Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature brain following hypoxiaeischemia (HI). We examined whether CBD neuroprotection is sustained over a prolonged period. Newborn Wistar rats underwent HI injury (10% oxygen for 120 min after left carotid artery electrocoagulation) and then received vehicle (HV, n ¼ 22) or 1 mg/kg CBD (HC, n ¼ 23). Sham animals were similarly treated (SV, n ¼ 16 and SC, n ¼ 16). The extent of brain damage was determined by magnetic resonance imaging, histological evaluation (neuropathological score, 0e5), magnetic resonance spectroscopy and Western blotting. Several neurobehavioral tests (RotaRod, cylinder rear test[CRT],and novel object recognition[NOR]) were carried...

The endocannabinoid system plays a key role in regulating a variety of physiological processes such as appetite control and energy balance, pain perception, and immune responses. Recent studies have implicated the endocannabinoid system in the regulation of bone cell activity and bone remodeling.These studies showed that endogenous cannabinoid ligands, cannabinoid receptors, and the enzymes responsible for ligand synthesis and breakdown all play important roles in bone mass and in the regulation of bone disease. These findings suggest that the endocannabinoid pathway could be of value as a therapeutic target for the prevention and treatment of bone diseases. Here, we review the role of the...

Cannabidiol (CBD), a non­psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and...

Neonatal hypoxic-ischemic encephalopathy (NHIE) is a devastating condition for which effective therapeutic treatments are still unavailable. Cannabinoids emerge as neuroprotective substances in adult animal studies; therefore, we aimed herein to test whether cannabinoids might reduce brain damage induced by hypoxiaischemia (HI) in newborn rats. Thus, 7-d-old Wistar rats (P7) were exposed to 8% O2 for 120 min after left carotid artery ligature, then received s.c. vehicle (VEH) (HIVEH), the cannabinoid agonist WIN55212 (WIN) (0.1 mg/kg), or WIN with the CB1 or CB2 receptor antagonist SR141617 (SR1) (3 mg/kg) or SR141588 (SR2) (2 mg/kg). Brain damage was assessed by magnetic resonance imaging (MRI) at 1,...

Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol 293: H3602–H3607, 2007. First published September 21, 2007; doi:10.1152/ajpheart.00098.2007.—Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined...

We have recently reported that in bone the cannabinoid CB1 receptor is present in sympathetic terminals. Here we show that traumatic brain injury (TBI), which in humans enhances peripheral osteogenesis and fracture healing, acutely stimulates bone formation in a distant skeletal site. At this site we demonstrate i) a high level of the main endocannabinoid, 2-arachidonoylglycerol (2-AG), and expression of diacylglycerol lipases, enzymes essential for 2-AG synthesis; ii) that the TBIinduced increase in bone formation is preceded by elevation of the 2-AG and a decrease in norepinephrine (NE) levels. The TBI stimulation of bone formation was absent in CB1-null mice. In wild-type animals it...

Traumatic brain injury can cause persistent challenges including problems with learning and memory. Previous studies suggest that the activation of the cannabinoid 1 receptor after a traumatic brain injury could be beneficial. We tested the hypothesis that posttraumatic brain injury administration of a cannabinoid 1 receptor agonist can rescue deficits in learning and memory. Young adult male rats were subjected to a moderately severe controlled cortical impact brain injury, with a subset given postinjury i.p. injections of a cannabinoid receptor agonist. Utilizing novel object recognition and the morris water task, we found that the brain-injured animals treated with the agonist showed a marked recovery.

Cannabinoid receptors play an important role in regulating bone mass and bone turnover. Studies in our laboratories have shown that young mice lacking type 1 cannabinoid receptor (CNR1-/-) had increased bone mass and were resistant to ovariectomy-induced bone loss. Other workers have reported that type 2 cannabinoid receptor knockout mice (CNR2-/-) develop age-related osteoporosis. The aim of this PhD thesis was to further investigate the role of CNR2 in bone metabolism in vitro and in vivo, using genetic and pharmacological approaches.

The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5 mg/kg, i.v.) was given 1 h following the procedure and every 24 h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis...