Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

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The time course of 11-nor-9-carboxy-Δ9-tetrahydrocannnabinol (THCCOOH) elimination in urine was characterized in 60 cannabis users during 24 h monitored abstinence on a closed research unit for up to 30 days. 6158 individual urine specimens were screened by immunoassay with values ≥50 ng/mL classified as positive. Urine specimens were confirmed for THCCOOH by gas chromatography/mass spectrometry following base hydrolysis and liquid-liquid or solid phase extraction. In 60%, the maximum creatinine normalized concentration occurred in the first urine specimen; in 40%, peaks occurred as long as 2.9 days after admission. Data were divided into three groups, 0 – 50, 51 – 150, and >150 ng/mg, based on the creatinine corrected initial THCCOOH concentration. There were statistically significant correlations between groups and number of days until first negative and last positive urine specimens; mean number of days were 0.6 and 4.3, 3.2 and 9.7, and 4.7 and 15.4 days respectively, for the three groups. These data provide guidelines for interpreting urine cannabinoid test results and suggest appropriate detection windows for differentiating new cannabis use from residual drug excretion.

AIMS To develop and empirically validate a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers. DESIGN Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers. SETTING For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days. PARTICIPANTS 48 (model development) and 67 (model validation) daily cannabis smokers were recruited. MEASUREMENTS All voided urine was collected and analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS, limit of quantification 2.5 ng/mL) and creatinine (mg/mL). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123,513 specimen pairs collected 2–30 days apart. FINDINGS A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns. CONCLUSIONS For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual CN-THCCOOH excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists, drug treatment staff, and workplace, military and criminal justice drug testing programs.

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

delta-9-Tetrahydrocannabinol (THC) kinetics and dynamics of self-reported psychologic "high" effect are analyzed in six subjects who smoked marijuana cigarettes of three different potencies. Correlation of the pharmacologic response to smoking a marijuana cigarette with plasma THC levels was done with compartmental models and phase plots. It was concluded that the effect compartment for psychologic high is directly coupled to the central (plasma) compartment. It was observed that effect is directly proportional to mean THC levels from approximately 1 to 4 hr after the start of smoking a marijuana cigarette.

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