Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used. The purpose of this systematic review is to summarize the data characterizing the potential for these compounds to act as substrates, inhibitors, or inducers of human drug metabolizing enzymes, with the aim of clarifying the significance of these properties in clinical care and drug interactions. In vitro data were identified that characterize cytochrome P-450 (CYP-450) enzymes as potential significant contributors to the primary metabolism of several exogenous cannabinoids: tetrahydrocannabinol (THC; CYPs 2C9, 3A4); cannabidiol (CBD; CYPs 2C19, 3A4); cannabinol (CBN; CYPs 2C9, 3A4); JWH-018 (CYPs 1A2, 2C9); and AM2201 (CYPs 1A2, 2C9). CYP-450 enzymes may also contribute to the secondary metabolism of THC, and UDP-glucuronosyltransferases have been identified as capable of catalyzing both primary (CBD, CBN) and secondary (THC, JWH-018, JWH-073) cannabinoid metabolism. Clinical pharmacogenetic data...

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Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Background and aims
The full burden of the opioid epidemic on US hospitals has not been described. We aimed to estimate how heroin (HOD) and prescription opioid (POD) overdose-associated admissions, costs, outcomes and patient characteristics have changed from 2001 to 2012.

Design
Retrospective cohort study of hospital admissions from the National Inpatient Sample (NIS).

Setting
United States of America.

Participants
Hospital admissions in patients aged 18 years or older admitted with a diagnosis of HOD or POD. The NIS sample included 94 492 438 admissions from 2001 to 2012. The final unweighted study sample included 138 610 admissions (POD: 122 147 and HOD: 16 463).

Measurements
Primary outcomes were rates of admissions per 100 000 people using US Census Bureau annual estimates. Other outcomes included in-patient mortality, hospital length-of-stay, cumulative and mean hospital costs and patient demographics. All analyses were weighted to provide national estimates.

Findings
Between 2001 and 2012, an estimated 663 715 POD and HOD admissions occurred nation-wide. HOD admissions increased 0.11 per 100 000 people per year [95% confidence interval (CI) = 0.04, 0.17], while POD admissions increased 1.25 per 100 000 people per year (95% CI = 1.15, 1.34). Total in-patient costs increased by $4.1 million dollars per year (95% CI = 2.7, 5.5) for HOD admissions and by $46.0 million dollars per year (95% CI = 43.1, 48.9) for POD admissions, with an associated increase in hospitalization costs to more than $700 million annually. The adjusted odds of death in the POD group declined modestly per year [odds ratio (OR) = 0.98, 95% CI = 0.97, 0.99], with no difference in HOD mortality or length-of-stay. Patients with POD were older, more likely to be female and more likely to be white compared with HOD patients.

Conclusions
Rates and costs of heroin and prescription opioid overdose related admissions in the United States increased substantially from 2001 to 2012. The rapid and ongoing rise in both numbers of hospitalizations and their costs suggests that the burden of POD may threaten the infrastructure and finances of US hospitals.

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Hospitalizations, costs and outcomes associated with heroin and prescription opioid overdoses in the United States 2001-12.

Background 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. Methods 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. Results 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. Conclusions 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.

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Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial.

The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers.

This paper reviews high-resolution mass spectrometry (HRMS) approaches using time-of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included.

High-resolution mass spectrometry in toxicology: current status and future perspectives

Drug trafficking is an important issue as it can be the source of the emerging of the other crimes. For several years, Afghanistan has lead the the supply of illegal opiate to the other countries in the world. As a part of United Nations, UNODC has contribute a lot of significant outputs along with Afghan Government through The Country Programme for Afghanistan. However, by 2012-2013, drug trafficking in Afghanistan increased at the highest point compare to the years before. This research aims to analyse the constraints of UNODC on combating drug trafficking in Afghanistan, that caused a significant increase of drug rafficking in Afghanistan. Descriptive-Analysis type is used in this research to describe the efforts of UNODC, then analyse the constraints of UNODC through the implementation of Country Programme. The result shows there are some external factors such as economic, socio-economic, and political, from Afghanistan, that obstruct the works of UNODC.

Qonita Milatina

Papers

Upaya united nations office on drugs and crime (unodc) dalam menangani drug trafficking di afghanistan periode 2012-2013