Labelling Issues and Potency Uncertainty in Commercial Cannabis Products

Written by Jon Gettman

October 22, 2023

ACE Label

Cannabis Interactions (Drugs.com)

This is an interactive dataset at Drugs.com.  According to the site, there are 393 drugs known to interact with cannabis, along with 1 alcohol/food interaction. Of the total drug interactions, 27 are major, and 366 are moderate.  The site provides reports on known interactions between cannabis and any specified drugs and provides a detailed report.

Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ. 2020 Mar 2;192(9):E206. doi: 10.1503/cmaj.191097. PMID: 32122975; PMCID: PMC7055953.

This is a short and detailed piece from the Canadian Medical Association Journal that should be read in full.  The assessment concludes with attention to “red flag” indicators:

“Though further research is needed, marijuana may have serious interactions with drugs including warfarin (increased international normalized ratio and risk of bleeding); clobazam (increased risk of benzodiazepine toxicity); central nervous system depressants and sympathomimetics (additive effects); and theophylline, clozapine and olanzapine (reduced efficacy). Patients should be advised about possible increased cannabinoid effects with concomitant CYP3A4 and 2C9 inhibitors (Appendix 1). Alternatives that do not interact with marijuana should be selected when clinically feasible.”

Read more!

Lopera V, Rodríguez A, Amariles P. Clinical Relevance of Drug Interactions with Cannabis: A Systematic Review. J Clin Med. 2022 Feb 22;11(5):1154. doi: 10.3390/jcm11051154. PMID: 35268245; PMCID: PMC8911401 

The full-text of this study is available for public review.  Here is the conclusion:

“The increased use of medicinal cannabis in the population allows for the development of studies providing the community with scientific supported information that can help to make decisions. This review found and established the clinical relevance of 19 pairs of cannabis–drug interactions, mostly at level 3 of clinical relevance, 1 interaction at level 1 (with warfarin), and 2 interactions at level 2 (with buprenorphine and tacrolimus). These interactions are mediated by a pharmacokinetic mechanism, and most of them are related to nervous system drugs. It is important to emphasize that the confirmation of these findings requires medical assessment and follow-up of on dosage, concentration, cannabis preparation used, and route of administration. Nevertheless, the information found is limited, and it is necessary to conduct clinical trials and to improve the evidence of the effects of cannabis–drug interactions on patients’ health.”

Labelling Issues and Potency Uncertainty in Commercial Cannabis Products

Numerous research findings indicate that cannabinoid products are not accurately labeled. A recent key finding (Schwabe, et al, 2023) is that 70% of the tested samples had THC levels more than 15% lower than the levels reported on the label.  Inaccurate labeling has consequences for patient and providers.  This selected annotated bibliography provides access to some of the most recent research in this area.  In addition, Smith et al (2022) also provide very interesting findings on diversity in cannabinoid and terpene content in commercial cannabis samples from 6 states.

Oldfield K, Ryan J, Doppen M, Kung S, Braithwaite I, Newton-Howes G. A systematic review of the label accuracy of cannabinoid-based products in regulated markets: is what’s on the label what’s in the product? Australasian Psychiatry. 2021;29(1):88-96. doi:10.1177/1039856220965334

This paper provides a literature review of research on label accuracy and contamination in cannabinoid products.  

The literature reviewed shows that there is labelling inaccuracy and that contaminants are present across the spectrum of cannabinoid-based products in regulated markets, the breadth and depth of which cannot be discerned. The review process itself highlights a concerning paucity and heterogeneity of relevant literature. To counter this, it is imperative that independent rigorous standardised testing and pharmacovigilance is undertaken to ensure that patient safety is not compromised as the demand for cannabinoid-based products grows.”

Smith CJ, Vergara D, Keegan B, Jikomes N (2022) The phytochemical diversity of commercial Cannabis in the United States. PLoS ONE 17(5): e0267498. https://doi.org/10.1371/journal.pone.0267498

From the abstract:  

“We analyzed the cannabinoid and terpene content of commercial Cannabis samples across six US states, finding distinct chemical phenotypes (chemotypes) which are reliably present. By comparing the observed phytochemical diversity to the commercial labels commonly attached to Cannabis-derived product samples, we show that commercial labels do not consistently align with the observed chemical diversity. However, certain labels do show a biased association with specific chemotypes.”

From the conclusion:

“We have shown that in the US, multiple, distinct chemotypes of commercial Cannabis are reliably present across regions. Due to the chemical complexity of these products, which may contain dozens of pharmacologically active compounds with potentially psychoactive or medicinal effects, we believe it is in the public interest to devise a classification system and naming conventions that reflect the true chemotaxonomic diversity of this plant. The general approach we have used in this study can serve as a basic guide for cannabis product segmentation and classification rooted in product chemistry. Consumer-facing labelling systems should be grounded in such an approach so that consumers can be guided to products with reliably different sensory and psychoactive attributes.”

Schwabe AL, Johnson V, Harrelson J, McGlaughlin ME (2023) Uncomfortably high: Testing reveals inflated THC potency on retail Cannabis labels. PLoS ONE 18(4): e0282396. https://doi.org/10.1371/journal.pone.0282396

From the abstract:

“Reports of inflated THC potency and “lab shopping” to obtain higher THC potency results have been circulating for some time, but a side-by-side investigation of the reported potency and flower in the package has not previously been conducted. Using HPLC, we analyzed THC potency in 23 samples from 10 dispensaries throughout the Colorado Front Range and compared the results to the THC potency reported on the packaging. Average observed THC potency was 14.98 +/- 2.23%, which is substantially lower than recent reports summarizing dispensary reported THC potency. The average observed THC potency was 23.1% lower than the lowest label reported values and 35.6% lower than the highest label reported values. Overall, ~70% of the samples were more than 15% lower than the THC potency numbers reported on the label, with three samples having only one half of the reported maximum THC potency. “

Gilman JM, Schmitt WA, Wheeler G, et al. Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts. JAMA Netw Open. 2021;4(4):e215490. doi:10.1001/jamanetworkopen.2021.5490

This research letter reports interesting and important data showing a lack of CBD metabolites in participants consuming CBD labeled products, and THC metabolites detected in users of CBD dominant products.  There is also data in which no cannabinoid metabolites were found in 20% of users of vaped cannabis.  

These findings indicate that adults using medical cannabis products may have incomplete or incorrect information regarding expected cannabinoid exposure from these purchased products, impeding informed patient choice and investigation of pharmacologic and therapeutic properties of cannabis products.”

Walter B. Wilson; Aaron A. Urbas, Ph.D.; Frances Scott, Ph.D., “Study Reveals Inaccurate Labeling of Marijuana as Hemp,” October 17, 2022, nij.ojp.gov:
https://nij.ojp.gov/topics/articles/study-reveals-inaccurate-labeling-marijuana-hemp

A key finding of this study is that “Analyses indicated that of the 53 samples examined, 49 were incorrectly labeled as hemp because they technically fit the federal classification of marijuana.”

Johnson E, Kilgore M, Babalonis S. Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim. J Cannabis Res. 2022 Jun 6;4(1):28. doi: 10.1186/s42238-022-00140-1. PMID: 35658956; PMCID: PMC9169299.

This study reviewed hemp-derived CBD products collected by the researchers in Central Kentucky.  It concludes that:

“nearly half of the products in this study were not properly labelled (i.e., not within a ± 10% margin of error). Consumers and practitioners should remain cautious of unregulated and often-mislabeled CBD products due to the risks of taking too much CBD (e.g., drug-drug interactions, liver enzyme elevations, increased side effects) and the consequences of taking too little (e.g., no clinical benefits due to underdosing). “

Spindle TR, Sholler DJ, Cone EJ, Murphy TP, ElSohly M, Winecker RE, Flegel RR, Bonn-Miller MO, Vandrey R. Cannabinoid Content and Label Accuracy of Hemp-Derived Topical Products Available Online and at National Retail Stores. JAMA Netw Open. 2022 Jul 1;5(7):e2223019. doi: 10.1001/jamanetworkopen.2022.23019. PMID: 35857320; PMCID: PMC9301515.

In this study, 

“A total of 105 products were purchased, 45 from retail locations and 60 online. Of the 89 products that listed a total amount of CBD on the label, 18% (16 products) were overlabeled (ie, contained >10% less CBD than advertised), 58% (52 products) were underlabeled (ie, contained >10% more CBD than advertised), and 24% (21 products) were accurately labeled.”

Johnson E, Kilgore M, Babalonis S. Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim. J Cannabis Res. 2022 Jun 6;4(1):28. doi: 10.1186/s42238-022-00140-1. PMID: 35658956; PMCID: PMC9169299.

This study reviewed hemp-derived CBD products collected by the researchers in Central Kentucky.  It concludes that:

 “nearly half of the products in this study were not properly labelled (i.e., not within a ± 10% margin of error). Consumers and practitioners should remain cautious of unregulated and often-mislabeled CBD products due to the risks of taking too much CBD (e.g., drug-drug interactions, liver enzyme elevations, increased side effects) and the consequences of taking too little (e.g., no clinical benefits due to underdosing).“

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