New target in the treatment of pain
Cannabinoids, such as THC, commonly associated with cannabis, are the compounds also produced by the body. One of their functions is to regulate the perception of pain. How can we activate them to effectively fight the pain, while avoiding psychotropic effects and addiction? The team of Dr. Katarzyna Starowicz-Bubak from the Institute of Pharmacology PAS in Kraków will try to answer this question.
The researcher analyses the interactions between endocannabinoids and endovanilloids. Cannabinoids produced inside our body are called endogenous (endocannabinoids). One of these is analog of THC (tetrahydrocannabinol) - anandamide. Endocannabinoid system is an internal system of the body. The results of the work of Dr. Starowicz-Bubak will indicate new directions in the treatment of neuropathic pain. The scientist investigates which systems, receptors or molecules can be affected to cure and relieve chronic pain.
"Our project will not result in a new injection or tablet, which will be available at the pharmacy after completion of the project. We will, however, identify molecules that best confirm our hypothesis, and examine their pharmacological properties" - explained Dr. Starowicz-Bubak. The results of her team can provide guidance to pharmaceutical companies on how to design drugs. At the stage of basic research, licenses or patents are not involved.
The researcher explained that cannabinoids are a group of substances including both naturally occurring compounds in Cannabis sativa, as well as their artificial counterparts. In the body, they regulate motor function, learning and memory processes, control appetite. Also important is their role in the regulation of pain perception.
"Endocannabinoids inhibit pain signals received by the body. Their action, however, involves a problem. If they are administered systemically, then activate all cannabinoid receptors they reach. Meanwhile, it is better not to activate the receptors located in brain regions, associated with memory and cognitive abilities. There may have adverse effects, such as drowsiness, dependence and psychotic symptoms" - said Dr. Starowicz-Bubak.
She explained that pain signal travels from the location of damaged tissue (for example arm or leg), through nerve fibres and spinal cord to the brain. It is a warning signal for the brain.
"Our work focuses maintaining the effectiveness of analgesic compounds, while avoiding side effects. We want to stimulate the cannabinoid receptors only where pain occurs, in specific places on the pain pathway. This is one of the strategies to combat pain by using compounds produced by our body" - said the scientist.
Unfortunately, these findings are not yet a "recipe" for a new analgesic. The researcher noted that endocannabinoids form in the body "on demand", that is, when a given cell or tissue needs them. Apart from signalling molecules, this system also consists of enzymes. They affect the formation of the compounds and then their decay.
"Cannabinoid molecules, such as anandamide, which we are researching, disappear from the environment as soon as they have worked, they are metabolized. Their short +life+ is the biggest problem in the use of endocannabinoids as painkillers. Scientists in many laboratories around the world are looking for ways to inhibit their degradation. If we can inhibit the activity of the enzyme that degrades the molecule, we will achieve a higher concentration of desired substances in the pain spot, and desired analgesic effect" - said Dr. Starowicz-Bubak. Such a compound inhibiting an enzyme is called inhibitor.
The scientist added that a promising substance has already been developed and entered the stage of testing on patients. The drug increases levels of anandamide and relieves various types of pain, without causing psychoactive effects. Unfortunately, studies conducted in patients with rheumatoid arthritis show that in humans this compound is ineffective.
\'We have identified the +culprit+. Our research shows that if we exclude one path of degradation, other, so-called alternative degradation pathways of the compound are activated. Complicated human body reacts quickly and tries to substitute the system we turn off. In addition, activation of alternative degradation mechanisms leads to the formation of a compound with action opposite to that which we expect. Compounds are produced that increase the perception of pain, compounds acting on vanilloid receptors" - explained the doctor.
Vanilloid system prevents the achievement of the analgesic effect because vanilloid receptors are pro-pain. Therefore, the objective is to keep this system off. In the LEADER project "Vanilloid Innovative Therapy" (acronym WINTER) scientists investigate whether a chemical compound (future drug) can contain two types of molecules. One type inhibits an enzyme and prevent a "good" anandamide from disappearing from our body, and the second prevents the activation of the "bad" vanilloid receptors. National Research and Development Centre allocated PLN 989 thousand to this project.
The research project is coming to an end. Scientists are close to demonstrating that the multi-track direction - polypharmacology - is a good strategy for pharmaceutical companies. This is how the companies should design research and look for effective drugs. Compounds should act on several systems, and not just on one specific, narrow purpose. The transformation of molecule into drug by confirming its clinical characteristics and safety in the treatment of certain diseases is the task for pharmaceutical companies.
PAP - Science and Scholarship in Poland, Karolina Olszewska
kol/ agt/ mrt/
tr. RL
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