Ho Claudia, Martinusen Dan, Lo Clifford
Fraser Health Renal Program, Surrey, BC, Canada.
University of British Columbia, Vancouver, Canada.
Can J Kidney Health Dis. 2019 Feb 22;6:2054358119828391. doi: 10.1177/2054358119828391. eCollection 2019.
Physical and psychological symptom burden in patients with advanced chronic kidney disease (CKD) is significantly debilitating; yet, it is often inadequately treated. Legalization of cannabis in Canada may attract increasing interest from patients for its medical use in refractory symptom management, but its indications and long-term adverse health impacts are poorly established, creating a challenge for clinicians to support its use. In this review, we summarize key clinical studies and the level of evidence for nonsynthetic cannabinoids in the treatment of common symptoms encountered in advanced stages of CKD, including chronic pain, nausea and vomiting, anorexia, pruritus, and insomnia.
Medline and Embase.
A search was conducted in MEDLINE and EMBASE (inception to March 1, 2018) on cannabis and CKD symptoms of interest, complemented with a manual review of bibliographies. Studies that examined synthetic cannabinoids that are manufactured to mimic the effects of ∆9-tetrahydrocannabinol such as dronabinol, levonantradol, nabilone, and ajulemic acid were excluded. We focused on studies with higher level of evidence where available, and quality of studies was graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence (1a to 5).
Based on studies conducted in patients without renal impairment, those treated with nonsynthetic cannabinoids were 43% to 300% more likely to report a ≥30% reduction in chronic neuropathic pain compared with placebo. However, there is currently insufficient evidence to recommend nonsynthetic cannabinoids for other medical indications, although preliminary investigation into topical endocannabinoids for uremia-induced pruritus in end-stage renal disease is promising. Finally, any benefits of cannabis may be offset by potential harms in the form of cognitive impairment, increased risk of mortality post-myocardial infarction, orthostatic hypotension, respiratory irritation, and malignancies (with smoked cannabis).
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.
Until further studies are conducted, the role of nonsynthetic cannabinoids for symptom management in patients with CKD should be limited to the treatment of chronic neuropathic pain. Clinicians need to be cognizant that nonsynthetic cannabinoid preparations, particularly smoked cannabis, can pose significant health risks and these must be cautiously weighed against the limited substantiated therapeutic benefits of cannabis in patients with CKD.
晚期慢性肾脏病（CKD）患者的身体和心理症状负担严重影响生活质量，但往往未得到充分治疗。加拿大大麻合法化可能会使患者对其在难治性症状管理中的医疗用途兴趣增加，但其适应证和长期健康不良影响尚不明确，这给临床医生支持其使用带来了挑战。在本综述中，我们总结了关键临床研究以及非合成大麻素治疗CKD晚期常见症状（包括慢性疼痛、恶心和呕吐、厌食、瘙痒和失眠）的证据水平。
Medline和Embase。
在MEDLINE和EMBASE（从创刊至2018年3月1日）中检索大麻与感兴趣的CKD症状相关文献，并人工查阅参考文献。排除研究合成大麻素（如屈大麻酚、左南曲朵、纳布啡和阿居米酸等，这些是为模拟∆9-四氢大麻酚的作用而制造的）的研究。我们重点关注现有证据水平较高的研究，并根据牛津循证医学中心证据水平（1a至5级）对研究质量进行分级。
基于在无肾功能损害患者中开展的研究，与安慰剂相比，接受非合成大麻素治疗的患者报告慢性神经性疼痛减轻≥30%的可能性高出43%至300%。然而，目前尚无足够证据推荐非合成大麻素用于其他医学适应证，尽管对局部内源性大麻素治疗终末期肾病尿毒症性瘙痒的初步研究前景良好。最后，大麻的任何益处可能会被认知障碍、心肌梗死后死亡风险增加、体位性低血压、呼吸道刺激以及恶性肿瘤（吸食大麻时）等潜在危害所抵消。
各研究间非合成大麻素制剂差异很大，样本量小，研究持续时间短。由于缺乏在CKD患者中开展的研究，建议主要从普通人群研究中推断得出。
在进一步研究开展之前，非合成大麻素在CKD患者症状管理中的作用应仅限于治疗慢性神经性疼痛。临床医生需要认识到，非合成大麻素制剂，尤其是吸食大麻，可能会带来重大健康风险，必须谨慎权衡其在CKD患者中有限的已证实治疗益处与这些风险。
