New research investigating the effects of anandamide as an airway relaxant, could lead to potential new treatments for asthma and other lung diseases.
In a new study, the endocannabinoid anandamide has been shown to act as an airway relaxant by dilating the lungs’ bronchial tubes affected in conditions such as asthma and COPD.
Anandamide is a fatty acid neurotransmitter, which is produced naturally by the human body and interacts with the endocannabinoid system (ECS). It is perhaps the best known endogenous cannabinoid, binding to both the CB1 and CB2 cannabinoid receptors, the same receptors that THC acts on.
Sometimes known as the ‘bliss’ molecule due to how it makes people feel, the name ‘anandamide’ is taken from the Sanskrit word ananda, which means ‘joy’ and is produced by the body after physical exercise, as well as being found in small amounts in chocolate.
Now researchers have found another potential benefit of anandamide; as an airway relaxant in animals with debilitating lung diseases.
Furthermore, they suggest that a deficiency in the endocannabinoid could be one of the causes of bronchial asthma.
Anandamide and the bronchial tubes
Obstructive lung diseases are the third most common cause of death worldwide. They include chronic obstructive pulmonary disease (COPD), which affects many smokers, as well as bronchial asthma.
During an asthma attack, the bronchial tubes contract so violently that it is no longer possible to exhale – and this can be life-threatening.
“Asthma is an inflammatory process, but what is fatal is the constriction of the bronchial tubes,” explains Annika Simon, lead author of the new study carried out at Ruhr-University Bochum in Germany.
“This is why we are very much interested in the regulation of this constriction.”
In a previous study, the researchers had focused on the body’s endocannabinoid system, specifically on its effect in the blood vessels of the lungs.
Professor Daniela Wenzel, a researcher in the Institute of Physiology, adds: “Since our results show that anandamide dilates the bronchial tubes, we wanted to understand the exact mechanism behind it.”
FAAH enzyme and Anandamide
According to the researchers, it quickly emerged that the two best-known receptors for anandamide (CB1 and CB2) are irrelevant for this regulation. Therefore, there must be an alternative signalling pathway through which the messenger substance anandamide acts on the bronchial tubes.
Professor Wenzel and the team showed that this alternative pathway uses an enzyme called fatty acid amide hydrolase (FAAH).
FAAH degrades anandamide, producing arachidonic acid, which in turn is converted to prostaglandin E2, which can dilate the bronchial tubes, she explains. Prostaglandin E2 acts via certain receptors and leads to an increase in the messenger substance cAMP (cyclic adenosine monophosphate).
“It is precisely this, the increase in cAMP, that is targeted by well-established inhalation medications against asthma,” says Professor Wenzel.
The goal is the same, but the path is different.
Professor Wenzel and her team gradually deciphered the signalling pathway and revealed that the enzyme FAAH is located both in the smooth muscle of the bronchial tubes and in the ciliated epithelium.
The increase in cAMP after anandamide administration could be detected both in the mouse model and in human bronchial cells.
Is asthma linked to an anandamide deficiency?
In order to find out whether anandamide could also work in asthma patients, the team used a disease model in mice where certain substances can be used to create artificial asthma.
In these animals, too, the administration of anandamide led to a widening of the bronchial tubes, suggesting that asthma doesn’t result in resistance to the compound, explains Professor Wenzel.
Moreover, the researchers found that asthmatic animals have less anandamide and other endocannabinoids in their bronchial system than healthy animals.
“Therefore, it’s possible that this anandamide deficiency is one of the causes of bronchial asthma,” concludes Professor Wenzel.
The discovery of the new signalling pathway could also open up new possibilities for intervening in the disease process, although we are still some way off that, she stresses.
“We can’t draw any direct conclusions regarding plant cannabinoids from the findings on endogenous cannabinoids ” Professor Wenzel commented.
Nevertheless, the findings of this study point towards a better understanding of the body’s endocannabinoid system, which could lead to new treatment options for lung diseases in the years to come.
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