Accumulation of bioactive metabolites in cultivated medical Cannabis

Richins, Richard D.; Rodriguez‐Uribe, Laura; Lowe, Kiah; Ferral, Rebekah; O’Connell, Mary A.

doi:10.1371/journal.pone.0201119

Cited by 84 publications

(81 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The enzymatic machinery of the plant cultivars do dictate terpene formation to a large degree (Table 3). Our data suggest that in some cases there were abnormally high total terpene concentrations in some products which are likely due to manufacturers "spiking" products with terpenes to either provide some natural medicinal properties that have been attributed to terpenes, 28,29 or to enhance the aroma, thereby misleading the consumer into thinking that the product was highly enriched with cannabinoids, despite phytocannabinoids having no scent or flavor.…”

Section: Discussionmentioning

confidence: 91%

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

Wakshlag¹,

Cital²,

Eaton³

et al. 2020

VMRR

View full text Add to dashboard Cite

Purpose: The use of veterinary low tetrahydrocannabinol (THC) Cannabis sativa (ie, hemp) products has increased in popularity for a variety of pet ailments. Low-THC Cannabis sativa is federally legal for sale and distribution in the USA, and the rise in internet commerce has provided access to interested consumers, with minimal quality control. Materials and Methods: We performed an internet word search of "hemp extract and dog" or "CBD product and dog" and analyzed 29 products that were using low-THC Cannabis sativa extracts in their production of supplements. All products were tested for major cannabinoids including cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), cannabigerol (CBG), and other minor cannabinoids, as well as their carboxylic acid derivatives (CBDA, THCA, CBGA) using an ISO/IEC 17025 certified laboratory. Products were also tested for major terpenes and heavy metals to understand constituents in the hemp plants being extracted and distributed. Results: All products were below the federal limit of 0.3% THC with variable amounts of CBD (0-88 mg/mL or g). Only two products did not supply a CBD or total cannabinoid concentration on their packaging or website, while 22/29 could supply a certificate of analysis (COA) from a third-party laboratory. Ten of the 27 products were within 10% of the total cannabinoid concentrations of their label claim with a median concentration of 93% of claims (0-154%). Heavy metal contamination was found in 4/29 products, with lead being the most prevalent contaminant (3/29). Conclusion: The products analyzed had highly variable concentrations of CBD or total cannabinoids with only 18 of 29 being appropriately labeled according to current FDA nonmedication, non-dietary supplement or non-food guidelines. Owners and veterinarians wanting to utilize CBD-rich Cannabis sativa products should be aware of low-concentration products and should obtain a COA enabling them to fully discuss the implications of use and calculated dosing before administering to pets.

show abstract

Section: Discussionmentioning

confidence: 91%

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

Wakshlag¹,

Cital²,

Eaton³

et al. 2020

VMRR

View full text Add to dashboard Cite

show abstract

“…4). Several authors have advocated the profiling of both cannabinoids and terpenoids in recent publications (Fischedick et al, 2010;Elzinga et al, 2015;Aizpurua-Olaizola et al, 2016;Hazekamp et al, 2016;Fischedick, 2017;Lewis et al, 2018;Orser et al, 2018;Richins et al, 2018;Sexton et al, 2018). The key advantage of this approach over merely profiling cannabinoids lies in the enormous diversity of terpenoids accumulated in cannabis (and in other plants as well), which significantly increases the power of statistical analyses.…”

Section: Utility Of Metabolite Profiling For Strain Differentiationmentioning

confidence: 99%

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

et al. 2019

View full text Add to dashboard Cite

Glandular trichomes are specialized anatomical structures that accumulate secretions with important biological roles in plantenvironment interactions. These secretions also have commercial uses in the flavor, fragrance, and pharmaceutical industries. The capitate-stalked glandular trichomes of Cannabis sativa (cannabis), situated on the surfaces of the bracts of the female flowers, are the primary site for the biosynthesis and storage of resins rich in cannabinoids and terpenoids. In this study, we profiled nine commercial cannabis strains with purportedly different attributes, such as taste, color, smell, and genetic origin. Glandular trichomes were isolated from each of these strains, and cell type-specific transcriptome data sets were acquired. Cannabinoids and terpenoids were quantified in flower buds. Statistical analyses indicated that these data sets enable the high-resolution differentiation of strains by providing complementary information. Integrative analyses revealed a coexpression network of genes involved in the biosynthesis of both cannabinoids and terpenoids from imported precursors. Terpene synthase genes involved in the biosynthesis of the major monoterpenes and sesquiterpenes routinely assayed by cannabis testing laboratories were identified and functionally evaluated. In addition to cloning variants of previously characterized genes, specifically CsTPS14CT [(2)-limonene synthase] and CsTPS15CT (b-myrcene synthase), we functionally evaluated genes that encode enzymes with activities not previously described in cannabis, namely CsTPS18VF and CsTPS19BL (nerolidol/linalool synthases), CsTPS16CC (germacrene B synthase), and CsTPS20CT (hedycaryol synthase). This study lays the groundwork for developing a better understanding of the complex chemistry and biochemistry underlying resin accumulation across commercial cannabis strains.

show abstract

“…Finally, future work could examine a broader profile of chemical profile contents including the missing cannabinoids and terpene data to allow for calculation of these inferences using ensemble effects which have become a popular analysis method [30]. Additionally, terpenoid compounds may be more information rich better in clustering the range of diverse Cannabis varieties [29,30], but perhaps a better approach would be a combined analysis of both cannabinoids and terpenoids [12,27] from multiple testing facilities.…”

Section: Plos Onementioning

confidence: 99%

Modeling cannabinoids from a large-scale sample of Cannabis sativa chemotypes

et al. 2020

View full text Add to dashboard Cite

The widespread legalization of Cannabis has opened the industry to using contemporary analytical techniques for chemotype analysis. Chemotypic data has been collected on a large variety of oil profiles inherent to the cultivars that are commercially available. The unknown gene regulation and pharmacokinetics of dozens of cannabinoids offer opportunities of high interest in pharmacology research. Retailers in many medical and recreational jurisdictions are typically required to report chemical concentrations of at least some cannabinoids. Commercial cannabis laboratories have collected large chemotype datasets of diverse Cannabis cultivars. In this work a data set of 17,600 cultivars tested by Steep Hill Inc., is examined using machine learning techniques to interpolate missing chemotype observations and cluster cultivars into groups based on chemotype similarity. The results indicate cultivars cluster based on their chemotypes, and that some imputation methods work better than others at grouping these cultivars based on chemotypic identity. Due to the missing data and to the low signal to noise ratio for some less common cannabinoids, their behavior could not be accurately predicted. These findings have implications for characterizing complex interactions in cannabinoid biosynthesis and improving phenotypical classification of Cannabis cultivars.

show abstract

Accumulation of bioactive metabolites in cultivated medical Cannabis

Cited by 84 publications

References 39 publications

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

Modeling cannabinoids from a large-scale sample of Cannabis sativa chemotypes

Contact Info

Product

Resources

About