Explore the vast range of titles available.

The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants. Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time. Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores. Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.

Defining cannabinoid stability in authentic oral fluid (OF) is critically important for result interpretation. There are few published OF stability data, and of those available, all employed fortified synthetic OF solutions or elution buffers; none included authentic OF following controlled cannabis smoking. An expectorated OF pool and a pool of OF collected with Quantisal™ devices were prepared for each of 10 participants. Δ⁹-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) stability in each of 10 authentic expectorated and Quantisal-collected OF pools were determined after storage at 4 °C for 1 and 4 weeks and at -20 °C for 4 and 24 weeks. Results within ±20% of baseline concentrations analyzed within 24 h of collection were considered stable. All Quantisal OF cannabinoid concentrations were stable for 1 week at 4 °C. After 4 weeks at 4 °C, as well as 4 and 24 weeks at -20 °C, THC was stable in 90%, 80%, and 80% and THCCOOH in 89%, 40%, and 50% of Quantisal samples, respectively. Cannabinoids in expectorated OF were less stable than in Quantisal samples when refrigerated or frozen. After 4 weeks at 4 and -20 °C, CBD and CBN were stable in 33%-100% of Quantisal and expectorated samples; by 24 weeks at -20 °C, CBD and CBN were stable in ≤ 44%. Cannabinoid OF stability varied by analyte, collection method, and storage duration and temperature, and across participants. OF collection with a device containing an elution/stabilization buffer, sample storage at 4 °C, and analysis within 4 weeks is preferred to maximize result accuracy.

There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆ 9 -tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2–348.5) within 1 h after last smoking, decreasing to 0.1–20.7 (median, 2.1) by 13.0–17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04–245.6) at 0.25 h to 0.12 to 0.17 (0.04–5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3–2.5 (range, 0.1–14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5-1000 ng/patch) and methadone (10-1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000-10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N = 5) and between-run (N = 20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs.

A comprehensive cannabinoid urine quantification method may improve clinical and forensic result interpretation and is necessary to support our clinical research. A liquid chromatography tandem mass spectrometry quantification method for ∆ 9 -tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), ∆ 9 -tetrahydrocannabinolic acid (THCAA), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), ∆ 9 -tetrahydrocannabivarin (THCV), 11-nor-9-carboxy-THCV (THCVCOOH), THC-glucuronide (THC-gluc), and THCCOOH-glucuronide (THCCOOH-gluc) in urine was developed and validated according to the Scientific Working Group on Toxicology guidelines. Sample preparation consisted of disposable pipette extraction (WAX-S) of 200 μL urine. Separation was achieved on a Kinetex C18 column using gradient elution with flow rate 0.5 mL/min, mobile phase A (10 mM ammonium acetate in water), and mobile phase B (15 % methanol in acetonitrile). Total run time was 14 min. Analytes were monitored in both positive and negative ionization modes by scheduled multiple reaction monitoring. Linear ranges were 0.5–100 μg/L for THC and THCCOOH; 0.5–50 μg/L for 11-OH-THC, CBD, CBN, THCAA, and THC-gluc; 1–100 μg/L for CBG, THCV, and THCVCOOH; and 5–500 μg/L for THCCOOH-gluc ( R 2  > 0.99). Analytical biases were 88.3–113.7 %, imprecisions 3.3–14.3 %, extraction efficiencies 42.4–81.5 %, and matrix effect −10 to 32.5 %. We developed and validated a comprehensive, simple, and rapid LC-MS/MS cannabinoid urine method for quantification of 11 cannabinoids and metabolites. This method is being used in a controlled cannabis administration study, investigating urine cannabinoid markers documenting recent cannabis use, chronic frequent smoking, or route of drug administration and potentially improving urine cannabinoid result interpretation.

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. PharmChek sweat patches (n = 682) were worn for periods of 2 h to 1 week during and up to 3 weeks after dosing. The mass of MAMP and AMP in each patch was measured by GC-MS, with a limit of quantification of 2.5 ng/patch. Results: MAMP was measurable in sweat within 2 h of dosing. After low and high doses, 92.9% and 62.5% of weekly sweat patches were positive, with a median (range) MAMP of 63.0 (16.8–175) and 307 (199–607) ng MAMP/patch, respectively; AMP values were 15.5 (6.5–40.5) and 53.8 (34.0–83.4) ng AMP/patch. Patches applied 2 weeks after the drug administration week had no measurable MAMP following the low doses, and only 1 positive result following the high doses. Using criteria proposed by the Substance Abuse Mental Health Services Administration, 85.7% (low) and 62.5% (high) weekly sweat patches from the dosing week were positive for MAMP, and all patches applied after the dosing week were negative. Conclusions: These data characterize the excretion of MAMP and AMP after controlled MAMP administration and provide a framework for interpretation of MAMP sweat test results in clinical and forensic settings.

Oral fluid (OF) is an alternative biological matrix for monitoring cannabis intake in drug testing, and drugged driving (DUID) programs, but OF cannabinoid test interpretation is challenging. Controlled cannabinoid administration studies provide a scientific database for interpreting cannabinoid OF tests. We compared differences in OF cannabinoid concentrations from 19 h before to 30 h after smoking a 6.8 % THC cigarette in chronic frequent and occasional cannabis smokers. OF was collected with the Statsure Saliva Sampler™ OF device. 2D-GC-MS was used to quantify cannabinoids in 357 OF specimens; 65 had inadequate OF volume within 3 h after smoking. All OF specimens were THC-positive for up to 13.5 h after smoking, without significant differences between frequent and occasional smokers over 30 h. Cannabidiol (CBD) and cannabinol (CBN) had short median last detection times (2.5–4 h for CBD and 6–8 h for CBN) in both groups. THCCOOH was detected in 25 and 212 occasional and frequent smokers’ OF samples, respectively. THCCOOH provided longer detection windows than THC in all frequent smokers. As THCCOOH is not present in cannabis smoke, its presence in OF minimizes the potential for false positive results from passive environmental smoke exposure, and can identify oral THC ingestion, while OF THC cannot. THC ≥ 1 μg/L, in addition to CBD ≥ 1 μg/L or CBN ≥ 1 μg/L suggested recent cannabis intake (≤13.5 h), important for DUID cases, whereas THC ≥ 1 μg/L or THC ≥ 2 μg/L cutoffs had longer detection windows (≥30 h), important for workplace testing. THCCOOH windows of detection for chronic, frequent cannabis smokers extended beyond 30 h, while they were shorter (0–24 h) for occasional cannabis smokers.

Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk.

The recent emergence and widespread availability of many new synthetic cannabinoids support the need for an accurate and high-throughput urine screen for these new designer drugs. We evaluated performance of the immunalysis homogeneous enzyme immunoassay (HEIA) to sensitively, selectively, and rapidly identify urinary synthetic cannabinoids. 2443 authentic urine samples were analyzed with the HEIA that targets JWH-018 N-pentanoic acid, and a validated LC–MS/MS method for 29 synthetic cannabinoids and metabolites. Semi-quantitative HEIA results were obtained, permitting performance evaluation at and around three cutoffs (5, 10 and 20 μg/L), and diagnostic sensitivity, specificity and efficiency determination. Performance challenges at ±25 and ±50% of each cutoff level, cross-reactivity and interferences also were evaluated. Sensitivity, specificity, and efficiency of the immunalysis HEIA K2 Spice kit with the manufacturer’s recommended 10 μg/L cutoff were 75.6%, 99.6% and 96.8%, respectively, as compared to the reference LC–MS/MS method with limits of detection of 0.1–10 μg/L. Performance at 5 μg/L was 92.2%, 98.1% and 97.4%, and for the 20 μg/L cutoff were 62.9%, 99.7% and 95.4%. Semi-quantitative results for in-house prepared standards were obtained from 2.5–30 μg/L, and documented acceptable linearity from 5–25 μg/L, with inter-day imprecision <30% (n = 17). Thirteen of 74 synthetic cannabinoids evaluated were classified as highly cross-reactive (≥50% at 10 μg/L); 4 showed moderate cross-reactivity (10–50% at 10 μg/L), 30 low cross-reactivity (<10% at 500 μg/L), and 27 <1% cross-reactivity at 500 μg/L. There was no interference from 102 investigated compounds. Only a mixture containing 1000 μg/L each of buprenorphine/norbuprenorphine produced a positive result above our proposed cutoff (5 μg/L) but below the manufacturer’s recommended cutoff concentration (10 μg/L). The Immunalysis HEIA K2 Spice kit required no sample preparation, had a high-throughput, and acceptable sensitivity, specificity and efficiency, offering a viable method for screening synthetic cannabinoids in urine that cross-react with JWH-018 N-pentanoic acid antibodies.