O

H3CT xN'

ch3 Hydroxy-LSD

3.6.10 Metabolic pathway of LSD.

3.6.10.3 Distribution

Plasma protein binding of LSD is >80%. As the drug penetrates the CNS, it is concentrated in the visual brain areas, and the limbic and reticular activating systems, correlating with perceived effects. LSD is also found in the liver, spleen and lungs.4 The volume of distribution is reported to be low at 0.28 L/kg.1 Wagner et al.5 described a two compartment open model for LSD with an elimination half life of 3 h.

3.6.10.4 Metabolism and Excretion

The metabolism and elimination of LSD in humans has received limited study. Animal studies demonstrated extensive biotransformation via N-demethylation, N-deethylation, and hydroxy-lation to inactive metabolites (Figure 3.6.10).6 In humans, demethylation and aromatic hydroxylation occur to produce N-desmethyl-LSD and 13- and 14-hydroxy-LSD. Hydroxy-lated metabolites undergo glucuronidation to form water soluble conjugates. Excretion into the bile accounts for approximately 80% of a dose.4 Concentrations of unchanged drug ranged from 1 to 55 ng/mL in the 24-h urine after ingestion of 200 to 400 ug LSD in humans.7 LSD or its metabolites were detectable for 34 to 120 h following a 300 ug oral dose in 7 human subjects.8 The clearance of LSD in humans is unknown.

1. Disposition of Toxic Drugs and Chemicals in Man 4th ed. Baselt, R.C., and Cravey, R.H. Chemical Toxicology Institute, Foster City, CA (1995).

2. Goldberger, B. A. : Lysergic Acid Diethylamide. In-Service Training and Continuing Education AACC/TDM, American Association for Clinical Chemistry, Inc., Washington, D.C. 14 (6): 99-100 (1993).

3. Van Woerkom, A.E.: The major hallucinogens and the central cytoskeleton: an association beyond coincidence? Towards sub-cellular mechanisms in schizophrenia. Medical Hypotheses 31:7-15 (1990).

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