Peroxisome proliferator-activated receptor-c (PPARc) has been reported to be involved in the etiology of pathological features of Alzheimer’s disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARc, which has been recently indicated as its putative binding site. CBD actions on bamyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade...

CONTEXT: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. PARTICIPANTS: Fifteen healthy, English-native, right-handed men who...

Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma.These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA...

Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons. We show that chemical promotion of CB1R activity increases feeding, and notably, CB1R activation also promotes neuronal activity of POMC cells. This paradoxical increase in POMC activity was crucial for CB1R-induced feeding, because designer-receptors-exclusively-activated-by-designer-drugs (DREADD)-mediated inhibition of POMC neurons diminishes, whereas DREADD-mediated activation of POMC neurons enhances CB1R-driven feeding. The Pomc gene encodes both the anorexigenic peptide α-melanocyte-stimulating hormone, and the opioid peptide β-endorphin. CB1R activation selectively increases...

Although marijuana is now consumed extensively, little is known of its biologic effects on the lung. To study this problem, the intrapulmonary inactivation of an aerosolized challenge of Staphylococcus aureus was quantified in rats exposed to graded amounts of fresh marijuana smoke. Controls inactivated 85.1 percent +/- 0.3 percent of the bacteria six hours after inoculation. Following an in vivo accumulative exposure to smoke from progressively increasing numbers of marijuana cigarettes for periods of ten minutes each hour for five consecutive hours, intrapulmonary bacterial inactivation was impaired in a dose-dependent manner. Evaluation of the effects of parenterally administered delta-9-tetrahydrocannabinol (THC) or of exposure to...

Effects of four cannabinoids [cannabidiol (CBD), delta 8-tetrahydrocannabinol, delta 9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17 beta-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 microM) competitively inhibited 2 alpha-hydroxy-testosterone (2 alpha-OH-T) and 16 alpha-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3,17-dione) and 7 alpha-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2 alpha- and 16 alpha-hydroxylations and noncompetitive inhibition for 6 alpha-hydroxylation, and of metyrapone, which inhibited only 6 beta-hydroxylation competitively. CBD also suppressed formation of 2 alpha-OH-T,...

Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them. Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.

Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that a distinct type of metabotropic glutamate receptor-5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex, which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in fragile X mental retardation protein-null mice. In these mutants, the macromolecular complex that links metabotropic glutamate receptor-5 to the...