SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

B3
EFFECTS AND BLOOD CONCENTRATIONS OF THC, H-OH-THC AND THCCOOH
FOLLOWING ORAL ADMINISTRATION OF 20 MG DRONABINOL OR OF A CANNABIS
DECOCTION CONTAINING 20 OR60 MG DELTA9-THC
A. MenetreyI, C. Giroud I *, M. Augsburgerl, L. Rothuizen 2 , M. Pin t, M. Appenzeller 2 , T. Buclin2, P.
ManginI ILaboratoire de toxicologie et chimie forensiques, Institut Universitaire de Medecine Legale,
Lausanne, 2Division specialisee de phannacoIogie et toxicologie cliniques, CHUV, Lausanne, Switzerland
Smoking and oral ingestion are the most popular methods of Cannabis recreational use. Oral therapeutic
administration, such as with Marinol® (synthetic THC (dronabinoJ) in sesame oil) was introduced in the US
to alleviate anorexia in HIV/AIDS patients and to ease nausea in cancer chemotherapy. THC is also
contained in hemp foods. In Switzerland, there is currently a great concern about the danger of driving
under the influence of Cannabis. Epidemiological studies have indeed shown that Cannabis alone or with
alcohol constitute the most frequent group of drugs detected in drivers involved in car accidents or in
driving under the influence of drugs. The main objective of our study was to assess the effects of an acute
oral intake of a medium to high dose ofTHC on driving capability. A hemp crude preparation containing
1.5 % delta9-THC and 4.4 % delta9-THC-A was pre-treated at 140°C for 30 min to obtain a powder with
4.9 % delta9-THC. From this powder containing 20 or 60 mg of delta9-THC, hemp milk decoctions were
prepared with a yield of about 80%. A double-blind, ethical committee approved study was carried out with
eight 20-30 years-old healthy male volunteers who were occasional Cannabis smokers. In 4 successive
sessions, volunteers were administered a placebo, a decoction made with 20 or 60 mg delta9-THC or 20 mg
dronabinol capsules in a randomised order. Blood samples were taken before administration and 1,2.5,4,
5.5, 7, 10 and 24 hours following ingestion. In the same time-period, clinical examination and
psychological tests were performed with a driving simulator. Blood levels of cannabinoids were determined
by NCI GC-MS according to a method adapted from Huang et ae with limits of quantification of 0.3
ng/mL forTHC, 0.8 ng/mL for II-OH-THC, and 0.1 ng/mL for THCCOOH.
Because of anxiety events, which resolved spontaneously, two volunteers were withdrawn from the study
after ingestion of the medium dose. Mean maximal concentrations [ng/mL] for THC, II-OH-THC and
THCCOOH as well as the times [hours] to the maximum blood levels are listed below:
Preparation
dronabinol
20 mg ~9-THC
milk decoction
16.5 mg ~9_THC
milk decoction
45.7 mg ~9-THC
Parameter THC II-OH-THC THCCOOH
I
Tmax 1
4 5.5
Cmax 2.8 3.9
27.8
Tmax
I
I
4
Cmax 3.8
4.7 27.8
Tmax
I
2.5 2.5
1
Cmax I 8.4 12.8 66.2
I
The individual results show there was a considerable inter-subject variability. Mean maximum
concentrations of 11-0H-THC exceeded the corresponding levels of THC. A 2 to 3 fold increase in
cannabinoid concentrations was achieved following ingestion of the strongest decoction. Almost similar
levels were measured after intake of the same dose of THC, regardless of the type of preparation (synthetic
THC or crude plant extract). Obvious effects were observed with the tracking test showing a 50 % mean
highest performance decrease after drinking the milk decoction containing 45.7 mg THC. Although a
relatively high dose of THC was taken and significant psychoactive effects and performance reduction
were noticed, THC and THCCOOH concentrations were much lower than those which are generally
measured after marijuana smoking. In conclusion, this study shows that oral intake of delta9-THC may
decrease human performance and exemplify the risks ofdriving under the influence of Cannabis.
Key words: dronabinol, cannabis, driving under the influence of drugs
3Huang W et aL J. Anal. Toxicol. 25: 531-537,2001
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