Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

Background And Objectives: Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers.

Tolerance to effects of high-dose oral δ9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers.

Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

Background: Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio.

Oral fluid and plasma cannabinoid ratios after around-the-clock controlled oral Δ(9)-tetrahydrocannabinol administration.

Background: Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies.

Methods: Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ(9)-tetrahydrocannabinol (THC, dronabinol) doses (40-120 mg/day) for 8 days.

Antagonist-elicited cannabis withdrawal in humans.

Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered.

CB1 - cannabinoid receptor antagonist effects on cortisol in cannabis-dependent men.

Background: The endocannabinoid system modulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effect of cannabinoid type 1 (CB1) receptor antagonism following chronic CB1 receptor stimulation in humans is unknown.

Objectives: To evaluate effects of the CB1 receptor antagonist rimonabant on the HPA axis in cannabis-dependent individuals.

Methods: Fourteen daily cannabis smokers received increasingly frequent 20 mg oral Δ9-tetrahydrocannabinol (THC) doses (60-120 mg/day) over 8 days to standardize cannabis tolerance.

Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH).

Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users.

Aims: To develop and validate empirically 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.

Disposition of cannabinoids in oral fluid after controlled around-the-clock oral THC administration.

Background: Oral fluid, a promising alternative matrix for drug monitoring in clinical and forensic investigations, offers noninvasive sample collection under direct observation. Cannabinoid distribution into oral fluid is complex and incompletely characterized due to the lack of controlled drug administration studies.

Methods: To characterize cannabinoid disposition in oral fluid, we administered around-the-clock oral Delta(9)-tetrahydrocannabinol (THC) (Marinol) doses to 10 participants with current daily cannabis use.

Implications of plasma Delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers.

Delta(9)-Tetrahydrocannabinol (THC) is commonly found in toxicological specimens from driving under the influence and accident investigations. Plasma cannabinoid concentrations were determined in 18 long-term heavy cannabis smokers residing on an in-patient research unit for seven days of monitored abstinence. THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) were quantified by two-dimensional gas chromatography-mass spectrometry with cryofocusing.

Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC.

Background: Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis and an active cannabinoid pharmacotherapy component. No plasma pharmacokinetic data after repeated oral THC administration are available.

Methods: Six adult male daily cannabis smokers resided on a closed clinical research unit.

Do Delta9-tetrahydrocannabinol concentrations indicate recent use in chronic cannabis users?

Aims: To quantify blood Delta(9)-tetrahydrocannabinol (THC) concentrations in chronic cannabis users over 7 days of continuous monitored abstinence.

Participants: Twenty-five frequent, long-term cannabis users resided on a secure clinical research unit at the US National Institute on Drug Abuse under continuous medical surveillance to prevent cannabis self-administration.

Measurements: Whole blood cannabinoid concentrations were determined by two-dimensional gas chromatography-mass spectrometry.

Intra- and intersubject whole blood/plasma cannabinoid ratios determined by 2-dimensional, electron impact GC-MS with cryofocusing.

Background: Whole-blood concentrations of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) are approximately half of those in plasma due to high plasma protein binding and poor cannabinoid distribution into erythrocytes. Whole blood is frequently the only specimen available in forensic investigations; controlled cannabinoid administration studies provide scientific data for interpretation of cannabinoid tests but usually report plasma concentrations. Whole-blood/plasma cannabinoid ratios from simultaneously collected authentic specimens are rarely reported.

Excretion of methamphetamine and amphetamine in human sweat following controlled oral methamphetamine administration.

Background: Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is important for interpreting sweat and hair testing results in judicial, workplace, and drug treatment settings.

Methods: Participants (n = 8) received 4 10-mg (low) oral doses of sustained-release S-(+)-MAMP HCl (d-MAMP HCl) within 1 week in a double-blind, institutional review board-approved study. Five participants also received 4 20-mg (high) doses 3 weeks later.

Simultaneous quantification of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry.

A two-dimensional (2D) gas chromatography/electron impact-mass spectrometry (GC/EI-MS) method for simultaneous quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in human plasma was developed and validated. The method employs 2D capillary GC and cryofocusing for enhanced resolution and sensitivity. THC, 11-OH-THC, and THCCOOH were extracted by precipitation with acetonitrile followed by solid-phase extraction.

Changing patterns of drug and alcohol use in fatally injured drivers in Washington State.

We have previously reported on patterns of drug and alcohol use in fatally injured drivers in Washington State. Here we revisit that population to examine how drug use patterns have changed in the intervening 9 years. Blood and serum specimens from drivers who died within 4 h of a traffic accident between February 1, 2001, and January 31, 2002, were analyzed for illicit and therapeutic drugs and alcohol.

Opioid disposition in human sweat after controlled oral codeine administration.

Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs.

Methods: Participants (n=20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek Sweat Patches; hourly patches were applied for 1 to 15 h (n=775) and weekly patches for 7 days (n=118).

Disposition of cocaine and its metabolites in human sweat after controlled cocaine administration.

Background: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings.

Methods: We evaluated cocaine excretion in 9 participants' sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study.