The present investigation assessed the neuroprotective efficacy of cannabidiol (CBD) in a kainic acid (KA) seizure model of temporal lobe epilepsy. Sixty-six male Sprague-Dawley rats were used. Each animal was housed individually in a clear polycarbonat...

Chronic cannabinoid exposure results in tolerance to cannabinoid-induced locomotor effects which are mediated by the cannabinoid receptors (CB1R) located in motor control region, such as cerebellum. In cerebellar cortex, acute activation of presynaptic CB1R suppresses parallel fibers (PF) synaptic inputs to Purkinje cells (PC). Whole-cell patch-clamp recordings have been carried out in PC to analyze the properties of evoked excitatory synaptic transmission in mice chronically exposed to Δ9-THC or to its vehicle. Paired-pulse facilitation (PPF) was used to analyze PF-PC short-term synaptic plasticity. We observed a decreased PPF in mice chronically treated with THC, indicating an increased release probability after prolonged cannabinoid exposure. In addition, inhibition of PF-PC synaptic transmission induced by the selective CB1R agonist CP55940 is decreased in THC-treated mice. This suggests that, following chronic THC treatment, functional tolerance to the CB1R agonist occurs at cerebellar PF-PC synapses,...

We have previously reported PET rCBF data from 5 volunteers following smoking of a marijuana cigarette (SNS 1998). The present study measured rCBF with PET using [O-15]water in 12 new volunteers (6M, 6F) who were occasional recreational users of marijuana. Subjects were imaged prior to and following smoking of a marijuana (20 mg THC) and placebo (marijuana with THC removed) cigarette as they repeatedly performed an auditory attention task. A double-blind design was used with order of THC and placebo counterbalnced across subjects. Subtraction of the post-placebo from the post-THC condition revealed dramatic rCBF increases in orbital frontal cortex, anterior cingulate, temporal pole, insula, and lateral cerebellum. Smoking marijuana decreased rCBF in L heschl’s gyrus, primary visual cortex, and a number of frontal regions (BA4, 6, 8, 10). Ventral brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana. The rCBF decreases in primary sensory cortices and...

Recent findings have provided the existence of a functional interaction between opioid, dopaminergic and cannabinoid systems on addictive related behaviours. We have analysed the consequences of nicotine administration on the behavioural responses induced by Δ9-tetrahydrocannabinol (THC). For this purpose, we have administrated THC (5 or 10 mg/kg) and nicotine (0.5 mg/kg) and evaluated acute responses, the development of tolerance and the somatic expression of THC withdrawal. Nicotine strongly potentiates hypothermia, antinociceptive responses and the decrease of locomotor activity induced by an acute injection of THC. The development of tolerance to THC responses was also modified by nicotine. Indeed, animals treated with THC alone developed a rapid tolerance to all the acute pharmacological responses. In contrast, the co-administration of nicotine decreased the degree of THC tolerance. Acute injection of the CB1 receptor antagonist SR 141716A (10 mg/kg) in THC-dependent mice precipitated somatic signs of...

Δ9-Tetrahydrocannabinol (Δ9-THC), the major psychoactive compound of marijuana, exerts direct cellular effects through the activation of G-protein-coupled CB1 and CB2 receptors located mainly in the brain and the immune system, respectively. The molecular mechanism by which cannabinoids alter gene expression in the brain is not well understood. The CB1 receptors coupled to Gi proteins activate both potassium channels and members of the mitogen-associated protein kinase family, and also inhibit adenylate cyclase and voltage-gated calcium channels. Moreover, there is evidence for an alternative CB1-mediated signalling pathway involving the activation of adenylate cyclase through stimulatory Gs proteins. The modulation of the phosphorylated cAMP-response element binding protein (p-CREB) by Δ9-THC was investigated in cerebellar granule cells, known to display an high distribution of CB1 receptors, to elucidate the cellular mechanism involved in CB1 receptors activation. Different concentrations (0, 0.3, 3, 30,...

Introduction: Limited therapeutic effects of current Alzheimer (AD) treatments highlight the need for new research approaches. Thereby drugs that target different aspects of AD pathology simultaneously could provide therapeutic benefits compared to more...

The chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) produces tolerance to its behavioral effects, and such tolerance can be associated with changes in cannabinoid receptor number as well as function. The purpose of the present study was to identify patterns of functional activity that accompany chronic Δ9-THC administration utilizing quantitative 2-[14C]deoxyglucose autoradiography (2DG). Male Sprague-Dawley rats were treated with Δ 9-THC (10 mg/kg, i.p.) or vehicle for either one or 21 days. Metabolic mapping with the 2DG method was applied 15 minutes after the final drug treatment. The single administration of Δ9-THC produced a global effect, significantly depressing rates of glucose utilization in 35 of 39 brain structures measured. In contrast, the administration of Δ9-THC, following repeated exposure, did not significantly alter rates of glucose utilization in the majority of structures analyzed. These data demonstrate that tolerance develops to the cerebral metabolic effects of Δ9-THC foll...

Read science policy and advocacy news from the week of January 5, 2018

Cannabidiol (CBD) is the second most common phytocannabinoid in the Cannabis Sativa, and recent evidence suggests great therapeutic potential, specially in the field of epilepsy. CBD has been shown to reduce neuronal lesion in central nervous system dis...

The world’s population is ageing. Population ageing is poised to become one of the most significant social transformations of the twenty-first century. a variety of insults In the present study we evaluated the effect of the same ultra-low dose of THC o...