Sunday, May 26, 2013

Update: Rabbi Kahn

NBC News has a report on my old Rabbi who is opening a cannabis dispensary in Washington, D.C.
But not all religious leaders approve of the rabbi's new venture. Some believe marijuana is immoral. Kahn disputes that charge.

"Morality is not part of the issue," Kahn said. "And what we're dealing with here is getting sick people medicine. We're talking about easing suffering."
You can also read about Rabbi Kahn's visit to Rockford.

H/T The Weed Blog which is full of Jewish/cannabis jokes.

Wednesday, May 8, 2013

Obesity And Endocannabinoids

Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons
Endocannabinoids act retrogradely at presynaptic sites to activate cannabinoid receptor type 1 (CB1) receptors, thereby
inhibiting neurotransmitter release and fine-tuning synaptic transmission. In murine models of obesity with leptin deficiency, we report that orexin-A neurons undergo a shift from predominant control by CB1-expressing excitatory to CB1-expressing inhibitory inputs. In addition, endocannabinoid biosynthesis is increased in these neurons. CB1 activation by endocannabinoids reduces the inhibition of orexinergic neurons in obese mice, thereby enhancing orexin-A release in target brain areas and contributing to hyperphagia and increased body weight, as well as to alterations of hormone levels typical of obesity.
The Daily Mail (UK) has Cannabis-like chemical could help keep couch potatoes slim
A natural cannabis-like chemical in the brain may hold the key to keeping couch potatoes slim, early research suggests.

Scientists in the US found that blocking the compound allowed mice to gorge on high fat food and take little exercise without putting on weight or becoming unhealthy.

The genetically modified animals produced limited amounts of the endocannabinoid 2-AG, a chemical related to the active ingredient in cannabis.

THC and Brain Cancer

Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.

In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy.

Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.

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From the NIH Hypothesis: cannabinoid therapy for the treatment of gliomas?

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Confirmation of the hypothesis: Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells

Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that delta(9)-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.

Full text of the report in pdf

Monday, May 6, 2013

Targeting the Endocannabinoid System to Treat Sepsis

From Signa Vitae:

ABSTRACT
The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state.

From the beginning of the paper:
Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death (figures 1,2). Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally. (1) Within the United States alone, the incidence of sepsis is around 750,000 annually, (2)resulting in more than 200,000 deaths.(3)

Older individuals with fragile immune systems are at a higher risk of developing sepsis after invasive surgical procedures. Concurrently, the proportion of our ageing population has been increasing steadily over the years with 8% of the population being over 60 years old in 1950, 11% in 2009, and predicted to be 22% in 2050. (4) As a result, the incidence of sepsis in North America is projected to rise along with the risk of patient mortality. (2) Unfortunately, current management of sepsis is limited to supportive care, and therapeutic intervention is mainly hindered by the complex pathophysiology and heterogeneous immuno-inflammatory nature of the disease. (5) Although supportive care is beneficial to septic patients, there are no specific therapeutic options available that target the immune system to eliminate septic related mortality. All of these facets have resulted in a significant cost to the heath care system. (2)

The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid 9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors. (7)

The conclusion:
Conclusion
The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.

There is more. Go to Signa Vitae and read the rest.

Sunday, May 5, 2013

Marijuana Cured My Cancer


Los Angeles City Council member Bill Rosendahl: "I thanked God... ...medical marijuana has saved my life."

I don't understand why the endocannabinoid system isn't better appreciated.

NIH: Endocannabinoids in the immune system and cancer.
Modulation of the endocannabinoid system interferes with cancer cell proliferation either by inhibiting mitogenic autocrine/paracrine loops or by directly inducing apoptosis....
And that is only one cite among thousands.

Go to nih.gov and use their search function to search - endocannabinoid cancer - we know a lot. And we are learning more every day.

H/T The Weed Blog

Thursday, May 2, 2013

Endocannabinoids And Autism

New Signaling Pathway found in individuals with Autism.
A recently released study found mutations in individuals with autism that block the action of molecules made by the brain.

The mutations refer to the endocannabinoid signaling pathway that act on the same receptors that are affected by the Marijuana drug. The findings implicate endocannabinoids, in the development of some autism cases and point to potential treatment strategies.

“Endocannabinoids are molecules that are critical regulators of normal neuronal activity and are important for many brain functions,” says first author Dr. Csaba Földy, of Stanford University Medical School. “By conducting studies in mice, we found that neuroligin-3, a protein that is mutated in some individuals with autism, is important for relaying endocannabinoid signals that tone down communication between neurons.”

“These findings point out an unexpected link between a protein implicated in autism and a signaling system that previously had not been considered to be particularly important for autism,” says senior author Dr. Thomas Südhof, also of Stanford. “Thus, the findings open up a new area of research and may suggest novel strategies for understanding the underlying causes of complex brain disorders.”

You can read more here and at Recovery from Autism and at Medical News Today.

Wednesday, May 1, 2013

Endocannabinoids And Obesity

Here is a report on a study of the endocannabinoid systems and obesity:
A switch that occurs in neurons within the hypothalamus could explain the body’s tendency to maintain higher, undesirable weight levels, rather than an ideal weight, according to new research. The switch involves receptors that trigger or inhibit the release of the orexin A peptide, which stimulates the appetite, among other behaviors.

The team of American and Italian neuroscientists found that in normal-weight mice, activation of this receptor decreases orexin A release. In obese mice, activation of this receptor stimulates orexin A release.

“The striking finding is that you have a massive shift of receptors from one set of nerve endings impinging on these neurons to another set,” says Ken Mackie, M.D., professor in the department of psychological and brain sciences in the College of Arts and Sciences at Indiana University Bloomington. “Before, activating this receptor inhibited the secretion of orexin; now it promotes it. This identifies potential targets where an intervention could influence obesity.” Dr. Mackie’s team at the Gill Center for Biomolecular Science at IU Bloomington collaborates with Vincenzo Di Marzo, Ph.D.’s team at the Institute of Biomolecular Chemistry in Pozzuoli, Italy.

Both teams study the endocannabinoid system, which is composed of receptors and signaling chemicals that occur naturally in the brain and have similarities to the active ingredients in marijuana. This neurochemical system is involved in a variety of physiological processes including appetite, pain, mood, stress responses, and memory.

You can read the abstract at NIH: Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons