Plants of the Cannabis genus are the only prolific producers of phytocannabinoids, compounds that strongly interact with the evolutionarily ancient endocannabinoid receptors shared by most bilaterian taxa. For millennia, the plant has been cultivated not only for these compounds, but also for food, rope, paper, and clothing. Today, specialized varieties yielding high-quality textile fibers, nutritional seed oil, or high cannabinoid content are cultivated across the globe. However, the genetic identities and histories of these diverse populations remain largely obscured. We analyzed the nuclear genomic diversity among 340 Cannabis varieties, including fiber and seed oil hemp, high cannabinoid drug-types, and feral populations. These analyses demonstrate the existence of at least three major groups of diversity with European hemp varieties more closely related to narrow leaflet drug-types (NLDTs) than to broad leaflet drug-types (BLDTs). The BLDT group appears to encompass less diversity than the NLDT, which reflects the larger geographic range of NLDTs, and suggests a more recent origin of domestication of the BLDTs. As well as being genetically distinct, hemp, NLDT, and BLDT genetic groups produce unique cannabinoid and terpenoid content profiles. This combined analysis of population genomic and trait variation informs our understanding of the potential uses of different genetic variants for medicine and agriculture, providing valuable insights and tools for a rapidly emerging valuable industry.

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As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA’s varieties contain only 27% of the THC levels and as much as 11–23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets. Investigation is urgently needed on the full diversity of Cannabis chemotypes known to be available to the public.

The kinetics of adsorption at the air/buffer solution interface of amyloid beta peptide, Aβ(1–42), whose bulk concentration (submicromolar) is more than two orders of magnitude lower than that typically used in other in vitro aggregation studies, has been studied using a Langmuir-Blodgett trough. The pressure–time curves exhibit a lag phase, wherein the surface pressure essentially remains at zero, and a rising phase, corresponding to the Aβ adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the Aβ bulk concentration and the solution temperature. A large activation energy (62.2 ± 4.1 KJ/mol) was determined and the apparent adsorption rate constant was found to be linearly dependent on the Aβ bulk concentration. Attenuated total reflection-IR spectra of the adsorbed Aβ transferred to a solid substrate and circular dichroism measurements of Aβ in the solution layer near the interface reveal that the natively unstructured Aβ in the bulk undergo a conformation change (folding) to mainly the α-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between Aβ conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall Aβ adsorption is kinetically controlled and the apparent rate constant is proportional to the Aβ bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate Aβ aggregation/fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial Aβ conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that Aβ fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that Aβ misfolding may occur before its adsorption onto a cell membrane. This general kinetic model should also find applications in adsorption studies of other types of biomolecules whose overall kinetics exhibits a lag phase that is dependent on the bulk concentration of the adsorbate.

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Forest fires produce malodorous phenols, bioaccumulated in grapes as odorless phenol glycosides (mono- to tri-), and produce unpleasant smoke tainted wines when these complexes are transformed by glycosidases in saliva. Metabolomic analyses were used to further understand smoke taint by quantitating marker phenolic diglycosides via UHPLC separations and MS/MS multiple reaction monitoring. A collection of grapes and wines provided data to forecast wine quality of grapes subjected to wildfire smoke infestations; the analytics used a panel of reference compounds ( 1 – 6 ). Overall, eight different Vitis vinifera varietals were examined from 2017–2021 vintages involving >218 distinct samples (wines and/or grapes) from 21 different American Viticulture Areas. Results acquired allowed correlation of phenolic diglycoside levels as a function of grape cultivar, varietal clones, and intensity of wildfire smoke. Baseline data were tabulated for nonsmoked samples (especially, Cabernet Sauvignon having a sum 1 – 6 of <6 μg/L) and then compared to those exposed to six other levels of smoke. Outcomes established that (1) analyzing paired samples (bottled wines versus smoke-exposed grapes) can provide diagnostic metabolomic data, (2) phenolic diglycosides are stable in wines aged for >2.5 years, and (3) major gaps exist in our current understanding of this pool of metabolites.

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25Plants of the Cannabis genus are the only producers of phytocannabinoids, terpenoid 26 compounds that strongly interact with evolutionarily ancient endocannabinoid receptors 27 shared by most bilaterian taxa. For millennia, the plant has been cultivated for these 28 compounds, but also for food, rope, paper, and clothing. Today, specialized varieties 29 yielding high-quality textile fibers, nutritional seed oil or high cannabinoid content are 30 cultivated across the globe. However, the genetic identities and histories of these diverse 31 populations remain largely obscured. We analyzed the nuclear genomic diversity among 32 339 Cannabis varieties, and demonstrate the existence of at least three major groups of 33 diversity. As well as being genetically distinct, each group produces unique cannabinoid 34 and terpenoid content profiles. This combined analysis of population genomic and trait 35 variation informs our understanding of the potential uses of different genetic variants for 36 medicine and agriculture, providing valuable insights and tools for a rapidly emerging, 37 valuable legal industry.38 39