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 via direct interactions with PrP, destabilization of PrPres aggregates, or alteration of the expression level or subcellular localization of PrPsen. However, CBD did inhibit the neurotoxic eff...

Heterozygous mutations in the Scn1a gene encoding the brain type-1 voltage-gated sodium channel Nav1.1 cause Dravet Syndrome (DS), a severe childhood disorder characterized by treatment-resistant epilepsy, cognitive deficits, and autism spectrum disorde...

Marijuana is the most widely used illicit drug among adolescents. We have previously shown that chronic treatment with the psychoactive component of cannabis, tetrahydrocannabinol (THC) during adolescence in rats, is associated with a schizophrenia-like...

The active principle of marijuana, delta-9-tetrahydrocannabinol (Δ9-THC), exerts its pharmacological effects throught selective cannabinoid receptors. The cannabinoid receptor CB1 is expressed in the nervous system and is densely located in basal ganglia, a group of brain nuclei that includes substantia nigra compacta and subthalamic nucleus and is involved in motor activity. The present study sought to determine the role of subthalamic nucleus in the Δ9-THC effect on nigral dopamine neuron activity by extracellular recording techniques in anaesthetized rats. Systemic administration of Δ9-THC (0.25-2 mg/kg) stimulated substantia nigra compacta neurons (by a 33.54 ± 8.63% n= 8). This stimulatory effect was completely abolished by previous blockage of excitatory amino acid receptors after kynurenic acid application (0.5 µM, i.c.v.; n=5). Similarly, destruction of the ipsilateral subthalamic nucleus by chemical lesion with ibotenic acid (10 µg/ml, 5 µl) completely blocked Δ9-THC effect (n=5). Neither kynureni...

We studied, here, the anti-inflammatory potential of cannabidiol (CBD), the major non-psychoactive component of cannabis. For that, we used microglial cells in culture that were isolated from post-natal mouse brain through a procedure that relies on the...

As cannabis becomes legalized, risks of cannabis and THC on neurodevelopment need to be understood. Abundant research has characterized risks of maternal exposure for producing adverse neurobehavioral effects in the offspring. However, comparatively lit...

Δ9-Tetrahydrocannabinol (THC), the psychoactive ingredient of cannabis, induces apoptosis in cultured cortical neurons prepared from neonatal rats1. However there is no evidence to suggest that THC is toxic to adult neurons2. This study was aimed at determining if post-natal development of the rat cortex influenced the ability of THC to activate components of the THC-induced apoptotic cascade in the rat cortex in vivo. Neonatal (4 day-old) and adult (3 month-old) male Wistar rats were anaesthetized by intraperitoneal injection of urethane (1.5g/kg). The THC group received subcutaneous injections of 10mg/kg THC in vehicle and the control group received injections of vehicle only (5% absolute alcohol, 5% Cremophor EL and 90% saline). Three hours later rats were killed humanely, half the cortex dissected and cortical slices prepared, and the other half brain frozen and prepared for cryostat sections. JNK activity was assessed by immunocytochemistry. Caspase-3 activity was measured using a fluorogenic assay an...

The present study investigated the potential of various doses of delta-9-tetrahydrocannabinol (THC), Ondansetron (5-HT3 receptor antagonist, OND) and a combined pretreatment of OND and THC to suppress cisplatin-induced emesis in the Suncus murinus. OND and THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone (0.02 mg/kg OND and 1.25 mg/kg THC) completely suppressed vomiting and retching. This suggests that a combination of lower doses of these agents may be an effective alternative treatment for vomiting that may have fewer side effects than higher doses of either agent alone.

We have recently shown that large doses of the cannabinoid CB1 receptor antagonist/inverse agonist SR 141716A induces emesis which can be reversed by Δ9-THC and synthetic cannabinoids. Furthermore, low nonemetic doses of SR 141716A block the antiemetic effect of Δ9-THC against cisplatin-induced vomiting. These studies implicate a role for endogenous cannabinoids in emetic circuits in the least shrew (Cryptotis parva). We investigated the role of 2-arachidonoylglycerol (2-AG), anandamide and methanandamide in causing emesis. 2-AG (0.25 - 10 mg/kg, i.p.) caused a dose-dependent increase in both vomiting frequency (ED50 = 1.13±1.1 mg/kg) and percent of shrews vomiting (ED50 = 0.48±3.48 mg/kg) in the 30 min observation period. Both anandamide (2.5 - 20 mg/kg) and methanandamide (5-10 mg/kg) failed to produce a dose-dependent emetic effect. The possible antiemetic action of psychoactive [Δ9-THC (1-5 mg/kg), WIN 55, 212-2 (0.25 - 5 mg/kg) and CP55, 940 (0.025 - 0.1 mg/kg)] and a nonpsychoactive cannabinoid (cann...

The potential of Δ-9-THC to interfere with place conditioning in rats was evaluated in three experiments. Experiment 1 was designed to evaluate the potential of a low dose of THC (0.5 mg/kg, ip) to interfere with the establishment and/or the expression of lithium-induced place avoidance. Since lithium produces nausea, this experiment aimed to evaluate the potential of THC to interfere with unconditioned or conditioned nausea in rats. As measured by resistance to extinction across test trial cycles, pretreatment with THC interfered with (but did not eliminate) lithium-induced place aversion learning without producing place conditioning on its own. In Experiment 2, THC eliminated a weaker lithium-induced place aversion produced by a single conditioning trial cycle. Experiment 3 evaluated whether the interference with place aversion learning was the result of interference with nausea or interference with learning. Rats were pretreated with THC prior to place preference conditioning with amphetamine. Indeed, T...