Considerations in assessing the abuse potential of psychedelics during drug development.

The recent increase in clinical research on the potential therapeutic uses of classic psychedelics has prompted the need to revisit the assessment of the abuse potential of these drugs. The term "classic psychedelic" is used in this manuscript to describe serotonergic 5-HT2A agonists that alter perception, cognition, and mood (i.e., psychedelic effects) and that are currently controlled in Schedule I of the Controlled Substances Act (CSA). Schedule I drugs are subject to the most restrictive controls under the CSA, as they are considered to have a high abuse potential and no currently accepted medical use in the United States (USA). However, these classic psychedelics were placed in Schedule I at the time the CSA was enacted in 1970, and their abuse potential has not been systematically assessed using modern methodology. This paper provides an overview of scientific evaluation of the abuse potential of classic psychedelics and delineates the data that will be needed in support of a recommendation for the rescheduling, if a drug product containing a classic psychedelic gains FDA approval. This article is part of the Special Issue on 'National Institutes of Health Psilocybin Research Speaker Series'.

CD10 immunohistochemistry stains enteric mucosa, but negative staining is unreliable in the setting of active enteritis.

Ileal pouch-anal anastomosis is the definitive therapy for ulcerative colitis that is refractory to medical treatment or that has developed neoplasia. Patients with this procedure are routinely followed using directed endoscopic biopsies to monitor for dysplasia in the rectal cuff, residual/recurrent ulcerative colitis, and nonspecific acute inflammation of the ileal pouch (pouchitis), which have different clinical management and outcomes. Thus, accurate localization of mucosal biopsies is crucial to a definitive histological diagnosis, but is complicated by overlapping clinical presentations of pouchitis and ulcerative colitis, post-surgical and inflammatory changes to the mucosa, and altered endoscopic anatomy, resulting in difficulty determining whether a mucosal biopsy is ileal or rectal in origin for both the endoscopist and the pathologist. We explored the utility of CD10 immunohistochemistry to aid diagnosis in this clinical setting by highlighting the enteric mucosa, based on previous studies showing its utility in brush border staining and in the diagnosis of microvillous inclusion disease. We found uniformly positive CD10 immunostaining in normal enteric mucosa, but variable loss of expression in the setting of active enteritis. Specifically, CD10 staining was lost in up to 10% of the mucosa in 1/12 ileostomies and 4/13 enteric anastomoses, in 10-80% of the mucosa in 9/10 cases of Crohn's ileitis, in 10-60% of the mucosa in 7/16 ileal pouches, and in 20-90% of the mucosa in 6/8 cases of backwash ileitis, usually in the presence of active inflammation. There was no CD10 expression by normal or diseased colonic mucosa. Therefore, while CD10 immunostaining identifies normal enteric mucosa with 100% specificity, negative staining does not definitively exclude small intestinal mucosa in the setting of active enteritis, a common condition in ileal pouch mucosa.

Extra-gastrointestinal stromal tumor of the pancreas: case report and a review of the literature.

Gastrointestinal (GI) stromal tumors are mesenchymal tumors that arise from the GI tract. In rare cases, these tumors are found in intra-abdominal sites unrelated to the GI tract and are immunohistochemically similar to their GI tract counterparts. Primary pancreatic GI stromal tumors are very rare, with only 4 previous cases reported.