Disease relevance of cannabidiol

• Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD) [1].
• Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC) [2].
• These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia [2].
• This potentiation was abolished by the cannabidiol analog O-1918 or by pertussis toxin but was unaffected by CB1 or CB2 antagonists [3].
• The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells [4].

Psychiatry related information on cannabidiol

• Additionally, the interactive effects of CBD and the antiepileptic drugs against maximal electroshock and audiogenic seizures were studied [5].
• When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract [6].
• Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg [6].
• Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents [7].
• Plasma levels of cannabidiol (CBD) were ascertained weekly in 14 Huntington's disease patients undergoing a double-blind, placebo-controlled, crossover trial of oral CBD (10 mg/kg/day = about 700 mg/day) for 6 weeks [8].

High impact information on cannabidiol

• Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression [9].
• These findings suggest that Abn-cbd and cannabidiol are a selective agonist and antagonist, respectively, of an as-yet-unidentified endothelial receptor for anandamide, activation of which elicits NO-independent mesenteric vasodilation, possibly by means of the release of EDHF [10].
• The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent [2].
• The gene encoding lactoferrin is an estrogen-responsive gene in the mouse uterus that was rapidly and transiently up-regulated by THC, but not by CBD, in ovariectomized mice in the absence of ovarian steroids [11].
• The cannabinoid analog "abnormal cannabidiol" (abn-cbd) causes endothelium-dependent vasodilation in rat isolated mesenteric arteries through a G protein-coupled receptor distinct from CB1 or CB2 [3].

Chemical compound and disease context of cannabidiol

• 2 cannabidiol- and 1 cannabinol-treated C57 B1/6 females with the fastest growing synovial sarcomas were pregnant and, in addition, 2 of them developed mammary adenocarcinomas, indicating that they were rich in estrogen [12].
• In another group of experiments, catalepsy was measured 30 min after haloperidol, clozapine or cannabidiol injections [13].
• Acute and subacute inhalation toxicity of Turkish marihuana, cannabichromene, and cannabidiol in rats [14].
• As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons [15].
• delta 9-Tetrahydrocannabinol, cannabidiol, cannabidiolic acid, tetrahydrocannabidiolic acid, cannabispirol, acetylcannabispirol, cannabispirone, and cannabispirenone in a low concentration did not affect the adhesion of Escherichia coli on cultured HEp-2 cells [16].

Biological context of cannabidiol

• In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Delta9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation [17].
• Influence of cannabidiol on secobarbital effects and plasma kinetics [18].
• Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis [19].
• The combinations of CBN and CBD with low-dose delta 9-THC (5 mg) did not induce significant bronchodilation but did exert interactive effects on heart rate and "high." A 20-day study of daily delta 9-THC (20 mg), CBN (600 mg), and CBD (1200 mg) did not indicate tolerance or reverse tolerance to any drug [20].
• Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium [21].

Anatomical context of cannabidiol

• A cytochrome P-450 isozyme (Mr = 51,600) was purified to apparent homogeneity from hepatic microsomes of mice pretreated with cannabidiol (CBD), a major constituent of marijuana [22].
• The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox) [19].
• Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells [21].
• Hashish: synthesis and central nervous system activity of some novel analogues of cannabidiol and oxepin derivatives of delta 9-tetrahydrocannabinol [23].
• Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated [24].

Associations of cannabidiol with other chemical compounds

• The cannabidiol analog O-1918 does not bind to CB(1) or CB(2) receptors and does not cause vasorelaxation at concentrations up to 30 microM, but it does cause concentration-dependent (1-30 microM) inhibition of the vasorelaxant effects of abn-cbd and anandamide [25].
• Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors [19].
• We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice [26].
• The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity [27].
• Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses [28].

Gene context of cannabidiol

• Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression [19].
• CBD was also shown to decrease the measurable quantity of both IL-1 and TNF [29].
• The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity [30].
• Concentrations of THC and CBD, comparable to plasma levels found after smoking marijuana (10-100 ng/ml), increased the concentration of measurable IFN (139 and 68%), while high concentrations of both cannabinoids (5-20 micrograms/ml) completely blocked synthesis and/or release of this cytokine [29].
• Macrophages from animals treated with cannabidiol at the dose of 30 mg kg(-1) either orally or i.p. produced higher levels of IL-12 and lower levels of IL-10 in comparison to controls, and the CB receptor antagonists did not prevent these effects [31].

Analytical, diagnostic and therapeutic context of cannabidiol

• The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis [32].
• Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo [19].
• Effects of cannabidiol in animal models predictive of antipsychotic activity [27].
• The influences of delta 9-tetrahydrocannabinol (THC) and cannabidiol on electrically evoked cortical potentials of conscious rats with chronically implanted electrodes were investigated [33].
• Determination of cannabidiol in plasma by electron-capture gas chromatography [34].

References