Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LYSERGIC ACID DIETHYLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

The role of serendipity in drug discovery.

Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry. "Serendipity" in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, i.e., aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. In the case of three drugs, i.e., potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, i.e., iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck.

Animals↗

The distribution of serotonin receptors in the human brain: high density of [3H]LSD binding sites in the raphe nuclei of the brainstem.

Serotonin receptors were localized autoradiographically in the human brainstem after in vitro labeling using [3H]lysergic acid diethylamide (LSD). Very high concentration of [3H]LSD binding sites, apparently belonging to the 5-HT1 class were localized in the raphe nuclei. Other areas of the brainstem presented only moderate or low receptor densities. Labeled areas were the nucleus interpeduncularis, periaqueductal gray matter, locus coeruleus and nucleus tractus solitarius. The choroid plexus was also labeled by [3H]LSD. The use of [3H]LSD binding as a marker for serotonin cells in the brainstem is suggested.

Autoradiography↗

Serotonergic agonists stimulate inositol lipid metabolism in rabbit platelets.

The metabolism of inositol phospholipids in response to serotonergic agonists was investigated in rabbit platelets. In platelets prelabelled with [3H]-inositol, in a medium containing 10 mM LiCl which blocks the enzyme inositol-1-phosphatase, 5-hydroxytryptamine (5-HT) caused a dose-dependent accumulation of inositol phosphates (IP). This suggests a phospholipase-C-mediated breakdown of phosphoinositides. Ketanserin, a selective 5-HT2 antagonist, was a potent inhibitor of the 5-HT response, with a Ki of 28 nM, indicating that 5-HT is activating receptors of the 5-HT2 type in the platelet. Lysergic acid diethylamide (LSD) and quipazine also caused dose-related increases in inositol phosphate levels, though these were considerably less than those produced by 5-HT. These results show that relatively small changes in phosphoinositide metabolism induced by serotonergic agonists can be investigated in the rabbit platelet, and this cell may therefore be a useful model for the study of some 5-HT receptors.

Animals↗

Daily LSD administration selectively decreases serotonin2 receptor binding in rat brain.

The effect of ten daily injections of saline or d-lysergic acid diethylamide (LSD) (260 micrograms/kg i.p.) on serotonin1 (5-hydroxytryptamine1, 5-HT1) and 5-HT2 receptor binding was determined in brain membranes from rats killed 24 h after the last injection. [3H]LSD (3.0 nM) was used with either 30.0 nM 5-HT or 70.0 nM cinanserin to estimate 5-HT1 and 5-HT2 receptors, respectively. LSD administration decreased 5-HT2 binding in cortex, striatum, hippocampus, and diencephalon/midbrain without altering 5-HT1 or total specific binding.

Animals↗

Age dependent changes in serotonin and dopamine receptors in Aplysia californica.

Age related changes in dopaminergic and serotonergic receptors were examined in Aplysia californica. In this study dopamine (DA) and serotonin (5-HT) receptor levels were examined for animals belonging to 4-, 5-, 6-, 8-, 9- and 12-month age groups. Receptors analysis was performed using radio-labeled d-[3H] lysergic acid diethylamide (LSD) as the specific ligand. Specific binding for 5-HT was found to be significantly greater than that for DA in the young (4-month post-hatch) animals. The total DA and 5-HT receptor levels changed significantly with age. Dopamine levels increased from 5.34 fmol/mg of protein at 4 months to 19.11 fmol/mg at 12 months. Serotonin receptor levels increased from 7.35 fmol/mg at 4 months to 20.45 at 12 months.

Aging↗

Detection of LSD and metabolite in rat hair and human hair.

To examine the feasibility of detecting lysergic acid diethylamide (LSD) and its metabolites in hair, LSD was administered to rats with pigmented hair at 0.05, 0.1, 0.5, 1, and 2 mg/kg intraperitoneally once per day for 10 successive days. The rats were shaved just before the first administration, and newly grown hair was collected 4 weeks later. After being washed with 0.1% sodium dodecyl sulfonate and water and being dried in a desiccator, each 20-mg hair sample was extracted with 2 mliter methanol-5N HCl (20:1) under ultrasonication for 1 h and stored at room temperature for 14 h. The extract was evaporated to dryness, extracted from 0.1M NaOH with dichloromethane, and derivatized with a mixture of trimethylsilylimidazole, bis-(trimethylsilyl)acetamide, and trimethylchlorosilane (3:3:2, v/v/v) for gas chromatographic-mass spectrometric (GC-MS) analysis using LSD-d10 or lysergic acid methylpropylamide (LAMPA) as the internal standard. Selected ions were monitored at m/z 395, 293, and 279 for TMS-LSD and at m/z 381, 279, and 254 for the trimethylsilyl derivative of N-demethyl-LSD (TMS-norLSD). LSD and norLSD were also detected by high-performance liquid chromatography (HPLC) with fluorometric detection (excitation, 315 nm; emission, 420 nm). LSD was detected in the rat hair following the lowest dose (0.05 mg/kg), whereas norLSD was only detectable in the hair following the highest dose (2 mg/kg). The same GC-MS and HPLC assays were applied to the analysis of hair from 17 self-reported LSD users, and LSD was detected in two of the samples.

Adolescent↗

Coma, hyperthermia, and bleeding associated with massive LSD overdose, a report of eight cases.

Eight patients were seen within 15 min of intranasal self-administration of large amounts of pure D-lysergic acid diethylamide (LSD) tartrate powder. Emesis and collapse occurred along with sign of sympathetic overactivity, hyperthermia, coma, and respiratory arrest. Mild generalized bleeding occurred in several patients and evidence of platelet dysfunction was present in all. Serum and gastric concentrations of LSD tartrate ranged from 2.1 to 26 ng/ml and 1000 to 7000 mug/100 ml, respectively. With supportive care, all patients recovered. Massive LSD overdose in humans is life-threatening and produces striking and distinctive manifestations.

Adult↗

Putative perception of rotating permanent magnetic fields following ingestion of LSD.

While sitting alone in complete darkness, 3 participants who had ingested psychotropic concentrations of lysergic acid diethylamide reported diffuse blobs of white, purplish, or greenish-yellow lights as two horseshoe magnets rotated at 0.5 Hz. The experiences were not reported when the magnets were stationary or removed from the apparatus. The estimated peak-to-peak variation in field strength at the distance of perception was between 50 and 500 nanoTesla. An association between these results and possible ergot-induced perceptions of "magnet light" reported during the last century by von Reichenbach (1851) is suggested.

Adult↗

Rave drugs: pharmacological considerations.

An increasingly prevalent component of today's adolescent and young adult culture are the rave or club drugs, such as Ecstasy, Rohypnol, gamma-hydroxybutyric acid, ketamine, Fry, lysergic acid diethylamide (LSD), and methamphetamine. Considering the incidence of accidental injury in this age group, young patients admitted to the operating room in emergency situations may be under the influence of one of these drugs. Each of these illicit drugs has distinct adverse physiological effects that may be compounded by the administration of anesthetic agents. Thus, it is important for the anesthetist to be cognizant of these drugs, their effects, and the potential risk factors they pose.

Adolescent↗

Drug effects on the repeated generalization of a visual discrimination acquired under one trial per day conditions.

Six pigeons were trained to respond under concurrent fixed-ratio extinction schedules of food reinforcement (FR 50) on the side keys of a three key chamber. Presence or absence of continuously-flashing, colored lights on the center key signalled which key pecking response (left or right) would be reinforced over the course of an entire experimental session; thus, the lights were analogous to a drug cue in drug-discrimination situations. In test (generalization) sessions of one FR in duration, the percentage of light on the center key was varied from 0 to 100%. During these sessions, saline, lysergic acid diethylamide (LSD; 0.04-0.20 mg/kg) and morphine (3.75 mg/kg) produced orderly, log-linear light generalization gradients, but only LSD shifted the gradient to the right (by approximately 50%). These results demonstrate the potential value of the method for assessing the effects of drugs on both exteroceptive (light) and interoceptive (drug) stimulus control. The method has the additional advantage that the effects of drugs on such control (i.e., on stimulus generalization) are relatively unaffected by corresponding effects on response control (e.g., rate of responding).

Animals↗

Characterization of specific binding sites labeled by [3H]LSD in coronal sections of paraformaldehyde-fixed rat brain.

Specific, high-affinity binding of [3H]lysergic acid diethylamide (LSD) in coronal sections of paraformaldehyde-fixed rat brain is described. Intracardiac perfusion of paraformaldehyde selectively altered 40% of the total binding sites normally labeled by [3H]LSD in unfixed sections. Competition by unlabeled LSD and serotonin (5-HT) was not altered by the fixation procedure. Competition by spiperone, however, revealed that the fixation procedure preferentially altered sites for which spiperone has high affinity. This technique should facilitate the combination of neuroanatomical techniques such as radioautography and immunocytochemistry.

Animals↗

Discriminative stimulus properties of cocaine. Effects of apomorphine, haloperidol, procaine and other drugs.

In pigeons trained to discriminate between the presence and absence of 3 mg/kg of cocaine, combinations of intramuscularly injected (i.m.) procaine (0.7-7.0 mg/kg) plus cocaine (0.3-3.0 mg/kg) did not alter the drug (cocaine)-dose generalization curve as compared to cocaine alone although tests with large doses of procaine given alone (30.0 and 56.0 mg/kg) engendered dose-related responding appropriate to cocaine. Apomorphine (0.56 mg/kg, i.m.) also elicited more than 50% cocaine-appropriate responding, as did doses of 10 mg/kg of intragastrically administered cocaine, given by gavage at the opening of the proventriculus; of the two treatment-test intervals (15 and 30 min) examined the generalization effect was greater at 30 min as compared to 15 min after administration. D-Lysergic acid diethylamide (0.1 mg/kg) morphine (3.0 mg/kg), pentobarbital (10.0 mg/kg), and delta 9-tetrahydrocannabinol (0.3 mg/kg) caused less than 16% pecking responses on the cocaine-appropriate key. The discriminative stimulus effects of cocaine (3.0 mg/kg) were attenuated in a dose-related manner by the neuroleptic haloperidol (dose range tested: 0.1-1.0 mg/kg). Neither the antagonism, nor the substitution tests with haloperidol were accompanied by a significant change in the percentage of responding on the initially selected position (key) by the pigeons.

Animals↗

Coma, hyperthermia and bleeding associated with massive LSD overdose. A report of eight cases.

Eight patients were seen within 15 minutes of intranasal self-administration of large amounts of pure D-lysergic acid diethylamide (LSD) tartrate powder. Emesis and collapse occurred along with signs of sympathetic overactivity, hyperthermia, coma and respiratory arrest. Mild generalized bleeding occurred in several patients and evidence of platelet dysfunction was present in all. Serum and gastric concentrations of LSD tartrate ranged from 2.1 to 26 nanograms per ml and 1,000 to 7,000 mug per 100 ml, respectively. With supportive care, all patients recovered. Massive LSD overdose in man is life-threatening and produces striking and distinctive manifestations.

Adult↗

Failure of ibogaine to produce phencyclidine-like discriminative stimulus effects in rats and monkeys.

The discriminative stimulus properties of ibogaine were investigated in rats trained to discriminate phencyclidine (PCP; 2.0 mg/kg, I.P.) from saline under a two-lever fixed-ratio (FR) 32 schedule of food reinforcement. Ibogaine (5.6-17.6 mg/kg, I.P.) showed a complete lack of substitution. Ibogaine (0.5-4.0 mg/kg, I.M.) also failed to generalize in rhesus monkeys trained to discriminate PCP (0.1 mg/kg, I.M.) from sham injection. Lysergic acid diethylamide (LSD), tested as a reference compound, produced partial substitution for PCP in rats and occasioned little responding on the PCP-associated lever in monkeys. These results demonstrate important differences between the behavioral effects of PCP and other types of hallucinogenic drugs such as LSD and ibogaine and do not support the hypothesis that the affinity of ibogaine for the PCP site on N-methyl-D-aspartate (NMDA) receptors plays a major role in its acute behavioral effects.

Animals↗

Mechanism of 5-hydroxytryptamine-induced biphasic responses of fowl rectum.

The present study investigated the mechanism of the biphasic action of 5-hydroxytryptamine (5-HT) on isolated fowl rectum. 5-HT (2.6 X 10(-6) M) very often produced a biphasic response i.e., an initial relaxation followed by contraction. Tetrodotoxin completely abolished the relaxatory component and partially inhibited the contraction. On the Remak's nerve denervated preparation (in which the non-adrenergic inhibitory and non-cholinergic excitatory neural elements are eliminated), 5-HT produced only contraction. Lysergic acid diethylamide or methysergide completely blocked the contractile component and significantly inhibited the relaxation. Caffeine, given alone, reduced the relaxation without affecting the contraction caused by 5-HT. Atropine, mepyramine, propranolol, pentolinium or indomethacin did not alter the biphasic responses to 5-HT. Thus, it is concluded that the 5-HT-induced relaxation is mediated by non-adrenergic inhibitory neurons, while the contractions of the fowl rectum are partly due to a direct myogenic action and partly mediated by an indirect stimulation of non-cholinergic excitatory neurons.

Animals↗

Club drug use among youths in treatment for substance abuse.

We describe lifetime rates of club drug use among 782 youths in treatment for substance abuse. Rates (%) for youths under eighteen (N = 486) were methylenedioxymethamphetamine (MDMA), 32.3; gamma-hydroxybutyrate (GHB), 7.0; lysergic acid diethylamide (LSD), 48.6; ketamine, 18.3; and methamphetamine, 30.2. For youths 18-32 (N = 289) rates (%) were MDMA, 37.0; GHB, 13.1; LSD, 42.9; ketamine, 17.0; and methamphetamine, 31.5. Older youths reported significantly more use of GHB than younger youths (p < .01). Youths reported using club drugs frequently outside of rave settings. Club drug use is common among youths in treatment for substance abuse and has spread beyond the rave culture.

Adolescent↗

The binding of [3H]-5-hydroxytryptamine to homogenates of human brain.

The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT) to homogenates of human brain has been studied. The specific binding is saturable, with a Kd (frontal cortex) of 12 /+- 2 nM, and is inhibited by non-radioactive 5-HT (IC50=26 nM) and D-Lysergic acid diethylamide (IC50=20 nM). Specific, but not non-specific binding of [3H]-5-TH was inhibited by incubation of the homogenates at 50 degrees C. The binding of [3H]-5-HT across the human brain was not uniform, the highest binding being found in the substantia nigra and hippocampus, and the lowest in the thalamus and pons. The Kd of the binding sites towards 5-HT did, however, appear to be similar for the different brain regions.

Animals↗

Determination of LSD in urine with high-performance liquid chromatography--mass spectrometry.

A rapid, specific, and sensitive high-performance liquid chromatography/mass spectrometry method has been developed for routine determination of lysergic acid diethylamide (LSD) in urine. It includes sample purification by extraction into an organic solvent and back-extraction to an acetate buffer, reversed-phase high-performance liquid chromatography, and detection with a single quadrupole mass spectrometer equipped with an atmospheric pressure ionization electrospray interface. Trideuterated LSD was used as internal standard. The limit of detection was 0.02 ng/mL and the calibration curve was linear from 0.05 to 10 ng/mL. Within-and between-day coefficients of variation were 3.5% and 4.0% respectively and extraction recovery was 91%.

Chromatography, Liquid↗