Lysergic acid diethylamide: radioimmunoassay

A radioimmnunoassay for d-lysergic acid diethylamide (LSD) is described. Antibodies to LSD were obtained by immunizing rabbits with a conjugate of LSD and human serum albumin. The specificity of the antibody was shown by competitive binding studies. The method has been used to detect the presence of LSD in human urines. Picogram amounts can be measured by this assay.     

Lysergic acid diethylamide: role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine)

Injections of D-lysergic acid diethylamide decrease the turnover rate of 5-hydroxytryptamine of rat brain, as measured from the conversion of (14)C-tryptophan into (14)C-5-hydroxytryptamine. The 2-bromolysergic acid diethylamide given in doses fivefold greater than those of lysergic acid diethylamide fails to change the rate of (14)C-tryptophan conversion into (14)C-5-hydroxytryptamine. The effect of D-lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.     

10-Methoxyharmalan,a potent serotonin antagonist which affects conditioned behavior

10-Methoxyharmalan, an alkaloid obtained by the cyclodehydration of melatonin, itself a derivative of serotonin, is a more potent serotonin antagonist than harmaline and is only slightly less active than lysergic acid diethylamide. It has a similar, yet slightly greater, effect on behavior as that of harmaline and is the most potent serotonin derivative, so far tested, that affects the avoidance-escape behavioral reflex     

Persistent increase in brain serotonin turnover after chronic administration of LSD in the rat

Lysergic acid diethylamide at doses of 20 micrograms per kilogram per day was administered orally to rats for I month. Eighteen hours after the final dose a 25 to 30 percent increase in the synthesis and turnover of serotonin was noted, as well as a moderate but significant increase in the concentration of tryptophan (18 percent) and serotonin (13 percent) in the brain.     

Serotonin: release in the forebrain by stimulation of midbrain raphé

Electrical stimulation of the midbrain raphé, an area in which neuronal perikarya containing serotonin are aggregated, produces an increase in 5-hydroxyindoleacetic acid and a decrease in serotonin in the forebrain. These changes indicate that serotonin in the brain can be released via a specific neural pathway, namely, the system of axons projecting into the forebrain from serotonin-containing neurons in the midbrain raphé.     

Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals

(+/-)-3,4-Methylenedioxyamphetamine (MDA), an amphetamine analog with hallucinogenic activity, produced selective long-lasting reductions in the level of serotonin, the number of serotonin uptake sites, and the concentration of 5-hydroxyindoleacetic acid in rat brain. Morphological studies suggested that these neurochemical deficits were due to serotonin nerve terminal degeneration. These results show that MDA has toxic activity for serotonin neurons in rats and raise the question of whether exposure to MDA and related hallucinogenic amphetamines can produce serotonin neurotoxicity in the human brain.     

A quantifiable behavioral correlate of psychotogen and tranquilizer actions

A representative psychotogen, lysergic acid diethylamide (LSD-25), in doses small enough to be devoid of gross effects, increases response latency in rats to a tone indicating the availability of water reward; this effect is greatly reduced by prophylactic administration of a representative phenothiazine tranquilizer, chlorpromazine (CPZ), in doses that per se do not affect performance. The nature of the chlorpromazine action and its competition with lysergic acid diethylamide is revealed by the effects of chlorpromazine in larger doses.     

( 3 H)lysergic acid diethylamide: cellular autoradiographic localization in rat brain

Intravenous administration of [(3)H]lysergic acid diethylamide(LSD) to rats resulted in accumulation of the drug in the brain within 15 minutes. Autoradiographic methods were used to differentiate free and bound [(3)H]LSD in brain tissue.Free [(3)H]LSD was generally distributed in the pituitary and pineal glands, cerebellum, hippocampus,and choroid plexus.Bound [(3)H]LSD was localized in neurons of the cortex, caudate nucleus, midbrain, and medulla,as well as in choroid plexus epithelium.     

Congenital malformations induced by mescaline, lysergic acid diethylamide, and bromolysergic acid in the hamster

Malformations of the brain, spinal cord, liver, and other viscera; body edema; and localized hemorrhages were found in fetal hamsters from mothers injected subcutaneously with a single dose of mescaline, lysergic acid diethylamide, or 2-bromo-D lysergic acid diethylamide on the 8th day of pregnancy. In addition, all three drugs produced an increase in the percentages of small fetuses per litter, of resorptions, and of fetal mortality.     

2,5-dimethoxy-4-methyl-amphetamine (STP): a new hallucinogenic drug

We have assessed the effects in normal control volunteers of 2,5-dimethoxy-4-methyl-amphetamine, the chemical present in the hallucinogenic drug STP, in two independent trials. In low doses, this compound produces a mild euphoria. Doses greater than 3 milligrams may cause pronounced hallucinogenic effects lasting about 8 hours and similar to those produced by hallucinogenic doses of lysergic acid diethylamide, mescaline, and psilocybin. 2,5-Dimethoxy-4-methyl-amphetamine, which is chemically related to mescaline and amphetamine, is about 100 times more potent as a hallucinogen than mescaline and only one-thirtieth as potent as lysergic acid diethylamide. Its psychological effects are not accentuated by chlorpromazine.     

Some neurons of the rat central nervous system contain aromatic-L-amino-acid decarboxylase but not monoamines

Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry. The majority of these neurons localized to area X of Rexed contact ependyma. Thus, spinal AADC neurons have the enzymatic capacity to catalyze directly the conversion of the amino acids tyrosine, tryptophan, or phenylalanine to their respective amines tyramine, tryptamine, or phenylethylamine. These amines normally present in the central nervous system may be of potential clinical significance as endogenous psychotomimetics.     

Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition

Sudden infant death syndrome is the leading cause of death in the postneonatal period in developed countries. Postmortem studies show alterations in serotonin neurons in the brainstem of such infants. However, the mechanism by which altered serotonin homeostasis might cause sudden death is unknown. We investigated the consequences of altering the autoinhibitory capacity of serotonin neurons with the reversible overexpression of serotonin 1A autoreceptors in transgenic mice. Overexpressing mice exhibited sporadic bradycardia and hypothermia that occurred during a limited developmental period and frequently progressed to death. Moreover, overexpressing mice failed to activate autonomic target organs in response to environmental challenges. These findings show that excessive serotonin autoinhibition is a risk factor for catastrophic autonomic dysregulation and provide a mechanism for a role of altered serotonin homeostasis in sudden infant death syndrome.     

Lysergic acid diethylamide: effect on embryos

Injection of lysergic acid diethylamide tartrate into mice in early pregnancy caused a 57 percent incidence of grossly abnormal embryos.     

Molecular structure of LSD

The molecular configuration of lysergic acid diethylamide (LSD) in crystals of the iodobenzoate has been determined by using x-ray diffraction techniques. The configuration shows strain and steric hindrance and the conformation is fixed. Some of the implications of this for the hallucinogenic activity of LSD are discussed.     

Lysergic acid diethylamine: mutagenic effects in Drosophila

d-Lysergic acid diethylamide causes a significant increase in recessive lethal mutations in the X chromosome of Drosophila males after intraperitoneal injection of massive doses.     

Leukocytes of humans exposed to lysergic acid diethylamide: lack of chromosomal damage

Leukocyte cultures from eight human subjects who had had recent exposure to large doses of lysergic acid diethylamide were examined for chromosome abnormalities. The number of abnormalities was not significantly greater than that in control cultures.     

Distinct monoamine oxidase A and B populations in primate brain

Monoclonal antibodies specific for monoamine oxidase (MAO) A and MAO B, respectively, were used to localize these enzymes in primate brain. The reagents recognized different populations of neurons: those that recognized MAO A were located in cell groups containing catecholamines, including the substantia nigra, nucleus locus coeruleus, nucleus subcoeruleus, and the periventricular region of the hypothalamus, whereas those that recognized MAO B were observed in serotonin regions, including the nucleus raphe dorsalis and nucleus centralis superior. These data illustrate the physiological independence of MAO A and B and show that neurons may be specialized for their degradative as well as their synthetic functions.     

Histochemical fluorescence of raphe neurons: selective enhancement by tryptophan

The histochemical fluorescence of those neurons in brainstem raphe nuclei which are presumed to contain serotonin is selectively and stereospecifically enhanced by L-tryptophan at doses that also produce an elevation in the concentration of serotonin. However, contrary to our assumptions, the increase in raphe fluorescence is not prevented by p-chlorophenylalanine, an inhibitor of serotonin synthesis. These results suggest that under some conditions derivatives of tryptophan other than, or in addition to, serotonin may be of significance in raphe neurons.     

Chromosomal effect in vivo of exposure to lysergic acid diethylamide

Chromosome studies of persons exposed to lysergic acid diethylamide, either self-administered or received during medical therapy, failed to demonstrate significant chromosomal damage.     

Drosophila melanogaster treated with LSD: absence of mutation and chromosome breakage

Injection of lysergic acid diethylamide in Drosophila melanogaster males induced no mutations or chromosome breaks in premeiotic, meiotic, or postmeiotic sperm. Tests included those for sex-linked lethals, sex-linked visibles, a specific visible (dumpy), and translocations. Some implications of these experiments are discussed.