Otsuka declined to comment to The American Independent on how close Sativex is to FDA approval or how far along the Phase III trials are, but Phase III is typically the final step in a drug’s path to pharmacies. Even getting to Phase III means the FDA has signed off on earlier test results and needs to see them confirmed in a large-scale study before advancing the drug.
In 1915, Walter Bradford Cannon, M.D., discovered the stress response– changes in emotions are accompanied by predictable changes in heart rate, blood pressure, respiration and digestion– and thereby made a significant contribution to psychology and medicine. However, Cannon presumed that the brain was in control of the entire process.
In 1960s and 1970s John and Beatrice Lacey were some of the first modern psychophysiological researchers to examine information flow between the brain and the heart and observe that the heart communicates with the brain in ways that significantly affect human perception and reactions to the world. In 1974, French neurophysiologists Gahery and Vigier discovered a neural pathway and mechanism whereby input from the heart to the brain could "inhibit" or "facilitate" the brain’s electrical activity ("Inhibitory effects in the cuneate nucleus produced by vago-aortic afferent fibers." Brain Research. Volume 75, Issue 2, 26 July 1974, Pages 241-246. DOI:10.1016/0006-8993(74)90744-6.). Working with cats, Gahery and Vigier stimulated the vagus nerve and found that the brain’s electrical response was reduced to about half its normal rate. Therefore, the new evidence suggested that the heart and nervous system were not simply following the brain’s directions as previously assumed since Cannon.
In 1991, an early pioneer in neurocardiology, Dr. J. Andrew Armour, introduced the concept of a functional "heart brain." Armour found that:
The heart’s nervous system contains around 40,000 neurons, called sensory neurites, which detect circulating hormones and neurochemicals and sense heart rate and pressure information. Hormonal, chemical, rate and pressure information is translated into neurological impulses by the heart’s nervous system and sent from the heart to the brain through several afferent (flowing to the brain) pathways. It is also through these nerve pathways that pain signals and other feeling sensations are sent to the brain. These afferent nerve pathways enter the brain in an area called the medulla, located in the brain stem. The signals have a regulatory role over many of the autonomic nervous system signals that flow out of the brain to the heart, blood vessels and other glands and organs. However, they also cascade up into the higher centers of the brain, where they may influence perception, decision making and other cognitive processes.
The new research showed that the brain and nervous system was really a "distributed parallel processing system" composed of distinct but interplaying groups of neuronal processing centers disbursed throughout the body. Further, the heart had its own built-in nervous system that functions and processes information independently of the brain or the previously identified nervous system (e.g. why a heart transplant works; also see "The heart reinnervates after transplantation." Ann Thorac Surg 2000;69:1769-1781.).
a highly complex, self-organized information processing center with its own functional "brain" that communicates with and influences the cranial brain via the nervous system, hormonal system and other pathways. These influences profoundly affect brain function and most of the body’s major organs, and ultimately determine the quality of life.
[w]hile two-way communication between the cognitive and emotional systems is hard-wired into the brain, the actual number of neural connections going from the emotional centers to the cognitive centers is greater than the number going the other way. [This in part explains] the tremendous power of emotions, in contrast to thought alone. Once an emotion is experienced, it becomes a powerful motivator of future behaviors, affecting moment-to-moment actions, attitudes and long-term achievements. Emotions can easily bump mundane events out of awareness, but non-emotional forms of mental activity (like thoughts) do not so readily displace emotions from the mental landscape.
So, an even more sophisticated application of recent research beyond the aforementioned computer-aided cranial brain-centric biofeedback technique is the self-moderated biofeedback technique of "meditation" or "psychophysiological coherence":
[..] individuals can gain more conscious control over the process of creating increased coherence within and between the mental and emotional systems than might be commonly believed. This, in turn, can lead to greater physiological coherence, manifesting as more ordered and efficient function in the nervous, cardiovascular, hormonal and immune systems. We call the resulting state psychophysiological coherence, as it involves a high degree of balance, harmony and synchronization within and between cognitive, emotional and physiological processes. Research has shown that this state is associated with high performance, reduced stress, increased emotional stability and numerous health benefits.
I don’t think it would make a bad situation worse. I don’t think much could be worse than the present situation that we have when we have the highest number of people in the world being criminalized– many for nonviolent crimes related to marijuana. What I think is horrible about all of this is that we criminalize young people and we use so many of our excellent resources– police resources– for things that are not causing us any problems.
For decades, our country has pursued a wasteful and ineffective policy of marijuana prohibition. As with alcohol prohibition, this approach has failed to control marijuana, and left its trade in the hands of an unregulated and increasingly violent black market. [..]
Our communities would be better served if the criminal justice resources we currently spend to investigate, arrest, and prosecute people for marijuana offenses each year were redirected toward addressing unsolved violent crimes. In short, the present policy is causing more harm than good, and is eroding respect for the law.
Moreover, we are deeply troubled by the consistent and dramatic reports of disproportionate enforcement of marijuana laws against young people of color. Marijuana laws were forged in racism, and have been demonstrated to be inconsistently and unfairly applied since their inception. These are independent reasons for their repeal.
Especially in the current economic climate, we must evaluate the efficacy of expensive government programs and make responsible decisions about the use of state resources. We find the present policies toward marijuana to be bankrupt, and urge their rethinking.
To test this hypothesis, Curran and her colleagues traveled to the homes of 134 volunteers, where the subjects got high on their own supply before completing a battery of psychological tests designed to measure anxiety, memory recall and other factors such as verbal fluency when both sober and stoned. The researchers then took a portion of the stash back to their laboratory to test how much THC and cannabidiol it contained.
The subjects were divided into groups of high (samples containing more than 0.75% cannabidiol) and low (less than 0.14%) cannabidiol exposure, and the data were filtered so that their THC levels were constant. Analysis showed that participants who had smoked cannabis low in cannabidiol were significantly worse at recalling text than they were when not intoxicated. Those who smoked cannabis high in cannabidiol showed no such impairment.
Ilan attributes the positive finding of Curran and her team to their more powerful methodology in analysing subjects’ own smoking preferences. In the United States, government policy dictates that only marijuana provided by the National Institute on Drug Abuse can be used for research — and it "is notorious for being low in THC and of poor quality", says Ilan.
Lester Grinspoon, professor emeritus of psychiatry at Harvard Medical School in Boston, Massachussetts, who has studied the effects of marijuana on patients since 1967, says that Curran’s study is important."Cannabis with high cannabidiol levels will make a more appealing option for anti-pain, anti-anxiety and anti-spasm treatments, because they can be delivered without causing disconcerting euphoria," he says.
In the pre-clinical study conducted under lead researcher, Sean McAllister, PhD at The California Pacific Medical Center Research Institute, cannabidiol (CBD) was delivered directly to cells and found to inhibit tumor mass size, proliferation and invasion of human cancer cells. Also, it was demonstrated that treatment with CBD significantly reduces primary tumor mass as well as the size and number. For more than ten years, McAllister and his scientific team have been investigating the genes responsible for the spread of cancer. Cannibadiol was found in 2007 to inhibit the gene that controls the spread of cancer:
According to cancer researcher Yvez Desprez, Ph.D., "The problem is not the cancer itself, the problem is the spread of the cancer. When this type of gene [Id-1] is expressed, the cells basically go crazy and they’re very aggressive and they metastasize everywhere in the body." Dr. McAllister says, "We could expect that if we create really effective inhibitors against it, we could potentially treat many types of aggressive cancers." (from "Marijuana compound could help fight breast cancer," Nov. 19, 2007, ABC’s KGO-TV San Francisco).
One of the most exciting aspects of this announcement is that CBD may provide one of the only low- or non-toxic therapeutic alternatives to conventional chemotherapy and its associated adverse effects:
Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxic therapies are urgently required. Id-1 [..] has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, down-regulated Id-1 gene expression in aggressive human breast cancer cells in culture. [.. W]e determined pathways leading to the down-regulation of Id-1 expression by CBD and consequently to the inhibition of the proliferative and invasive phenotype of human breast cancer cells. [.. T]wo different syngeneic models of tumor metastasis to the lungs were chosen to determine whether treatment with CBD would reduce metastasis in vivo. We show that CBD inhibits human breast cancer cell proliferation and invasion [..]. Moreover, [..] we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression. (from "Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis," Sept. 22, 2010)
Although this is the very careful, conditional language of the bench scientist, this is a pretty big deal– even for research considered at an early stage.
[.. t]he findings will need to be followed up with clinical trials in humans to see if the CBD is safe, and whether the beneficial effects can be replicated. Several cancer drugs based on plant chemicals are already used widely, such as vincristine – which is derived from a type of flower called Madagascar Periwinkle and is used to treat breast and lung cancer. It will be interesting to see whether CBD will join them. (from "Cannabis compound ‘halts cancer’" Nov. 19, 2007, BBC News)
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