% (-100%-76%) for haircare products, +18% (-100%-1076%) for cosmetics, and -1% (-100%-4468%) for food/drinks. CBD label accuracy did not differ significantly between products with external testing claims versus those without (t40 = 0.23, p = 0.82). Overall, 24% of the 97 (total) products made a cosmetic or beauty claim (e.g., "skin looks more youthful"), 40% made a therapeutic claim (e.g., "pain relief"), and 86% made a health halo effect claim (e.g., "paraben-free," "dye-free," etc.). Most products (63%) did not include a disclaimer that claims had not been evaluated by the FDA. Conclusions: Most of the products included in this sample were inaccurately labeled for CBD content, including those claiming to have been tested by third party laboratories. A notable finding was that 10 products did not contain any CBD. Many products made therapeutic claims or used marketing tactics to seemingly convey they were safe/healthy, but only about one-third included disclaimers that these statements had not been evaluated by the FDA. These findings highlight the need for proper regulatory oversight of cannabinoid-containing products to ensure quality assurance and deter misleading or unfounded health claims in product marketing.

Stability of Nano-Emulsified Cannabidiol in Acidic Foods and Beverages.

Introduction: Food and beverage products containing cannabidiol (CBD) is a growing industry, but some CBD products contain Δ9-tetrahydrocannabinol (Δ9-THC), despite being labeled as "THC-free". As CBD can convert to Δ9-THC under acidic conditions, a potential cause is the formation of Δ9-THC during storage of acidic CBD products. In this study, we investigated if acidic products (pH ≤ 4) fortified with CBD would facilitate conversion to THC over a 2-15-month time period. Materials and Methods: Six products, three beverages (lemonade, cola, and sports drink) and three condiments (ketchup, mustard, and hot sauce), were purchased from a local grocery store and fortified with a nano-emulsified CBD isolate (verified as THC-free by testing). The concentrations of CBD and Δ9-THC were measured by Gas Chromatography Flame Ionization Detector (GC-FID) and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), respectively, for up to 15 months at room temperature. Results: Coefficients of variation (CVs) of initial CBD concentrations by GC-FID were <10% for all products except ketchup (18%), showing homogeneity in the fortification. Formation of THC was variable, with the largest amount observed after 15 months in fortified lemonade #2 (3.09 mg Δ9-THC/serving) and sports drink #2 (1.18 mg Δ9-THC/serving). Both beverages contain citric acid, while cola containing phosphoric acid produced 0.10 mg Δ9-THC/serving after 4 months. The importance of the acid type was verified using acid solutions in water. No more than 0.01 mg Δ9-THC/serving was observed with the condiments after 4 months. Discussion: Conversion of CBD to THC can occur in some acidic food products when those products are stored at room temperature. Therefore, despite purchasing beverages manufactured with a THC-free nano-emulsified form of CBD, consumers might be at some risk of unknowingly ingesting small amounts of THC. The results indicate that up to 3 mg Δ9-THC from conversion can be present in a serving of CBD-lemonade. Based on the previous studies, 3 mg Δ9-THC might produce a positive urine sample (≥15 ng/mL THC carboxylic acid) in some individuals. Conclusion: Consumers must exert caution when consuming products with an acidic pH (≤4) that suggests that they are "THC-Free," because consumption might lead to positive drug tests or, in the case of multiple doses, intoxication.

Pharmacokinetics and pharmacodynamics of five distinct commercially available hemp-derived topical cannabidiol products.

Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol (Δ9-THC)). CBD-containing topical products have surged in popularity, but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N = 46) received one of six study drugs: a CBD-containing cream (N = 8), lotion (N = 8), patch (N = 7), balm (N = 8), gel (N = 6) or placebo (N = 9; matched to an active formulation). The protocol included three phases conducted over 17 days: (i) an acute drug application laboratory session, (ii) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7 and 10) (iii) a 1-week washout phase. In each phase, whole blood, oral fluid and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC-MS-MS) for CBD, Δ9-THC and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor and physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7-10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products, and no urine samples tested "positive" for cannabis using current US federal workplace drug testing criteria (immunoassay cut-off of 50 ng/mL and confirmatory LC-MS-MS cut-off of 15 ng/mL). Unexpectedly, nine participants (seven lotions, one patch and one gel) exhibited Δ9-THC oral fluid concentrations ≥2 ng/mL (current US federal workplace threshold for a "positive" test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.