Background: Cannabis is increasingly used for management of chronic pain; however, the benefits and harms of this therapy remain uncertain. We conducted a systematic review to inform harms associated with inhaled cannabis for chronic pain. Methods: We searched MEDLINE, EMBASE, PsychInfo, and Web of Science for non-randomized studies reporting on harms associated with inhaled cannabis use, from inception to October 6, 2021. We used random-effects models for meta-analyses and assessed the certainty of evidence using the GRADE approach. Results: We identified 29 eligible studies enrolling 174,562 participants that reported 145 adverse events. Moderate certainty evidence suggests inhaled cannabis use is probably associated with dry mouth (prevalence: 56%; 95%CI 49 to 64), thirst (prevalence: 44%; 95% CI 33 to 55), fatigue (prevalence: 38%; 95%CI 31 to 45), nausea (prevalence: 17%; 95%CI 8 to 27), increased appetite (prevalence: 13%; 95%CI 9 to 18), dizziness (prevalence: 10%; 95%CI 6 to 14), diarrhea (prevalence: 9%; 95%CI 3 to 18), confusion (prevalence: 9%; 95%CI 5 to 13), mood changes (prevalence: 8%; 95%CI 4 to 15), hallucinations (prevalence: 7%; 95%CI 4 to 10), amnesia (prevalence: 6%; 95%CI 3 to 11), impaired coordination (prevalence: 5%; 95%CI 4 to 6), and disorientation (prevalence: 3%; 95%CI 1 to 7). Moderate certainty evidence shows that, compared to non-users, inhaling cannabis is probably associated with increased risk of shortness of breath (risk difference [RD]: 7%; 95%CI 4 to 10). Conclusions: Our review found moderate certainty evidence that dry mouth, thirst, and fatigue are probably frequently experienced with inhaled cannabis use. Several other adverse events are also probable associated with inhaled cannabis use but were less common. Rigorously conducted cohort studies are needed to inform harms associated with inhaled medical cannabis for chronic pain. / Thesis / Master of Science (MSc) / Increasing recognition of harms associated with long-term opioid therapy for management of chronic pain has generated enthusiasm for alternatives, including medical cannabis which is often consumed through inhalation. This review assesses the harms associated with the use of inhaled cannabis for management of chronic pain. Among serious adverse events, we found that inhaled cannabis is likely associated with amnesia, disorientation, impaired coordination, hallucinations, confusion, dizziness, chronic wheeze, and shortness of breath. Inhaled cannabis may be associated with palpitations, paranoia, anxiety, and cannabis dependence. The effects of inhaled cannabis on lung cancer, depression, and psychosis were uncertain. Among less serious adverse events, we found that inhaled cannabis is likely associated with thirst, fatigue, increased appetite, nausea, mood changes, diarrhea, and dry mouth. Inhaled cannabis may be associated with red eyes, vomiting, phlegm, asthma, and cough. The effects of inhaled cannabis on euphoria and irritability were uncertain.

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