Abstract Marijuana ( Cannabis sativa ) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ 9 -tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long half-life and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and...

Please use this link to access this publication. Abstract Recent advances in the research of medicinal cannabis has placed the non-intoxicating cannabinoid cannabidiol (CBD) at the front of scientific research. The reasons behind this popularity is the compound’s therapeutic properties, alongside a safe profile of administration lacking addictive properties such as euphoric state of mind and a wide dosing range. Oral administration of CBD is challenging due to poor solubility in the gastro-intestinal system and susceptibility to extensive first pass metabolism. As a result, the practice in clinic and investigational trials is to administer cannabinoids in edible oils or oil-based solutions. Nonetheless, reported pharmacokinetics of cannabinoids and CBD in particular are not uniform among...

Abstract Background Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis. Objective To test the pharmacokinetics, analgesic effect, cognitive performance and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ9-Tetrahydrocannabinol (THC) in patients with chronic pain. Methods In a randomized, three-arms, double-blinded, placebo-controlled, cross-over trial, 27 patients received a single inhalation of Δ9-THC: 0.5mg, 1mg, or a placebo. Δ9-THC plasma levels were measured at baseline and up to 150-min post-inhalation. Pain intensity and safety parameters were recorded on a 10-cm visual analogue scale (VAS) at pre-defined time points. The...

Abstract Considering data from in vitro and in vivo studies, cannabidiol (CBD) seems to be a promising candidate for the treatment of both somatic and psychiatric disorders. The aim of this review was to collect dose(s), dosage schemes, efficacy and safety reports of CBD use in adults from clinical studies. A systematic search was performed in PubMed, Embase and Cochrane library for articles published in English between January 1, 2000 and October 25, 2019. The search terms used were related to cannabis and CBD in adults. We identified 25 studies (927 patients; 538 men and 389 women), of which 22 studies were controlled clinical trials (833 patients) and...

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...