CBD toxicity study in rats established safety limits for long-term oral consumption

A 90-day oral toxicity study in rats established a no-observed-adverse-effect level (NOAEL) of 460 mg/kg/day for males and 230 mg/kg/day for females, with most changes reversing after a 35-day recovery period.

Tallon, Mark J et al.·Regulatory toxicology and pharmacology : RTP·2023·Moderate Evidenceanimal
RTHC-04974AnimalModerate Evidence2023RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
animal
Evidence
Moderate Evidence
Sample
Not reported

What This Study Found

CBD was tolerated up to 460 mg/kg/day in males over 90 days. Some non-adverse organ and tissue changes occurred, and all changes except those at the highest dose reversed during the 35-day recovery period. Prenatal screening showed reduced body weight at the highest dose but no malformations.

Key Numbers

NOAEL: 460 mg/kg/day (males), 230 mg/kg/day (females). 14-day tolerance up to 460 mg/kg/day. 90-day study with 35-day off-dose recovery. Prenatal study showed reduced body weight at highest dose but no gross abnormalities.

How They Did This

Three toxicology experiments in Sprague-Dawley rats: prenatal development screening, 14-day sighting study, and OECD-compliant 90-day subchronic oral toxicity study with 35-day recovery period. Doses: 0, 30, 115, 230, and 460 mg/kg/day of CBD isolate.

Why This Research Matters

As CBD products proliferate in consumer markets, establishing formal safety limits through standard toxicology testing provides a scientific basis for regulatory decisions about acceptable doses.

The Bigger Picture

Consumer CBD products typically deliver doses far below these NOAELs, even when accounting for body weight differences between rats and humans. However, rat toxicology data requires safety factors before translating to human recommendations.

What This Study Doesn't Tell Us

Animal study with uncertain human translation. Used purified CBD isolate, not whole-plant extract. Standard safety factors (typically 100x) are applied when extrapolating animal NOAELs to human recommended doses. Sex differences in NOAEL suggest hormonal interactions not fully understood.

Questions This Raises

  • ?Why do female rats show lower NOAEL than males?
  • ?Would whole-plant extracts containing other cannabinoids produce different toxicity profiles?
  • ?How do these NOAELs translate to human equivalent doses?

Trust & Context

Key Stat:
NOAEL: 460 mg/kg/day (males), 230 mg/kg/day (females) over 90 days
Evidence Grade:
OECD-compliant toxicology study with multiple dose levels and recovery period. Standard regulatory evidence for safety assessment.
Study Age:
Published 2023.
Original Title:
Subchronic oral toxicity assessment of a cannabis extract.
Published In:
Regulatory toxicology and pharmacology : RTP, 144, 105496 (2023)
Database ID:
RTHC-04974

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

How much CBD is safe?

This rat study found no adverse effects up to 460 mg/kg/day for males and 230 mg/kg/day for females over 90 days. However, translating animal doses to humans requires significant safety factors. Most consumer CBD products deliver doses well below what would be concerning based on these findings.

What happened to the rats at high CBD doses?

At the highest dose (460 mg/kg/day), some organ and tissue changes were observed, but most reversed during the 35-day recovery period. In prenatal testing, the highest dose reduced maternal body weight and food consumption but caused no malformations or pregnancy complications.

Read More on RethinkTHC

Cite This Study

RTHC-04974·https://rethinkthc.com/research/RTHC-04974

APA

Tallon, Mark J; Child, Robert. (2023). Subchronic oral toxicity assessment of a cannabis extract.. Regulatory toxicology and pharmacology : RTP, 144, 105496. https://doi.org/10.1016/j.yrtph.2023.105496

MLA

Tallon, Mark J, et al. "Subchronic oral toxicity assessment of a cannabis extract.." Regulatory toxicology and pharmacology : RTP, 2023. https://doi.org/10.1016/j.yrtph.2023.105496

RethinkTHC

RethinkTHC Research Database. "Subchronic oral toxicity assessment of a cannabis extract." RTHC-04974. Retrieved from https://rethinkthc.com/research/tallon-2023-subchronic-oral-toxicity-assessment

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.