Familial Atrial Fibrillation

Suggested by The entropic anarchy of the endocannabinoid system.

Pharmacology Is Coming Around

I just got a pitch for a new book on pharmacology. Pharmacology Condensed. Here is what they say about the body's endocannabinoid system.

Cannabinoids are extracts of Cannabis sativa, the marijuana plant, the psychoactive properties of which have been known to humankind for thousands of years. The main active component of marijuana is tetrahydrocannabinol (THC) and recent work has shown that, surprisingly, substances similar to THC occur in the human body and constitute part of the ‘endocannabinoid system’ which has a vital and hitherto unsuspected role in bodily function.

That is a very limited view. Because THC is not the only important cannabinoid. CBD - cannabidiol is another one - among many. But it is a start.

How Cannabis Cures Cancer

Dennis Hill explains how cannabis kills cancer cells in: How Cannabis Oil Works to Kill Cancer Cells.

First let’s look at what keeps cancer cells alive, then we will come back and examine how the cannabinoids CBD (cannabidiol) and THC (tetrahydrocannabinol) unravels cancer’s aliveness.

In every cell there is a family of interconvertible sphingolipids that specifically manage the life and death of that cell. This profile of factors is called the “Sphingolipid Rheostat.” If endogenous ceramide(a signaling metabolite of sphingosine-1-phosphate) is high, then cell death (apoptosis) is imminent. If ceramide is low, the cell is strong in its vitality.

Very simply, when THC connects to the CB1 or CB2 cannabinoid receptor site on the cancer cell, it causes an increase in ceramide synthesis which drives cell death. A normal healthy cell does not produce ceramide in the presence of THC, thus is not affected by the cannabinoid.

There is much more. Follow the link to read it.

Cannabinoid Profiles

Discoverer of THC Dr. Raphael Mechoulam is an Israeli professor of Medicinal Chemistry and Natural Products at the Hebrew University of Jerusalem in Israel.

THC - Delta-9 Tetrahydrocannabinol

THCA - Tetrahydrocannabinolic Acid

THCV - Tetrahydrocannabivarin

CBD - Cannabidiol

CBN - Cannabinol

CBG - Cannabigerol

CBC - Cannabichromene

Cannabinoids And The Reason Why The Establishment Hates Them, Dr Bob Melamede 30Aug2013

Doctor Bob had to put his shirt on. I'd have to put on a few more garments than that to be presentable for video blogging. Dr. Bob notes that the whole is greater than the sum of its parts. That points to the fact that a given cannabis plant cannabinoid mix may be more effective than a single individual cannabinoid.

Scientific Research and Real Facts about the Cannabinoids in Cannabis narrated by an old buddy of mine Peter Coyote.

Cannabis CBD Videos

Here are a few videos about CBDs.


Greenwerkz - How to Get R4

Ganja Geezer

A schizophrenic reports on CBD:

Low THD Hi CBD cannabis strain developed in Israel:




More CBD videos

CBD - Charlotte's Web

This is a video about a special strain of Med Pot with one of the CBDs greatly enhanced.

CB2

Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[34] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [34]

Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.

Pass it on.

H/T The Weed Blog

Helping Schizophrenics

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.

You can find out more about cannabidiol at Endocannabinoids - The Science.

Cannabidiol Reduces Tobacco Use

You can find the full report at Science Direct.

The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. We conducted a pilot, randomised double blind placebo controlled study set out to assess the impact of the ad-hoc use of cannabidiol (CBD) in smokers who wished to stop smoking. 24 smokers were randomised to receive an inhaler of CBD (n = 12) or placebo (n = 12) for one week, they were instructed to use the inhaler when they felt the urge to smoke. Over the treatment week, placebo treated smokers showed no differences in number of cigarettes smoked. In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~ 40% during treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, combined with the strong preclinical rationale for use of this compound, suggest CBD to be a potential treatment for nicotine addiction that warrants further exploration.

CBDs and Breast Cancer

Sean McAllister, PhD said: "CBD could spell the end of breast cancer".

delta9-tetrahydrocannabinol (THC), a mixed CB1 and CB2 receptor agonist, is the primary active constituent of Cannabis sativa and is currently being used in a clinical trial for the treatment of aggressive recurrent glioblastoma multiforme (GBM). Cannabinoids are also being used in clinical trials for purposes unrelated to their direct anticancer activity. The compounds have been reported to be well tolerated during chronic oral and systemic administration. In addition to delta9-THC, cannabidiol (CBD), cannabinol (CBN) and cannabigerol (CBG) are also present in reasonable quantities in Cannabis. CBN has low affinity for CB1 and CB2 receptors, whereas the non-psychotropic cannabinoids, CBD and CBG, have negligible affinity for the cloned receptors. We have determined that these additional cannabinoids are also effective and inhibiting aggressive cancers. Importantly, we have discovered in vitro that a synergistic increase in the antiproliferative and apoptotic activity of cannabinoids can be produced by combining specific ratios of CB1 and CB2 receptors agonists with non-psychotropic cannabinoids.

We are currently determining the molecular mechanism that may explain the synergistic increase in anticancer activity that is observed with the combination treatments. We are also studying whether this combination strategy will lead to greater antitumor activity in vivo.

In addition to the combination therapy project, we are working in collaboration with Dr. Pierre Desprez to develop novel inhibitors of Id-1 using cannabinoid compounds. Id-1 is a helix-loop-helix protein that acts as an inhibitor of basic helix-loop-helix transcription factors that control cell differentiation, development and carcinogenesis. Past research of Id-1 expression in normal and cancerous breast cells, as well as in mouse mammary glands and in human breast cancer biopsies, demonstrated that increased Id-1 expression was associated with a proliferative and invasive phenotype. Specifically, it was found that Id-1 was constitutively expressed at a high level in aggressive breast cancer cells and human biopsies, and that aggressiveness was reverted in vitro and in vivo when Id-1 expression was targeted using antisense technology. Importantly, we have recently discovered that CBD, a nontoxic cannabinoid that lacks psychoactivity, can inhibit Id-1 gene expression in metastatic breast cancer cells and consequently their aggressive phenotype. The down-regulation of expression was the result of the inhibition of the endogenous Id-1 promoter and corresponding mRNA and protein levels. CBD and compounds based off of its structure can therefore potentially be used as therapeutic agents. CBD also inhibits breast cancer metastasis in vivo.

H/T High on Health: CBD in the Food Supply

CBD Science - HPLC Analysis

I used to do electronics design for and also some assembly work on HPLC equipment for Chromatronix in Berkeley, CA. About '67.

SC Laboratories.

A video about HPLC, which when I worked in the field was High Pressure Liquid Chromatography.


Another CBD video. delta9-THC - appetite enhancer. Lists a number of uses for the compound and side effects. Dr Raphael Mechoulam is the Israeli doctor who discovered delta9-THC.


CB2

Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[34] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [34]

Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.

Pass it on.

Update: A different CBD - cannabidiol.


Also see this post CBD - Chalotte's Web.

Update: 20 Feb 2013 1741z

The electronic side of HPLC analysis.

Endocannabinoids - The Science

Today I'd like to do something Republicans do when confronted with a question. Look at the science. The science I'd like to look at is the science of endocannabinoids. Let's start with a definition. An endocannabinoid is a marijuana-like substance produced by the body that acts on specific receptors in the body. There are two known cannabinoid receptor systems in the body. They are the CB1 system and the CB2 system.

Since this is for a non-biochemistry trained audience (I'm an electrical engineer by trade) I'm going to make some simplifications. Those of you who are better trained please excuse my lapses unless they are egregious.

The CB1 system is mostly distributed in nerve tissue of the brain and the spine. The CB2 system is found in the immune system, the peripheral nervous system, the brain, and the digestive system. Various endocannabinoids in the body can either activate or inhibit the operation of the various systems by binding to the receptors in the system. Regulation is achieved by a balance of the chemicals involved. The systems can also evolve by increasing or decreasing the number of receptor sites in response to stimulation (bonding) or a lack of stimulation to those sites.

One of the neurotransmitters in the body that affects these systems is called anandamide which comes from a Sanskrit word which means bliss. The CB1 and CB2 receptors in the body were discovered by tracking where delta9-THC (one of the active ingredients in marijuana) traveled in the body and which receptors it was bound to. From the facts developed by that kind of study a team led by Dr. Raphael Mechoulam at the Hebrew University in Israel discovered the anandamide molecule. As discoverers they got to name it. Dr. Mechoulam is one of the pioneers in the field of cannabinoid science. Why he hasn't won a Nobel for his work is beyond me, unless it has something to do with the prejudices against cannabis. Let me quote (slightly edited for ease of text rendering) from his wiki:

Raphael Mechoulam (born 1930) is an Israeli professor of Medicinal Chemistry and Natural Products at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of delta9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.

All the above is probably enough general information to get you started if you want to delve deeper into the subject matter. Now I want to look at a more controversial aspect of all this. Marijuana. And specifically medical marijuana. As you can see from the above information, cannabinoids in the body affect a large number of systems in the body. I particularly like this quote from the CB2 wiki on the subject.

Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[34] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [34]

That explains why some people claim wonder drug status for marijuana. Except things are not quite as simple as that. Marijuana is not marijuana. What do I mean by that? The anandamide analogs in cannabis are called generically CBDs. They include such chemicals as Cannabigerols (CBG), Cannabidiols (CBD), Tetrahydrocannabinols (THC), Cannabinol (CBN), and a number of other compounds. Their expression in a given cannabis plant varies. Some of the cannabinoids bind to various CB system receptors and some of them prevent binding to a receptor, mimicking the function of the various endocannabinoids in the body. So marijuana is not marijuana. Since there is no regulation in the marijuana industry due to its illegality at the Federal level this has led to various novel names for the different cannabis strains. Names such as "Northern Lights" and "Charlotte's Web". "Charlotte's Web" was named for a child with severe pediatric epilepsy. The strain called "Charlotte's Web" was developed especially to treat her condition. Thus the name. You can check out this eleven minute video introduced by a doctor and her mother to learn more about how this strain was developed and used.

Well obviously we need regulation of medical marijuana. Don't we? My answer is yes. Absolutely. But surprisingly what we are getting is self regulation. And it seems to be working fairly well. Various companies are springing up to fill the analysis void. They do High Pressure Liquid Chromatography and Mass Spectroscopy on submitted marijuana samples to determine the quantities of the various CBDs in the samples. One such company is SC Laboratories in California, but there are a number of others around the country in medical marijuana states.

Obviously the subject is involved and I could go on at much greater length. But I'm not going to do that. Instead I'll leave you with what I think are a few more helpful links.

FDA To Study Cannabis For PTSD - includes a video.
What If Cannabis Cured Cancer - with an appearance by Raphael Mechoulam in the video.
CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. Translation: if you are predisposed to heart disease regular cannabis use may improve your odds of living.
Marijuana Stops Lung Cancer
DEA Judge Rules On Medical Marijuana. The Judge says, "Marijuana, in its natural form, is one of the safest therapeutically active substances known to man."
Conditions treatable by cannabis with links to the medical literature.

And finally to wind this all up what is my political stance on the matter?

Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.