One way CBD appears to reduce the”cytokine storm” that damages the lungs and kills many individuals with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is proven to reduce inflammation and whose levels are dramatically reduced in the face of this storm.
Dental College of Georgia and Medical College of Georgia researchers reported this summer CBD’s ability to boost oxygen levels and reduce inflammation in addition to physical lung damage in their lab model of deadly adult respiratory distress syndrome, or ARDS.
Now they have shown that apelin levels go way down with the viral infection, which has killed 1 million people globally, and that CBD quickly helps normalize those amounts together with lung function.
“It was dramatic in both directions,” says Dr. Babak Baban, DCG immunologist and associate dean for research, of shifting apelin levels in both circulating blood and lung tissue.
Ideally with ARDS it would increase in areas of the lungs where it’s needed to improve blood and oxygen flow to compensate and to protect.”-Dr. Babak Baban, DCG Immunologist and Associate Dean for Research, Medical College of Georgia at Augusta University
Blood levels of the peptide dropped close to zero in their ARDS version and increased 20 times with CBD, they report in the Journal of Cellular and Molecular Medicine.
Apelin is a pervasive peptide produced by cells in the heart, lung, brain, fat tissue and blood, and is an important regulator in bringing both blood pressure and inflammation down, says Baban, the study’s corresponding author.
When our blood pressure becomes high, by way of instance, apelin levels should go up in the right area, like endothelial cells that line blood vessels, to help bring it down. Apelin should do the exact same to help normalize the significant increases in inflammation in the lungs and related breathing difficulties associated with ARDS.
But when they looked at their ARDS model, apelin did not do either, and rather decreased in the lung tissue itself and the general circulation. Until they gave CBD.
They reported that this summer in the journal Cannabis and Cannabinoid Research that treatment with CBD reduced excessive lung inflammation, enabling improvements in lung function, heathier oxygen levels, and repair of some of the structural damage to the lungs which are timeless with ARDS. The researchers said then more work was required, including discovering how CBD produced the substantial changes in addition to human trials, before it should be included as part of a treatment regimen for COVID-19.
Now they’ve correlated those improvements with regulation of apelin. While they don’t attribute all CBD’s advantages to apelin, they say the peptide clearly has a significant role in this scenario. They also don’t yet know whether the novel coronavirus, or CBD for that matter, have an immediate effect on apelin, or whether those are downstream consequences, but they’re already pursuing answers to these unknowns.
“It is an association; we do not know yet about causative, but it’s a really good indicator of this disease,” Baban says of the bottom line impact of the viral disease on apelin levels.
The familiar spiked virus enters human cells via the also pervasive angiotensin-converting enzyme 2, or ACE2, receptor. “The spike proteins possess only the ideal docking mechanism,” says coauthor Yu. And there’s plenty of common ground between ACE2 and apelin, including the fact that lots of cell types and tissues have , including the lungs.
In actuality, apelin and ACE2 work together to regulate a healthy cardiovascular system and they’re factors in pretty much any condition, like obesity or hypertension, that harm the cardiovascular system, Baban states.
Like other disease, the novel coronavirus seems to upset their positive partnership. The virus’ binding to the receptor for ACE2 was demonstrated to decrease ACE2 levels and increase levels of the potent blood vessel constrictor angiotensin II, because less angiotensin II gets degraded and fewer vasodilators get generated, which worsens the patient’s prognosis.
“Instead of ACE2 helping blood vessels relax, it helps the virus get in the host where it makes more virus rather than helping the lungs relax and do their job,” says Yu.
While the investigators are still putting the pieces together, reduced levels of ACE2 appear to enable less apelin and less protection.
However it happens, their finding of dramatic reductions in apelin in the face of ARDS, makes levels of the protective peptide a potential early biomarker for ARDS and response to treatment efforts, they say.
The new finding was their first in learning more about how CBD generates the beneficial effects they found in their model of ARDS.
Next steps include better understanding the interaction between CBD, apelin and the novel coronavirus including why apelin goes down in the face of the virus and why CBD brings it up. That includes exploring how eliminating apelin impacts ARDS and if CBD produces the identical lung advantage without apelin.
Probably the virus suppresses something which suppresses apelin, they say and CBD interferes. But they doubt the apelin-CBD interaction is the only way the compound, the next most prevalent found in the marijuana plant, works in this and other scenarios.
The studies were enabled by the researchers’ development of a safe, relatively inexpensive model of ARDS by giving a synthetic analog of double-stranded RNA called POLY (I:C). The novel coronavirus also has double-stranded RNA, while ours is single-stranded, so this analog produced a response similar to the virus, including the intense lung damage that has caused the need for ventilator and other intense support measures for patients, and is a major cause of death.
Much as with the SARS-CoV-2 infection, the result is the”cytokine storm” that reflects an over-the-top immune reaction in the lungs, which causes an attack rather than protection.
A third group, the treatment group, obtained POLY ((I:C) and CBD over the same timeframe.
This time they seemed and also found significantly reduced apelin levels in the mice which developed COVID-like symptoms compared to controls. Treatment with CBD normalized the immune response and apelin levels, along with oxygen levels and discoloration and swelling in the lungs feature of this deadly ARDS.
While it has diverse jobs in different places, and levels may rise and fall depending on what’s required, its levels are always measurable from the lungs, one of the reasons it should be a great biomarker, and it’s also generally considered protective, they say.
Apelin’s important, diverse functions include helping ensure the placenta is well supplied with blood and the oxygen and nutrients it carries during a pregnancy. In actuality, DCG and MCG investigators chose to look at apelin because of the work of Dr. Évila Lopes Salles, a postdoctoral fellow with Baban at the DCG Department of Oral Biology and the study’s first author, who was looking at the peptide’s significant effect in gestation and clear anti inflammatory role, Baban says.
CBD seems to be a pure apelin agonist, the investigators say.
