“Psoriasis is a common skin disorder characterized by hyper proliferation of keratinocytes. Although the exact pathophysiology of psoriasis is not entirely understood, immune system and its interaction with nervous system has been postulated and investigated as the underlying mechanism. The interaction between these two systems through cholinergic anti-inflammatory pathway and also endocannabinoid system, may suggest cannabinoids as potential addition to anti-psoriatic armamentarium.”
Tag Archives: treatment
Expression analysis of cannabinoid receptors 1 and 2 in B cells during pregnancy and their role on cytokine production.
“The endocannabinoid system consists in a family of lipids that binds to and activates cannabinoid receptors. There are two receptors so far described, the cannabinoid receptor 1 (CB1) and 2 (CB2).
In the context of pregnancy, the endocannabinoid system was shown participates in different key aspects of reproductive events. B-lymphocytes are pleiotropic cells belonging to the adaptive arm of the immune system. Besides immunoglobulin production, B-lymphocytes were recently shown to be actively involved in antigen presentation as well as cytokine production, thus playing a central role in immunity.
In this study we first aimed to characterize the expression of CB1 and CB2 receptors in B cells during pregnancy and then analyze the impact of their activation in term of cytokine production by B cells from pregnant and non-pregnant mice.
We observed that the expression of CB1 and CB2 receptors in B-lymphocytes is differentially regulated during pregnancy. While CB2 expression is down regulated CB1 is augmented in B-lymphocytes of pregnant mice.
Additionally, the treatment of activated B-lymphocytes with specific CB1 and CB2 agonists, showed a different response in term of cytokine production. Particularly, CB1 against boosted the production of the anti-inflammatory cytokine IL-10 by activated B-lymphocytes from pregnant mice.”
A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease.
“Huntington’s disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD.
We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex®, a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex® and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks.
The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores.
Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex® as compared to placebo. No significant molecular effects were detected on the biomarker analysis.
Sativex® is safe and well tolerated in patients with HD, with no SAE or clinical worsening.
No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers.
Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations. Clincaltrals.gov identifier: NCT01502046.”
Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains.
“Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson’s disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat.
Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.”
The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages
“Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder.
The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells.
The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children.
In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls.
This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.
This study demonstrates a biomolecular effect of GcMAF in BMDMs from autistic patients, providing further evidence for a positive use of this molecule in autism treatment. It also seems likely that the CB2R is a potential therapeutic target for Autism and autism spectrum disorders (ASDs) interventions.”
Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.
“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.
Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.
Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.
SIGNIFICANCE STATEMENT:
The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.
However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.
Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”
The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.
“The authors present case histories indicating that a number of patients find cannabis (marihuana) useful in the treatment of their bipolar disorder.
Some used it to treat mania, depression, or both. They stated that it was more effective than conventional drugs, or helped relieve the side effects of those drugs.
One woman found that cannabis curbed her manic rages; she and her husband have worked to make it legally available as a medicine. Others described the use of cannabis as a supplement to lithium (allowing reduced consumption) or for relief of lithium’s side effects.
Another case illustrates the fact that medical cannabis users are in danger of arrest, especially when children are encouraged to inform on parents by some drug prevention programs.
An analogy is drawn between the status of cannabis today and that of lithium in the early 1950s, when its effect on mania had been discovered but there were no controlled studies.
In the case of cannabis, the law has made such studies almost impossible, and the only available evidence is anecdotal. The potential for cannabis as a treatment for bipolar disorder unfortunately can not be fully explored in the present social circumstances.”
Pharmacological management of agitation and aggression in Alzheimer’s Disease: a review of current and novel treatments.
“Agitation and aggression are common neuropsychiatric symptoms of Alzheimer’s disease and are highly prevalent in people with dementia. When pharmacological intervention becomes necessary, current clinical practice guidelines recommend antipsychotics, cholinesterase inhibitors (ChEIs), and some antidepressants.
However, those interventions have modest to low efficacy, and those with the highest demonstrated efficacy have significant safety concerns. As a result, current research is focusing on novel compounds that have different mechanisms of action and that may have a better balance of efficacy over safety.
The purpose of this review is to evaluate novel pharmacological therapies for the management of agitation and aggression in AD patients. We performed a comprehensive literature search to identify recent novel drugs that are not included in most clinical practice guidelines or are currently undergoing clinical trials for the treatment of agitation and/or aggression in AD.
This review suggests that novel treatments, such as cannabinoids, lithium, non-steroidal anti-inflammatory drugs, analgesics, narcotics, and newer antiepileptic drugs, may provide a safer alternative treatment options for the management of agitation and aggression in AD and requires further study in order to clarify their risks and benefits.”
http://www.ncbi.nlm.nih.gov/pubmed/27137221
http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/
Study: Cannabinoids Limit Neuroblastoma Cell Proliferation
“The administration of the cannabinoids THC and CBD limit cancer activity in neuroblastoma cells in culture and in animals, according to preclinical data published in the journal Current Oncology.
Neuroblastoma is an aggressive form of childhood cancer that often goes inadequately addressed by conventional treatment.
Investigators reported that both types of cannabinoids reduced neuroblastoma cell viability, but that CBD demonstrated superior anti-cancer ability. The study is the first to document the anti-cancer properties of CBD in this particular cancerous cell line.
They concluded, “Our findings about the activity of CBD in nbl (neuroblastoma) support and extend previous findings about the anti-tumor activities of CBD in other tumors and suggest that cannabis extracts enriched in CBD and not in THC could be suitable for the development of novel non-psychotropic therapeutic strategies in nbl.” http://enewspf.com/2016/04/21/study-cannabinoids-limit-neuroblastoma-cell-proliferation/
“In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/?report=reader
The endogenous cannabinoid system protects against colonic inflammation
“Excessive inflammatory responses can emerge as a potential danger for organisms’ health.
Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.
The major active constituent of the plant Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol, and a variety of natural and synthetic cannabinoids have been shown to possess antinociceptive and anti-inflammatory activities.
For millennia, Cannabis preparations have been used in folk medicine for the treatment of a wide variety of disorders, including those affecting the gastrointestinal tract. A century ago, extracts of Cannabis were used in the US to treat gastrointestinal pain of different origins, gastroenteritis, and diarrhea. There are also anecdotal reports suggesting that marijuana may be effective in alleviating symptoms of Crohn disease.
In conclusion, this study shows that the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.
These results strongly suggest that modulation of the physiological activity of the endogenous cannabinoid system during colonic inflammation might be a promising therapeutic tool for the treatment of several diseases characterized by inflammation of the gastrointestinal tract.”
https://www.jci.org/articles/view/19465
“A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation. As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.” http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7