??9-Tetrahydrocannabinol, 11-Hydroxy-??9-Tetrahydrocannabinol and 11-Nor-9-Carboxy-??9-Tetrahydrocannabinol in Human Plasma After Controlled Oral Administration of Cannabinoids

Abstract

A clinical study to investigate the pharmacokinetics and pharmacodynamics of oral tetrahydrocannabinol was performed. This randomized, double-blind, placebo-controlled, within-subject, inpatient study compared the effects of THC-containing hemp oils in liquid and capsule form to dronabinol (synthetic THC) in doses used for appetite stimulation. The National Institute on Drug Abuse Institutional Review Board approved the protocol and each participant provided informed consent. Detection times and concentrations of THC, 11-hydroxy-Delta-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta-tetrahydrocannabinol (THCCOOH) in plasma were determined by gas chromatography-mass spectrometry [limits of quantification (LOQ)=0.5, 0.5, and 1.0 ng/mL, respectively] after oral THC administration. Six volunteers ingested liquid hemp oil (0.39 and 14.8 mg THC/d), hemp oil in capsules (0.47 mg THC/d), dronabinol capsules (7.5 mg THC/d), and placebo. Plasma specimens were collected during and after each dosing condition. THC and 11-OH-THC concentrations were low and never exceeded 6.1 ng/mL. Analytes were detectable 1.5 hour after initiating dosing with the 7.5 mg THC/d regimen and 4.5 hour after starting the 14.8 mg THC/d sessions. THCCOOH was detected 1.5 hour after the first dose, except for the 0.47 mg THC/d session, which required 4.5 hour for concentrations to reach the LOQ. THCCOOH concentrations peaked at 3.1 ng/mL during dosing with the low-dose hemp oils. Plasma THC and 11-OH-THC concentrations were negative for all participants at all doses within 15.5 hours after the last THC dose. Plasma THCCOOH persisted for at least 39.5 hours after the end of dosing and at much higher concentrations (up to 43.0 ng/mL). This study demonstrated that subjects who used high THC content hemp oil (347 mug/mL) as a dietary supplement had THC and metabolites in plasma in quantities comparable to those of patients using dronabinol for appetite stimulation. There was a significant correlation between body mass index and Cmax and body mass index and number of specimens positive for THC and 11-OH-THC.

Excretion of Δ9-tetrahydrocannabinol in sweat

“…An explanation for the negative sweat patches may be that there is less THC in blood available to distribute into sweat following oral ingestion compared to smoking, due to degradation in the stomach and first pass metabolism via the oral route. For subjects in the present study, Goodwin et al reported plasma THC concentrations less than 6.1 μg/L [21]. Subjects smoking a cigarette containing 15.8 mg THC had mean maximum plasma THC concentrations of 84.3 μg/L [23].…”

“…Various oral doses were administered three times daily for five consecutive days during the study period and included doses up to 14.8 mg THC daily for the five-day regimens. For the same subjects, Goodwin et al reported that all plasma THC concentrations were less than 6.1 μg/L [21]. Measured plasma THC concentrations during this oral administration study were much lower than THC concentrations observed during cannabis smoking [23].…”

“…A more detailed description of the subjects was published previously [21,22]. The protocol was a randomized, double blind, double-dummy and placebo-controlled study design.…”

“…dronabinol, Sativex ® , or hemp oil, or cannabis smoking. Goodwin et al found that plasma concentrations of THC after oral ingestion of THC were lower than those following equivalent smoked doses [21]. Lower circulating amounts of THC may reduce the amount of parent drug found in sweat.…”

Impact of Dronabinol on Quantitative Electroencephalogram (qEEG) Measures of Sleep in Obstructive Sleep Apnea Syndrome

“…These effects remained statistically significant for relative theta power but were less evident and not statistically significant for relative sigma power when considering the full 8-hour PSG recording period. This temporal pattern could be expected based on the pharmacokinetics of the drug, as the first-compartment plasma elimination half-life of oral dronabinol is 2 to 3 hours, 15,16 and with daily dosing, plasma concentrations return to or near to baseline levels within 4 to 5 hours of drug administration.…”