“Sativex® is an exclusive cannabinoid-based drug approved for the treatment of spasticity due to Multiple Sclerosis (MS).
The most common side effects include dizziness, nausea, and somnolence. However, it is still under debate whether the drug could cause negative cognitive effects.
The aim of our study was to investigate the effect of Sativex® on functional and psychological status in cannabis-naïve MS patients.
“Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes.
Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection.
Cannabidiol could be a good candidate.
Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.
Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio.
The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone.
The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult.”
“The mechanism of action of cannabidiol, one of the major constituents of cannabis, is not well understood but a noncompetitive interaction with mu opioid receptors has been suggested on the basis of saturation binding experiments.
The aim of the present study was to examine whether cannabidiol is an allosteric modulator at this receptor, using kinetic binding studies, which are particularly sensitive for the measurement of allosteric interactions at G protein-coupled receptors.
In addition, we studied whether such a mechanism also extends to the delta opioid receptor. For comparison, (-)-Delta9-tetrahydrocannabinol (THC; another major constituent of cannabis) and rimonabant (a cannabinoid CB1 receptor antagonist) were studied.
The present study shows that cannabidiol is an allosteric modulator at mu and delta opioid receptors. This property is shared by THC but not by rimonabant.”
“Delta9-tetrahydrocannabinol (delta9-THC), cannabinol and cannabidiol are three important natural cannabinoids from the Marijuana plant (Cannabis sativa).
Using [35S]GTP-gamma-S binding on rat cerebellar homogenate as an index of cannabinoid receptor activation we show that: delta9-THC does not induce the maximal effect obtained by classical cannabinoid receptor agonists such as CP55940.
Moreover at high concentration delta9-THC exhibits antagonist properties.
Cannabinol is a weak agonist on rat cerebellar cannabinoid receptors and cannabidiol behaves as an antagonist acting in the micromolar range.”
“(-)-Cannabidiol (CBD) is a major, non psychotropic constituent of cannabis.
It has been shown to cause numerous physiological effects of therapeutic importance.
We have reported that CBD derivatives in both enantiomeric series are of pharmaceutical interest. Here we describe the syntheses of the major CBD metabolites, (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series. The starting materials were the respective CBD enantiomers and their DMH homologs.
The binding of these compounds to the CB(1) and CB(2) cannabinoid receptors are compared.
Surprisingly, contrary to the compounds in the (-) series, which do not bind to the receptors, most of the derivatives in the (+) series bind to the CB(1) receptor in the low nanomole range. Some of these compounds also bind weakly to the CB(2) receptor.”
“Cannabidiol, a major component of marijuana, protects nerves, and exerts antispasmodic, anti-inflammatory and anti‑anxiety effects.
In the current study, the protective effect of cannabidiol was observed to prevent hydrogen peroxide (H2O2)‑induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells.
Taken together, these results suggest that cannabidiol potentially exerts its protective effect on LDH via the suppression of anti‑apoptosis, anti‑inflammation and anti‑oxidative activities in nucleus pulposus cells.”
“CBD, the most abundant nonpsychoactive constituent of Cannabis sativa (marijuana) plant, exerts antiinflammatory effects in various disease models and alleviates pain and spasticity associated with multiple sclerosis in humans.
In this study, we have investigated the effects of cannabidiol (CBD) on myocardial dysfunction, inflammation, oxidative/nitrosative stress, cell death and interrelated signaling pathways, using a mouse model of type I diabetic cardiomyopathy and primary human cardiomyocytes exposed to high glucose.
These data suggest that preventing permeability changes at the BBB could represent an as yet unrecognized mechanism of CBD-induced neuroprotection in ischaemic stroke, a mechanism mediated by activation of PPARγ and 5-HT1A receptors.”
“Cannabinoids, components of the Cannabis sativa (marijuana) plant, are known to exert potent anti-inflammatory, immunomodulatory and analgesic effects through activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells.
The limitation of the therapeutic utility of the major cannabinoid, Δ9-tetrahydrocannabinol, is the development of psychoactive effects through central nervous system CB1 receptor. In contrast, cannabidiol (CBD), one of the most abundant cannabinoids of Cannabis sativa with reported antioxidant, anti-inflammatory, and immunomodulatory effects is well tolerated without side effects when chronically administered to humans and is devoid of psychoactive properties due to a low affinity for the CB1 and CB2 receptors.
A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes.
In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-κB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs).
HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-κB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs.
Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment.
Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.
Collectively, our results suggest that the nonpsychoactive cannabinoid CBD have significant therapeutic benefits against diabetic complications and atherosclerosis by attenuating HG-induced mitochondrial superoxide generation, increased NF-κB activation, upregulation of iNOS and adhesion molecules, 3-NT formation, monocyte-endothelial adhesion, TEM of monocytes, and disruption of the endothelial barrier function.
This is particularly encouraging in light of the excellent safety and tolerability profile of CBD in humans.”
“Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract.
Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice.