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WesternU researcher challenges Chemotherapy-induced vomiting beliefs

by Rodney Tanaka

August 19, 2009

Read 3 mins

Chemotherapy-induced vomiting is one of the most severe side effects associated with cancer treatment and is a major reason why cancer patients discontinue therapy.

Dr. Nissar A. Darmani, Assistant Dean for Basic Medical Sciences and Research, College of Osteopathic Medicine of the Pacific (COMP) at the Western University of Health Sciences, challenges the long-accepted anatomical and neurotransmitter basis of chemotherapy-induced vomiting that suggest the first phase, also known as the immediate phase of vomiting, is due to the release of Serotonin in the gut, and the second phase, also referred to as the delayed phase, is due to the release of Substance P in the brainstem.

“”The problem with chemotherapy-induced emesis is we can’t stop the vomiting,”” said Darmani, and further elaborated that how only 80 percent of current cancer patients respond to treatment without vomiting with modern antiemetic drug cocktails. “”Based on new anatomical and temporal changes in neurotransmitter levels both in the brain and gut, we need to use time-based differential cocktails of drugs to completely prevent both vomiting phases.””

Recent results from his study of the least shrews, a small mammal that vomits, and more recent human studies, suggest endogenous chemicals exist in the body such as Serotonin, Dopamine, Substance P, Prostaglandins and Leukotrienes, which are temporally released in the gut as well as in the brainstem demonstrating that multi-neurotransmitters are concurrently involved in production of both phases of vomiting in the brain and in the gut.

“”This new proposal will change all relevant medical textbooks and how scientists view vomiting and what happens after a cancer patient takes chemotherapeutics, “”Darmani said.

Darmani recently published an invited review article in Chemical Reviews called “”Evidence for a Re-Evaluation of the Neurochemical and Anatomical Bases of Chemotherapy-Induced Vomiting.”” Dr. Andrew Ray, a WesternU postdoctoral fellow in his laboratory at the time, also contributed to the article. The cited review consists of 41 pages and cites 471 references.

The journal is considered a high impact journal with an approximate impact factor of 23, comparable to Science. An impact factor is a complex formula based on how many times a paper from a journal gets cited.

With more than 70 published manuscripts, Darmani, with this most recent publication, has created a summary of his new findings on emesis, the action of vomiting, as well as findings used from other laboratories, to modernize the old neurotransmitter foundation of chemotherapy-induced vomiting.

Darmani, from Afghanistan, came to America in 1988 from Great Britain to pursue his postdoctoral research at Medical College of Virginia on the effects of marijuana and other drug of abuse and how people get addicted.

Darmani continued to research marijuana even when his research interest was changed from cocaine. An avid reader, Darmani read about a little creature called the shrew and realized they vomit – mice and rats can’t vomit because they have not developed a vomiting reflex – and animals are needed to research diseases. The least shrew is ideal because it has vomiting tendencies similar to those of humans and is very small.

In 2001 Darmani published and first described the mechanism of action of cannabinoids. His research laboratory became the first to show how marijuana stops chemotherapy-induced vomiting. At the time, this study confirmed what hippies from the 1960s and ’70s already knew.

In 2005 he brought a National Institute of Health (NIH) grant worth more than $1 million to WesternU from A.T. Still University (ATSU), Kirksville College of Osteopathic Medicine in Missouri. This grant, called “”Mechanisms of Cannabinoids Antiemetic Actions,”” was funded by the National Institute of Cancer from 2004-09.

Steven Henriksen, PhD, vice president for research and biotechnology at WesternU, oversees all research at the University and believes the work being conducted in support of this review represent an approach that is championed at WesternU for understanding human and animal diseases and their possible cure.

“”Drs. Darmani and Ray have written a timely and thought provoking review of neurochemical basis of chemotherapy-induced vomiting,”” Henriksen said of the side effect of treating many forms of cancer. “”In the review, they provide a comprehensive discussion of the anatomical, physiological and neurochemical underpinnings of this behavior and introduce a revised hypothesis for a mechanism for the complex central and peripheral network of neural and neuro-mediator partners in this complex behavior. This review, and the new hypothesis offered, will provide scientists ample opportunity for further pre-clinical investigations to further test and hone in on the complete understanding of this complex behavior.””


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