Medscape Medical News
High-THC cannabis products were associated with small reductions in chronic pain severity but with higher rates of adverse events, according to an updated systematic review published December 23, 2025, in Annals of Internal Medicine.
Overview
The review included 25 placebo-controlled randomized trials (2303 participants), most with neuropathic pain. Trial duration ranged from 4–16 weeks. Products were classified by THC-to-CBD ratio (high, comparable, low), formulation (synthetic, purified, extracted), and route of administration.
Efficacy Findings
• High THC-to-CBD (THC-only, oral synthetic/purified):
Mean pain reduction vs placebo: −0.78 points on a 10-point scale (95% CI −1.59 to −0.08).
• Comparable THC-to-CBD (oromucosal, extracted):
Mean difference: −0.54 points (95% CI −0.95 to −0.19).
These effects were statistically significant but clinically small. The magnitude was less than reported in the group’s earlier 2022 review, likely due to inclusion of additional negative THC-only trials.
• Low THC-to-CBD products (including CBD-dominant):
No meaningful reduction in pain severity.
Subgroup analyses showed:
• Nabilone demonstrated a moderate reduction in pain.
• Dronabinol did not show significant pain reduction.
• Combined purified THC + synthetic CBD showed no significant analgesic benefit (limited data).
Adverse Events
THC-containing products were consistently associated with increased adverse events:
• Increased risk of:
– Dizziness
– Nausea
– Sedation
• Synthetic or purified THC-only products had moderate-to-large increased risk of any adverse event.
• Extracted products with comparable THC-to-CBD ratios also increased dizziness, nausea, and sedation.
Low THC/CBD products showed minimal harms but minimal benefit.
Clinical Interpretation
The key message:
THC-containing cannabis products provide slight short-term benefit for mostly neuropathic chronic pain but at the cost of frequent adverse effects.
CBD-dominant products did not show meaningful pain benefit in this analysis.
Limitations
• Heterogeneity in product composition and reporting.
• Short trial duration (up to 16 weeks).
• Limited assessment of long-term harms, including psychosis risk or cannabis use disorder.
• Variable availability and regulatory differences limit generalizability.
Editorial Perspective
An accompanying editorial emphasized:
• CBD lacks compelling evidence as a standalone analgesic.
• Evidence remains inconsistent across cannabinoid preparations and pain types.
• Standardized trial products may not reflect real-world state-regulated cannabis products.
Key Points
• High-THC products → small pain reduction (~0.5–0.8 points on a 10-point scale).
• Increased dizziness, nausea, and sedation.
• CBD-dominant products → little to no benefit.
• Evidence quality variable; long-term safety unclear.
• Clinical decision-making should balance modest benefit against common adverse effects.
For clinicians, this reinforces a cautious, individualized risk-benefit discussion when patients inquire about cannabis for chronic pain — particularly neuropathic pain — with expectations set appropriately regarding magnitude of relief and side effects.
We would like to thank Medscape Medical News for allowing us to summarize this study.