Category Archives: Endocannabinoid System

Cannabidiol for the Prevention of Graft-Versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

Posted on by

“Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT).

Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT…

The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/26033282

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells.

Posted on by

“Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression.

Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts…

Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection.”

http://www.ncbi.nlm.nih.gov/pubmed/26034207

Primary Macrophage Chemotaxis Induced by Cannabinoid Receptor 2 Agonists Occurs Independently of the CB2 Receptor.

Posted on by

“Activation of CB2 has been demonstrated to induce directed immune cell migration. However, the ability of CB2 to act as a chemoattractant receptor in macrophages remains largely unexplored…

Taken together our results conclusively demonstrate that CB2 is not a chemoattractant receptor for murine macrophages. Furthermore we show for the first time that JWH133, HU308, L-759,656 and L-759,633 have off-target effects of functional consequence in primary cells and we believe that our findings have wide ranging implications for the entire cannabinoid field.”

http://www.ncbi.nlm.nih.gov/pubmed/26033291

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

Posted on by

“We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size…

We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia…”

http://www.ncbi.nlm.nih.gov/pubmed/26032254

http://www.thctotalhealthcare.com/category/stroke-2/

Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.

Posted on by

Cannabinoid CB1 receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail…

In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis.”

http://www.ncbi.nlm.nih.gov/pubmed/26024113

http://medical-dictionary.thefreedictionary.com/chemotaxis

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been ….

Posted on by

“The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine.

Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science.

However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research.

Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis.

Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence…

The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache.

Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research.

Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered.

Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits.

Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications.”

http://www.ncbi.nlm.nih.gov/pubmed/26015168

http://www.thctotalhealthcare.com/category/headachemigraine/

Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples High Excitability rats.

Posted on by

“Several evidences suggest that endocannabinoids exert a neurotrophic effect on developing mesencephalic dopamine neurons.

Since an altered mesocorticolimbic system seems to underlie hyperactivity and attention deficit in clinical and animal studies of attention deficit hyperactivity disorder(ADHD), prenatal elevation of anandamide has been induced…

The data suggest a corrected unbalance between the two dopamine systems that apparently leads to reducedhyperactivity and modified scanning times in this animal model of ADHD.

This, in turn, might open new strategies in the treatment of a subset of ADHD cases.”

http://www.ncbi.nlm.nih.gov/pubmed/12732229

Association between cannabinoid receptor gene (CNR1) and childhood attention deficit/hyperactivity disorder in Spanish male alcoholic patients

Posted on by

“The CB1 receptor is encoded by the CNR1 gene (6q14–q15), which is known to carry a nine-allele microsatellite polymorphism containing repeats of a single trinucleotide, ATT, which localizes to the 3’UTR of the gene and has been related to drug dependency states in Caucasian populations.

Moreover, a link has been found between this polymorphism and the properties of the event-related wave p300, some studies having suggested that p300 variations might function as a marker for an underlying, hereditary, predisposition to alcoholism.

Moreover, a direct relationship has been found between p300 wave fluctuations and attention deficit/hyperactivity disorder (ADHD). In recent years, the relationship between ADHD and addictions has been stressed. ADHD has been linked to the malfunctioning of catecholaminergic systems, which also play a fundamental role in the brain’s rewarding system.

These data suggest that the link between the cannabinoid system and the p300 wave could be related to some aspects of ADHD.

In this study, we found a quantitative relationship between the largest-sized alleles of the CNR1 gene and the presence of ADHD during childhood in Spanish male alcoholic patients…

To the best of our knowledge, this is the first study relating the CNR1-gene polymorphisms with ADHD in alcoholic patients.

These data are consistent with the fact that the cannabinoid system is known to affect dopaminergic transmission, with the malfunctioning of the dopaminergic system being regarded as a potential physiopathological cause of ADHD. Further studies are needed to determine the functional basis of the observed association.”

http://www.nature.com/mp/journal/v8/n5/full/4001278a.html

Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

Posted on by

Logo of wtpa

“Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoidreceptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory.

…the CNR1 gene may be a risk factor forADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.

These data provide support for a putative role of endogenous cannabinoids in ADHD, and PTSD.

The CNR1gene may contribute to shared underlying risk continua, such as emotional dysregulation in response to stress, across these diverse diagnostic groups. Increased amygdala activity, poor stress reactivity as reflected by HPA response, and poor prefrontal cortical modulation is a plausible underlying mechanism of liability that may be shared across disorders.

Taken together with the current findings, we suggest that this gene may be an important risk variant in the emotional regulation difficulties underlying ADHD, PTSD, and possibly other co-morbid conditions (such as mood disorder); however, the role of CNR1 is likely small, particularly at the level of psychiatric diagnosis, so future work using more refined phenotypes or endophenotypes of affect regulation are necessary.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685476/

Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications.

Posted on by

“Knockout (KO) mice invalidated for the dopamine transporter (DAT) constitute a powerful animal model of neurobiological alterations associated with hyperdopaminergia relevant to schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

CONCLUSIONS:

These data indicate a dysregulated striatal endocannabinoid neurotransmission associated with hyperdopaminergic state.

Restoring endocannabinoid homeostasis in active synapses might constitute an alternative therapeutic strategy for disorders associated with hyperdopaminergia.

In this process, TRPV1 receptors seem to play a key role and represent a novel promising pharmacological target.”

http://www.ncbi.nlm.nih.gov/pubmed/16199010