• Effects of Glycemic Control on Dental Implant Stabilization for Patients with Type 2 Diabetes

      Slevin, Terry; Oates, Thomas W. (2017)
      This study evaluated the effects of hyperglycemia on dental implant integration using resonance frequency analysis in 161 patients over a four-month period following placement of two mandibular implants. HbA1c levels were determined at the time of surgery, two and four months following placement. Stability was normalized relative to the change from baseline. Implant stability was analyzed for associations relative to HbA1c categories (<6%, 6.0-7.9%, 8.0-9.9%, 10.0-12.0%). Statistically significant differences were noted with respect to change in RFA relative to HbA1c and time with the poorly controlled group showing the greatest mean decrease in stability (p<0.001). The calculated time for implants to return to baseline levels of stability increased in direct proportion to increasing hyperglycemia, with the poorly controlled group taking twice as long to return to baseline as the control group. This study demonstrates important compromises in implant stabilization in type 2 diabetic patients in direct relation to increasing HbA1c levels consistent with alterations in bone healing for patients with worsening glycemic control.
    • Free and Glucuronidated Cannabinoids, Subjective, Physiological and Psychomotor Effects and In Vitro Cannabinoid Stability Following Controlled Smoked Cannabis Administration

      Schwope, David M.; Huestis, Marilyn (2011)
      Delta9-tetrahydrocannabinol (THC) is the illicit drug most frequently observed in accident and driving under the influence of drugs (DUID) investigations. Whole blood is often the only available specimen collected during such investigations. However, whole blood cannabinoid concentrations (including phase II cannabinoid glucuronide metabolites) and relationships between subjective and psychomotor effects and cannabinoid blood concentrations following cannabis smoking have not been examined. Furthermore, there was no analytical method to investigate whole blood cannabinoid glucuronides directly. Nine male and one female chronic, heavy cannabis smokers resided on a closed research unit and smoked ad libitum one 6.8% THC cannabis cigarette. Whole blood and plasma specimens were collected up to 22 h after smoking. THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide were directly quantified by a new, validated liquid chromatography-tandem mass spectrometry method. Specimens were analyzed within 24 h of collection to obviate stability issues. Assessments were performed before and up to 6 h after smoking, including subjective (visual analog scales [VAS] and Likert scales), physiological (heart rate, blood pressure, respirations) and psychomotor (critical tracking and divided attention tasks) measures. Analytical method linearity (R<super>2</super> ≥ 0.997) ranged from 0.5-50 μg/L (THC-glucuronide), 1.0-100 μg/L (THC, 11-OH-THC, THCCOOH, CBD and CBN) and 5.0-250 μg/L (THCCOOH-glucuronide). Median whole blood (plasma) observed C<sub>max</sub> were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH-THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. CBD and CBN were not detectable after 1 h. THC significantly increased VAS responses and heart rate, with concentration-effect curves demonstrating counter-clockwise hysteresis. No differences were observed for critical tracking or divided attention task performance in this cohort of heavy, chronic cannabis smokers. These are the first authentic human whole blood cannabinoid metabolite data following controlled cannabis smoking. Minor cannabinoids and cannabinoid glucuronide data were evaluated as markers of recent cannabis use. These findings will improve interpretation of whole blood and plasma cannabinoid results, further identification of recent cannabis intake, and inform our understanding of impairment and subjective effects following acute smoked cannabis.
    • Pharmacodynamics, Pharmacokinetics, and Cannabinoid Stability Following Smoked Cannabis in Occasional and Frequent Cannabis Smokers

      Desrosiers, Nathalie Anne; Huestis, Marilyn (2014)
      Cannabis is the most commonly consumed illicit drug worldwide. As few studies characterized differences between occasional and frequent cannabis smokers, we developed a controlled cannabis administration study to investigate pharmacodynamic and pharmacokinetic differences between these groups. Eleven occasional and 14 frequent smokers smoked one 6.8% delta9-tetrahydrocannabinol (THC) cannabis cigarette ad libitum over 10 min. Psychomotor, working memory, risk-taking, subjective, and physiological effects were monitored, and blood, plasma, oral fluid (OF), urine, and breath collected for up to 30 h after smoking. Optimal storage conditions for urinary cannabinoid stability were defined. Draeger DrugTest 5000 onsite OF testing device performance was determined, and a new OF quantification assay for six cannabinoids was developed. Occasional cannabis smokers had increased psychomotor tracking errors and impaired divided attention and reaction time after controlled cannabis smoking, while frequent smokers demonstrated partial tolerance to cannabis' psychomotor effects. Occasional smokers reported longer and more intense subjective effects compared to frequent smokers. Frequent smokers had higher blood and plasma cannabinoid concentrations, even after accounting for residual baseline concentrations. In OF, frequent smokers had significantly longer windows of cannabinoid detection with various screening and confirmation cutoffs. The DrugTest 5000's diagnostic sensitivity, specificity, and efficiency with a 5-µg/L screening cutoff and THC confirmation at 2 µg/L with Quantisal, Statsure and Oral-Eze OF collection devices were 74.0-90.7, 75.0-94.1, and 80.0-87.9%, respectively. Performance varied based on the different analytes included in the confirmation analysis. Frequent smokers had significantly higher urinary THC-glucuronide, 11-nor-9-carboxy-THC (THCCOOH), THCCOOH-glucuronide, and total THCCOOH concentrations than occasional smokers after smoking cannabis, even after normalizing for urinary creatinine concentrations. Frozen storage provided optimal cannabinoid stability in urine, with THC-glucuronide and THCCOOH-glucuronide being stable for up to 6 months. Our new validated method for the analysis of cannabinoids in OF is the most comprehensive method developed to date. Limits of quantification (LOQ) were 15 ng/L for THCCOOH and 0.2 µg/L for THC, 11-hydroxy-THC, tetrahydrocannabivarin, cannabidiol, and cannabigerol. Our data will aid scientists in cannabinoids identification and interpretation in clinical, driving under the influence of cannabis, criminal justice, anti-doping, and workplace drug testing settings and in the development of evidence-based drug policy.