“Δ9 -tetrahydrocannabinol (∆9 -THC) is a cannabinoid CB1 /CB2 receptor agonist that produces therapeutic effects such as analgesia and anti-emetic effects…
Collectively, the current results show that pharmacological increases in endogenous AEA and 2-AG simultaneously through inhibition of FAAH and MAGL, respectively, mimics the discriminative stimulus effects of Δ9 -THC.”
http://jpet.aspetjournals.org/content/early/2015/02/24/jpet.115.222836.long
“The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist…
Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.”
http://www.ncbi.nlm.nih.gov/pubmed/25712641
http://www.thctotalhealthcare.com/category/neuropathic-pain/
“Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others.
Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract.
These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut.
…the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field.
Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency.
The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.”
“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).
These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…
This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…
The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.
These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.
They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”
http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw
“Vulnerability to drug addiction depends upon the interactions between the biological make-up of the individual, the environment, and age. These interactions are complex and difficult to tease apart.
Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure.
In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) have been considered a putative protective and risk factor, respectively, that can influence one’s susceptibility to continued drug abuse as well as the transition to addiction.
This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons.
Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle.
In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented.
Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.”
“There is accumulating evidence that cannabidiol (CBD) has anti-inflammatory properties that could be exploited for the symptomatic relief of IBD.
This proof-of-concept double blind, randomised, placebo controlled trial assessed the efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC…
…several signals suggest that GWP42003 may be beneficial for the symptomatic treatment of UC…”
“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.
In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…
The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.
The effect of THC was in part mediated by the cannabinoid receptor CB1.
These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.
THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…
In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models.
This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.
In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.
The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”
“One of the most promising potential medical applications of cannabinoids involves their ability to protect cells from a variety of toxic events.
Cannabinoids have been reported to protect neurons from death…
Cannabinoids, such as the pharmacologically active component of marijuana (-)Δ9-tetrahydrocannabinol (THC)…
The neuroprotective effects of Δ9-tetrahydrocannabinol (THC) were examined…
Protective effects of Delta(9)-tetrahydrocannabinol… THC may function as an antioxidant to increase cell survival…
THC can produce receptor-independent neuroprotective or cellular protective effects at micromolar concentrations as a result of its antioxidant properties…
In conclusion, THC produces a potent neuroprotective effect…”
“Excitotoxic neuronal death underlies many neurodegenerative disorders…
Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity…
…desensitization of CB(1) receptors diminishes the neuroprotective effects of cannabinoids.
This study demonstrates the importance of agonist efficacy and the duration of treatment on the neuroprotective effects of cannabinoids.
It will be important to consider these effects on neuronal survival when evaluating pharmacologic treatments that modulate the endocannabinoid system.”
http://www.ncbi.nlm.nih.gov/pubmed/17140550
“Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity” http://molpharm.aspetjournals.org/content/69/3/691.long
“Cannabinoids protect neurons from excitotoxic injury…
Endogenous or exogenous cannabinoids have shown neuroprotective effects…
The main finding reported here is that cannabinoids protect neurons from excitotoxic injury by a mechanism that involves the activation of CB1R and inhibition of NOS and PKA….
Cannabinoid receptor agonist drugs protect neurons…
By identifying the signaling pathways responsible for cannabinoid effects in animal models of disease and their human counterparts, it may be possible to design more specific and therefore more efficacious cannabinoid-based therapies.”
http://molpharm.aspetjournals.org/content/69/3/691.long