Abstract Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the...

Abstract Background: Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond. Objectives: To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants. Methods: Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n...

ABSTRACT: Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. The self reported prevalence of marijuana use during pregnancy ranges from 2% to 5% in most studies. A growing number of states are legalizing marijuana for medicinal or recreational purposes, and its use by pregnant women could increase even further as a result. Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician–gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes...

Abstract As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S....

Abstract   We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide, are lower in the brains of adult cannabis users (CUs) (34 ± 11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23 ± 5 years of age). Eighteen healthy volunteers (HVs) and fourteen CUs underwent a positron emission tomography scan using the FAAH radioligand [11C]CURB. Regional [11C]CURB binding was calculated using an irreversible two-tissue compartment model with a metabolite-corrected arterial plasma input function. The FAAH C385A genetic polymorphism (rs324420) was...

Abstract Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6%...

Abstract Purpose: Minnesota's medical cannabis program is unique, in that it routinely collects patient-reported scores on symptoms. This article focuses on changes in symptom severity reported by patients with cancer during their first 4 months of program participation. Materials and methods: Patients with cancer in Minnesota's medical cannabis program reported symptoms (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) at their worst over the last 24 hours before each medical cannabis purchase. Baseline scores on each of the eight symptoms were statistically compared with the average symptom scores reported in the first 4 months of program participation. Symptom scores were also calculated...

Abstract Workplace urine drug testing for an inactive THC metabolite is common in both federally regulated and non-regulated drug testing. A positive result does not document impairment, or even recent use, when impairment is likely the most important parameter being searched for by the drug testing procedure. Most cannabinoid testing does not detect imported synthetics. Currently, urine is the most widely tested matrix, but blood, plasma, oral fluid, and hair may also be accepted in federally regulated testing in the future. This article will discuss the history, the status quo, and the possible near term future of workplace testing for marijuana in employees.

Abstract Background: A substantial proportion of people using cannabis report using it to improve sleep. Yet, little research exists on the associations between the timing of cannabis use and sleep. This study examines the time elapsed between cannabis use and sleep start time and its association with two of the main indicators of sleep continuity: (1) sleep onset latency (SOL) and (2) number of awakenings (NOA) throughout the night. Methods: Each morning, for 7 consecutive days, daily cannabis users (n = 54) reported on the timing of previous night's cannabis use and sleep indicators on their smartphones. Mixed effects models examined the relations of within- and...