Development and Validation of a GC-FID Method for the Quantitation of 20 Different Acidic and Neutral Cannabinoids.

For decades, Cannabis sativa had been illegal to sell or consume around the world, including in the United States. However, in light of the recent 2018 Farm Bill and the legalization of hemp across the US, various cannabis preparations have flooded the market, making it essential to be able to quantitate the levels of the different acidic and neutral cannabinoids in C. sativa and to have a complete cannabinoid profile of the different chemovars of the cannabis plant. A GC-FID method was developed and validated for the analysis of 20 acidic and neutral cannabinoids as trimethylsilyl (TMS) derivatives. The analyzed cannabinoids include cannabidivarinic acid (CBDVA), cannabidiolic acid (CBDA), cannabinolic acid (CBNA), cannabielsoic acid (CBEA), cannabicyclolic acid (CBLA), cannabichromenic acid (CBCA), trans-Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA), trans-Δ9-tetrahydrocannabinolic acid A (Δ9-THCAA), cannabigerolic acid (CBGA), cannabidiol (CBD), cannabicyclol (CBL), cannabidivarin (CBDV), trans-Δ9-tetrahydrocannabivarin (THCV), cannabichromene (CBC), trans-Δ8-tetrahydrocannabinol (Δ8-THC), trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabigerol (CBG), cannabinol (CBN), cannabicitran (CBT), and cannabielsoin (CBE). The method limit of detection (LOD) was as low as 0.1 µg/mL, while the limit of quantitation ranged from 0.25 µg/mL to 0.5 µg/mL. The precision (%RSD) was < 10%, while trueness ranged from 90 - 107%. The developed method is simple, accurate, and sensitive for the quantitation of all 20 acidic and neutral cannabinoids. Finally, the proposed method was successfully applied to the quantitation of the cannabinoids in different cannabis chemovars grown at the University of Mississippi.

Proteomics-Based Approach for Detailing the Allergenic Profile of Cannabis Chemotypes.

Allergic sensitization to cannabis is an emerging public health concern and is difficult to clinically establish owing to lack of standardized diagnostic approaches. Attempts to develop diagnostic tools were largely hampered by the Schedule I restrictions on cannabis, which limited accessibility for research. Recently, however, hemp was removed from the classified list, and increased accessibility to hemp allows for the evaluation of its practical clinical value for allergy diagnosis. We hypothesized that the proteomic profile is preserved across different cannabis chemotypes and that hemp would be an ideal source of plant material for clinical testing. Using a proteomics-based approach, we examined whether distinct varieties of cannabis plant contain relevant allergens of cannabis. Cannabis extracts were generated from high tetrahydrocannabinol variety (Mx), high cannabidiol variety (V1-19) and mixed profile variety (B5) using a Plant Total Protein Extraction Kit. Hemp extracts were generated using other standardized methods. Protein samples were subjected to nanoscale tandem mass spectrometry. Acquired peptides sequences were examined against the Cannabis sativa database to establish protein identity. Non-specific lipid transfer protein (Can s 3) level was measured using a recently developed ELISA 2.0 assay. Proteomic analysis identified 49 distinct potential allergens in protein extracts from all chemotypes. Most importantly, clinically relevant and validated allergens, such as profilin (Can s 2), Can s 3 and Bet v 1-domain-containing protein 10 (Can s 5), were identified in all chemotypes at label-free quantification (LFP) intensities > 106. However, the oxygen evolving enhancer protein 2 (Can s 4) was not detected in any of the protein samples. Similarly, Can s 2, Can s 3 and Can s 5 peptides were also detected in hemp protein extracts. The validation of these findings using the ELISA 2.0 assay indicated that hemp extract contains 30-37 ng of Can s 3 allergen per µg of total protein. Our proteomic studies indicate that relevant cannabis allergens are consistently expressed across distinct cannabis chemotypes. Further, hemp may serve as an ideal practical substitute for clinical testing, since it expresses most allergens relevant to cannabis sensitization, including the validated major allergen Can s 3.

Effect of Gamma Irradiation on Cannabinoid, Terpene, and Moisture Content of Cannabis Biomass.

In recent years, cannabis has been proposed and promoted not only as a medicine for the treatment of a variety of illnesses, but also as an industrial crop for different purposes. Being an agricultural product, cannabis inflorescences may be contaminated by environmental pathogens at high concentrations, which might cause health problems if not controlled. Therefore, limits have to be placed on the levels of aerobic bacteria as well as yeast and mold. To ensure the safety of cannabis plant material and related products, a remediation process has to be put in place. Gamma irradiation is a sterilization process mainly used for pharmaceuticals, foods, cosmetics, agricultural, and herbal products including cannabis plant material. This study was designed to determine the effect of irradiation on the microbial count as well as on the chemical and physical profiles of the cannabis biomass, particularly cannabinoids, terpenes, and moisture content. The full cannabinoid profile was measured by GC/FID and HPLC analysis, while terpene profile and moisture content were determined using GC/MS and Loss on Drying (LoD) methods, respectively. Analyses were conducted on the samples before and after gamma irradiation. The results showed that the minimum and maximum doses were 15 and 20.8 KiloGray (KGY), respectively. Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) were determined. The study showed that irradiation has no effect on the cannabinoids and little effect on terpenes and moisture content, but it did result in the virtual sterilization of the plant material, as evidenced by the low levels of bacterial and fungal colony-forming units (CFUs) < 10 after gamma irradiation.

Microbial Biotransformation of Cannabidiol (CBD) from Cannabis sativa.

Microbial biotransformation of cannabidiol was assessed using 31 different microorganisms. Only Mucor ramannianus (ATCC 9628), Beauveria bassiana (ATCC 7195), and Absidia glauca (ATCC 22 752) were able to metabolize cannabidiol. M. ramannianus (ATCC 9628) yielded five metabolites, namely, 7,4″ß-dihydroxycannabidiol (1: ), 6ß,4″ß-dihydroxycannabidiol (2: ), 6ß,2″ß-dihydroxycannabidiol (3: ), 6ß,3″α-dihydroxycannabidiol (4: ), and 6ß,7,4″ß-trihydroxycannabidiol (5: ). B. bassiana (ATCC 7195) metabolized cannabidiol to afford six metabolites identified as 7,3″-dihydroxycannabidivarin (6: ), 7-hydroxycannabidivarin-3″-carboxylic acid (7: ), 3″-hydroxycannabidivarin (8: ), 4″ß-hydroxycannabidiol (9: ), and cannabidivarin-3″-carboxylic acid (10: ) along with compound 1: . Incubation of cannabidiol with A. glauca (ATCC 22 752) yielded three metabolites, 6α,3″-dihyroxycannabidivarin (11: ), 6ß,3″-dihyroxycannabidivarin (12: ), and compound 6: . All compounds were evaluated for their antimicrobial and antiprotozoal activity.

Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis.

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C21 terpeno-phenolic compounds specific to Cannabis. The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.

Validating a predictive model of cannabinoid inheritance with feral, clinical, and industrial Cannabis sativa.

PREMISE: How genetic variation within a species affects phytochemical composition is a fundamental question in botany. The ratio of two specialized metabolites in Cannabis sativa, tetrahydrocannabinol (THC) and cannabidiol (CBD), can be grouped into three main classes (THC-type, CBD-type, and intermediate type). We tested a genetic model associating these three groups with functional and nonfunctional alleles of the cannabidiolic acid synthase gene (CBDAS). METHODS: We characterized cannabinoid content and assayed CBDAS genotypes of >300 feral C. sativa plants in Minnesota, United States. We performed a test cross to assess CBDAS inheritance. Twenty clinical cultivars obtained blindly from the National Institute on Drug Abuse and 12 Canadian-certified grain cultivars were also examined. RESULTS: Frequencies of CBD-type, intermediate-type, and THC-type feral plants were 0.88, 0.11, and 0.01, respectively. Although total cannabinoid content varied substantially, the three groupings were perfectly correlated with CBDAS genotypes. Genotype frequencies observed in the test cross were consistent with codominant Mendelian inheritance of the THC:CBD ratio. Despite significant mean differences in total cannabinoid content, CBDAS genotypes blindly predicted the THC:CBD ratio among clinical cultivars, and the same was true for industrial grain cultivars when plants exhibited >0.5% total cannabinoid content. CONCLUSIONS: Our results extend the generality of the inheritance model for THC:CBD to diverse C. sativa accessions and demonstrate that CBDAS genotyping can predict the ratio in a variety of practical applications. Cannabinoid profiles and associated CBDAS segregation patterns suggest that feral C. sativa populations are potentially valuable experimental systems and sources of germplasm.

Correction to: New trends in cannabis potency in USA and Europe during the last decade (2008-2017).

In the original publication, table 2 contained data that should not have been included in table 2 and also was not discussed in the body of the manuscript.

New trends in cannabis potency in USA and Europe during the last decade (2008-2017).

Through the potency monitoring program at the University of Mississippi supported by National Institute on Drug Abuse (NIDA), a total of 18108 samples of cannabis preparations have been analyzed over the last decade, using a validated GC/FID method. The samples are classified as sinsemilla, marijuana, ditchweed, hashish, and hash oil (now referred to as cannabis concentrate). The number of samples received over the last 5 years has decreased dramatically due to the legalization of marijuana either for medical or for recreational purposes in many US states. The results showed that the mean Δ9-THC concentration has increased dramatically over the last 10 years, from 8.9% in 2008 to 17.1% in 2017. The mean Δ9-THC:CBD ratio also rose substantially from 23 in 2008 to 104 in 2017. There was also marked increase in the proportion of hash oil samples (concentrates) seized (0.5-4.7%) and their mean Δ9-THC concentration (6.7-55.7%) from 2008 to 2017. Other potency monitoring programs are also present in several European countries such as The Netherlands, United Kingdom, France, and Italy. These programs have also documented increases in Δ9-THC concentrations and Δ9-THC:CBD ratios in cannabis. These trends in the last decade suggest that cannabis is becoming an increasingly harmful product in the USA and Europe.

Analysis of Terpenes in Cannabis sativa L. Using GC/MS: Method Development, Validation, and Application.

Terpenes are the major components of the essential oils present in various Cannabis sativa L. varieties. These compounds are responsible for the distinctive aromas and flavors. Besides the quantification of the cannabinoids, determination of the terpenes in C. sativa strains could be of importance for the plant selection process. At the University of Mississippi, a GC-MS method has been developed and validated for the quantification of terpenes in cannabis plant material, viz., α-pinene, ß-pinene, ß-myrcene, limonene, terpinolene, linalool, α-terpineol, ß-caryophyllene, α-humulene, and caryophyllene oxide. The method was optimized and fully validated according to AOAC (Association of Official Analytical Chemists) guidelines against reference standards of selected terpenes. Samples were prepared by extraction of the plant material with ethyl acetate containing n-tridecane solution (100 µg/mL) as the internal standard. The concentration-response relationship for all analyzed terpenes using the developed method was linear with r2 values > 0.99. The average recoveries for all terpenes in spiked indoor cultivated samples were between 95.0 - 105.7%, with the exception of terpinolene (67 - 70%). The measured repeatability and intermediate precisions (% relative standard deviation) in all varieties ranged from 0.32 to 8.47%. The limit of detection and limit of quantitation for all targeted terpenes were determined to be 0.25 and 0.75 µg/mL, respectively. The proposed method is highly selective, reliable, and accurate and has been applied to the simultaneous determination of these major terpenes in the C. sativa biomass produced by our facility at the University of Mississippi as well as in confiscated marijuana samples.

Detection and Quantification of Cannabinoids in Extracts of Cannabis sativa Roots Using LC-MS/MS.

A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)-trans-Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans-Δ8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa. Acetonitrile : methanol (80 : 20, v/v) was used for extraction; d3-cannabidiol and d3- tetrahydrocannabinol were used as the internal standards. All 10 cannabinoids showed a good regression relationship with r2 > 0.99. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in extracts of cannabis roots. To our knowledge, this is the first report for the quantification of cannabinoids in cannabis roots.

Determination of Acid and Neutral Cannabinoids in Extracts of Different Strains of Cannabis sativa Using GC-FID.

Cannabis (Cannabis sativa L.) is an annual herbaceous plant that belongs to the family Cannabaceae. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two major phytocannabinoids accounting for over 40% of the cannabis plant extracts, depending on the variety. At the University of Mississippi, different strains of C. sativa, with different concentration ratios of CBD and Δ9-THC, have been tissue cultured via micropropagation and cultivated. A GC-FID method has been developed and validated for the qualitative and quantitative analysis of acid and neutral cannabinoids in C. sativa extracts. The method involves trimethyl silyl derivatization of the extracts. These cannabinoids include tetrahydrocannabivarian, CBD, cannabichromene, trans-Δ8-tetrahydrocannabinol, Δ9-THC, cannabigerol, cannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area ratio with R2 > 0.999 for all 10 cannabinoids. The precision and accuracy of the method were found to be ≤ 15% and ± 5%, respectively. The limit of detection range was 0.11 - 0.19 µg/mL, and the limit of quantitation was 0.34 - 0.56 µg/mL for all 10 cannabinoids. The developed method is simple, sensitive, reproducible, and suitable for the detection and quantitation of acidic and neutral cannabinoids in different extracts of cannabis varieties. The method was applied to the analysis of these cannabinoids in different parts of the micropropagated cannabis plants (buds, leaves, roots, and stems).

Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches.

Accumulating evidence suggests that the endocannabinoid system is a promising target for the treatment of a variety of health conditions. Two paths of cannabinoid drug development have emerged. One approach is focused on developing medications that are directly derived from the cannabis plant. The other utilizes a single molecule approach whereby individual phytocannabinoids or novel cannabinoids with therapeutic potential are identified and synthesized for pharmaceutical development. This commentary discusses the unique challenges and merits of botanical vs single molecule cannabinoid drug development strategies, highlights how both can be impacted by legalization of cannabis via legislative processes, and also addresses regulatory and public health considerations that are important to consider as cannabinoid medicine advances as a discipline.

Cannabis cultivation: Methodological issues for obtaining medical-grade product.

As studies continue to reveal favorable findings for the use of cannabidiol in the management of childhood epilepsy syndromes and other disorders, best practices for the large-scale production of Cannabis are needed for timely product development and research purposes. The processes of two institutions with extensive experience in producing large-scale cannabidiol chemotype Cannabis crops-GW Pharmaceuticals and the University of Mississippi-are described, including breeding, indoor and outdoor growing, harvesting, and extraction methods. Such practices have yielded desirable outcomes in Cannabis breeding and production: GW Pharmaceuticals has a collection of chemotypes dominant in any one of eight cannabinoids, two of which-cannabidiol and cannabidivarin-are supporting epilepsy clinical trial research, whereas in addition to a germplasm bank of high-THC, high-CBD, and intermediate type cannabis varieties, the team at University of Mississippi has established an in vitro propagation protocol for cannabis with no detectable variations in morphologic, physiologic, biochemical, and genetic profiles as compared to the mother plants. Improvements in phytocannabinoid yields and growing efficiency are expected as research continues at these institutions. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Functional identification of valerena-1,10-diene synthase, a terpene synthase catalyzing a unique chemical cascade in the biosynthesis of biologically active sesquiterpenes in Valeriana officinalis.

Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [(13)C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes.

Phosphoric acid loaded azo (-N═N-) based covalent organic framework for proton conduction.

Two new chemically stable functional crystalline covalent organic frameworkds (COFs) (Tp-Azo and Tp-Stb) were synthesized using the Schiff base reaction between triformylphloroglucinol (Tp) and 4,4'-azodianiline (Azo) or 4,4'-diaminostilbene (Stb), respectively. Both COFs show the expected keto-enamine form, and high stability toward boiling water, strong acidic, and basic media. H3PO4 doping in Tp-Azo leads to immobilization of the acid within the porous framework, which facilitates proton conduction in both the hydrous (σ = 9.9 × 10(-4) S cm(-1)) and anhydrous state (σ = 6.7 × 10(-5) S cm(-1)). This report constitutes the first emergence of COFs as proton conducting materials.

Evaluation of dispensaries' cannabis flowers for accuracy of labeling of cannabinoids content.

BACKGROUND: Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis products are marketed in dispensaries in different forms, most abundantly as flowers intended for smoking and sometimes vaping. All samples used in this study were obtained directly from law enforcement. The sample collection process was facilitated and funded by the National Marijuana Initiative (NMI), part of the High-Intensity Drug Trafficking Area (HIDTA) program. This initial report focuses on cannabis flowers. Similar studies with other cannabis products will be the subject of a future report. METHODS: A total of 107 Δ9-THC cannabis flower samples were collected by law enforcement from adult commercial use cannabis dispensaries, located in three different states (Colorado, Oregon, and California) and analyzed in this study for cannabinoid concentration. Samples were analyzed by GC-FID following our previously published procedure. DISCUSSION: The label claims for total Δ9-THC content ranged from 12.04 to 58.20% w/w, while GC-FID results showed a concentration ranging from 12.95 to 36.55% w/w. Of the evaluated 107 products, only 32 samples have Δ9-THC content within ± 20% of the labeled content. However, the remaining 75 samples were found to be out of the ± 20% acceptance criteria. The degree of agreement for the tested samples using ± 20% tolerance with label claims was only 30%. The results of this study indicate that there is a need for more stringent regulations to ensure that product labeling is accurate, as 70% of the evaluated products did not meet the ± 20% acceptance criteria. This highlights the importance of healthcare professionals and patients being vigilant about the Δ9-THC content, as inaccurate labeling of cannabis products could potentially result in adverse health effects. Furthermore, there is a pressing need for more rigorous regulation of commercial cannabis products in the United States.

Mechanochemical synthesis of chemically stable isoreticular covalent organic frameworks.

Three thermally and chemically stable isoreticular covalent organic frameworks (COFs) were synthesized via room-temperature solvent-free mechanochemical grinding. These COFs were successfully compared with their solvothermally synthesized counterparts in all aspects. These solvent-free mechanochemically synthesized COFs have moderate crystallinity with remarkable stability in boiling water, acid (9 N HCl), and base [TpBD (MC) in 3 N NaOH and TpPa-2 (MC) in 9 N NaOH]. Exfoliation of COF layers was simultaneously observed with COF formation during mechanochemical synthesis. The structures thus obtained seemed to have a graphene-like layered morphology (exfoliated layers), unlike the parent COFs synthesized solvothermally.

Chemically stable multilayered covalent organic nanosheets from covalent organic frameworks via mechanical delamination.

A series of five thermally and chemically stable functionalized covalent organic frameworks (COFs), namely, TpPa-NO2, TpPa-F4, TpBD-(NO2)2, TpBD-Me2, and TpBD-(OMe)2 were synthesized by employing the solvothermal aldehyde-amine Schiff base condensation reaction. In order to complete the series, previously reported TpPa-1, TpPa-2, and TpBD have also been synthesized, and altogether, eight COFs were fully characterized through powder X-ray diffraction (PXRD), Fourier transform IR (FT-IR) spectroscopy, (13)C solid-state NMR spectroscopy, and thermogravimetric analysis. These COFs are crystalline, permanently porous, and stable in boiling water, acid (9 N HCl), and base (3 N NaOH). The synthesized COFs (all eight) were successfully delaminated using a simple, safe, and environmentally friendly mechanical grinding route to transform into covalent organic nanosheets (CONs) and were well characterized via transmission electron microscopy and atomic force microscopy. Further PXRD and FT-IR analyses confirm that these CONs retain their structural integrity throughout the delamination process and also remain stable in aqueous, acidic, and basic media like the parent COFs. These exfoliated CONs have graphene-like layered morphology (delaminated layers), unlike the COFs from which they were synthesized.

Characterization of Cannabis sativa allergens.

BACKGROUND: Allergic sensitization to Cannabis sativa is rarely reported, but the increasing consumption of marijuana has resulted in an increase in the number of individuals who become sensitized. To date, little is known about the causal allergens associated with C sativa. OBJECTIVE: To characterize marijuana allergens in different components of the C sativa plant using serum IgE from marijuana sensitized patients. METHODS: Serum samples from 23 patients with a positive skin prick test result to a crude C sativa extract were evaluated. IgE reactivity was variable between patients and C sativa extracts. IgE reactivity to C sativa proteins in Western blots was heterogeneous and ranged from 10 to 70 kDa. Putative allergens derived from 2-dimensional gels were identified. RESULTS: Prominent IgE reactive bands included a 23-kDa oxygen-evolving enhancer protein 2 and a 50-kDa protein identified to be the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. Additional proteins were identified in the proteomic analysis, including those from adenosine triphosphate synthase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and luminal binding protein (heat shock protein 70), suggesting these proteins are potential allergens. Deglycosylation studies helped refine protein allergen identification and demonstrated significant IgE antibodies against plant oligosaccharides that could help explain cross-reactivity. CONCLUSION: Identification and characterization of allergens from C sativa may be helpful in further understanding allergic sensitization to this plant species.

Validation and Quantitation of Fifteen Cannabinoids in Cannabis and Marketed Products Using High-Performance Liquid Chromatography-Ultraviolet/Photodiode Array Method.

Background: Cannabis sativa is a psychoactive plant indigenous to Central and South Asia, traditionally used both for recreational and religious purposes, in addition to folk medicine. Cannabis is a rich source of natural compounds, the most important of which are commonly known as cannabinoids that cause a variety of effects through interaction with the endocannabinoid system. Materials and Methods: In this study, a high-performance liquid chromatography-ultraviolet/photodiode array (PDA) method was developed and validated for the analysis of 15 cannabinoids in cannabis plant materials and cannabis-based marketed products. These cannabinoids are cannabidivarinic acid, cannabidivarin, cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, delta-9-tetrahydrocannabivarin, delta-9-tetrahydrocannabivarinic acid, cannabinol, delta-9-tetrahyrocannabinol, delta-8-tetrahyrocannabinol, cannabicyclol, cannabichromene, delta-9-tetrahyrocannabinolic acid A, and cannabichromenic acid. The separation was carried out using a reversed-phase Luna® C18(2) column and a mobile phase consisting of 75% acetonitrile and 0.1% formic acid in water. A PDA detector was used, and data were extracted at λ=220 nm. Principal component analysis of cannabis four varieties was performed. Results: The method was linear over the calibration range of 5-75 µg/mL with R2>0.999 for all cannabinoids. This method was sensitive and gave good baseline separation of all examined cannabinoids with limits of detection ranging between 0.2 and 1.6 µg/mL and limits of quantification ranging between 0.6 and 4.8 µg/mL. The average recoveries for all cannabinoids were between 81% and 104%. The measured repeatability and intermediate precisions (% relative standard deviation) in all varieties ranged from 0.35% to 9.84% and 1.11% to 5.26%, respectively. Conclusions: The proposed method is sensitive, selective, reproducible, and accurate. It can be applied for the simultaneous determination of these cannabinoids in the C. sativa biomass and cannabis-derived marketed products.