The overall goal of the research described in this proposal - carried out in collaboration with Dr. Leo Hollister, Veterans Administration Hospital, Palo Alto, CA 94304 - is (1) to study the slow elimination of delta1-tetrahydrocannabinol (=delta9-THC, """"""""THC"""""""") the major psychoactive compound of marijuana - in chronic marihuana smokers as revealed by plasma THC concentrations and urinary THC-metabolite levels. Levels will be monitored for 4 weeks after discontinuation of smoking and to allow unequivocal interpretation each subject will receive a loading dose of deuterium labeled THC. We will also (2) study the metabolite pattern of interindividual differences in the metabolism of THC by semiquantitation analysis of major urinary metabolites after smoking and oral administration of THC to light and heavy users. Possible (3) differences in metabolite pattern with time (during the first 12 h after smoking) will also be assessed. To carry out these studies which have implications for the risk assessment of marijuana but are also of general scientific and forensic interest it is necessary to (4) improve the methodology for stabilizing, separating and assaying urinary THC-metabolites (HPLC) and to (5) synthesize labeled and non-labeled urinary THC-metabolites. We will also attempt to correlate urinary cannabinoid EMIT assays with chemical analysis and also investigate the relative responses of human urinary metabolites in the EMIT assay. We believe we have unique knowledge/experience and facilities which could warrant a grant to a non-US laboratory: e.g. we have identified over 90% of the human urinary THC-metabolites and we have 10 of these in isolated form. We have the only laboratory that routinely and specifically has measured subnanogram plasma levels of THC in man - this is necessary to measure levels of THC after discontinuation of smoking. Grants for the clinical parts of these investigations will be funded separately.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA003926-01
Application #
3208772
Study Section
(DABB)
Project Start
1985-09-30
Project End
1988-08-31
Budget Start
1985-09-30
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Karolinska Institute
Department
Type
DUNS #
350582235
City
Stockholm
State
Country
Sweden
Zip Code
171 77
Winecker, R E; Goldberger, B A; Tebbett, I et al. (1997) Detection of cocaine and its metabolites in amniotic fluid and umbilical cord tissue. J Anal Toxicol 21:97-104
Szirmai, M; Halldin, M M (1995) A urinary metabolite of delta 1-tetrahydrocannabinol. The first synthesis of 4"",5""-bisnor-delta 1-tetrahydrocannabinol-7,3""-dioic acid, and a deuterium labelled analogue. Bioorg Med Chem 3:899-906
Baek, S H; Szirmai, M; Halldin, M M (1991) Synthesis of optically active (-)-11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid. Pharmacol Biochem Behav 40:487-9
Kang, S Y; Kleinman, P H; Woody, G E et al. (1991) Outcomes for cocaine abusers after once-a-week psychosocial therapy. Am J Psychiatry 148:630-5
Kleinman, P H; Miller, A B; Millman, R B et al. (1990) Psychopathology among cocaine abusers entering treatment. J Nerv Ment Dis 178:442-7
Johansson, E; Gillespie, H K; Halldin, M M (1990) Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol. J Anal Toxicol 14:176-80
Johansson, E; Halldin, M M (1989) Urinary excretion half-life of delta 1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking. J Anal Toxicol 13:218-23
Johansson, E; Noren, K; Sjovall, J et al. (1989) Determination of delta 1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomed Chromatogr 3:35-8
Johansson, E; Halldin, M M; Agurell, S et al. (1989) Terminal elimination plasma half-life of delta 1-tetrahydrocannabinol (delta 1-THC) in heavy users of marijuana. Eur J Clin Pharmacol 37:273-7
Johansson, E K; Hollister, L E; Halldin, M M (1989) Urinary elimination half-life of delta-1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking. NIDA Res Monogr 95:457-8

Showing the most recent 10 out of 12 publications