Abstract Introduction As patients who receive cannabidiol (CBD) may have co-existing renal morbidities, it is important to understand whether dose adjustments are necessary to mitigate the risk of exposure-related toxicity. This study was conducted to evaluate the pharmacokinetics, safety, and tolerability of CBD in patients with renal impairment. Methods The pharmacokinetics and safety of a single oral 200 mg dose of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (Epidiolex® in the USA; 100 mg/mL) were assessed in subjects with mild, moderate, or severe renal impairment (n = 8/group) relative to matched subjects with normal renal function (n = 8). Blood samples were collected until 48 h post-dose and...

Abstract A popular method of inhaling marijuana is by heating marijuana liquid (vaping). We study exhaled aerosol within experimental rooms in two inhabited homes and determine peak concentrations, decay and removal rates, and source emissions. These parameters allow a simple exposure model to be developed. The experimental approach was to measure particle concentrations from one or multiple puffs of marijuana liquid within the experimental rooms. Commercial cartridges containing marijuana liquid of varying CBD:THC ratios (2:1, 7:1, 8:1, and 18:1) were compared. PM2.5 concentrations were measured continuously by optical monitors (SidePak and PurpleAir monitors) and by mass measurements (Piezobalances). The mass measurements in a subsample were...

Abstract The psychoactive component in cannabis, delta-9-tetrahydrocannabinol, can restrict fetal growth and development. Delta-9-tetrahydrocannabinol has been shown to negatively impact cellular proliferation and target organelles like the mitochondria resulting in reduced cellular respiration. In the placenta, mitochondrial dysfunction leading to oxidative stress prevents proper placental development and function. A key element of placental development is the proliferation and fusion of cytotrophoblasts to form the syncytium that comprises the materno-fetal interface. The impact of delta-9-tetrahydrocannabinol on this process is not well understood. To elucidate the nature of the mitochondrial dysfunction and its consequences on trophoblast fusion, we treated undifferentiated and differentiated BeWo human trophoblast cells,...

Abstract 1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9–tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC...

Please use this link to access this publication. Key Points Question  What is the magnitude and duration of driving impairment following vaporization of cannabis containing varying concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)? Findings  In this crossover clinical trial that included 26 healthy participants who underwent on-road driving tests, the standard deviation of lateral position (SDLP, a measure of lane weaving, swerving, and overcorrecting) at 40 to 100 minutes following vaporized consumption was 18.21 cm for CBD-dominant cannabis, 20.59 cm for THC-dominant cannabis, 21.09 cm for THC/CBD-equivalent cannabis, and was 18.26 cm for placebo. At 240 to 300 minutes, the SDLP was 19.03 cm for CBD-dominant...

Abstract Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in...

Abstract Products derived from the plant Cannabis sativa are widely appreciated for their analgesic properties and are employed for the treatment of chronic neuropathic pain. Only nabiximols, a product composed of two extracts containing similar percentages of the two cannabinoids cannabidiol and delta-9-tetrahydrocannabinol, is approved by regulatory authorities for neuropathic pain and spasticity due to multiple sclerosis in many European countries and Canada. It is also included in pharmacovigilance systems monitoring the occurrence of adverse drug reactions. However, it is not the same for the great variety of other cannabis preparations widely used for medical purposes. This creates a situation characterized by insufficient knowledge...

Abstract Background and Purpose Adolescent cannabis use is associated with adult psychopathology. When Δ9-tetrahydrocannabinol (THC), mainly in high doses, is administered to adolescence rats there are also long lasting effects in adults. This study aims to determine the specific adult bio-behavioural profile after adolescent low-dose THC, which better mirrors adolescent recreational cannabis use. Experimental Approach Adolescent male Sprague–Dawley rats were treated with escalating low-dose of THC. In adulthood, they were evaluated for their spontaneous locomotion, sensorimotor gating, higher order and spatial cognitive functions. Dopaminergic activity and cannabinoid receptor expression were measured in distinct brain regions. Hippocampal neurogenic activity of neural stem cells was determined...

Abstract Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently...

Abstract The increasing legal availability of cannabis has important implications for road safety. This systematic review characterised the acute effects of Δ9-THC on driving performance and driving-related cognitive skills, with a particular focus on the duration of Δ9-THC-induced impairment. Eighty publications and 1534 outcomes were reviewed. Several measures of driving performance and driving-related cognitive skills (e.g. lateral control, tracking, divided attention) demonstrated impairment in meta-analyses of “peak” Δ9-THC effects (p’s<0.05). Multiple meta-regression analyses further found that regular cannabis users experianced less impairment than ‘other’ (mostly occasional) cannabis users (p = 0.003) and that the magnitude of oral (n = 243 effect estimates [EE]) and inhaled (n = 481 EEs) Δ9-THC-induced...