Please use this link to access this publication. Abstract Background 4−20% of people report using cannabis during pregnancy, thereby it is essential to assess the associated risks. There is some evidence that prenatal cannabis exposure (PCE) may be associated with increased risk for developing of obesity and diabetes later in life, however this has not been well explored under controlled conditions. The aim of this study was to use a translational THC vapor model in rodents to characterize the effects of PCE on adiposity, glucose metabolism, and feeding patterns in adulthood, with focus on potential sex differences. Methods Pregnant Sprague Dawley rats were exposed...

Please use this link to access this publication. Abstract Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included ‘cannabidiol’, ‘tetrahydrocannabinol’, and ‘cytochrome P450’. A total of...

Abstract Although prescribing information (PI) is often the initial source of information when identifying potential drug-drug interactions, it may only provide a limited number of exemplars or only reference a class of medications without providing any specific medication examples. In the case of medical cannabis and medicinal cannabinoids, this is further complicated by the fact that the increased therapeutic use of marijuana extracts and cannabidiol oil will not have regulatory agency approved PI. The objective of this study was to provide a detailed and comprehensive drug-drug interaction list that is aligned with cannabinoid manufacturer PI. The cannabinoid drug-drug interaction information is listed in this...

Abstract The UDP-glucuronosyltransferase (UGT) family of enzymes play a central role in the metabolism and detoxification of a wide range of endogenous and exogenous compounds. UGTs exhibit a high degree of structural similarity and display overlapping substrate specificity, often making estimations of potential drug-drug interactions difficult to fully elucidate. One such interaction yet to be examined may be occurring between UGTs and cannabinoids, as the legalization of recreational and medicinal cannabis and subsequent co-usage of cannabis and therapeutic drugs increases in the United States and internationally. In the present study, the inhibition potential of the major cannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN),...

Abstract Aim: Δ9-Tetrahydrocannabinol (Δ9-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ9-THC in mice and whether Δ9-THC had any impact ex-vivo and in-vitro on NAT activity. Methods: Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ9-THC (0.10, 0.50 or 2.0 mg/kg/mL, ip) or amphetamine (AMP, 5.0 mg/kg/mL, ip); while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the...

  Abstract INTRODUCTION: In recent years, cannabinoids have been shown to have beneficial effects on diabetic vascular complications. Vascular complications due to fructose-induced hyperinsulinemia (HI) and diabetic vascular complications have similar mechanisms. The aim of this experimental study was to observe whether the cannabinoid agonist delta-9-tetrahydrocannabinol (THC) has an ameliorating effect on fructose-induced HI and vascular responses in the aortic ring of rats with HI. METHODS: A total of 24 rats were categorized into 4 groups: control (standard food pellets and water), HI (water containing 10% fructose provided for 12 weeks), THC (1.5 mg/kg/day intraperitoneal administration for 4 weeks), and THC+HI. Body weight was...

Abstract Prenatal cannabis use is a significant problem and poses important health risks for the developing fetus. The molecular mechanisms underlying these changes are not fully elucidated but are thought to be attributed to delta-9-tetrahydrocannabinol (THC), the main bioactive constituent of cannabis. It has been reported that THC may target the mitochondria in several tissue types, including placental tissue and trophoblast cell lines, and alter their function. In the present study, in response to 48-h THC treatment of the human extravillous trophoblast cell line HTR8/SVneo, we demonstrate that cell proliferation and invasion are significantly reduced. We further demonstrate THC-treatment elevated levels of cellular reactive...

Abstract The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At...

Please use this link to access this publication. Abstract The use of cannabidiol (CBD), the non-psychotropic compound derived from Cannabis sativa, for therapeutic purposes is growing exponentially by targeting the management of multiple medical disorders, including metabolic-related diseases. Nevertheless, substantial questions have emerged in concerning the potential metabolic disturbances in adulthood as consequence of the long-term uses of CBD during early years of life. Therefore, we studied whether chronic CBD injections (5, 10 or 30 mg/kg; i.p.) given to juvenile rats (from post-natal day [PND] 30) for 14 days might influence in adulthood the activity of metabolic markers, such as glucose, total cholesterol, triglycerides...

Abstract The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently...