Investigating the phytochemical diversity and anti-inflammatory activity of a non-psychoactive genotype of Cannabis sativa L. from India

Singh M.K., Bhatt D., Singh S., Mishra S., Shankar U., Maurya A., Verma R.K., Tandon S., Chauhan A., Bawankule D.U., Verma R.S.

El Oihabi M., Soultana M., Ammari M., Ben Allal L., Fakih Lanjri A.

Many civilizations are aware of the medical benefits of Cannabis sativa. Due to its intricacy, several plant parts have historically been used in ethnomedicine. This paper reviewed the diversity and variability of chemical composition in Cannabis sativa under the effect of extraction conditions and genetic, geographical, and environmental factors. Equally, we summarized the most relevant environmental uses of Cannabis sativa and its derivatives in relationship to its ecological plasticity and diversity of chemical compounds. Analyzed papers showed that Cannabis sativa is rich in chemical compounds that vary depending on the used parts, genotypes, and geographical and environmental of growth areas.

Raeber J., Poetzsch M., Schmidli A., Favrod S., Steuer C.

AbstractCannabis sativa L. has been the most discussed medicinal plant in recent years. In particular, the dynamic shift from a formerly illicit and tightly controlled substance to a plant recognized for both medicinal and recreational purposes has brought C. sativa into the global spotlight. Due to the ongoing international legalization processes, fast and convenient analytical methods for the quality control of C. sativa flowers for medicinal and recreational purposes are of tremendous interest. In this study, we report the development and validation of a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based method applying atmospheric pressure chemical ionization (APCI) to fully quantify 16 terpenes and 7 cannabinoids including their acidic forms by a single chromatographic method. The method presented here is unique and simple, as it eliminates the need for derivatization reactions and includes the unconventional analysis of volatile compounds by liquid chromatography. Samples were prepared by a simple and fast ethanolic extraction. Separation was accomplished within 25 min on a reversed-phase C18 column. Method validation was conducted according to international guidelines regarding selectivity, accuracy, precision, robustness, and linearity. Detection was done in multiple reaction monitoring, which allowed the simultaneous quantification of co-eluting analytes applying two selective mass transitions. In addition, due to reproducible in-source decarboxylation, the acidic forms of cannabinoids were reliably quantified using mass transitions of the neutral forms. The accuracy given as the bias was below 15% for all analytes. Matrix effects for cannabinoids were studied by spiking Humulus lupulus extracts with the analytes at varying concentrations. APCI did not show susceptibility toward ion suppression or enhancement. In addition, the recovery effect after spiking was between 80 and 120% for terpenes. Further, 55 authentic C. sativa extracts were fully quantified, and the obtained results for the terpene profiles were compared to state-of-the-art gas chromatography coupled to flame ionization detection. Comparable results were achieved, emphasizing the method’s applicability for cannabinoids and terpenes. Further, acquired metabolite patterns for C. sativa samples were studied, identifying a relationship between cannabinoid and terpene patterns, as well as the abundance of myrcene in CBD-dominant C. sativa strains. Graphical Abstract

Hunde Gonfa Y., Beshah Tessema F., Bachheti A., Rai N., Getachew Tadesse M., Nasser Singab A., Kumar Chaubey K., KumarBachheti R.

Plant-based phytochemicals are known for their potential sources of anti-inflammatory agents. Various studies reported the potential disease-healing efficiency of medicinal plants’ crude extracts, pure compounds, and their metal/metal oxide nanoparticles (M/MONPs) against inflammation. The purpose of this paper is to review the current research status of phytochemicals of medicinal plants and their nanoparticles as anti-inflammatory agents reported by various studies. Phytochemicals representing the class of flavonoids, terpenoids, polyphenols, saponins, tannins, alkaloids, anthraquinones, chemical constituents of essential oils, and some of their M/MONPs were reported from about 50 medicinal plants for the treatment of inflammatory diseases. The natural products of these plants demonstrated promising anti-inflammatory activities to treat skin, liver, cardiovascular, joint, gastrointestinal, neurological, and lung inflammation diseases. Besides, the mechanism of anti-inflammatory actions of phytochemicals and their M/MONPs agents are also summarized briefly. Various studies of phytochemistry, M/MONPs, and anti-inflammatory activities of phytochemicals from medicinal plants have developed novel, safe, and lesser side effects agents. Hence, this review may draw the attention of scholars more toward the investigation of natural products of medicinal plants and their nanoparticles in the treatment of different health disorders.

Lapierre É., Monthony A.S., Torkamaneh D.

In the 18th century, Carolus Linnaeus created a formalized system of classification of living organisms based on their anatomic relationships, which we know as taxonomic nomenclature. Historically, the genus Cannabis has been described three ways under this system: Cannabis sativa by C. Linnaeus in 1753, Cannabis indica by J.B. Lamarck in 1785, and Cannabis ruderalis by D.E. Janischewsky in 1924, with these taxonomic classifications having been derived from physical, morphological, chemical, and geographical data. Today, this confusing taxonomy has led to an ongoing debate about whether the genus Cannabis consists of a single species or multiple distinct species or subspecies. Recently, genome sequencing and bioinformatics have provided greater resolution of taxonomic assignments at the species level. As a result, some previously discussed classification frameworks have been brought into question. The aim of this review is to provide a historical context for the confusion surrounding the taxonomy of the genus Cannabis and highlight recent research on genomics-based taxonomical approaches to clarify the question of Cannabis taxonomy. We suggest that the latest evidence shifts away from the previous multiple species framework and points towards the genus Cannabis consisting of a highly diverse monotypic species.

Staben J., Koch M., Reid K., Muckerheide J., Gilman L., McGuinness F., Kiesser S., Oswald I.W., Koby K.A., Martin T.J., Kaplan J.S.

IntroductionCannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD’s potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD’s beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied.MethodsHere, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors.ResultsWe observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends.DiscussionOur results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD.

Giovannoni S., Lancioni C., Vaccarini C., Sedan D., Andrinolo D., Castells C.

Absolute content of terpenes in inflorescences of two strains of Cannabis sativa L., CAT 1 and CAT 3, has been determined. Twenty terpenes commonly present in these samples were quantified by solid phase microextraction combined with gas chromatography and flame ionization detection (SPME/GC-FID). High amounts of β-myrcene, α-pinene, β-pinene, limonene, (E)-β-ocimene, β-caryophyllene, α-humulene, (E)-nerolidol, and linalool, were found in both strains. Lower concentrations (< 20 µg·g-1) of other terpenes were also determined. Only (E)-β-ocimene was detected at 50 µg·g-1 in CAT 3 whereas it was below the LOD in CAT 1. Concentrations of other compounds for which standards were not available, were estimated based on a response factor obtained from the calibration curves of compounds with similar chemical structures. Fingerprints of both CAT strains were obtained and the identities of most volatile compounds were assigned using gas chromatography coupled to mass spectrometer detector (GC-MS). Additionally, an assessment of variability of terpenes was achieved by analyzing ten plants of each strain grown under controlled conditions and harvested at the same time. This variability was about 20%, considering terpenes at concentration above 20 µg·g-1.

Chen C., Pan Z.

• Legal regulations on hemp cannabidiol and terpenes around the world are summarized. • Current status and challenges of adding CBD and terpenes in foods are discussed. • Recent advances and research needs in hemp processing technologies are highlighted. Hemp ( Cannabis Sativa L.) is a broadly grown plant worldwide. In recent years, the cannabidiol (CBD) and terpene species in hemp have drawn increasing research interests due to their human health benefits and pharmaceutical values such as anti-anxiety, pain-relief, relaxation promotion, anti-inflammation and antimicrobial activities. However, the research and application of hemp CBD and terpenes in food systems are scarcely reported, because of various legal regulations, consumer basis and technological challenges. In addition, processing technologies of hemp such as drying, extraction and purification for stable productions of high quality and food-safe CBD and terpene for food purposes have not been extensively studied, lacking thorough reviews. Therefore, in this comprehensive review, the basic characteristics of hemp CBD and terpenes, and their related legal regulations around the world are summarized; the status and technological challenges in the incorporation of hemp CBD and terpenes in food products, and in processing technologies of hemp biomass are identified and discussed; potential solutions, future trends, and research needs are highlighted. The findings from this review may excite more food-related research on hemp processing and CBD/terpenes applications in foods. It can also help the hemp industry to improve the processing efficiency of hemp as a valuable bioresource, and for food manufacturers to shape their paths to use hemp CBD and terpenes as future functional food ingredients.

Zheljazkov V.D., Maggi F.

Hemp (Cannabis sativa L.) synthesizes and accumulates a number of secondary metabolites such as terpenes and cannabinoids. They are mostly deposited as resin into the glandular trichomes occurring on the leaves and, to a major extent, on the flower bracts. In the last few years, hemp for production of high-value chemicals became a major commodity in the U.S. and across the world. The hypothesis was that hemp biomass valorization can be achieved through distillation and procurement of two high-value products: the essential oil (EO) and cannabinoids. Furthermore, the secondary hypothesis was that the distillation process will decarboxylate cannabinoids hence improving cannabinoid composition of extracted hemp biomass. Therefore, this study elucidated the effect of steam distillation on changes in the content and compositional profile of cannabinoids in the extracted biomass. Certified organic CBD-hemp strains (chemovars, varieties) Red Bordeaux, Cherry Wine and Umpqua (flowers and some upper leaves) and a T&H strain that included chopped whole-plant biomass, were subjected to steam distillation, and the EO and cannabinoids profile were analyzed by gas chromatography-mass spectrometry (GC–MS) and HPLC, respectively. The distillation of hemp resulted in apparent decarboxylation and conversion of cannabinoids in the distilled biomass. The study demonstrated a simple method for valorization of CBD-hemp through the production of two high-value chemicals, i.e. EO and cannabinoids with improved profile through the conversion of cannabidiolic acid (CBD-A) into cannabidiol (CBD), cannabichromenic acid (CBC-A) into cannabichromene (CBC), cannabidivarinic acid (CBDV-A) into cannabidivarin (CBDV), cannabigerolic acid (CBG-A) into cannabigerol (CBG), and δ-9-tetrahydrocannabinolic acid (THC-A) into δ-9-tetrahydrocannabinol (THC). In addition, the distilled biomass contained CBN while the non-distilled did not. Distillation improved the cannabinoids profile; e.g. the distilled hemp biomass had 3.4 times higher CBD in variety Red Bordeaux, 5.6 times in Cherry Wine, 9 times in variety Umpqua, and 6 times in T&H compared to the original non-distilled samples, respectively. Most of the cannabinoids remained in the distilled biomass and small amounts of CBD were transferred to the EO. The CBD concentration in the EO was as follows: 5.3% in the EO of Umpqua, 0.15% in the EO of Cherry Wine and Red Bordeaux and 0.06% in the EO of T&H. The main 3 EO constituents were similar but in different ratio; myrcene (23.2%), (E)-caryophyllene (16.7%) and selina-3,7(11)-diene (9.6%) in Cherry Wine; (E)-caryophyllene (~ 20%), myrcene (16.6%), selina-3,7(11)-diene (9.6%), α-humulene (8.0%) in Red Bordeaux; (E)-caryophyllene (18.2%) guaiol (7.0%), 10-epi-γ-eudesmol (6.9%) in Umpqua; and (E)-caryophyllene (30.5%), α-humulene (9.1%), and (E)-α-bisabolene (6.5%) in T&H. In addition, distillation reduced total THC in the distilled biomass. Scanning electron microscopy (SEM) analyses revealed that most of the glandular trichomes in the distilled biomass were not disturbed (remained intact); that suggest a possibility for terpenes evaporation through the epidermal membrane covering the glandular trichomes leaving the cannabinoids in the trichomes. This explained the fact that distillation resulted in terpene extraction while the cannabinoids remained in the distilled material.

Filer C.N.

Introduction:Cannabis is a valuable plant, cultivated by humans for millennia. However, it has only been in the past several decades that biologists have begun to clarify the interesting Cannabis biosynthesis details, especially the production of its fascinating natural products termed acidic cannabinoids. Discussion: Acidic cannabinoids can experience a common organic chemistry reaction known as decarboxylation, transforming them into structural analogues referred to as neutral cannabinoids with far different pharmacology. This review addresses acidic and neutral cannabinoid structural pairs, when and where acidic cannabinoid decarboxylation occurs, the kinetics and mechanism of the decarboxylation reaction as well as possible future directions for this topic. Conclusions: Acidic cannabinoid decarboxylation is a unique transformation that has been increasingly investigated over the past several decades. Understanding how acidic cannabinoid decarboxylation occurs naturally as well as how it can be promoted or prevented during harvesting or storage is important for the various stakeholders in Cannabis cultivation.

Radwan M.M., Chandra S., Gul S., ElSohly M.A.

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.

Lo M., Benfodda Z., Bénimélis D., Fontaine J., Molinié R., Meffre P.

Tillandsia is a genus belonging to the Bromeliaceae family, most of which are epiphytes. The flowers of some of the Tillandsia species are very fragrant, but the volatile composition has been scarcely reported. In this report, we studied the chemical composition of volatile compounds emitted by the flowers of Tillandsia xiphioides using the HS-SPME/GC-MS method. The extraction conditions (fiber, temperature, and time) were optimized using a multivariate approach, and the composition of the extracted volatiles was determined by gas chromatography coupled with mass spectrometry (GC-MS). In total, 30 extracted compounds were identified. Two extraction methods are necessary for the efficient extraction of the volatile compounds. These results were applied to profile two forms of T. xiphioides.

Duggan P.J.

The science of cannabis and cannabinoids encompasses a wide variety of scientific disciplines and can appear daunting to newcomers to the field. The encroachment of folklore and ‘cannabis culture’ into scientific discussions can cloud the situation further. This Primer Review is designed to give a succinct overview of the chemistry of cannabis and cannabinoids. It is hoped that it will provide a useful resource for chemistry undergraduates, postgraduates and their instructors, and experienced chemists who require a comprehensive and up to date summary of the field. The Review begins with a brief overview of the history and botany of cannabis, then goes on to detail important aspects of the chemistry of phytocannabinoids, endocannabinoids and synthetic cannabinomimetics. Other natural constituents of the cannabis plant are then described including terpenes and terpenoids, polyphenolics, alkaloids, waxes and triglycerides, and important toxic contaminants. A discussion of key aspects of the pharmacology associated with cannabinoids and the endocannabinoid system then follows, with a focus on the cannabinoid receptors, CB1 and CB2. The medicinal chemistry of cannabis and cannabinoids is covered, highlighting the range of diseases targeted with cannabis and phytocannabinoids, as well as key aspects of phytocannabinoid metabolism, distribution, and delivery. The modulation of endocannabinoid levels through the inhibition of key endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) is then discussed. The Review concludes with an assessment of the much touted ‘entourage effect’. References to primary literature and more specialised reviews are provided throughout.

Tahir M.N., Shahbazi F., Rondeau-Gagné S., Trant J.F.

Cannabis has been integral to Eurasian civilization for millennia, but a century of prohibition has limited investigation. With spreading legalization, science is pivoting to study the pharmacopeia of the cannabinoids, and a thorough understanding of their biosynthesis is required to engineer strains with specific cannabinoid profiles. This review surveys the biosynthesis and biochemistry of cannabinoids. The pathways and the enzymes’ mechanisms of action are discussed as is the non-enzymatic decarboxylation of the cannabinoic acids. There are still many gaps in our knowledge about the biosynthesis of the cannabinoids, especially for the minor components, and this review highlights the tools and approaches that will be applied to generate an improved understanding and consequent access to these potentially biomedically-relevant materials.

Chiurchiù E., Sampaolesi S., Allegrini P., Ciceri D., Ballini R., Palmieri A.