What Is the Best CBD Oil for Kidney Disease?
Are you looking for CBD products that may help with common symptoms of chronic kidney disease (CKD)? Read on to know more about the best CBD oil for kidney disease to help you decide which product to choose to improve wellness.
Compare the CBD Oil for Kidney Disease in 2025
- Spruce 750mg Lab Grade CBD Oil Editor's Pick
- NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil Best Organic
- Spruce 2400mg Lab Grade CBD Oil Editor's Pick
- Avida Full Spectrum CBD Oil Tincture 500mg Best Seller
- cbdMD CBD Oil Tincture Natural 1500mg Best Natural Alternative
- CBDistillery THC Free CBD Oil Tinctures Best THC-Free
- cbdMD CBD Oil Tincture Natural 750mg Best Customer Rated
- NuLeaf Naturals 300mg Full Spectrum Hemp CBD Oil Best Starter
- Hemp Bombs 750mg CBD Oil Best Flavor Range
- Royal CBD Full Spectrum CBD Oil Most Transparent
What Is the Best CBD Oil for Kidney Disease?
What Is the Best CBD Oil for Kidney Disease?
1. Spruce 750mg Lab Grade CBD Oil
cbdc overall score
4.8
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Mid-strength |
No other flavors |
Natural peppermint flavor |
|
Made from 100% organic and natural ingredients |
Overview
Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.
2. NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil
cbdc overall score
5.0
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Pure CBD hemp |
No other flavors |
All natural |
|
Approximately 300 drops total |
Overview
Natural remedy for various illnesses. NuLeaf Naturals’ CBD oil is a whole-plant extract containing a full spectrum of naturally occurring synergistic cannabinoids and terpenes.
3. Spruce 2400mg Lab Grade CBD Oil
cbdc overall score
5.0
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Extra Strength |
Tastes bitter |
No artificial flavoring or colors |
No THC-free option |
Made from 100% organic and natural ingredients |
Overview
The largest bottle of CBD oil that Spruce offers contains 2,400mg of CBD. This is full-spectrum CBD oil, which is the maximum possible potency. Each high potency dropper full contains 80mg of CBD. There are no flavorings in it, which allows for the most CBD to fit in the 30ml bottle.
4. Avida Full Spectrum CBD Oil Tincture 500mg
cbdc overall score
4.6
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Light Spearmint flavor |
No other flavor |
Non-THC, Non-detected in drug test |
Overview
Avida Extracts Full Spectrum CBD oil is the latest iteration of the brand’s advanced Avida CORE Spectrum technology. They use a proprietary full spectrum blend, resulting in the highest naturally occurring Phyto-cannabinoids and Terpenes with THC (<0.3) to support your health.
5. cbdMD CBD Oil Tincture Natural 1500mg
cbdc overall score
4.7
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Various delicious flavors to choose from |
cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options |
Has vegan, organic, and gluten-free ingredients |
|
Free shipping for this particular product within USA |
|
World-class customer service team |
Overview
cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.
6. CBDistillery THC Free CBD Oil Tinctures
cbdc overall score
4.4
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
60-Day Satisfaction Guarantee |
Dropper is a bit shaky |
Various strengths |
|
Oil extracted from aerial plant parts of US grown industrial hemp |
|
Sourced from non-GMO industrial hemp grown in the USA through natural farming practices |
Overview
CBDistillery’s Isolate CBD Oil Tinctures harness the power of pure CBD. CBD Isolate Oil Tinctures include 0.0% THC. When you use CBDistillery CBD Isolate Oil Tinctures, you can be assured you’re using the highest quality CBD on the market.
7. NuLeaf Naturals 300mg Full Spectrum Hemp CBD Oil
cbdc overall score
4.6
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Pure CBD hemp |
No other flavors |
All natural |
A bit pricey compared to competitors |
Approximately 100 drops total |
Overview
This is one of several concentrations from NuLeaf Naturals. As the lowest concentration, it is the company’s best option for those new to CBD oil. The product is lab-tested and fully organic. It is full-spectrum, so it contains THC in small quantities.
8. cbdMD CBD Oil Tincture Natural 750mg
cbdc overall score
4.4
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Vegan and Gluten free |
Does not ship internationally |
Has a third-party lab test |
|
Wide variety of CBD strengths and sizes |
Overview
A 750mg bottle of cbdMD’s Broad Spectrum Oil Tincture does not contain THC. It also has a fairly wide flavor range which is perfect for those who prefer other taste. Vegan consumers are considered since cbdMD offers Vegan products. Aside from all of that, another reason why people love cbdMD is because it’s free from harmful chemicals.
9. Hemp Bombs 750mg CBD Oil
cbdc overall score
3.9
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Wide variety of flavors |
Incomplete information about the product |
Lab test results are complete |
Does not ship to all international countries |
30-day money-back guarantee |
Overview
Hemp Bombs offer CBD Oil Tinctures that come in a 30ml bottle containing 750mg of CBD. They provide a wide range of flavors perfect for those that have a knack for sweets. Consumers can safely intake this because it’s free of chemicals and pesticides. Hemp Bombs also offer a 20% off on products upon subscription.
10. Royal CBD Full Spectrum CBD Oil
cbdc overall score
3.7
CBDC Evaluation Table/Score
Pros | Cons |
---|---|
Rich in phytochemicals including CBD, CBC, CBG, and a variety of flavorful terpenes |
Shipping not specified on website |
More flavors to choose from |
3rd party lab result is currently not available on website |
Extracts contain a whole array of cannabinoids and terpenes from the hemp plant — rather than pure CBD isolate |
Overview
Excellent products and superb customer service. Whenever you want to ask them about the dosage, recommended consumption methods, or which CBD oil will work best for you, just give them a call, send them a message, or get in touch with their social media channels. They won’t leave you with any unanswered questions.
How CBD May Help With Kidney Disease
The endocannabinoid system (ECS) is a nerve cell signaling system that regulates the central nervous system’s function and maintains homeostasis(1).
The ECS consists of cannabinoid receptors CB1 and CB2(2).
CB1 receptors, which are found in the central nervous system, help regulate pain response(3). Meanwhile, CB2 receptors work in the immune system and have anti-inflammatory functions(4). Â
CBD (cannabidiol) has been reported to help manage obesity and weight loss through interaction with CB2 receptors in the ECS. These receptors may give anti-obesity benefits by reducing weight gain and inflammation(5).
Obesity may cause hypertension or high blood pressure(6). Meanwhile, high blood pressure can be linked to kidney failure(7).Â
When blood vessels narrow during high blood pressure, blood flow is reduced. This narrowing eventually damages and weakens the kidneys, which may lead to chronic kidney disease(8).
Additionally, a study in 2018 showed that a low dose of CBD has significantly reduced the resting blood pressure of participants(9).Â
Meanwhile, results of a study suggest that cannabis-based medicines containing cannabinoids like CBD and THC (tetrahydrocannabinol) may also be used for symptom management of some kidney disease symptoms(10).
Studies suggest that CBD may have analgesic properties that can alleviate and help treat chronic pain(11). Kidney disease may show symptoms of back pain(12).Â
A study has shown that people who suffer from kidney disease may have trouble sleeping(13). Meanwhile, CBD and THC have demonstrated that they may have therapeutic potential to treat insomnia(14).
Benefits of Using CBD for Kidney Disease
Analgesics or pain medication used to relieve pain and inflammation from kidney disease may pose detrimental risks if taken in high doses. Additionally, long-term use of these medications may also cause kidney injury(15). Â
According to the National Kidney Foundation, overuse of painkillers may reduce kidney function(16).
Meanwhile, studies have shown that CBD may help relieve chronic pain(17) and have certain anti-inflammatory benefits(18). Additionally, no evidence suggests that CBD can adversely affect kidney function(19).
How Long Does CBD Take to Help With Kidney Disease?
The CBD form, dosage, and administration can determine how long it takes for CBD products to take effect in the body.Â
CBD topicals such as creams, ointments, and edibles take as long as two to four hours before taking effect(20).Â
CBD tinctures and sublingual administration of CBD oil are usually felt within 15 to 30 minutes due to it directly entering the bloodstream(21).Â
How Long Will CBD Help With Kidney Disease?
There are no current clinical studies on how long the effects of CBD in the system can last to help with kidney disease.Â
However, CBD may last in the body depending on the dosage, frequency of consumption, and method of administration(22).
How to Use CBD Oil for Kidney DiseaseÂ
There are several methods to administer CBD oil, such as:
- Oral administration: Oral ingestion allows CBD to pass through the gastrointestinal tract before entering the bloodstream.Â
Edibles and gummies are some examples of oral CBD products.Â
- Sublingual administration: Sublingual (under the tongue) administration lets CBD directly enter the bloodstream as it bypasses the digestive tract.
CBD tinctures are applied under the tongue using droppers or sprays.
- Topical application: Topical CBD products are applied to the skin for localized pain relief(23). CBD creams, ointments, balms, and lotions are examples of CBD topical products.
- Inhalation method: CBD may be inhaled using CBD vape pens. Vaping is a quick way to administer CBD into the body(24).
However, reports have indicated that vaping is linked to lung disease(25). Thus, caution is advised for those who would like to vape CBD. Â
Note that the FDA currently does not endorse CBD oil to treat chronic kidney disease or renal disease. If you experience symptoms of kidney disease, consult your doctor before trying CBD.Â
CBD Dosage for Kidney Disease
There is no set CBD dosage for kidney disease. However, in using CBD or any supplement in general, it is essential to start with small doses.
Start with a low-strength dose and build up slowly to medium or high-strength amounts and observe how it affects you(26).
Talk with your doctor about using CBD products to help with kidney disease. They can recommend the proper CBD dosage for your medical condition.Â
Is CBD Safe for People With Kidney Disease?
Generally speaking, CBD is safe and well-tolerated by the body(27). Additionally, according to the World Health Organization(WHO) report, it is also non-addictive(28).
However, CBD may cause side effects such as drowsiness, lightheadedness, nausea, and diarrhea(29).Â
CBD may also interact with other medications such as antidepressants and pain medications(30).Â
Depression is linked to individuals suffering from chronic kidney disease(31).Â
Consult with your doctor first if you plan to use CBD products with any of these medications.Â
Risks and Side Effects of Using CBD for Kidney Disease
The side effects of CBD may include diarrhea, fatigue, dry mouth, drowsiness, and loss of appetite(32).
CBD products may also contain a grapefruit warning, which means CBD may interfere with the effects of medications for specific medical conditions. This interference may prevent drugs from getting absorbed by the body(33).
Medications that usually have a grapefruit warning are:
- antibiotics
- antiepileptic drugs (AEDs)
- blood pressure medications
- blood thinners
- cholesterol medications
- immunosuppressants
- mood medications
- pain medications
The severity of the interactions caused between grapefruit and the medication may vary depending on the drug’s composition, the amount of grapefruit consumed, and the individual’s health condition(34).
Legality of CBD
In a federal capacity, hemp-derived CBD products with 0.3% or less THC are considered a legal substance(35).
The only FDA-approved cannabis-derived drug is Epidiolex(36). Made with cannabidiol, this drug is prescribed to control seizures caused by two rare forms of epilepsy in children. Â
Some states permit the use of medical marijuana or medical cannabis. Verifying state laws before purchasing CBD oil products is strongly advised.
Product Frequently
Asked Questions
-
How can CBD help with kidney disease?
A study suggests that cannabis-based medicines containing cannabinoids like CBD and THC may be used to manage some symptoms of kidney disease(37).
Individuals with kidney disease often experience back pain(38). CBD may have pain-relieving properties that can reduce chronic pain(39).
Moreover, individuals who suffer from chronic kidney disease or kidney damage may also experience insomnia(40). CBD and THC may have properties to treat insomnia(41).
-
What evidence or research exists to say that CBD helps with kidney disease?
According to a journal published in 2020, chronic pain is one of the leading symptoms of kidney disease or late-stage renal disease(42).
A study has suggested that CBD may induce anti-inflammatory and analgesic effects that may help with chronic pain(43). In addition, CBD does not affect kidney function(44).
-
Is there any evidence that CBD can make kidney disease worse?
No current evidence suggests that CBD can negatively affect kidney function(45).Â
CBD in general is safe and well-tolerated by humans(46). Additionally, CBD does not have the potential for abuse(47).
However, using CBD may have side effects such as lightheadedness, drowsiness, nausea, and diarrhea(48).
Consult your doctor first before taking any CBD products.
-
Will CBD interact with any current medication I may be taking for kidney disease?
CBD products may contain a grapefruit warning. Thus, the use of CBD may interfere with the effects of some medications, such as antidepressants and pain medications(49).
Consult your doctor before taking CBD alongside these medications.
-
Are there other treatments I should consider alongside CBD to help with kidney disease?
Treatment for kidney disease usually involves controlling renal function and reducing the signs, symptoms, and complications caused by the disease(50).
Treatment options include:
- High blood pressure medications.
- Anti-inflammatory medication
- Iron supplementsÂ
- Cholesterol medicationÂ
- Low protein diet
If the kidneys are severely damaged, treatment for end-stage kidney disease or renal failure, such as dialysis or a kidney transplant, may be needed(51).
-
Can I fail a drug test if I use CBD for kidney disease?
CBD is non-psychoactive(52) and does not cause a euphoric high(53). However, CBD products may contain trace amounts of THC, which can build up in the body if taken regularly(54).
An increased level of THC in the bloodstream may cause a positive drug test.
-
What is the dosage for kidney disease?
There is no set CBD dosage for kidney disease. Dosage may vary depending on weight and diet(55). Â
It is essential to consult your doctor first so they may recommend the correct dose for you.
-
What are the benefits of CBD for kidney disease?
Certain pain medications such as painkillers may increase the risk of kidney disease in people who have normal kidney function(56). Â
Using CBD products does not affect kidney function(57).
Additionally, a study has suggested that CBD may have analgesic and anti-inflammatory benefits(58). These properties may be beneficial to those with kidney disease. Individuals with kidney disease may experience chronic pain(59).
- The Endocannabinoid System, Our Universal Regulator
https://www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator - The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390812/ - The Endocannabinoid System, Our Universal Regulator
https://www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator - The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435344/#:~:text=CB2%20is%20believed%20to%20be,during%20brain%20injury%20%5B58%5D. - Role of Cannabinoids in Obesity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163475/ - Obesity-Induced Hypertension
https://www.ahajournals.org/doi/10.1161/circresaha.116.305697#:~:text=Major%20consequences%20of%20being%20overweight,(BP)%20is%20nearly%20linear. - High Blood Pressure and Chronic Kidney Disease. page. 7
https://www.kidney.org/sites/default/files/docs/hbpandckd.pdf - High Blood Pressure & Kidney Disease
https://www.niddk.nih.gov/health-information/kidney-disease/high-blood-pressure - A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470879/ - Is there a legitimate role for the therapeutic use of cannabinoids for symptom management in chronic kidney disease?
https://pubmed.ncbi.nlm.nih.gov/21269798/ - Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107012/ - Chronic Kidney Disease (CKD) Symptoms, Treatment, Causes & Prevention
https://www.kidneyfund.org/kidney-disease/chronic-kidney-disease-ckd/ - Insomnia in Patients With Chronic Kidney Disease
https://pubmed.ncbi.nlm.nih.gov/26355254/#:~:text=Insomnia%20and%20poor%20self%2Dperceived,and%20increased%20morbidity%20and%20mortality - Cannabis, Cannabinoids, and Sleep: a Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/28349316/#:~:text=Recent%20findings%3A%20Preliminary%20research%20into,impair%20sleep%20quality%20long%2Dterm. - Pain Medicines (Analgesics)
https://www.kidney.org/atoz/content/painmeds_analgesics - ibid.
- Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107012/ - Antioxidative and Anti-Inflammatory Properties of Cannabidiol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/ - The nephrologist’s guide to cannabis and cannabinoids
https://journals.lww.com/co-nephrolhypertens/fulltext/2020/03000/the_nephrologist_s_guide_to_cannabis_and.15.aspx - Healing With CBD, page. 193.
https://drive.google.com/file/d/1AGlxnhS2SoFeOXEuysv75bd_C9pEnwsU/view - ibid. page. 192.
- Ibid. page. 195
- Healing With CBD. page 210
https://drive.google.com/file/d/1AGlxnhS2SoFeOXEuysv75bd_C9pEnwsU/view - Best way to take CBD
https://www.projectcbd.org/guidance/best-way-take-cbd - Can vaping damage your lungs? What we do (and don’t) know
https://www.health.harvard.edu/blog/can-vaping-damage-your-lungs-what-we-do-and-dont-know-2019090417734 - CBD dosing
https://www.projectcbd.org/guidance/cbd-dosing - Cannabidiol (CBD), page 5.
https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf - Cannabinoid (CBD) Pre-Review Report, page 14.
https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf - What are the benefits of CBD — and is it safe to use?
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it’s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products. - Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/ - Depression and chronic kidney disease: A review for clinicians
https://pubmed.ncbi.nlm.nih.gov/24658294/ - What are the benefits of CBD — and is it safe to use?
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700 - Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use
www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/ - Grapefruit Juice and Some Drugs Don’t Mix
https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix - FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)
https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd - FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy
https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms - Is there a legitimate role for the therapeutic use of cannabinoids for symptom management in chronic kidney disease?
https://pubmed.ncbi.nlm.nih.gov/21269798/ - Chronic Kidney Disease (CKD) Symptoms, Treatment, Causes & Prevention
https://www.kidneyfund.org/kidney-disease/chronic-kidney-disease-ckd/ - Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107012/ - Insomnia in Patients With Chronic Kidney Disease
https://pubmed.ncbi.nlm.nih.gov/26355254/#:~:text=Insomnia%20and%20poor%20self%2Dperceived,and%20increased%20morbidity%20and%20mortality - Cannabis, Cannabinoids, and Sleep: a Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/28349316/#:~:text=Recent%20findings%3A%20Preliminary%20research%20into,impair%20sleep%20quality%20long%2Dterm. - Pain management for patients with chronic kidney disease in the primary care setting
https://journals.lww.com/tnpj/fulltext/2020/01000/pain_management_for_patients_with_chronic_kidney.4.aspx#:~:text=Pain%20is%20routinely%20reported%20by,(PD)%2C%20experience%20pain. - Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107012/ - The nephrologist’s guide to cannabis and cannabinoids
https://journals.lww.com/co-nephrolhypertens/fulltext/2020/03000/the_nephrologist_s_guide_to_cannabis_and.15.aspx - ibid.
- Cannabidiol (CBD), page 5.
https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf - Cannabinoid (CBD) Pre-Review Report, page 14.
https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf - What are the benefits of CBD — and is it safe to use?
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it’s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products. - Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use
www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/ - Chronic kidney disease
https://www.mayoclinic.org/diseases-conditions/chronic-kidney-disease/diagnosis-treatment/drc-20354527 - ibid.
- Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246936/ - Cannabidiol (CBD)-what we know and what we don’t
https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476 - Can You Take CBD and Pass a Drug Test?
https://www.consumerreports.org/cbd/can-you-take-cbd-and-pass-a-drug-test/ - ibid.
- Pain Medicines (Analgesics)
https://www.kidney.org/atoz/content/painmeds_analgesics - The nephrologist’s guide to cannabis and cannabinoids
https://journals.lww.com/co-nephrolhypertens/fulltext/2020/03000/the_nephrologist_s_guide_to_cannabis_and.15.aspx - Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107012/ - The Prevalence and Severity of Chronic Pain in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/33680484/