Aging & Longevity

Age differences in endocannabinoid tone are ameliorated after recent cannabis use.

TL;DR

Older adults exhibited lower baseline endocannabinoid levels than younger adults, but acute cannabis use produced broad endocannabinoid elevations across all age groups, with larger increases in AEA and DEA specifically in older adults.

Key Findings

At baseline, older adults exhibited lower levels of AEA and DEA compared to younger adults, and lower LEA compared to midlife adults.

  • Sample included N=142 adults divided into younger (21-24 years, n=38), midlife (25-54 years, n=73), and older (55-71 years, n=31) age groups.
  • Age-related differences were observed specifically for AEA, DEA, and LEA at the pre-use baseline assessment.
  • These findings are consistent with the hypothesis that an age-related decline in endocannabinoid system (ECS) activity exists.
  • No baseline age differences were reported for 2-AG, PEA, SEA, or OEA.

Acute cannabis use increased six of seven endocannabinoids (AEA, DEA, LEA, PEA, SEA, and OEA) across all age groups.

  • All six endocannabinoids showed statistically significant increases (all p < .001) following cannabis use.
  • Measurements were taken approximately 1 hour after flower cannabis use or approximately 2 hours after edible cannabis use.
  • 2-AG was the only endocannabinoid that showed no increase following acute cannabis use.
  • Elevations were described as 'broad endocannabinoid elevations after cannabis use regardless of age.'

Increases in AEA and DEA following acute cannabis use were larger in older adults compared to younger age groups.

  • A significant TimeƗAge interaction was observed for AEA and DEA specifically.
  • This differential response suggests that older adults may be more reactive to cannabis-induced endocannabinoid elevations for these specific compounds.
  • The larger increases in older adults occurred in the same endocannabinoids (AEA and DEA) that were lower at baseline in older adults.
  • These findings indicate that acute cannabis use may partially ameliorate age-related differences in endocannabinoid tone.

An age-related decline in endocannabinoid system activity is posited to contribute to conditions such as chronic pain and Alzheimer's disease.

  • Cannabis is increasingly used by older adults to alleviate age-related conditions.
  • The study assayed seven endocannabinoids: AEA, 2-AG, DEA, LEA, PEA, SEA, and OEA.
  • The study framed age-related ECS decline as a motivating rationale for examining how cannabinoids affect ECS activity across the lifespan.

The study found both age-related differences at baseline and age-related differences in acute endocannabinoid responses to cannabis.

  • The study employed a pre-use and post-use design with assessments before and approximately 1-2 hours after cannabis use depending on administration route.
  • Age groups were categorized as younger (21-24), midlife (25-54), and older (55-71).
  • Findings indicated 'broad endocannabinoid elevations after cannabis use regardless of age, alongside age-related differences at baseline and in acute responses.'

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Citation

Morris A, Mueller R, Sempio C, Klawitter J, Bryan A, Bidwell L, et al.. (2026). Age differences in endocannabinoid tone are ameliorated after recent cannabis use.. Scientific reports. https://doi.org/10.1038/s41598-025-27618-1