The endocannabinoid system changes with aging in ways that may worsen chronic pain, and cannabinoids show theoretical promise for age-related pain — but clinical evidence in older populations remains limited.
Geriatricians managing chronic pain, older adults considering cannabinoid therapy, pain researchers studying age-related mechanisms.
What the researchers found
This review explored the intersection of aging, chronic pain, and the endocannabinoid system (ECS), building a case for why cannabinoids might be particularly relevant for older adults.
The key biological insight is that aging involves a process called "inflammaging" — chronic low-grade inflammation driven by immune system changes (immunosenescence). This persistent inflammation disrupts the normal pain resolution process, contributing to the chronic pain conditions common in older adults: osteoarthritis, neuropathies, and musculoskeletal degeneration.
The endocannabinoid system plays a role in modulating both inflammation and pain perception. The review synthesized evidence that ECS function changes with age — receptor density, endocannabinoid levels, and enzyme activity all shift — potentially contributing to the dysregulated inflammatory and pain responses seen in older adults.
Phytocannabinoids (THC and CBD) interact with this system and have demonstrated anti-inflammatory and analgesic properties in preclinical models. However, the review acknowledged that clinical evidence specifically in elderly populations is limited, and the pharmacokinetic changes of aging (altered metabolism, body composition, drug sensitivity) add complexity to cannabinoid dosing in this group.
Why it matters
Older adults bear the highest burden of chronic pain and are also the demographic where cannabis use is growing fastest. Yet most cannabinoid pain research has been conducted in younger populations. This review provides the biological rationale for why cannabinoids might work differently — potentially better or worse — in aging bodies, and highlights the gap between the theoretical promise and the clinical evidence.
The numbers in context
Common age-related pain conditions reviewed: osteoarthritis, neuropathies, musculoskeletal degeneration. ECS changes with aging: altered receptor density, endocannabinoid levels, and enzyme activity. Inflammaging characterized by sustained pro-inflammatory mediator production and impaired resolution mechanisms.
How the study worked
Narrative review examining the endocannabinoid system's role in pain and inflammation during aging. Synthesized preclinical and clinical evidence on age-related ECS changes, inflammaging mechanisms, and therapeutic potential of phytocannabinoids (THC, CBD) for age-related chronic pain.
Who was studied
Review of existing literature on cannabinoids and pain in older adults.
What this study cannot tell us
Narrative review drawing primarily on preclinical evidence. Limited clinical trial data on cannabinoids specifically in elderly populations. The inflammaging framework, while well-established, doesn't fully explain all chronic pain in older adults. Individual variation in aging makes generalization difficult.
How to read the evidence
Narrative review integrating aging biology and cannabinoid pharmacology — provides a strong theoretical framework but clinical evidence in older populations is still developing.
When this study was published
Published in 2026, addressing a research gap that is becoming increasingly urgent as cannabis use among older adults accelerates.
The bigger picture
This connects the aging-specific concerns raised in the older driver study (RTHC-00266) and the longitudinal older adult data (RTHC-00223) to the broader pain evidence (RTHC-00233, RTHC-00225). The pharmacokinetic aging changes that may amplify driving impairment (RTHC-00266) are the same changes that complicate therapeutic dosing. And the drug interaction review (RTHC-00265) is particularly relevant here, since older adults typically take multiple medications that could interact with cannabinoids.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Do age-related ECS changes make older adults more or less responsive to cannabinoid therapy? What are the optimal cannabinoid doses for pain in older adults given their altered pharmacokinetics? Can cannabinoids reduce the need for NSAIDs and opioids in geriatric pain management?
Read the original research
Therapeutic use of cannabinoids in age-related pain: Current evidence and clinical perspectives.
Pharmacological research, 225, 108130
Pharmacological Research is a reputable journal focusing on drug research and pharmacology.
Citation
Pulone, Sabina; Moulton, Chantalle; Nucera, Saverio; Ilari, Sara; Muscoli, Carolina; Tasciotti, Ennio. (2026). Therapeutic use of cannabinoids in age-related pain: Current evidence and clinical perspectives.. Pharmacological research, 225, 108130. https://doi.org/10.1016/j.phrs.2026.108130
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