CBD oil side effects on kidneys

Introduction

The side effects of Cannabidiol (CBD) oil reported so far include dry mouth, fatigue, change in appetite, and nausea. But, does CBD oil cause side effects on kidneys? Let us review in this post. 

To precisely understand the gravity of the situation, let us begin with some background facts about kidney disease.

• 10% of people worldwide are affected by Chronic Kidney Disease (CKD). And the number of deaths is increasing each year due to a lack of access to affordable treatment.
• CKD was ranked 18th in the 2010 Global Burden of Disease study.
• CKD is progressively getting identified as a global health problem. 
• The WHO reports that kidney diseases increase the risks of five other complications that include diabetes, hypertension, cardiovascular diseases, HIV, and malaria. 

These alarming facts indicate the pressing need for spreading primary awareness and information about chronic kidney disease among susceptible populations that could help prevent delays in diagnosis and treatment.

What is chronic kidney disease? (CKD)

Let us quickly recall the vital functions performed by the kidneys.

• Kidneys are responsible for producing varieties of hormones that include vitamin D, erythropoietin (EPO), calcitriol, and renin.
• Regulate the flow of body fluids, water, minerals, electrolytes, chemicals, etc.
• Removal and excretion of excess fluids, toxins, and waste products.

When the kidneys are no longer able to carry out these functions, they create lasting damage over time eventually causing chronic kidney disease. (CKD)

If this damage is irreversible, they stop functioning and result in Kidney failure, also called end-stage renal disease (ESRD). At this stage, dialysis or kidney transplant are the only options to support affected patients to stay alive.

Equally important to note that CKD leads to other associated health conditions that affect the blood vessels, heart, nerves, and bones. 

Common causes of kidney disease

Diabetes and high blood pressure are the leading causes of kidney failure cases. 

Some of the other causes that lead to kidney failure are:

• Glomerulonephritis(GN): Glomeruli are tiny clusters of looping blood vessels that filter the blood sent to the kidneys. Damage or inflammation in the glomeruli leads to a leak of proteins and red blood cells through the urine. The excretion process of the kidneys also gets obstructed in such a condition. Hence, waste begins to build up in the blood leading to kidney failure. Infection, toxic drugs, diabetic nephropathy, or lupus are possible causes that lead to such a condition.
• IgA Nephropathy another form of glomerular disease.
• Systemic sclerosis is a condition that arises due to the overproduction of proteins and collagen in various tissues. 
• Genetic reasons that cause polycystic kidney disease.
• Severe urinary tract infection. 
• Prostate enlargement.
• Hypertension.
• Goodpasture Syndrome is a rare autoimmune disease that affects the lungs and kidneys.
• Nephrotic syndrome is another cause that leads to kidney disease. In this condition, the protein content becomes very high in the urine but very low in the blood, accompanied by other complications like high cholesterol, swelling in feet, hands, etc. Although not a disease in itself, it may occur along with other conditions.
• Infection, liver damage or elevated liver enzymes, low blood pressure, blockage in the bladder, injury, or prolonged sickness, and hospitalization could cause a sudden renal failure leading to Acute Kidney Injury (AKI)
• Other generic causes include old age, family history, heart disease, ethnicity, etc.

Side effects of CBD oil and Symptoms of kidney diseases – An analogy

General symptoms of kidney diseases.

• External Itching, Renal Itching or Rash, Uremic pruritus ( chronic itching accompanied by pain)
• Muscle cramps
• Nausea and vomiting 
• Loss of appetite
• Swelling 
• Disturbed sleep
• Short breath
• Frequent urge to urinate
• Back pain
• Diarrhea
• Sexual dysfunction is common in CKD and ESRD

Now let us look at some of the side effects of Cannabidiol(CBD)

• A 2011 study¹ points out that some studies report that CBD can induce side effects like blocking the liver to metabolize drugs, decreased fertilization capacity, decreased hepatic drug metabolism, decreased activities of drug transporting mechanism, and decreased cell viability.

• References from a 2019 study² report excessive sleepiness, sedation and lethargy, fatigue, decreased appetite, diarrhea, vomiting, and abdominal pain.  

We see similarities between the side effects of CBD and the symptoms of kidney disease. That does prompt us to inquire further. Let us discuss.

Some takeaways from the same 2019 study³ are:

• Since the Intraperitoneal ( IP) and Intravenous (IV) routes provided higher bioavailability, they increased the adverse effects and toxicity of CBD. However, the occurrence of such situations is likely in patients receiving treatment for epilepsies and psychiatric disorders. 
• Further research is needed to investigate the after-effects of chronic administration of CBD on hormones, enzymes, interactions with other drugs, drug transporters, and toxicity that affects the DNA.
• Excessive sleepiness and sedative effects of CBD are dose-dependent. In most cases, they occur when administered along with other anti-epileptic drugs, central nervous system (CNS) depressants, and alcohol.
• Broad dosage range and self-medication also influence the adverse side effects of CBD. The study also points to the variability in CBD products available in the form of tablets, capsules, sprays, e-liquids, and oils as a risk that adds to its adverse effects. 

A recent study⁴ indicates that currently available research related to cannabis is biased towards recreational cannabis. 

In the same lines, synthetic cannabinoids (developed for research purposes) are now turning out to be dangerous recreational drugs. Moreover, synthetic cannabinoids do not get detected on standard blood and urine tests. Hence could mislead nephrologists treating patients with AKI. 

Cannabinoid Hyperemesis Syndrome (CHS) is occasionally associated with prerenal AKI.

Other takeaways from this study:

• CBD may increase tacrolimus levels. But a small case study showed that a low dose of CBD administered for chronic pain in kidney transplant patients did not change tacrolimus levels. 

( Tacrolimus test or TAC, is conducted to assess the amount of the drug in the blood to make sure if it has reached a therapeutic level and is below the toxic level. )

Reference from the 2017 study⁵: TAC is an immunosuppressant and used in patients with heart, liver, kidney, or pancreas transplantation.

Adding to this inference, another study⁶ reports the importance of TAC in immunosuppressive therapy in kidney transplantation. At the same time also points out the increased risk of post-transplant diabetes. 

• THC and CBD may interact with the metabolism of prescription medications.
• At a dose of 200mg of oral CBD, maximum plasma concentration showed no change.
• High doses of CBD could increase liver enzymes.
• There is no evidence so far to suggest that CBD has any adverse effect on kidney function.
• If CKD patients used cannabis, they should use the lowest dose and avoid the smoking route to evade pulmonary complications. 

Potential effects of CBD on kidneys: what does the research say?

• The 2017 study⁷ points out the presence of CB1 and CB2 receptors are found in kidneys and could be activated by cannabis ingredients. But considering the type of kidney disease and state of injury, experimental studies show that its effects on kidneys could be detrimental and beneficial.
• Contrary to the above, a 2019 study⁸ reports that although CB1 and CB2 are expressed in the kidneys, the effects of the endocannabinoid system (ECS) in the kidneys are not yet well understood. 
• But the study indicates that preliminary investigations on synthetic cannabinoids used as topicals in uremic pruritus in ESRD are promising.
• When it comes to symptoms of kidney diseases, neuropathic pain is highly relevant in patients with CKD. But, the study concludes that the role of cannabis in symptom management for CKD is limited. It is worth recalling here, the post CBD for back pain highlights the role of topical application of CBD, and its potential to block nociceptive and neuropathic pain. 
• However,⁴ the 2020 study reports that patients with progressive CKD may be more inclined to use medical cannabis for symptom management. It also adds that the National Academies concluded the existence of valuable evidence for the use of cannabis and cannabinoids to treat chronic pain. 

Kidney disease and COVID 19

While the world is still fighting the novel coronavirus, research on it is in swift progress. The magnitude of the epidemic has jolted the medical research fraternity across the globe. 

In this scenario, a new report reveals that people hospitalized for COVID-19 treatment are at a higher risk of developing Acute Kidney Injury(AKI). Kidney tubular injury, increased blood clotting, kidney infections are some of the after-effects of COVID-19, adds the report. Moreover, patients who have recovered from COVID-19 related AKI continue to show lowered kidney functions. 

Therefore, the study recommends such patients get regular consultations from kidney specialists. 

What are the simple lab tests to detect kidney functions?

Kidney diseases are common, painful but they can be treated with early diagnosis. Simple urine and blood tests can help us check our kidney functions.

1. A urine test called albumin creatinine ratio (ACR test) detects the presence of the protein albumin in the urine. Excess protein would indicate CKD and also signal the risk of heart attacks. 
2. A blood test checks the glomerular filtration rate (GFR) and blood sugar (diabetes one of the leading causes of CKD). The GFR will show if your kidneys are functioning well and at what rate the body is removing waste. In healthy conditions, kidneys should be filtering 100 ml/ minute. If it falls below 60 ml/min,  consult a nephrologist immediately.

Key takeaways

• High blood pressure (hypertension) and diabetes are the most common causes of kidney disease. Some simple lifestyle practices could prevent the incidence of the disease. For example, regular exercise, keeping track of your weight, meditation, avoiding alcohol and smoking, reducing salt intake, taking a healthy diet, etc.  

• Kidney diseases are silent and progress without showing any symptoms. Therefore early detection could support timely treatment. Periodical urine and a blood test could help prevent the risk of developing CKD other associated complications. 

• Cannabidiol (CBD), the non-psychoactive compound extracted from hemp plants, possesses immense health benefits and has become a part of routines for many people. Parallelly, clinical evidence is also growing in support of CBD for its potential in managing several conditions that include epilepsy, pain management, depression, anxiety, etc. Although plenty of studies report on their safety profile, the physiological effects of cannabis and cannabinoids on the kidney need more research.

• There are knowledge gaps about concluding the positive or negative effects of CBD on kidneys. They are: trials conducted so far are with a small number of patients with kidney disease, scarce research on the subject of chronic administration of CBD, the effect of CBD on the immune function, hormones, and genotoxicity.

• Besides prescription medication, alternative treatments for managing CKD symptoms are limited. Therefore there is high demand for CBD products. There is a need for guidance and education to patients and healthcare professionals about CBD’s use and side effects for kidney disease.

• The study⁴ emphasizes that consumers should be more informed while using CBD products as the markets remain unregulated.  

• Ensuring to buy high-quality CBD products, checking for proper labels, and third-party lab results are practices that customers could follow. At the same time, chronic kidney disease or acute kidney injury patients self-administering CBD products must be vigilant about drug interactions and consult with their nephrologists. 

References

1. Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49. doi: 10.2174/157488611798280924. PMID: 22129319 [↩]
2. Huestis MA, Solimini R, Pichini S, Pacifici R, Carlier J, Busardò FP. Cannabidiol Adverse Effects and Toxicity. Curr Neuropharmacol. 2019;17(10):974-989.doi:10.2174/1570159X17666190603171901 [↩]
3. Huestis MA, Solimini R, Pichini S, Pacifici R, Carlier J, Busardò FP. Cannabidiol Adverse Effects and Toxicity. Curr Neuropharmacol. 2019;17(10):974-989. doi:10.2174/1570159X17666190603171901 [↩]
4. Rein JL. The nephrologist’s guide to cannabis and cannabinoids. Curr Opin Nephrol Hypertens. 2020;29(2):248-257. doi:10.1097/MNH.0000000000000590 [↩] [↩] [↩]
5. Yuan D, Fang Z, Sun F, et al. Effect of Vitamin D and Tacrolimus Combination Therapy on IgA Nephropathy. Med Sci Monit. 2017;23:3170-3177. Published 2017 Jun 29. doi:10.12659/msm.905073 [↩]
6. Jouve T, Noble J, Rostaing L, Malvezzi P. Tailoring tacrolimus therapy in kidney transplantation. Expert Rev Clin Pharmacol. 2018 Jun;11(6):581-588. doi: 10.1080/17512433.2018.1479638. Epub 2018 May 25. PMID: 29779413. [↩]
7. Park F, Potukuchi PK, Moradi H, Kovesdy CP. Cannabinoids and the kidney: effects in health and disease. Am J Physiol Renal Physiol. 2017 Nov 1;313(5):F1124-F1132. doi: 10.1152/ajprenal.00290.2017. Epub 2017 Jul 26. PMID: 28747360; PMCID: PMC5792153. [↩]
8. Ho C, Martinusen D, Lo C. A Review of Cannabis in Chronic Kidney Disease Symptom Management. Can J Kidney Health Dis. 2019;6:2054358119828391. Published 2019 Feb 22. doi:10.1177/2054358119828391 [↩]