All the samples of D8 and D9-THCP were toxic to lung cells:
The Impact of Hemp Derived Cannabinoid Potency from Consumer Product Goods on in vitro Lung and Liver Cells
“Abstract
Background: The surge in the popularity of cannabis has led to an increase in the number of companies producing hemp-derived consumable cannabinoid products. Despite extensive exploration of cannabinoid efficacy, safety remains underreported. Any contaminants that are not deemed analytes of interest are ignored, leaving their identities and safety profiles a mystery. The unregulated nature of the cannabinoid market places the onus on reputable companies to set industry standards for product cleanliness.
Objective: This study aimed to address this gap by assessing high and low potency forms of three popular hemp-derived cannabinoids – Delta 8-tetrahydrocannabinol (Δ8-THC), Hexahydrocannabinol (HHC), and Delta 9-tetrahydrocannabiphorol (Δ9-THCP).
Methods: After identifying contaminants, the products were evaluated for toxicity in vitro using one liver and two lung cell lines in an effort to simulate the effects of oral consumption and inhalation.
Results: Our study revealed that none of the compounds exhibited toxicity in the liver cell line, while all of the compounds exhibited toxicity in both of the lung cell lines – with the exception of one high-potency HHC sample.
Conclusion: These findings highlight the critical need for stringent quality control in the cannabinoid industry, emphasizing the importance for both companies and consumers to prioritize clean, well-tested products to ensure safety in an increasingly unregulated market.
Discussion
Δ8-THC and Δ9-THCP are synthetically obtained through intramolecular cyclization of CBD and CBDP in the presence of an acid and solvent. During this reaction, different THC isomers are generated, as shown in Figure 3. On the other hand, HHC is obtained via hydrogenation of Δ9-THC or Δ8-THC. These isomers are found in THC commercial products.
The in vitro data did not indicate that low- and high-potency cannabinoid products would differ in their toxicity to lung or liver cells. None of the compounds were toxic to the THLE-3 line, while all of the compounds were toxic to both the HLF and HSAEC lines, with the exception of WC-16, a high-potency HHC sample, in the HLF cell line. WC-16 was also an outlier in the other two cell lines. It had no common contaminant shared with the other samples tested. All other samples shared common minor cannabinoid contaminants. The contaminants found within WC-16 could be causing a protective or null effect, reducing cytotoxicity of the sample to the tested cell lines. Further investigations are being actively conducted, and further characterization is needed to identify whether cannabinoid contaminants can be helpful or therapeutic, in the sense that they may exhibit protective effects or lessen the effects of the tested major cannabinoids’ toxicity.32
This study has potential limitations. Both the HSAEC and the HLF cells were chosen to simulate smoking, mimicking the possible interactions that the compounds might impose when absorbed through the upper respiratory tract. The THLE-3 cells were chosen to simulate oral consumption, mimicking the possible implications that the compounds might impose on the liver. Testing various other cells would diversify screening. All statistical limits were tested on cells seeded with proper cell density and run in triplicate at various concentrations. SI Figures 20 and 21 are statistical analyses of the plated cells with varied concentrations, and IC50 values generated from study, respectively. Further experimentation is needed to identify the impact of cannabinoid potency. Our group plans to run experiments using in vivo methodology (lab-on-a-chip, rat model, etc) to see the impact of varying potency on lung and liver models.
Conclusion
This research underscores the critical need for rigorous scientific inquiry into the safety profile of various cannabinoids, including the identification of a myriad of byproducts that result from the synthesis process, and the safety testing that both consumer-ready products and individual contaminants need to undergo.
This inquiry highlights the complexities surrounding cannabinoid safety, emphasizing the importance of considering the possible impurities in the cannabinoid products and how they affect the toxicity of these compounds in a biological system. The presence of understudied cannabinoid contaminants represent a potential risk to users due to their lack of thorough pharmacological characterization. This lack of understanding could lead to unforeseen levels of intoxication and underscores the importance of further research into these compounds’ effects.
Moving forward, continued scientific investigation is imperative to ensure the safe and responsible utilization of hemp derived cannabinoids for medicinal and recreational purposes, while mitigating potential risks to individual and public health, as limited studies are available with more to be conducted in the future.”
Read the study at: https://journals.sagepub.com/doi/epub/10.1177/1934578X241299497