“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…”
“Cancer anorexia-cachexia syndrome (CACS) is a complex metabolic syndrome, different from malnutrition and sarcopenia, which is very common in cancer patients. Treatment for CACS is based on nutritional support and CACS pathophysiology-modulating drugs. The most commonly used are megestrol acetate (MA) and corticosteroids. The efficacy of MA has been confirmed by multiple clinical trials and meta-analyses. Glucocorticoids are also effective but should only be used for short periods and in selected cases. Future strategies should include intensified research into potentially effective drugs (ω-3 fatty acids, thalidomide, cannabinoids, ghrelin, bortezomib, and COX-2 inhibitors), combined treatment and new drugs (anti-IL-6 monoclonal antibodies, melanocortin, β-2 antagonists, and androgen receptor-modulating analogues). We propose a review based on the literature on the pathophysiology of CACS, the diagnostic criteria and treatment, and future strategies.”
“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.”
“Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO). While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST) following the protocol of the German Research Network on Neuropathic Pain (DFNS). Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11) suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG). These data emphasize the high prevalence of neuropathic pain and hyperalgesia in patients with NMO. The degree of mechanical hyperalgesia reflecting central sensitization of nociceptive pathways seems to be controlled by the major brain endocannabinoid 2-AG.”
“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.”
“Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity, whose pathogenesis relies on paradoxical changes of emotional memory processing. An ideal treatment would be a drug able to block the pathological over-consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. While the latter benefit from antidepressant medications, no drug is available to control the cognitive symptomatology. Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.”
“In contextual fear conditioning animals have to integrate various elemental stimuli into a coherent representation of the condition and then associate context representation with punishment. Although several studies indicated the modulating role of endocannabinoid system (ECS) on the associative learning, ECS effect on contextual fear conditioning requires further investigations. The present study assessed the effects of the increased endocannabinoid anandamide (AEA) tone on acquisition, retrieval and extinction of the contextual fear conditioning…
The present study indicates that ECS controls the extinction of aversive memories in the contextual fear conditioning.”
“A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not.
… we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not.
Patients who had ever smoked cannabis had significantly higher current and premorbid IQ compared to patients who had never used cannabis…”
“Cancer patients using cannabis report better influence from the plant extract than from synthetic products… We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients…
All cancer or anticancer treatment-related symptoms showed significant improvement.
No significant side effects except for memory lessening in patients with prolonged cannabis use were noted.
Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients.”
http://www.ncbi.nlm.nih.gov/pubmed/23956774
Full Text: http://www.hindawi.com/journals/ecam/2013/510392/