Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets.

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.

Novel structural components of the ventral disc and lateral crest in Giardia intestinalis.

Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP) with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment.