High-Dose Oral CBD Produced Surprisingly Low Blood Levels With a 2-5 Day Elimination Half-Life
Despite receiving approximately 700 mg/day of oral CBD, Huntington's Disease patients achieved mean plasma levels of only 5.9 to 11.2 ng/mL, with CBD clearing from the body over 2-5 days after discontinuation.
Quick Facts
What This Study Found
Researchers developed and validated a method to measure CBD in blood plasma, then used it to track CBD levels in 14 Huntington's Disease patients receiving high-dose oral CBD (10 mg/kg/day, approximately 700 mg/day) for six weeks.
Despite the high oral dose, mean plasma CBD levels ranged from only 5.9 to 11.2 ng/mL across the six weeks. This represented poor oral bioavailability, meaning most of the ingested CBD was not reaching the bloodstream.
One week after stopping CBD, plasma levels averaged 1.5 ng/mL and were virtually undetectable thereafter. The elimination half-life was estimated at 2 to 5 days. There were no gender differences in either CBD levels or elimination half-life.
Importantly, no delta-1-THC (the major psychoactive cannabinoid) was detected in any patient's blood, confirming CBD did not convert to THC in the human body at this dose.
Key Numbers
Fourteen patients. CBD dose: 10 mg/kg/day (approximately 700 mg/day). Plasma levels: 5.9-11.2 ng/mL over 6 weeks. One week post-cessation: 1.5 ng/mL. Elimination half-life: 2-5 days. Assay sensitivity: 500 pg/mL. No gender differences.
How They Did This
Pharmacokinetic study within a double-blind crossover trial. Plasma CBD levels were measured weekly using trimethylsilyl derivatization, capillary gas chromatography, and ion trap mass spectrometry in positive ion chemical ionization mode. Assay sensitivity: approximately 500 pg/mL. Precision: approximately 10-15%.
Why This Research Matters
This study revealed a critical pharmacological challenge for oral CBD: very low bioavailability. Patients taking 700 mg/day achieved plasma levels well below concentrations shown to be active in laboratory studies. This has major implications for CBD dosing and product formulation.
The Bigger Picture
The bioavailability problem identified here remains one of the central challenges of oral CBD therapeutics. Modern CBD formulations (lipid-based, nanoemulsions) attempt to address exactly this issue. The finding that CBD does not convert to THC in humans was also important for regulatory and safety discussions.
What This Study Doesn't Tell Us
Fourteen patients is a small pharmacokinetic sample. Patients had Huntington's Disease, which could affect drug metabolism. Only oral CBD was tested; other routes of administration would produce different pharmacokinetic profiles.
Questions This Raises
- ?Would different formulations dramatically improve CBD bioavailability?
- ?Do the low plasma levels explain the lack of efficacy in the companion clinical trial?
- ?What plasma CBD concentration is needed for therapeutic effects in different conditions?
Trust & Context
- Key Stat:
- 700 mg/day oral CBD produced only 5.9-11.2 ng/mL in plasma
- Evidence Grade:
- A pharmacokinetic study embedded within a controlled clinical trial. Rigorous analytical methods but small sample size.
- Study Age:
- Published in 1991. CBD formulation science has advanced substantially, with modern products achieving better bioavailability.
- Original Title:
- Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans.
- Published In:
- Pharmacology, biochemistry, and behavior, 40(3), 517-22 (1991)
- Authors:
- Consroe, P(4), Kennedy, K(2), Schram, K(2)
- Database ID:
- RTHC-00040
Evidence Hierarchy
Watches what happens naturally without intervening.
What do these levels mean? →Frequently Asked Questions
How much CBD actually gets into the blood?
In this study, 700 mg/day of oral CBD produced mean plasma levels of only 5.9-11.2 ng/mL, indicating very low oral bioavailability.
Does CBD convert to THC in the body?
No. Despite high doses over six weeks, no THC was detected in any patient's blood, confirming CBD does not convert to the psychoactive compound in the human body.
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Cite This Study
https://rethinkthc.com/research/RTHC-00040APA
Consroe, P; Kennedy, K; Schram, K. (1991). Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans.. Pharmacology, biochemistry, and behavior, 40(3), 517-22.
MLA
Consroe, P, et al. "Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans.." Pharmacology, 1991.
RethinkTHC
RethinkTHC Research Database. "Assay of plasma cannabidiol by capillary gas chromatography/..." RTHC-00040. Retrieved from https://rethinkthc.com/research/consroe-1991-assay-of-plasma-cannabidiol
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.