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Mravec et al. (2008). Neurobiology of Cancer and Mind-Body Medicine’s Hypnotherapy

Bhattacharjee & Khuda-Bukhsh. (2012). Two Homeopathic Remedies Provide Protective Effects Against Hepatotoxicity Induced by Carcinogens…

Mravec et al. (2008). Neurobiology of Cancer and Mind-Body Medicine’s Hypnotherapy

Bhattacharjee & Khuda-Bukhsh. (2012). Two Homeopathic Remedies Provide Protective Effects Against Hepatotoxicity Induced by Carcinogens…

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June 26, 2012 by Werner Absenger

In this paper Mravec, Gidron, & Hulin, (2008) discuss some of the known facts about the nervous system and tumorigenesis, but also ask if the brain is capable of monitoring and/or modulating the creation of cancer cells (tumorigenesis). This is crucial especially if we would like to consider the mind-body modality of hypnotherapy to be utilized by cancer patients.

The Abstract:

The interactions between the nervous, endocrine and immune systems are studied intensively. The communication between immune and cancer cells, and multilevel and bi-directional interactions between the nervous and immune systems form the basis for a hypothesis assuming that the brain might observe and regulate the processes associated with the development and progression of cancer. The aim of this article is to describe the data supporting this hypothesis.

The Bottom Line:

According to Yapko (2003) the premise of hypnotherapy is “…the client has valuable abilities that are present but hidden, abilities that can be uncovered and used in a deliberate way to overcome symptoms and problems” (p. 18).

Division 30 of the American Psychological Association has this to say about hypnotherapy: “When using hypnosis, one person (the subject) is guided by another (the hypnotist) to respond to suggestions for changes in subjective experience, alterations in perception, sensation, emotion, thought or behavior” (Division 30, APA, n.d.).

As part of an assignment in one of my graduate hypnosis courses, I was asked to come up with my own interpretation of hypnotherapy, given that there seems to be no definitive answer so far. Based on the readings of Hammond (1998), Krippner (2004) and Yapko (2003) my working definition of hypnosis would be:

“Clinical Hypnosis is a COMMUNICATIONS technique between hypnotist and subject to AMPLIFY (to a possible power of a gazillion) the subject’s AWARENESS of his/her innate ability to heal and thus directly impact the subject’s physiology in order to overcome deliberately symptoms and problems.”

A more academically correct term would be to the nth power! I guess I like a gazillion, because it illustrates the scope and impact of hypnosis much better than nth power.

To continue down this path, lets look if hypnotherapy has ever been used successfully to bring about physiological changes in the body. One such physiological change that comes to mind is accelerated healing. Two papers, Ginandes, Brooks, Sando, Jones, & Aker (2003) and Ginandes & Rosenthal (1999) shed more light on the possibility. The lead author of both papers, Dr. Ginandes of Harvard Medical School, showed that subjects hypnotherapy groups experienced accelerated healing for postsurgical wound healing (2003) and the healing of bone fractures (1999). Dr. Dabney Ewin, M.D. (1983) of Tulane University, on the other hand, has extremely compelling cases for the efficacy of hypnosis in burn patients.

This brings me back to the article “Neurobiology of cancer: Interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain by Mravec et al. (2008).

The authors start with a brief review of the neuro-endocrine-immune interaction as the base for the neurobiology of peripheral diseases such as cancer. Mravec et al. (2008) cite research that points towards the existence of a “sixth sense” so to speak, that is able to detect signals that otherwise are undetectable by the body’s five senses.

They say

“The role of the immune system in tumorigenesis is of relevance to the CNS [central Nervous system] since the nervous and immune systems can bi-directionally communicate by using a conventional chemical language employing peptide and non-peptide neurotransmitters, hormones, cytokines and common receptors” (p.151).

Then Mravec et al. (2008) go on to elaborate on known clinical and experimental data that substantiate the notion that the brain monitors and modulates the creation of cancer cells.

They cite different animal studies which“…might support the assumption that CNS receives signals related to tumorigenesis” (p. 152), before elaborating on human studies that show differences in the activity of brain regions, such as “… reduced prefrontal activation in cancer patients versus control…” (p. 152).

Mravec et al. (2008) then go on to explain their views on the impact of psychosocial factors and stress on cancer incidence and progression. I will elaborate on these in a future post, as they deserve independent analysis.

This brings us to part three of their paper (my favorite) titled “Nervous system and tumorigenesis: questions, assumptions, and hypotheses” (Mravec et al., 2008, p. 154).

The immune system’s sensory functions to detect and monitor tumor cells and Mravec et al. (2008) hypothesize that the cancer cells release molecules that might serve as messengers to directly “inform” (p. 154) the brain about the state of the creation of cancer cells.

Mravec et al. (2008) explore two indirect pathways, a slow, less informative, non-specific humoral pathway. Cytokines are part of this pathway and the authors go on to say that cytokines stimulate the production of prostaglandins, which in turn might be “…crucial messengers that constitute the links between circulatory cytokines and CNS” (p. 154).

The other indirect pathway mentioned by the authors is the neural pathway, which might be exceedingly location-specific and fast. In other words, the immune system can reach the CNS via peripheral nerves with cytokines playing a significant role, as well. This is illustrated by data that show “…vagal sensory neurons themselves express mRNA for IL-1 receptors, suggesting a direct reaction of afferent vagal fibers to peripheral IL-1” (Mravec et al., 2008, p. 154). This means that cytokines might activate the vagus nerve to disseminate information from the immune system to the CNS.

One last example I’ll list here is a situation in which levels of pro-inflammatory cytokines are low, but nonetheless, somehow these low levels of cytokines are able to contribute to the formation of cancer cells. This involves paraganglia (visceral sensors) that support the transmission of data from the immune system to the brain via the vagus nerve. These structures contain cells that are able to manifest IL-1 receptors, providing a vital link between immune and nervous system (Mravec et al., 2008).

What about direct transmission of information about cancer to the brain?

Mravec et al. (2008) speculate that chemical compounds during tumorigenesis provide enough information to the brain in order for the brain to recognize cancer cells. While uncertain, Mravec et al. (2008) speculate that there might a signaling model specific to tumorigenesis at play, which would allow the brain to “detect” cancers.

Because of this “detection” Mravec et al. (2008) speculate that tumorigenesis could be modulated via neurotransmitters that act on cancer cells.

Then the authors go on into a long explanation (which will be explored in future posts) on how the brain might modulate tumorigenic activities. I am going to jump to the last two points Mravec et al. (2008) make, as it pertains directly to mind-body medicine and hypnosis.

Modulation of tumorigenesis by the brain as a new therapeutic approach.

Mravec et al. (2008) hypothesize and cite research that immunomodulation of the autonomic nervous system could represent a new approach to cancer therapy. This could be achieved by mapping areas of the brain, which regulate various immune functions. For example, natural-killer cell (NK) activity is germane to quash cancer cells, whereas elevated right-hemisphere activity is associated with reduced NK cell activity.

So, if one could then modify the activity of the specific brain regions and structures that are associated with the regulation of specific immune functions, as suggested by Mravec et al. (2008), one then could claim to use immunomodulation effectively as cancer treatment.

And finally, we have come full circle in the role of the CNS, tumor interactions, and mind-body medicine as a therapeutic approach.

Hypnotherapy has been shown to affect brain structures in many different shapes and forms (Halsband, 2006; Halsband, Mueller, Hinterberger, & Strickner, 2009; Rainville, Hofbauer, Bushnell, Duncan, & Price, 2002).

Hypnotherapy has also been used successfully in the cancer patients (Montgomery et al., 2007; Richardson, Smith, McCall, & Pilkington, 2006; Spiegel & Bloom, 1983) just to name a few.

Here, is the website of The Society of Psychological Hypnosis for a bunch of exceptionally reliable information about hypnosis. If you truly desire a front row seat to over one hundred interviews with the world’s greatest hypnosis researchers and clinicians, I encourage you to visit Dr. Eric Willmarth’s site featuring the Willmarth Hypnosis Interviews.

While there are exciting times ahead for hypnotherapy and its role in cancer treatment, please understand that hypnotherapy is used successfully with cancer patients already. As always, please discuss the pros and cons with your primary health care provider, and please, do your homework in finding a reputable hypnotherapist. You might want to start your search by visiting two organizations, which I am a member of The Society of Psychological Hypnosis and SCEH, the Society for Clinical & Experimental Hypnosis.

Image Credit:

Schönpflug, F. (1906). Der Hypnotizeur Fritz Schönpflug. Retrieved from Images from the History of Medicine (NLM) website at http://www.nlm.nih.gov/hmd/ihm/.

References:

Division 30, APA. (n.d.). The official Division 30 definition and description of hypnosis. Retrieved June 26, 2012, from http://psychologicalhypnosis.com/info/the-official-division-30-definition-and-description-of-hypnosis/

Ewin, D. M. (1983). Emergency Room Hypnosis for the Burned Patient. American Journal of Clinical Hypnosis, 26(1), 5–8. doi:10.1080/00029157.1983.10404130

Ginandes, C., Brooks, P., Sando, W., Jones, C., & Aker, J. (2003). Can medical hypnosis accelerate post-surgical wound healing? Results of a clinical trial. The American Journal of Clinical Hypnosis, 45(4), 333–351. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12722936

Ginandes, C., & Rosenthal, D. (1999). Using hypnosis to accelerate the healing of bone fraactures: A randomized controlled pilot study. Alternative Therapies in Health and Medicine, 5(2), 67–75. Retrieved from http://search.ebscohost.com/login.aspx?direct=true&db=cmedm&AN=10069091&site=ehost-live&scope=site

Halsband, U. (2006). Learning in trance: Functional brain imaging studies and neuropsychology. Journal of Physiology-Paris, 99, 470–482. doi:10.1016/j.jphysparis.2006.03.015

Halsband, Ulrike, Mueller, S., Hinterberger, T., & Strickner, S. (2009). Plasticity changes in the brain in hypnosis and meditation. Contemporary Hypnosis, 26(4), 194–215. doi:10.1002/ch.386

Hammond, D. C. (1998). Hypnotic induction and suggestion. Chicago, IL: American Society of Clinical Hypnosis. Retrieved from http://asch.net/books.htm

Krippner, S. (2004). Hypnotic-like procedures used by indigenous healing practitioners. Presented at the Annual Convention of the American Society of Clinical Hypnosis, Anaheim, CA. Retrieved from http://stanleykrippner.com/papers/asch.2004.htm

Montgomery, G. H., Bovbjerg, D. H., Schnur, J. B., David, D., Goldfarb, A., Weltz, C. R., Schechter, C., et al. (2007). A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. JNCI Journal of the National Cancer Institute, 99(17), 1304–1312. doi:10.1093/jnci/djm106

Mravec, B., Gidron, Y., & Hulin, I. (2008). Neurobiology of cancer: Interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain. Seminars in Cancer Biology, 18(3), 150–163. doi:10.1016/j.semcancer.2007.12.002

Rainville, P., Hofbauer, R. K., Bushnell, M. C., Duncan, G. H., & Price, D. D. (2002). Hypnosis modulates activity in brain structures involved in the regulation of consciousness. Journal of Cognitive Neuroscience, 14(6), 887–901. doi:10.1162/089892902760191117

Richardson, J., Smith, J. E., McCall, G., & Pilkington, K. (2006). Hypnosis for Procedure-Related Pain and Distress in Pediatric Cancer Patients: A Systematic Review of Effectiveness and Methodology Related to Hypnosis Interventions. Journal of Pain and Symptom Management, 31, 70–84. doi:10.1016/j.jpainsymman.2005.06.010

Spiegel, D., & Bloom, J. R. (1983). Group therapy and hypnosis reduce metastatic breast carcinoma pain. Psychosomatic Medicine, 45(4), 333–339. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/6622622

Yapko, M. (2003). Trancework : an introduction to the practice of clinical hypnosis (3rd ed.). New York: Brunner-Routledge.

Writing an essay, paper, or report? Cite this story:

APA: W Absenger. (2012.06.26). Mravec et al. (2008). Neurobiology of cancer and mind-body medicine [Web log post]. Retrieved from The Alternative Medicine Blog at http://amacf.org/2012/06/mravec-et-al-2008-neurobiology-of-cancer-and-mind-body-medicine.html

MLA: Absenger, Werner. ” Mravec et al. (2008). Neurobiology of Cancer and mind-body medicine.” The Alternative Medicine Blog. The Alternative Medicine Blog. 26 June. 2012. Web. Insert your date of access here.

June 21, 2012 by Werner Absenger

This team of researchers looked at the effects of potentized cholesterinum used with another homeopathic remedy, Natrum Sulphuricum on carcinogen-induced hepatotoxicity. In other words, the researchers wanted to see if these two homeopathic remedies could reduce damage of cancer causing agents fed to mice.

The Abstract

The purpose of the study was to evaluate whether potentized cholesterinum (Chol) intermittently used with another homeopathic remedy, Natrum Sulphuricum (Nat Sulph) can provide additional benefits in combating hepatotoxicity generated by chronic feeding of carcinogens, p-dimethylaminoazobenzene (p-DAB), and phenobarbital (PB).

Mice were categorized into subgroups: normal untreated (Gr-1); normal + alcohol “vehicle” (Alc) (Gr-2), 0.06% p-DAB + 0.05% PB (Gr-3), p-DAB + PB + Alc (Gr-4), p-DAB + PB + Nat Sulph-30 (Gr-5), p-DAB + PB + Chol-200 (Gr-6), p-DAB + PB + Nat Sulph-30 + Chol-200 (Gr-7), p-DAB + PB + Nat Sulph-200 (Gr-8), and DAB + PB + Nat Sulph-200 + Chol-200 (Gr-9).

Hepatotoxicity was assessed through biomarkers like aspartate and alanine aminotransferases (AST and ALT), acid and alkaline phosphatases (AcP and AlkP), reduced glutathione content (GSH), glucose 6-phosphate dehydrogenase (G6PD), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), and analysis of lipid peroxidation (LPO) at 30, 60, 90, and 120 days and antioxidant biomarkers like superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) were assayed.

Electron microscopic studies (scanning and transmission) and gelatin zymography for matrix metalloproteinases were conducted in liver. The feeding of the homeopathic drugs showed intervention in regard to the increased activities of AST, ALT, AcP, AlkP, GGT, LDH, and LPO and decreased activities of G6PD, SOD, CAT, GR, and GSH noted in the intoxicated mice, more appreciable in Groups 7 and 9. Thus, combined therapy provided additional antihepatotoxic and anticancer effects (Bhattacharjee & Khuda-Bukhsh, 2012, p. 1).

The Bottom Line:

If you are unfamiliar with homeopathy, here is a little more information to become familiarized with the principles of homeopathy. The Western medical tradition generally frowns up homeopathy. That is because remedies are usually diluted to the point at which one could say that too few molecules remain of the original substance in the heavily diluted remedy. In other words, the remedy has been subjected to trituration, dynamization and succession, sometimes beyond Avogadro’s limit (Bhattacharjee & Khuda-Bukhsh, 2012), thus causing great controversy among scientist.

The authors of this paper talk about Natrum Sulphuricum (Nat Sulph) -30 and 200 and cholesterinum (Chol) -200.

To put this in perspective here is a paragraph from Creighton University School of Medicine:

“Supposing 40g of calcium (one mole) were diluted by homeopathic principles starting from 100% pure substance. Avogadro’s number tells us that we have 6.02×10²³ molecules per mole. By 7C the remedy would be expected to contain about 6 billion calcium molecules, and by about 11C, it would be expected to have only about 60 ((1/100)¹¹ x 6.02×10²³ = 60.2). At the 12C (or 24X) dilution, there is a 50/50 chance of one molecule being present. The dilution at which one would expect to have only one molecule does depend upon the starting number of molecules, but assuming that we started with all the atoms estimated to be in the universe, about 6×10⁷⁹ then we end up with a 50% chance to have one molecule left at 40C (or 80X), still far more concentrated than the 200C dilutions that are commonly dispensed (Creighton University School of Medicine, n.d.).

To add to the dilemma of understanding and providing evidence for homeopathic remedies is the clinical trials are plagued with problems. Pitari (2007) points out that, amongst others, homeopathic research requires more rigorous trials and more specific trail methodology. The author presents and illustration in her paper on how to more effectively design research in homeopathic medicine in order to provide credible evidence either for or against efficacy.

Having show that homeopathy is not without controversy, lets look at the results from Bhattacharjee & Khuda-Bukhsh (2012). Because this research was performed on mice, it was possible to tightly control the experiment’s condition.

Observers were blinded as to whether the samples came from the homeopathic remedy groups or placebo treated group and mice were randomized into 9 groups (24 animals in each group), each group receiving a different diet consisting of (Bhattacharjee & Khuda-Bukhsh, 2012, p. 2):

Group 1- Diet 1: Normal
Group 2 – Diet 2: Normal + Alc
Group 3 – Diet 3: p-DAB+PB
Group 4 – Diet 4: p-DAB + PB + Alc
Group 5 – Diet 5: p-DAB + PB + Nat Sulph-30
Group 6 – Diet 6: p-DAB + PB + Chol-200
Group 7 – Diet 7: p-DAB + PB + Nat Sulph-30 + Chol-200
Group 8 – Diet 8: p-DAB + PB + Nat Sulph-200
Group 9- Diet 9: p-DAB + PB + Nat Sulph-200 + Chol-200

In the result section Bhattacharjee & Khuda-Bukhsh (2012) report that on autopsy groups 1 and 2 showed healthy liver, while all the other animals showed tumor growth who received the carcinogens for 60 days or more.

Interestingly enough though the authors report that

As compared to all carcinogen fed mice showing distinct sign of tumor formation in the form of pale reddish multiple nodules, the incidence and intensity of tumor was found to be greater in the carcinogen fed mice (more pronounced in the p-DAB+PB and p-DAB+PB+Alc fed series) at 60, 90, and 120 days, the incidence and growth of tumors found in the drug fed series was less, both numerically and qualitatively. Further, in the conjoint drug fed series, the number of tumors was also lesser than in the single drug fed series (Bhattacharjee & Khuda-Bukhsh, 2012, p.5).

Differences were statistically significant and Nat Sulph-30 plus Chol-200 fed mice positive activities were most pronounced at the 90 day and the 120 intervals, with Nat Sulph-200 alone showing considerable ameliorative effect, while a combination of Nat Sulph-200 and Chol-200 showed the greatest effects (Bhattacharjee & Khuda-Bukhsh, 2012, p. 5).

Here is table 1 from their paper:

In their conclusion the authors reiterate that we don’t know the mechanism of action involved for homeopathic remedies, but proposed a hypothesis that

…Potentized homeopathic drugs might have the ability to act as a ‘molecular trigger’ for switching ‘on and ‘off’ certain relevant gene action/interaction, a series of biochemical changes could follow, that in turn could bring about the alteration observed in the parameters of the present study (Bhattacharjee & Khuda-Bukhsh, 2012, p. 9).

Furthermore the authors point towards nanoparticle research that demonstrated alteration of the “…physico-chemical property of the drug and its biological action during the process of homeopathic dynamization” (Bhattacharjee & Khuda-Bukhsh, 2012, p. 9).

Based on this research one could speculate that both homeopathic remedies could be used to treat human liver disorders associated with cancerous lesions (Bhattacharjee & Khuda-Bukhsh, 2012, p. 9).

But there is one caveat of course, more studies should be performed by other researchers to either confirm or refute these most peculiar findings.

Why peculiar? Remember, based on the tenets of classical physics, chemistry and other know facts about the universe these results should have NOT manifested in the first place.

References:

Bhattacharjee, N., & Khuda-Bukhsh, A. R. (2012). Two homeopathic remedies used intermittently provide additional protective effects against hepatotoxicity induced by carcinogens in mice. Journal of Acupuncture and Meridian Studies, In Press. doi:10.1016/j.jams.2012.05.004

Creighton University School of Medicine. (n.d.). Dynamization. Retrieved June 21, 2012, from http://altmed.creighton.edu/Homeopathy/philosophy/dilution.htm

Pitari, G. (2007). Scientific Research in Homeopathic Medicine: Validation, Methodology and Perspectives. Evidence-Based Complementary and Alternative Medicine, 4(2), 271–273. doi:10.1093/ecam/nel085

Image Credit:

Monnier, H. (n.d.). L’Homéopate et l’alléopate, en présence chez Mr. Jobard, se traient de polissons, se prennent à la gorge et le malade meurt faute de Secours. Retrieved from the Images of History of Medicine website http://www.nlm.nih.gov/hmd/ihm/

Writing an essay, paper, or report? Cite this story:

APA: W Absenger. (2012.06.21). Bhattacharjee & Khuda-Bukhsh. (2012). Two homeopathic remedies provide protective effects against hepatotoxicity induced by carcinogens [Web log post]. Retrieved from The Alternative Medicine Blog at http://amacf.org/2012/06/bhattacharjee-khuda-bukhsh-2012-two-homeopathic-remedies-provide-protective-effects-against-hepatoto.html

MLA: Absenger, Werner. “Bhattacharjee & Khuda-Bukhsh. (2012). Two homeopathic remedies provide protective effects against hepatotoxicity induced by carcinogens ” The Alternative Medicine Blog. The Alternative Medicine Blog. 21 June. 2012. Web. Insert your date of access here.

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