Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of Cannabis Sativa L. has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping. While this horticultural process is used extensively in the cannabis industry, few studies exist examining the chemical data that may differentiate phenotypes aromatically. To gain insight into the diversity of secondary metabolite profiles between progeny, we analyzed five ice water hash rosin extracts created from five different phenotypes of the same crossing using comprehensive 2-dimensional gas chromatography coupled to time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence detection. These results were then correlated to results from a human sensory panel, which revealed specific low-concentration compounds that strongly influence sensory perception. We found aroma differences between certain phenotypes that are driven by key minor, nonterpenoid compounds, including the newly reported 3-mercaptohexyl hexanoate. We further report the identification of octanoic and decanoic acids, which are implicated in the production of cheese-like aromas in cannabis. These results establish that even genetically similar phenotypes can possess diverse and distinct aromas arising not from the dominant terpenes, but rather from key minor volatile compounds. Moreover, our study underscores the value of detailed chemical analyses in enhancing cannabis selective breeding practices, offering insights into the chemical basis of aroma and sensory differences.

Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis.

Cannabis sativa L. produces a wide variety of volatile secondary metabolites that contribute to its unique aroma. The major volatile constituents include monoterpenes, sesquiterpenes, and their oxygenated derivates. In particular, the compounds ß-myrcene, D-(+)-limonene, ß-caryophyllene, and terpinolene are often found in greatest amounts, which has led to their use in chemotaxonomic classification schemes and legal Cannabis sativa L. product labeling. While these compounds contribute to the characteristic aroma of Cannabis sativa L. and may help differentiate varieties on a broad level, their importance in producing specific aromas is not well understood. Here, we show that across Cannabis sativa L. varieties with divergent aromas, terpene expression remains remarkably similar, indicating their benign contribution to these unique, specific scents. Instead, we found that many minor, nonterpenoid compounds correlate strongly with nonprototypical sweet or savory aromas produced by Cannabis sativa L. Coupling sensory studies to our chemical analysis, we derive correlations between groups of compounds, or in some cases, individual compounds, that produce many of these diverse scents. In particular, we identified a new class of volatile sulfur compounds (VSCs) containing the 3-mercaptohexyl functional group responsible for the distinct citrus aromas in certain varieties and skatole (3-methylindole) as the key source of the chemical aroma in others. Our results provide not only a rich understanding of the chemistry of Cannabis sativa L. but also highlight how the importance of terpenes in the context of the aroma of Cannabis sativa L. has been overemphasized.

Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder.

Introduction: Cannabidiol (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. Methods: Here, 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. Results: We 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. Discussion: Our results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD.

Identification of a New Family of Prenylated Volatile Sulfur Compounds in Cannabis Revealed by Comprehensive Two-Dimensional Gas Chromatography.

Cannabis sativa L. produces over 200 known secondary metabolites that contribute to its distinctive aroma. Studies on compounds traditionally associated with the scent of this plant have focused on those within the terpenoid class. These isoprene-derived compounds are ubiquitous in nature and are the major source of many plant odors. Nonetheless, there is little evidence that they provide the characteristic "skunk-like" aroma of cannabis. To uncover the chemical origins of this scent, we measured the aromatic properties of cannabis flowers and concentrated extracts using comprehensive two-dimensional gas chromatography equipped with time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence. We discovered a new family of volatile sulfur compounds (VSCs) containing the prenyl (3-methylbut-2-en-1-yl) functional group that is responsible for this scent. In particular, the compound 3-methyl-2-butene-1-thiol was identified as the primary odorant. We then conducted an indoor greenhouse experiment to monitor the evolution of these compounds during the plant's lifecycle and throughout the curing process. We found that the concentrations of these compounds increase substantially during the last weeks of the flowering stage, reach a maximum during curing, and then drop after just one week of storage. These results shed light on the chemical origins of the characteristic aroma of cannabis and how volatile sulfur compound production evolves during plant growth. Furthermore, the chemical similarity between this new family of VSCs and those found in garlic (allium sativum) suggests an opportunity to also investigate their potential health benefits.

Chemical and Toxicological Characterization of Vaping Emission Products from Commonly Used Vape Juice Diluents.

Recent reports have linked severe lung injuries and deaths to the use of e-cigarettes and vaping products. Nevertheless, the causal relationship between exposure to vaping emissions and the observed health outcomes remains to be elucidated. Through chemical and toxicological characterization of vaping emission products, this study demonstrates that during vaping processes, changes in chemical composition of several commonly used vape juice diluents (also known as cutting agents) lead to the formation of toxic byproducts, including quinones, carbonyls, esters, and alkyl alcohols. The resulting vaping emission condensates cause inhibited cell proliferation and enhanced cytotoxicity in human airway epithelial cells. Notably, substantial formation of the duroquinone and durohydroquinone redox couple was observed in the vaping emissions from vitamin E acetate, which may be linked to acute oxidative stress and lung injuries reported by previous studies. These findings provide an improved molecular understanding and highlight the significant role of toxic byproducts in vaping-associated health effects.