CBD may provide support for kidney disease through its anti-inflammatory, antioxidant, and analgesic benefits.
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Kidney disease is a severe disease so any potential treatment options should be discussed with a medical doctor. This condition can quickly lead to serious consequences.
Glance at any dialysis discussion board and you’ll find many questions about dietary supplements and alternative drugs, including medical marijuana. While seeking out information is an important part of being empowered to fight kidney disease, the internet is full of doubtful claims and outright false information. Separating fact from fiction—and understanding that supplements and alternative drugs can interact with prescribed drugs or cause harm in other ways—is especially important for kidney patients.
Joshua L. Rein, DO, who led the study, told Healio’s Nephrology News & Issues that kidney patients who may be using cannabis should be aware of potential effects on their kidneys. He said some patients may be using it to treat some of the symptoms of their kidney disease, explaining, “Patients with kidney disease experience significant symptom burden.” And symptoms, such as nausea, lack of appetite and chronic pain, “are all valid issues for medical marijuana usage.”
During the American Society of Nephrology’s Kidney Week conference in October, researchers shared their findings from a recent study on marijuana (or cannabis) use and its effects on kidneys. The research was led by a team at the Icahn School of Medicine at Mount Sinai in New York, who studied kidney disease progression in cannabis users. They found that chronic kidney disease (CKD) patients’ kidney function declined faster in those who used cannabis, compared to those who did not.
The study did not show cannabis to cause kidney disease, or a decrease in kidney function in people who do not already have CKD. Rein believes additional research into the effects of cannabis on CKD patients and kidney health in general is needed.
A growing number of states are legalizing medical marijuana, and some have made it legal for recreational use. But just because a drug is legal, that does not make it safe, or a good idea, for kidney patients.
Due to a lack of studies conducted in patients with CKD, we identified 3 systematic reviews that examined nonsynthetic cannabinoids in patients without renal impairment for a variety of pain conditions. In a large meta-analysis (n = 1370) of nonsynthetic cannabinoids by Whiting et al, 53 7 trials on nabiximols as Sativex ® oromucosal spray (natural extract of 27 mg THC and 25 mg CBD per mL, maximum dose of 8 sprays/3 h or 48 sprays/24 h) and 1 trial on smoked cannabis (3.56% THC inhaled thrice a day for 5 days) were pooled together and included diabetic neuropathy, central neuropathic pain from multiple sclerosis, HIV-associated sensory neuropathy, fibromyalgia, rheumatoid arthritis, and cancer pain. Although a greater proportion of patients in the cannabinoid group achieved a minimum of 30% pain reduction compared with placebo, which is considered moderately clinically meaningful, 54 statistical significance was not achieved (odds ratio [OR] = 1.4 [95% confidence interval (CI) = 0.99-2.00], I 2 = 47.6%). The greatest benefit was driven by the single randomized controlled trial (RCT) with smoked cannabis (OR = 3.43 [95% CI = 1.03-11.48]), 55 which was similar to the effect size seen in a pooled analysis of inhaled cannabinoids by Andreae et al that did achieve statistical significance. Nabiximols demonstrated greater pain reduction on several pain scales, but findings were not consistent across trials and there was no difference in average quality-of-life scores according to the EQ-5D health status index (weighted mean difference= −0.01 [95% CI = −0.05 to 0.02]; 3 trials). Moderate heterogeneity was introduced to the meta-analysis due to the wide assortment of pain conditions that were pooled together. Other limitations of individual studies included short duration of follow-up, ineffective participant blinding secondary to the psychoactive effects of THC, incomplete outcome reporting, and unclear blinding of outcome observer, leading to possible high risk of detection and performance bias. Whiting et al concluded that based on GRADE methodology, there was overall moderate quality evidence to support the use of cannabinoids in the treatment of chronic pain, which indicates that further research is likely to have an impact on the confidence of estimated effects and potentially change the estimate.
Evidence to support the use of nonsynthetic cannabinoids for CINV is less established: nonsynthetic cannabinoids in CINV were studied in only 3 small RCTs (n < 20) in the form of Sativex ® oromucosal spray and inhaled marijuana 67 -69 (level of evidence 2b). Compared with placebo, Sativex ® oromucosal spray achieved greater complete antiemetic response in 16 patients refractory to standard antiemetic prophylaxis (corticosteroids, 5-HT3 receptor antagonists, metoclopramide) while receiving moderate emetogenic chemotherapy regimens (OR = 3.22, 95% CI = 0.01-0.75). 70 Two older, small RCTs combined preparations of nonsynthetic oral THC followed by inhaled THC if vomiting persisted and found that THC was effective as an antiemetic for low emetogenic chemotherapy regimens, but not for chemotherapy of high emetogenic potential 68,69 (level of evidence 2b). In the study with high emetogenic chemotherapy, THC plasma concentrations achieved were low and the authors attributed this to inadequate inhalation of THC by inexperienced patients. Studies also demonstrated that inhaled cannabis achieved better therapeutic plasma concentrations of THC than the oral route and a linear relationship existed between increasing THC plasma concentration and antiemetic effect. Incidences of nausea and vomiting were 44%, 21%, and 6% with concentrations of <5.0 ng/mL, 5.0 to 10.0 ng/mL, and >10 ng/mL, respectively. Similar to previous studies, the rate of adverse drug reaction (ADR) was high: 80% of patients experienced sedation in the study with low emetogenic chemotherapy. Evidence to support the use of nonsynthetic cannabinoids in CINV is significantly limited by small study sizes and low doses of THC used (1.95%).
What this adds
This review summarizes the evidence for the use of nonsynthetic cannabinoids in common symptoms encountered in chronic kidney disease and potential risks in relevance to renal impairment.
On a procédé à une recherche dans MEDLINE et EMBASE (de leur création jusqu’au 1 er mars 2018) sur le cannabis et les symptômes d’intérêt en contexte d’IRC, puis à un examen manuel des biographies. Ont été exclues les études portant sur le dronabinol, le levonantradol, le nabilone et l’acide ajulémique, des cannabinoïdes synthétiques fabriqués pour reproduire les effets du ∆9-tétrahydrocannabinol. Nous nous sommes intéressés aux études pour lesquelles le niveau de preuve était le plus élevé, et leur qualité a été établie avec le tableau de l’Oxford Centre for Evidence-based Medicine Levels of Evidence (niveaux 1a à 5).
Finally, excretion of THC, mostly as acidic metabolites, occurs predominantly via feces (65%-80%) over days to weeks as a result of significant enterohepatic recirculation and high protein binding. 6 Only 20% to 35% of THC is excreted through the urine; its high lipophilicity leads to high tubular reabsorption and low renal excretion of the unchanged drug. 6,42 The pharmacokinetics of other cannabinoids resemble THC in that there is a large volume of distribution and high protein binding; as a result, they are unlikely to be effectively removed by conventional hemodialysis or peritoneal dialysis. 43 As THC and CBD elimination is primarily achieved through the fecal route with minimal renal excretion, renal dose adjustment is unnecessary for the 2 most abundant cannabinoids in cannabis. Furthermore, in spite of the paucity of pharmacokinetic data of other cannabinoids and their metabolites, the clinical significance of potential accumulation in renal impairment is low given their relative trace amounts in nonsynthetic cannabis. It is unclear whether other compounds, chemical contaminants, or adulterants, particularly in recreational cannabis, may pose nephrotoxic risks. Until clinical trials of cannabis are conducted in severe renal impairment, close monitoring is still highly warranted in CKD.