“It has been observed cannabinoid CB1 receptor signalling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson’s disease (PD) patients. These evidences suggest that the blocking of cannabinoid CB1 receptors might be beneficial to improve movement disorders as a sign of PD…
These results support this theory that cannabinoid CB1 receptor antagonists might be useful to alleviate movement disorder in PD…”
“Previously, we found that chronic methamphetamine treatment altered CB1 R-dependent cAMP/PKA/DARPP-32/T34/PP2B signaling and decreased levels of CB1 R protein and mRNA in the nucleus accumbens. These findings suggested the existence of signaling interplay between mesolimbic dopamine and CB1 R. In the current study, we further investigate interactions between CB1 R and D2 R signaling. Activation of either CB1 R or D2 R increased ERK1/2 phosphorylation, while co-stimulation of CB1 R and D2 R evoked an additive effect on the phospho-ERK1/2 signal. This effect was mediated through a PTX-sensitive Gαi/o pathway in primary striatal cells. Furthermore, the mRNA level of CB1 R was increased via D2S R by treatment with D2 R agonist quinpirole in D2S R/C6 glioma cells. This effect could be suppressed by co-treatment with the ERK1/2 inhibitor U0126. To test if D2S R could transcriptionally regulate CB1 R, the 5′-untranslated region (5′-UTR) of the CNR1 gene was sequenced from rat brain. Results showed that the CNR1 gene includes two exons, which contain 375 bp. of 5′-UTR and are separated by a 17-kb. intron. A luciferase reporter assay showed that the maximal D2S R-responsive promoter activity is located in the -1 to -222 region of CNR1 promoter. Overall, we demonstrate previously unidentified crosstalk between D2 R and CB1 R via ERK1/2 signaling that enhances the expression of CB1 R by modulating its promoter activity.”
“Navigation of retinal projections towards their targets is regulated by guidance molecules and growth cone transduction mechanisms. Here, we present in vitro and in vivo evidences that the cannabinoid receptor 2 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action on axon guidance….
Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R.”
“Epilepsy is the most prevalent neurological disease and is characterised by recurrent seizures. Here we investigate: (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDS) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors.
CDBV BDSs exerted significant anticonvulsant effects…
CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor, and were of comparable efficacy to purified CBDV.
These findings strongly support the further clinical development of CBDV BDSs for treatment of epilepsy.”
http://www.ncbi.nlm.nih.gov/pubmed/23902406
“The cannabinoid 1(CB1 ) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ9 -tetrahydrocannabivarin (THCV) for their ability to produce these behavioural effects characteristic of CB1 receptor inverse agonism in rats.
…we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour),..
THC, THCV and CBDV suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential…
The pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists.
As well, these compounds may have therapeutic potential in reducing nausea.”
“Antagonists (inverse agonists) of the cannabinoid-1 (CB1) receptor showed promise as new therapies for controlling obesity and related metabolic function/liver disease.
These agents, representing diverse chemical series, shared the property of brain penetration due to the initial belief that therapeutic benefit was mainly based on brain receptor interaction. However, undesirable CNS-based side effects of the only marketed agent in this class, rimonabant, led to its removal, and termination of the development of other clinical candidates soon followed. Re-evaluation of this approach has focused on neutral or peripherally restricted (PR) antagonists.
Supporting these strategies, pharmacological evidence indicates most if not all of the properties of globally acting agents may be captured by molecules with little brain presence. Methodology that can be used to eliminate BBB penetration and the means (in vitro assays, tissue distribution and receptor occupancy determinations, behavioral paradigms) to identify potential agents with little brain presence is discussed.
Focus will be on the pharmacology supporting the contention that reported agents are truly peripherally restricted. Notable examples of these types of compounds are: TM38837 (structure not disclosed); AM6545 (8); JD5037 (15b); RTI-12 (19).”
“Presynaptic long-term depression (LTD) of synapse efficacy generally requires coordinated activity between presynaptic and postsynaptic neurons and a retrograde signal synthesized by the postsynaptic cell in an activity-dependent manner.
In this study, we examined LTD in the rat nucleus tractus solitarii (NTS), a brainstem nucleus that relays homeostatic information from the internal body to the brain.
We found that coactivation of N-methyl-D-aspartate receptors (NMDARs) and type 1 cannabinoid receptors (CB1Rs) induces LTD at the first central excitatory synapse between visceral fibers and NTS neurons. This LTD is presynaptically expressed. However, neither postsynaptic activation of NMDARs nor postsynaptic calcium influx are required for its induction. Direct activation of NMDARs triggers cannabinoid-dependent LTD. In addition, LTD is unaffected by blocking 2-arachidonyl-glycerol synthesis, but its induction threshold is lowered by preventing fatty acid degradation.
Altogether, our data suggest that LTD in NTS neurons may be entirely expressed at the presynaptic level by local anandamide synthesis.”
“Cannabidiol, a non-psychoactive component of cannabis, has been reported to have interactions with Delta(9)-tetrahydrocannabinol (Delta(9)-THC)…
In the present study, we investigated whether cannabidiol modulates the pharmacological effects of Delta(9)-THC…
Cannabidiol potentiated pharmacological effects of Delta(9)-THC via CB(1) receptor-dependent mechanism.
These findings may contribute in setting the basis for interaction of cannabinoids and to find a cannabinoid mechanism in central nervous system.”
“A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on. Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.”
“It’s already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer a new path for cancer prevention or treatment.”
More: http://www.medicinenet.com/script/main/art.asp?articlekey=91511
“…taking substances similar to those found in cannabis might one day help to treat colon cancer.
Raymond DuBois and colleagues at the University of Texas, Houston, discovered that a key receptor for cannabinoids – compounds similar to the active ingredient of cannabis – is turned off in most types of human colon cancer cells.
Similarly, mice genetically engineered to develop colon tumours developed more of them if the receptor, called CB1, was knocked out What’s more, tumours shrank when the genetically engineered mice were injected with a cannabinoid.
One suggestion is that lack of CB1 encourages tumour growth because the receptor normally interacts with cannabinoids made by the body to prompt cells to die. This opens up a possible two-step treatment for colon cancer…”
http://www.newscientist.com/article/mg19926685.000-cannabis-compound-clue-to-colon-cancer.html