“Abnormal dopamine (DA) transmission in the striatum plays a pivotal role in attention-deficit/hyperactivity disorder (ADHD).
As striatal DA signalling modulates the endocannabinoid system (ECS), the present study was aimed at investigating cannabinoid CB1 receptor (CB1R) function in a model of ADHD…
Our results point to CB1Rs as novel molecular players in ADHD, and suggest that therapeutic strategies aimed at interfering with the ECS might prove effective in this disorder.”
“Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited.
Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication…
In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity.”
“Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids, N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception, but with minimal cannabimimetic side effects.
Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to CB1 receptor functional tolerance, which represents another challenge in this potential therapeutic strategy.
Therefore, the present study tested whether full FAAH inhibition, combined with partial MAGL inhibition, would produce sustained antinociceptive effects with minimal cannabimimetic side effects…
Thus, full FAAH inhibition combined with partial MAGL inhibition reduces neuropathic and inflammatory pain states, with minimal cannabimimetic effects.”
Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice.
We generated and used knockout mice lacking DAGL-α (Dagla-/-) to assess the behavioral consequences of reduced endocannabinoid levels in the brain…
Our findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses.”
“Endocannabinoids and ceramides have demonstrated growth inhibition, cell death induction and pro-apoptotic activity in cancer research.
In the present study, we describe the profiles of two major endocannabinoids, ceramides, free fatty acids and relevant metabolic enzymes in 47 pairs of human colorectal cancer tissues and adjacent non-tumor tissues…
Elevation of AEA and alteration of ceramides (C16, C24, C18, C20) may qualify as potential endogenous biomarkers and novel drug targets for colorectal cancer.”
“The ‘endocannabinoid system’ (ECS), comprising endogenous ligands (endocannabinoids) and their regulating enzymes, together with the cannabinoid receptors, has attracted a great deal of attention because it affects not only all facets of human reproduction, from gametogenesis through to parturition and beyond, but also targets key mechanisms affecting some hallmarks of cancer.
Recent evidence showing that cannabinoid receptors play a very important role in the development of malignancies outside of the reproductive organs suggests a similar role for the ECS in the establishment or continued development of gynaecological malignancy.
The paucity of studies in this area suggests that research using animal models is needed to evaluate endocannabinoid signalling in cancer networks. Future randomized clinical studies should reveal whether endocannabinoids or their derivatives prove to be useful therapeutic targets for gynaecological and other cancers.”
“Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are the most biologically active members, are polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome proliferator-activated receptors. Depending on the target engaged, these bioactive mediators can regulate different signalling pathways, at both central and peripheral levels.
The biological action of eCBs is tightly controlled by a plethora of metabolic enzymes which, together with the molecular targets of these substances, form the so-called “endocannabinoid system”.
The ability of eCBs to control manifold peripheral functions has received a great deal of attention, especially in the light of their widespread distribution in the body.
In particular, eCBs are important regulators in blood, where they modulate haematopoiesis, platelet aggregation and apoptosis, as well as chemokine release and migration of immunocompetent cells.
Here, we shall review the current knowledge on the pathophysiological roles of eCBs in blood. We shall also discuss the involvement of eCBs in those disorders affecting the haematological system, including cancer and inflammation.
Knowledge gained to date underlines a fundamental role of the eCB system in blood, thus suggesting that it may represent a therapeutic promise for a broad range of diseases involving impaired hematopoietic cell functions.”
“The anti-tumor properties of cannabinoids have recently been evidenced, mainly with delta9-tetrahydrocannabinol (THC).
Here we investigated whether the most potent endogenous cannabinoid, arachidonylethanolamide (AEA), could be a candidate.
We observed that AEA induced apoptosis in long-term and recently established glioma cell lines via aberrantly expressed vanilloid receptor-1 (VR1).
In contrast with their role in THC-mediated death, both CB1 and CB2 partially protected glioma against AEA-induced apoptosis.
These data show that the selective targeting of VR1 by AEA or more stable analogues is an attractive research area for the treatment of glioma.”
“Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines.
The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CB1 and CB2 cannabinoid receptors mediated a protective effect…
Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs.”
“Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents.
Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia.
Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.
Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine…
Pretreatment with CBD attenuated the amphetamine-disruptive effects…
These results corroborate findings indicating that CBD induces antipsychotic-like effects.
In addition, they pointed to the nucleus accumbens as a possible site of these effects.”
http://www.ncbi.nlm.nih.gov/pubmed/25943166
http://www.thctotalhealthcare.com/category/schizophrenia/