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CBD helps reduce lung damage from COVID by increasing levels of protective peptide One way CBD appears to reduce the “cytokine storm” that damages the lungs and kills many patients with COVID-19 May be worth further exploring cannabinoids as potential cancer treatment, say researchers It may be worth exploring further the use of cannabidiol (‘CBD’) oil as a potential lung cancer treatment, suggest doctors in BMJ Case Reports after dealing with a daily user whose lung tumour shrank without the aid of conventional treatment. The body’s own endocannabinoids are […]

CBD helps reduce lung damage from COVID by increasing levels of protective peptide

One way CBD appears to reduce the “cytokine storm” that damages the lungs and kills many patients with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is known 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 improve oxygen levels and reduce inflammation as well as physical lung damage in their laboratory 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 worldwide, and that CBD quickly helps normalize those levels along 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.

Blood levels of the peptide dropped close to zero in their ARDS model and increased 20 times with CBD, they report in the Journal of Cellular and Molecular Medicine.

“CBD almost brought it back to a normal level,” Dr. Jack Yu, physician scientist and chief of pediatric plastic surgery at MCG, says of the apparent first connection between CBD and apelin.

Apelin is a pervasive peptide made 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 gets high, for example, apelin levels should go up in the right place, like endothelial cells that line blood vessels, to help bring it down. Apelin should do the same to help normalize the significant increases in inflammation in the lungs and related breathing difficulties associated with ARDS.

“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,” Baban says. But when they looked at their ARDS model, apelin didn’t do either, and instead decreased in both the lung tissue itself and the general circulation. Until they gave CBD.

They reported 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 that are classic with ARDS. The investigators said then more work was needed, including finding how CBD produced the significant changes as well as human trials, before it should be included as part of a treatment regimen for COVID-19.

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Now they have correlated those improvements with regulation of apelin. While they don’t attribute all CBD’s benefits to apelin, they say the peptide clearly has an important role in this scenario. They also don’t yet know whether the novel coronavirus, or CBD for that matter, have a direct effect on apelin, or if these are downstream consequences, but they are already pursuing answers to those unknowns.

“It is an association; we don’t know yet about causative, but it is a very good indicator of the disease,” Baban says of the bottom line impact of the viral infection on apelin levels.

The now familiar spiked virus enters human cells via the also pervasive angiotensin-converting enzyme 2, or ACE2, receptor. ”The spike proteins have just the right docking mechanism,” says coauthor Yu. And there is plenty of common ground between ACE2 and apelin, including the fact that many cell types and tissues have both, including the lungs.

Apelin and ACE2 also normally work together to control blood pressure, and upregulation of both may be helpful in cardiovascular disease, including heart failure, by decreasing blood pressure while increasing the heart’s ability to pump. In fact, apelin and ACE2 work together to regulate a healthy cardiovascular system and they are factors in pretty much any condition, like obesity or hypertension, that hurt the cardiovascular system, Baban says.

Like other disease, the novel coronavirus appears to upset their positive partnership. The virus’ binding to the receptor for ACE2 has been shown to decrease ACE2 levels and increase levels of the powerful blood vessel constrictor angiotensin II, because less angiotensin II gets degraded and fewer vasodilators get produced, which worsens the patient’s prognosis.

“Instead of ACE2 helping blood vessels relax, it helps the virus get into the host where it makes more virus instead of helping the lungs relax and do their job,” says Yu.

While the researchers 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 produces the beneficial effects they saw 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 affects ARDS and if CBD produces the same lung benefit without apelin.

Likely the virus suppresses something that suppresses apelin, they say and CBD interferes. But they doubt the apelin-CBD interaction is the only way the compound, the second most prevalent found in the marijuana plant, works in this and other scenarios.

The studies were enabled by the investigators’ 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 extreme lung damage that has led to the need for ventilator and other extreme 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 response in the lungs, which results in an attack rather than protection.

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For these studies, a control group received intranasal saline for three consecutive days while the COVID-19 model received POLY (I:C) intranasally for three days. A third group, the treatment group, received POLY ((I:C) and CBD over the same timeframe.

This time they looked and also found significantly reduced apelin levels in the mice that developed COVID-like symptoms compared to controls. Treatment with CBD normalized the immune response and apelin levels, along with oxygen levels and swelling and scarring in the lungs characteristic of the deadly ARDS.

“The apelinergic system is a very, very ubiquitous signaling system,” Yu says. While it has diverse jobs in different places, and levels may rise and fall depending on what is needed, its levels are consistently measurable in the lungs, one of the reasons it should be a good biomarker, and it’s also generally considered protective, they say.

Apelin’s important, diverse roles include helping ensure the placenta is well supplied with blood and the oxygen and nutrients it carries during a pregnancy. In fact, DCG and MCG investigators decided to look at apelin because of the work of Dr. Évila Lopes Salles, a postdoctoral fellow with Baban in the DCG Department of Oral Biology and the study’s first author, who was looking at the peptide’s significant impact in gestation and clear anti-inflammatory role, Baban says.

Synthetic agonists that increase apelin levels exist and are showing promise in the laboratory for cardiovascular disease, including slowing the growth rate of weak points in blood vessels called aneurysms. CBD appears to be a natural apelin agonist, the researchers say.

Daily use of cannabidiol (‘CBD’) oil may be linked to lung cancer regression

It may be worth exploring further the use of cannabidiol (‘CBD’) oil as a potential lung cancer treatment, suggest doctors in BMJ Case Reports after dealing with a daily user whose lung tumour shrank without the aid of conventional treatment.

The body’s own endocannabinoids are involved in various processes, including nerve function, emotion, energy metabolism, pain and inflammation, sleep and immune function.

Chemically similar to these endocannabinoids, cannabinoids can interact with signalling pathways in cells, including cancer cells. They have been studied for use as a primary cancer treatment, but the results have been inconsistent.

Lung cancer remains the second most common cancer in the UK. Despite treatment advances, survival rates remain low at around 15% five years after diagnosis. And average survival without treatment is around 7 months.

The report authors describe the case of a woman in her 80s, diagnosed with non-small cell lung cancer. She also had mild chronic obstructive pulmonary disease (COPD), osteoarthritis, and high blood pressure, for which she was taking various drugs.

She was a smoker, getting through around a pack plus of cigarettes every week (68 packs/year).

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Her tumour was 41 mm in size at diagnosis, with no evidence of local or further spread, so was suitable for conventional treatment of surgery, chemotherapy, and radiotherapy. But the woman refused treatment, so was placed under ‘watch and wait’ monitoring, which included regular CT scans every 3-6 months.

These showed that the tumour was progressively shrinking, reducing in size from 41 mm in June 2018 to 10 mm by February 2021, equal to an overall 76% reduction in maximum diameter, averaging 2.4% a month, say the report authors.

When contacted in 2019 to discuss her progress, the woman revealed that she had been taking CBD oil as an alternative self-treatment for her lung cancer since August 2018, shortly after her original diagnosis.

She had done so on the advice of a relative, after witnessing her husband struggle with the side effects of radiotherapy. She said she consistently took 0.5 ml of the oil, usually three times a day, but sometimes twice.

The supplier had advised that the main active ingredients were Δ9-­tetrahydrocannabinol (THC) at 19.5%, cannabidiol at around 20%, and tetrahydrocannabinolic acid (THCA) at around 24%.

The supplier also advised that hot food or drinks should be avoided when taking the oil as she might otherwise feel stoned. The woman said she had reduced appetite since taking the oil but had no other obvious ‘side effects’. There were no other changes to her prescribed meds, diet, or lifestyle. And she continued to smoke throughout.

This is just one case report, with only one other similar case reported, caution the authors. And it’s not clear which of the CBD oil ingredients might have been helpful.

“We are unable to confirm the full ingredients of the CBD oil that the patient was taking or to provide information on which of the ingredient(s) may be contributing to the observed tumour regression,” they point out.

And they emphasise: “Although there appears to be a relationship between the intake of CBD oil and the observed tumour regression, we are unable to conclusively confirm that the tumour regression is due to the patient taking CBD oil.”

Cannabis has a long ‘medicinal’ history in modern medicine, having been first introduced in 1842 for its analgesic, sedative, anti-inflammatory, antispasmodic and anticonvulsant effects. And it is widely believed that cannabinoids can help people with chronic pain, anxiety and sleep disorders; cannabinoids are also used in palliative care, the authors add.

“More research is needed to identify the actual mechanism of action, administration pathways, safe dosages, its effects on different types of cancer and any potential adverse side effects when using cannabinoids,” they conclude.

Notes for editors
Please note: out of respect for patient confidentiality we don’t have the names or contact details of the cases reported in this journal.

Funding: None declared

Link to Academy of Medical Sciences labelling system
https://press.psprings.co.uk/ AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Single case report
Subjects: People

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