• Building a Scientific Basis for Oral Fluid Cannabinoid Testing; Cannabinoid Disposition in Oral Fluid Following Smoked Cannabis, Oral Delta-9-tetrahydrocannabinol (THC), and Sativex® and During Extended Cannabis Abstinence

      Lee, Dayong; Huestis, Marilyn (2013)
      Oral fluid (OF) testing offers simple, non-invasive and observable sample collection. Cannabinoids are usually the most prevalent analytes in illicit drug testing. Thus, scientific data are required to document sensitive and specific cannabinoids detection in OF if this technology is to be accepted for drug monitoring. The NIDA Chemistry and Drug Metabolism Section developed multiple clinical protocols to evaluate OF cannabinoid disposition during extended abstinence and following smoked cannabis, oral THC, and Sativex® (oromucosal spray containing approximately 1:1 THC and cannabidiol [CBD]). During extended abstinence, median THC and 11-nor-9-carboxy-THC (THCCOOH) detection windows were 24 h and 13 days, respectively, in chronic cannabis smokers; CBD and cannabinol (CBN) were detected only on admission. After a single smoked 6.8% THC cigarette, THC concentrations were 10-fold higher than CBD and CBN concentrations. Cannabinoids rapidly declined within 3 h; THCCOOH showed a more delayed elimination pattern. After single and multiple oral THC doses, parent cannabinoid concentrations reflected residual excretion from previous self-administered smoked cannabis, whereas THCCOOH concentrations were influenced by oral THC dose regimen. Conversely, parent cannabinoid concentrations were highly increased after Sativex, with CBD concentrations as high as THC's, distinguishing Sativex intake from smoked cannabis. Different cannabinoids had distinct elimination profiles and detection windows, which were influenced by administration route, dose, and prior drug intake history. Quantification of multiple cannabinoids is useful for establishing cutoff criteria for different drug testing programs; CBD and CBN may identify recent intake, while THCCOOH minimizes the potential for false positive results due to passive environmental exposure. Dry mouth, bloody OF samples, and OF cannabinoid stability may influence accurate cannabinoid quantification and should be controlled. OF/plasma cannabinoid ratios exhibited large inter-subject variability after smoking and during oral THC dosing, precluding blood concentration prediction from OF concentrations. There was a possible association among OF cannabinoids, smoking behavior, and cannabis tolerance/withdrawal/residual drug effects, suggesting that OF testing could be valuable for monitoring in cannabis dependence treatment programs. The present research provides an important body of data on cannabinoid OF disposition, improving interpretation of cannabinoid OF test results, formulating evidence-based drug control policy, and managing cannabinoid pharmacotherapy.
    • The Role of pH in Patients Receiving Long Term Bisphosphonate Therapy

      Alhouli, Munawer; Meiller, Timothy F. (2013)
      Purpose: Bisphosphonate (BP)-associated osteonecrosis of the jaw (BON) lacks a defined pathophysiologic mechanism and treatment regimen. This current study was designed to be part of a parent BON pathogenesis series of protocols to investigate the contributing factors of causation. The following hypothesis was tested: Subjects receiving long term bisphosphonate therapy that have developed BON have a more acidic oral environment i.e. as measured by salivary pH than normal (no BP exposure) subjects and those receiving long term bisphosphonate therapy that have not developed BON. This study assessed the pH of saliva in subjects receiving long term bisphosphonate therapy so that possible oral buffers could eventually be developed and investigated as possible treatments i.e. to reduce the acidic effects BPs such as zoledronic acid (ZA) have in BON wound healing. Methods: Using the fully IRB approved HIPAA partial waiver for recruitment, subjects were selected based on history and physical examination in order to document previous and/or current use of bisphosphonates. Standard of care physical examination was used to determine the presence or absence of BON lesions intraorally. As part of a fully IRB approved protocol the informed consent process was used and for those willing to participate and having signed the consent document, we collected the single sample of saliva. We employed these ex-vivo studies using pH measurement on ~5 ml of fresh unstimulated whole saliva collected over a 5 minute time period at this single visit. Results: Ex-vivo, we have shown in this study that patients with active lesions of BON have more acidic saliva as compared to those without BON or in those not taking a BP. Conclusion: These findings suggest that acidic salivary pH is directly associated with BON, may play a role in the initiation and prolongation of oral BON and may eventually support the potential role of using salivary buffers to offset acidic saliva as an adjunct therapeutic treatment for BON, specifically to speed wound healing.