BACKGROUND AND PURPOSE Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than D9 -tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. EXPERIMENTAL APPROACH We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size...

Prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the CNS of the protease-resistant prion protein (PrPres), a structurally misfolded isoform of its physiological counterpart PrPsen. Both neuropathogenesis and prion infectivity are related to PrPres formation. Here, we report that the nonpsychoactive cannabis constituent cannabidiol (CBD) inhibited PrPres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related cannabinoid analogs were either weak inhibitors or noninhibitory. Moreover, after intraperitoneal infection with murine scrapie, peripheral injection of CBD limited cerebral accumulation of PrPres and significantly increased the survival time of infected mice. Mechanistically, CBD did not appear to inhibit PrPres accumulation...

The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3–30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with...

D-9-tetrahydrocannabinol (D-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether D-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by D-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of D-9-THC, CBD, or...

Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti‐in‐ flammatory and anti‐anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell‐shaped dose‐response was observed, which limits its clinical use. In the present study, we have studied in mice the anti‐inflammatory and anti‐nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between...

Increasing interest in the biology, chemistry, pharmacology, and toxicology of cannabinoids and in the development of cannabinoid medications necessitates an understanding of cannabinoid pharmacokinetics and disposition into biological fluids and tissues. A drug's pharmacokinetics determines the onset, magnitude, and duration of its pharmacodynamic effects. This review of cannabinoid pharmacokinetics encompasses absorption following diverse routes of administration and from different drug formulations, distribution of analytes throughout the body, metabolism by different tissues and organs, elimination from the body in the feces, urine, sweat, oral fluid, and hair, and how these processes change over time. Cannabinoid pharmacokinetic research has been especially challenging due to low analyte...

Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on Δ9 -tetrahydrocannabinol (Δ9 -THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug.

Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously...

Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child’s seizures. Nineteen responses met the inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of...

In 2010 a review by Hazekamp and Grotenhermen covered controlled clinical trials of the years 2006-2009 on cannabis-based medicines, which followed the example of the review by Ben Amar (2006). The current review reports on the more recent clinical data available from 2010-2014. A systematic search was performed in the scientific database of PubMed, focused on clinical studies that were randomized, (double) blinded, and placebo-controlled. The key words used were: cannabis, marijuana, marihuana, hashish, cannabinoid(s), tetrahydrocannabinol, THC, CBD, dronabinol, Marinol, nabilone, Cannador, nabiximols and Sativex. For the final selection, only properly controlled clinical trials were retained. Open-label studies were excluded, except if they were...