SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

M23
~9-TETRAHYDROCANNABINOL (THC), 11-HYDROXy-~9-TETRAHYDROCANNABlNOL (11­
OH-THC) AND 11-NOR-9-CARBOXy-~9-TETRAHYDROCANNABINOL (THCCOOH) IN
HUMAN PLASMA FOLLOWING ORAL ADMINISTRATION OF HEMP OIL.
Wesenyalsh Nebro'*, Allan Barnes', Richard A. Gustafson 2 , Eric T. Moolchan l and Marilyn A. Huestis l : '
Chemistry and Drug Metabolism Section, IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD
21224; 2 Jacksonville Naval Air Station, Jacksonville, FL 32212
Usefulness of therapeutic oral cannabinoids is being investigated for several medicinal applications.
Cannabis is among the most abused psychoactive substances causing behavioral and physiological changes
that necessitate testing to detect impairment. In recent years, hemp oil products derived from cannabis
have been introduced into the U.S. Analysis of hemp oils reveals that THC is present in a range of
concentrations. A clinical study to investigate the pharmacokinetics and pharmacodynamics of oral THC
was performed. The randomized, double blind, placebo-controlled within-subject, inpatient study
compared the effects of hemp oil in liquid and capsule form to dronabinol (synthetic THC) doses consistent
with therapy for appetite-stimulation. The NIDA IRB approved this study and each participant provided
informed consent. One aspect of this study was to determine the detection times and levels ofTHC, 11-0H­
THC and THCCOOH in plasma following oral THC administration. Hemp oil dosing followed
manufacturer's recommendations. Five healthy volunteers with a history of marijuana abuse ingested
commercially available hemp oils/capsules of differing THC concentrations. Five dosing conditions (0.0,
0.39,0.47,7.5, and 14.8 mg/day) of oil/capsules were administered three times daily with meals for five
consecutive days followed by a ten-day washout period before the next dosing session began. Plasma
samples were collected prior to and following each of the five dosing conditions throughout the study and
were frozen at -20°C until analysis. Plasma was extracted by SPE (200 mg Clean Screen® ZSDAU020,
United Chemical Technologies). The extracts were derivatized with BSTFA (l%TMCS), separated and
quantified on a GCIMS(Agilent) operated in the positive chemical ionization mode with SIM monitoring.
The following table lists the mean minimum and maximum concentrations (ng/mL) for all plasmas
collected from 30 minutes before the first dose to 2 days after the last dose for each session for five
subjects:
THC ll-OH-THC THCCOOH
Session Dose Amount Min Max Min Max Min Max
~gh Potency Hemp Oil 14.8 mg/day 0.0 6.5 0.0 5.6 0.0 15.2
Dronabinol Capsules 7.5 mg/day 0.0 3.6 0.0 2.6 0.0 24.4
~emp Oil Capsules 0.47 mg/day 0.0 0.0 0.0 0.0 0.0 2.5
Low Potency Hemp Oil 0.39 mg/day 0.0 1.2 0.0 3.8 0.0 3.1
Placebo__ ~_ c.JJ.0 mg/day 0.0 ~~ 0.0 0.0 0.0 0.0
~-
Drug levels of plasmas varied within the same dose between subjects. In general, the THC, 11-0H-THC,
and THCCOOH levels were low and erratic across the collection timeline after all doses. The peak
concentrations and time to peak concentrations varied, sometimes considerably, between subjects. In
general, the maximum concentrations of 1I-0H-THC were seen in the liquid hemp oil sessions. The
sessions in which capsules were administered had lower concentrations, less than the low dose of hemp oil
administered, or zero concentrations. Plasma THC and 11-0H-THC were negative for all participants and
for all doses by 16 hours after the last THC dose. Plasma THCCOOH persisted for a longer period oftime
following the two highest doses of 7.5 mg/day dronabinol and 14.8 mg/day THC in hemp oil. Ohlsson et
al. (Clin. Pharmacol. Ther., 1980, 28:409) reported that orally administered (20 mg cookie) THC yielded
low and irregular plasma concentrations compared to intravenous and inhaled THC. Bioavailability of
orally administered THC is low. This may be due to poor absorption, degradation by stomach acid, or
biotransformation to metabolites via first pass through the liver.
Keywords: Oral Administration ofTHC, Plasma, GCIMS.
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