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 Cannabidiol (CBD) has been shown to inhibit mouse hepatic mixed-function oxidations of several drugs after acute treatment, whereas repetitive treatment resulted in the restoration of drug-metabolizing capabilities. We have found that acute CBD treatment modestly decreased cytochrome P-450 content but markedly decreased hexobarbital hydroxylase, erythromycin N-demethylase, and 6 beta-testosterone hydroxylase activities. Repetitive CBD treatment, on the other hand, resulted in the restoration of cytochrome P-450 content as well as hexobarbital hydroxylase and erythromycin N-demethylase activities. However, after such repeated treatments a fresh dose of CBD can once again inactivate erythromycin N-demethylase activity but not hexobarbital hydroxylase activity. The resistance of hexobarbital hydroxylase to...

Abstract Sepsis is an inflammatory condition that is associated with reduced propulsive gastrointestinal motility (ileus). A therapeutic option to treat sepsis is to promote intestinal propulsion preventing bacterial stasis, overgrowth and translocation. Recent evidence suggests that anti-oxidants improve sepsis-induced ileus. Cannabidiol, a non-psychotropic component of Cannabis sativa, exerts strong anti-oxidant and anti-inflammatory effects without binding to cannabinoid CB(1) or CB(2) receptors. Cannabidiol also regulates the activity of fatty acid amide hydrolase (FAAH) which is the main enzyme involved in endocannabinoid breakdown and which modulates gastrointestinal motility. Because of the therapeutic potential of cannabidiol in several pathologies, we investigated its effect on sepsis-induced ileus and...

Abstract There is increasing interest in the use of cannabis and its major non-intoxicating component cannabidiol (CBD) as a treatment for mental health and neurodevelopmental disorders, such as autism spectrum disorder (ASD). However, before launching large-scale clinical trials, a better understanding of the effects of CBD on brain would be desirable. Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). However, differences in glutamate and GABA pathways in ASD mean...

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...

Having chronic pain can make it difficult to sleep through the night. And having a lack of sleep can compound the effects of any health issue, leading to a vicious cycle. This study shows that moderate cannabis use can help to maintain sleep throughout the entire night for those with chronic pain.   Objectives Medical cannabis (MC) is increasingly being used for treatment of chronic pain symptoms. Among patients there is also a growing preference for the use of MC to manage sleep problems. The aim of the current study was to examine the associations between use of whole plant cannabis and sleep problems...

Abstract Background: A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters. Objective: This trial assessed the safety, tolerability and PK of CBD oral solution in healthy adult volunteers, as well as the effect of food on CBD PK parameters. Methods: The study consisted of three arms: single ascending dose (1500, 3000, 4500 or 6000 mg CBD [n = 6 per group]/placebo [n = 8; 2 per CBD dose group]), multiple dose (750 or 1500 mg CBD...

Abstract Objective: Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia. Method: In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S). Results: After 6 weeks...