Updated on November 15, 2021
Other pain medications — such as acetaminophen or opiate medications — are metabolized by the liver and eliminated through the kidneys. These drugs have been shown to cause damage to the sensitive cells making up the kidneys, which can lead to a worsening of the condition.
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With that said, many people with kidney disease are turning to CBD as an adjunctive treatment option along with other medications and diet/lifestyle modifications.
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Using this information, you can calculate what a low dose, medium dose, or high dose of CBD may look like.
Note. CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease.
Despite the numerous phytocannabinoids found in marijuana, studies have primarily focused on the most abundant and major active components, cannabidiol (CBD), a nonpsychoactive phytocannabinoid that activates the body’s endocannabinoid system (ECS) during pain, nausea, or inflammation, and ∆9-tetrahydrocannabinol (THC), the principal psychoactive ingredient in marijuana. 19 Effects of THC include muscle relaxation, analgesia, antiemesis, and sedation, but psychosis, anxiety, and psychoactive effects limit its potential therapeutic benefits. 20,21 While THC is a partial agonist of both CB1 and CB2 receptors, CBD is an antagonist with low affinity for both receptors that indirectly inhibits the reuptake and hydrolysis of the endogenous ligand anandamide. 22 Because CBD inhibits the metabolism of THC into its psychoactive metabolite 11-hydroxyTHC, it mitigates THC-induced paranoia and anxiety and potentiates the nonpsychoactive effects of THC through its indirect mechanism. 17 CBD has less analgesic and antiemetic effects than THC; however, its anxiolytic, antipsychotic, anticonvulsant, and neuroprotective properties have raised great interest in its potential therapeutic role. 23 -26
The majority of evidence in pain was derived from patients with neuropathic pain associated with peripheral neuropathy, post-herpetic neuralgia, nerve or spinal cord injury, complex regional pain syndrome, HIV, and diabetes. Despite the exclusion of patients with renal impairment from studies, treatment of neuropathic pain is highly relevant in patients with CKD due to its common occurrence as a diabetic complication in this population. Based on systematic reviews of low to moderate heterogeneity, there is sufficient evidence that, compared with placebo, nonsynthetic cannabinoids can achieve a moderate reduction of chronic neuropathic pain, defined as a minimum of 30% pain reduction 57 (level of evidence 1a). As estimated in the meta-analysis by Andreae et al, the NNT is 5.6 with nonsynthetic cannabinoids. 56 In contrast, a more recent Cochrane systematic review that was published beyond our search date reported the NNT to achieve ≥30% and 50% pain reduction to be 11 (risk difference [RD] = 0.09 [95% CI = 0.03-0.15], P = .004, I 2 = 34%) and 20 (61% vs 29%; RD = 0.38 [95% CI = 0.18-0.58]), respectively. 60 While the study pooled data from both synthetic and nonsynthetic cannabinoids and would have been excluded from our review, the results were primarily driven by nabiximols in the form of the oromucosal spray. These benefits were outweighed, however, by an increase in adverse effects of the nervous system (number needed to harm [NNH] of 3) and associated with higher treatment withdrawal due to adverse events (NNT = 25). With respect to the lower NNT observed in a review by Andreae et al, the authors of the Cochrane review attributed the difference to the inclusion of unpublished studies with negative reviews and the exclusion of studies of short duration (less than 12-week duration) and vague definitions of neuropathic pain in their analysis. When compared with other pharmacological treatments, the NNT to achieve at least moderate pain benefit as defined by Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) for gabapentin in diabetic neuropathy is 6.6 (95% CI = 4.9-9.9) at doses ≥900 mg daily in patients without renal impairment, suggesting nonsynthetic cannabinoids have lower to comparable efficacy at best. 61 Currently, there is inconclusive evidence to comment on the effects of cannabis on other specific types of pain such as cancer pain and multiple sclerosis.
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Adverse Effects of Marijuana
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Finally, it is worth noting that for heavy cannabis users, cannabis withdrawal syndrome has been noted to occur during conventional hemodialysis. Nervousness, irritability, restlessness, twitch, nausea, stomach pain, increased appetite, and muscle pain occurred in one case report at hour 3 of dialysis as THC may be more dialyzed than previously thought. 107 In addition, there are at least 7 case reports of cannabinoid hyperemesis syndrome–associated prerenal acute kidney injury and dehydration from intractable vomiting and, in a few cases, concomitant compulsive hot showering. 108 -114 Cannabinoid hyperemesis syndrome is associated with chronic cannabinoid use and is characterized by recurrent nausea, vomiting, abdominal pain, and frequent hot bathing, a learned behavior that temporarily alleviates the syndrome. Clinicians should be aware that cannabinoid hyperemesis syndrome may initially be viewed as uremic symptoms so a routine inquiry into cannabis use is prudent. 115
With respect to metabolism, cannabinoids are mainly dependent on the liver and, to a lesser extent, on the heart and lungs. 28 -30 Specifically, hepatic cytochrome 450 (CYP450) isoenzymes 2C9 and 3A4 are involved in the metabolism of THC, while CBD is metabolized by 3A4, but inhibits 2C9, 2D6, and 2C19. 31 -33 Data on drug interactions between marijuana use and other medications are scarce, but similar to the effects of polycyclic aromatic hydrocarbons in cigarette smoking, inhalation of marijuana results in CYP1A1 and CYP1A2 induction. 34 As a result, marijuana can not only increase the clearance of drugs that are CYP1A2 substrates, such as chlorpromazine, clozapine, olanzapine, and theophylline, but the combined use of tobacco and marijuana can also have additive clearance on these drugs. 30,35,36 Moreover, the effect on drug clearance is dependent on the frequency of marijuana use: increased clearance of theophylline was only observed with the use of ≥2 marijuana joints per week, but not with occasional use or <1 joint per week. 37 As a CYP3A4 substrate, THC serum concentration is reduced by strong CYP3A4 inducers such as rifampin and ketoconazole, which have been documented to alter the metabolism of Δ9-THC/CBD oral mucosal spray (Sativex ® ). 38 Other CYP3A4 and CYP2C9 inhibitors such as clarithromycin, cyclosporine, voriconazole, fluconazole, verapamil, amiodarone, cotrimoxazole, metronidazole, and fluoxetine would also be expected to inhibit THC elimination. For CBD, inhibition of CYP2D6 can reduce the metabolism of warfarin and diclofenac, thereby raising serum levels. 39 By inhibiting CYP2C19, CBD can also increase the plasma concentration of clobazam and its active metabolite N-desmethylclobazam. 40 The product monograph of Sativex ® also warns of increased effects of amitriptyline and fentanyl due to CYP2C19 and CYP3A4 interactions. 41 As a result, during both initiation and discontinuation of marijuana use, consideration should be given to possible altered drug response from such interactions.
Nonsynthetic cannabinoid preparations were highly variable between studies, sample sizes were small, and study durations were short. Due to an absence of studies conducted in CKD, recommendations were primarily extrapolated from the general population.
Although increased appetite is a known effect, there is currently inadequate evidence to support or disprove the use of nonsynthetic cannabinoids as appetite stimulants in uremia-induced anorexia and cachexia in patients with CKD due to a lack of studies in this population. There is some literature to support the short-term use of cannabis and oral cannabinoids in improving appetite and weight gain in patients with HIV- and AIDS-associated wasting syndrome, but the pathophysiology of this condition is significantly different from uremic anorexia. As well, these benefits have not been replicated in other types of anorexia including cancer-associated anorexia and anorexia nervosa.