cannabidiol and Ischemia

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9)-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9)-tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.

Topics: Cannabidiol; Cannabinoids; Humans; Huntington Disease; Ischemia; Neurodegenerative Diseases

Cannabidiol, a cannabinoid and serotonin receptor antagonist, may alleviate hyperphagia without the side effects of rimonabant (for example depression and reduced insulin sensitivity). Similar to the peroxisome proliferator-activated receptor-gamma agonists, it may also help the differentation of adipocytes. Cannabidiol has an immunomodulating effect, as well, that helps lessen the progression of atherosclerosis induced by high glucose level. It may also be effective in fighting ischaemic diseases, the most harmful complications of metabolic syndrome. However, it can only be administered as an adjuvant therapy because of its low binding potency, and its inhibiting effect of cytochrome P450 enzymes should also be considered. Nevertheless, it may be beneficially used in adjuvant therapy because of its few side effects.

Topics: Adipocytes; Appetite Depressants; Atherosclerosis; Cannabidiol; Cannabinoid Receptor Antagonists; Disease Progression; Humans; Hyperphagia; Ischemia; Metabolic Syndrome; Obesity; Piperidines; PPAR gamma; Pyrazoles; Rimonabant

Cannabinoids, used for centuries for recreational and medical purposes, have potential therapeutic value in stroke treatment. Cannabidiol (CBD), a non-psychoactive compound and partial agonist of TRPV2 channels, is efficacious in many neurological disorders. We investigated the effects of CBD or Δ9-tetrahydrocannabinol (THC) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Neuronal TRPV2 expression decreased after OGD, but it increased in activated, phagocytic microglia. CBD increased TRPV2 expression, decreased microglia phagocytosis, and increased rod microglia after OGD. THC had effects contrary to those of CBD. Our results show that cannabinoids have different effects in ischemia. CBD showed neuroprotective effects, mediated, at least in part, by TRPV2 channels, since the TRPV2 antagonist tranilast blocked them, while THC worsened the neurodegeneration caused by ischemia. In conclusion, our results suggest that different cannabinoid molecules play different roles in the mechanisms of post-ischemic neuronal death. These different effects of cannabinoid observed in our experiments caution against the indiscriminate use of cannabis or cannabinoid preparations for recreational or therapeutic use. It was observed that the positive effects of CBD may be counteracted by the negative effects caused by high levels of THC.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Glucose; Ischemia; Microglia; Neuroprotective Agents; Oxygen; Rats; TRPV Cation Channels

Current treatments for stroke, which account for 6.5 million global deaths annually, remain insufficient for treatment of disability and mortality. One targetable hallmark of stroke is the inflammatory response following infarct, which leads to significant damage post-infarct. Cannabinoids and their endogenous targets within the CNS have emerged as potential treatments for neuroinflammatory indications. We and others have previously shown that synthetic agonists of the cannabinoid CB2 receptor reduce infarct size and microglial activation in rodent models of stroke. The non-cannabinoid receptor mediated effects of the phytocannabinoid cannabidiol (CBD) have also shown effectiveness in these models. The present aim was to determine the single and combined effects of the cannabis-derived sesquiterpene and putative CB2 receptor agonist β-caryophyllene (BCP) and CBD on permanent ischemia without reperfusion using a mouse model of photothrombosis. Because BCP and CBD likely work through different sites of action but share common mechanisms of action, we sought to determine whether combinations of BCP and CBD were more potent than either compound alone. Therefore we determined the effect of BCP (3-30 mg/kg IP) and CBD (3-30 mg/kg IP), given alone or in combination (30:3, 30:10, and 30:30 BCP:CBD), on infarct size, microglial activation, and motor performance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Cannabidiol; Disease Models, Animal; Drug Therapy, Combination; Ischemia; Male; Mice, Inbred C57BL; Microglia; Polycyclic Sesquiterpenes