Cannabis includes numerous cannabinoids such as Δ9-THC, the psychoactive component responsible for intoxication, and CBD, which lacks intoxicating properties. The plant also contains terpenes, flavonoids, and over 140 additional cannabinoids like Δ8-THC. A 2018 survey of 27,169 North American adults found that 27% had used cannabis medicinally, primarily for pain, anxiety, and sleep disorders. Despite this widespread use, a 2021 systematic review revealed that only one-third of clinicians felt knowledgeable about cannabinoids, with 86% requesting additional education. Given this gap, this review examines therapeutic applications of cannabis in adults, associated risks, and clinical guidance for screening and managing cannabis use in healthcare settings.
The study searched PubMed for English-language studies published from January 2010 to September 2025, identifying 2,576 articles. The authors prioritized studies with larger and more recent samples, favoring randomized controlled trials when available. A total of 124 studies were included: 21 clinical guidelines, 7 systematic reviews, 27 meta-analyses, 10 RCTs, 17 nonsystematic reviews, 30 observational studies, and 12 other studies. For treatment comparisons, standardized mean differences of 0.2, 0.5, and 0.8 were considered small, medium, and large effects, respectively.
The endocannabinoid system includes CB1 receptors in the central nervous system, which mediate psychoactive effects of Δ9-THC, and CB2 receptors in peripheral tissues that modulate inflammation. While pharmaceutical-grade cannabinoids undergo rigorous FDA approval for specific conditions, dispensary products lack consistent quality standards and often contain higher Δ9-THC concentrations than those used in clinical trials. FDA-approved indications include chemotherapy-induced nausea and vomiting, appetite stimulation in HIV/AIDS, and specific pediatric seizure disorders, showing small to moderate treatment effects. However, evidence is insufficient for most other medical conditions, and guidelines recommend against cannabis use as first-line treatment for chronic pain and strongly advise against its use for psychiatric disorders, as high-potency cannabis may precipitate psychosis and suicidality. Key risks include cannabis use disorder, increased cardiovascular events with daily use, psychiatric symptoms with high-potency products, and neurocognitive deficits. Clinicians should screen for contraindications such as pregnancy, schizophrenia, or ischemic heart disease, and counsel patients on harm reduction and informed use strategies including using the lowest effective dose, preferring low-potency products, avoiding inhaled routes, monitoring drug interactions, and abstaining from driving for 6-12 hours after use.
Takeaway: Cannabis or cannabinoids show evidence for limited FDA-approved indications, but evidence is insufficient for most medical uses, and clear guidance from clinicians is essential to weigh benefits against risks through informed discussions and harm reduction strategies.