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PubMed1985

Axonal transport of a heat shock protein in the rabbit visual system.

Intraocular injection of [35S]methionine was used to demonstrate the pronounced induction of a 74-kDa heat shock protein in the rabbit retina after a 3 degrees C increase in body temperature was generated by intravenous administration of D-lysergic acid diethylamide. Two-dimensional polyacrylamide gel electrophoresis and fluorography revealed that the induced heat shock protein underwent axonal transport from retinal ganglion cells into the optic nerve and subsequently down the contralateral optic tract to synaptic termini in the visual projection area. Since the heat shock protein took more than 8 days to move down the optic nerve to the superior colliculus, it is transported by slow rather than by fast axonal transport.

Animals↗
PubMed1993

Serotonin receptor cDNA cloned from Lymnaea stagnalis.

Serotonin (5-HT) is a major neurotransmitter that influences various behaviors, neuronal plasticity, learning, and memory in molluscs. Although the physiology of 5-HT transmission in molluscs is well studied, little is known about the pharmacology and diversity of the 5-HT receptor system. Based on the high homology of genes coding for guanine nucleotide-binding protein (G protein)-coupled receptors, we have cloned a gene for the Lymnaea stagnalis 5-HT (5HTlym) receptor. The putative receptor protein, 509 amino acids long, has highest homology with the Drosophila 5-HT receptors and mammalian 5HT1 receptors. As revealed by RNA blot-hybridization analysis, two mRNA species of 2.3 and 3.2 kb are detected in the central nervous system of Lymnaea. Transient expression of 5HTlym in COS-7 cells showed saturable [3H]lysergic acid diethylamide binding with an estimated dissociation constant of 0.9 nM. The 5HTlym receptor exhibited a mixed 5HT-like pharmacology that cannot be precisely categorized with existing mammalian classification nomenclature. However, the 5HTlym receptor does display some characteristics that have been attributed to the putative mammalian vascular 5HT1-like receptor.

Amino Acid Sequence↗
PubMed1993

Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.

We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothepin > 5-carboxamidotryptamine > 5-HT. For REC17, the rank of potency was ergotamine > 5-carboxamidotryptamine > methiothepin > methysergide > 5-HT. Both were insensitive to 5-HT1A, 5-HT1D or 5-HT2 serotonergic ligands [8-hydroxy-2-(di-n-propylamino)tetralin, sumatriptan, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The mRNAs encoding MR22 were detected in the CA1 region of hippocampus, the medial habenula, and raphe nuclei. In contrast, mRNAs encoding REC17 were found throughout the rat central nervous system. We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors.

Amino Acid Sequence↗
PubMed1996

Functional reconstitution in situ of 5-hydroxytryptamine2c (5HT2c) receptors with alphaq and inverse agonism of 5HT2c receptor antagonists.

Membranes prepared after infection of Sf9 cells with recombinant baculovirus containing the rat 5HT2c receptor DNA, but not after infection with wild-type virus, expressed high affinity binding sites for 125I-lysergic acid diethylamide and [3H]mesulergine. The receptor site density reached an optimum of 50-70 pmol/mg membrane protein at 60 h postinfection. Extraction of peripheral membrane proteins from the postnuclear membrane fraction with 6 M urea depleted GTPgammaS-binding 4-fold without decreasing 5HT2c receptor binding activity. Urea-extracted Sf9 membranes expressing the 5HT2c receptor catalyzed the activation of squid retinal alphaq but not bovine retinal alphat or bovine alphao/alphai. Productive interaction of 5HT2c receptors with squid alphaq was enhanced by the addition of betagamma dimers prepared from either bovine brain or bovine rod outer segment discs. While the addition of serotonin increased 5HT2c receptor-catalyzed GTPgammaS binding to alphaq, the unoccupied receptor was also catalytically active. The 5HT2c receptor antagonists, mesulergine, mianserin, and ketanserin competitively inhibited 5HT activation of the receptor with predicted rank-order affinities; and mianserin and ketanserin markedly inhibited basal 5HT2c receptor activity. Interestingly, this "inverse agonist" efficacy did not correlate with antagonist affinity for the 5HT2c receptor. Baculoviral expression of the 5HT2c receptor and urea extraction of postnuclear Sf9 cell membranes have provided a high density of in situ, uncoupled, G-protein-linked receptor useful for reconstitution with purified G-protein subunits. This has allowed for independent manipulation of receptor and G-protein chemical concentrations and has revealed that a G-protein-linked receptor can possess a significant basal catalytic activity and that antagonist compounds can act as inverse agonists of this basal activity at the level of receptor activation of G-proteins.

Animals↗
PubMedDate not supplied

Boletus manicus Heim.

Boletus manicus Heim [Boletaceae] is a species of fungus found in Papua New Guinea. It is reported to have psychoactive properties. The chemistry of this species is poorly understood. The available chemical data indicates that B. manicus contains trace amounts of three unidentified indolic substances. The chemical structure of these substances has not yet been determined. For these indoles to be active in trace amounts they must be as potent as d-lysergic acid diethylamide (LSD).

Agaricales↗
PubMed1994

Increasing use of "Ecstasy" (MDMA) and other hallucinogens on a college campus.

We conducted a random survey of illicit drug use by undergraduate students at a private southern university in 1990 and compared the results with results from a similar 1986 survey of that college's student population. During the 4 years since the first study, the prevalence of cocaine use declined from 39% to 21%, and use of traditional amphetamines declined from 22% to 12%. No significant differences were found in the use of marijuana--68% in 1986, 64% in 1990--or in use of LSD (lysergic acid diethylamide)--14% in 1986, 17% in 1990. The use of mescaline/psilocybin increased from 8% to 24% and the use of MDMA, known as "Ecstasy" (3,4-methylenedioxymethamphetamine), increased from 16% to 24%. Mescaline/psilocybin and Ecstasy were more likely than the other drugs to have been used first during the students' college years, according to the 1990 study.

3,4-Methylenedioxyamphetamine↗
PubMed1999

Inhalant abuse and the abuse of other drugs.

AIMS: To examine the relationship between inhalant abuse and other substances of abuse. DESIGN: Survey using a structured interview administered by a single trained interviewer. SETTING: A juvenile detention facility. PARTICIPANTS: 209 children incarcerated at the facility over a 3-month period. SELECTION PROCEDURE: Consecutive sample. INTERVENTIONS: None. MEASUREMENTS/FINDINGS: The structured interview was adapted from the American Drug and Alcohol Survey, which has been extensively used to obtain substance abuse epidemiologic data. We collected information on inhalants, alcohol, marijuana, downers, pep pills, lysergic acid diethylamide (LSD), cocaine, designer drugs, phencyclidine (PCP), Talwin and Ritalin, speed, and narcotics. The chi-square or Fisher exact test were used when appropriate. Mean ages of initial experimentation were as follows: inhalants, 9.7 years; marijuana, 11.9 years; alcohol (inebriated), 12.0 years; cigarettes, 11.2 years; for the remaining substances of abuse, the mean age was 13.2-14.7 years. Thirty subjects had used inhalants. Significant relationships were found between inhalants and cocaine (p = .004), Talwin and Ritalin (p = .001), downers (p = .01), and narcotics (p = .003). CONCLUSIONS: For children incarcerated in a juvenile detention facility in our community, inhalant abuse is associated with the later use of other substances of abuse. If this finding is replicated in other populations, it underscores the need for effective preventive strategies.

Administration, Inhalation↗
PubMed2000

Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

Administration, Oral↗
PubMed2006

Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10-year retrospective study.

OBJECTIVE: The aim of this study was to investigate the link between the use of specific types of substances and suicidality in adolescent inpatients with schizophrenia and schizoaffective disorder. METHODS: We performed a 10-year naturalistic retrospective study of 178 adolescent inpatients diagnosed as suffering from either schizophrenia or schizoaffective disorder. A comparison was made between the suicide-attempting adolescent inpatients and the non-attempting subjects, by the use of specific types of substances, measurements of psychotic, depressive, and aggressive symptoms, and clinical data reported during their hospitalization. RESULTS: The suicide attempters reported considerably greater usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene-dioxy-methylamphetamine (MDMA) were also used significantly more by this group. However, no differences were found in the usage of cannabis, amphetamines, cocaine, and opiates. The suicide-attempting patients were found to have had more previous psychiatric admissions, a greater level of deliberate self-harm behavior, and a higher level of suicide ideation, but a decreased severity of psychotic symptoms. CONCLUSIONS: This study is the first report of the association between specific types of substances and suicidality in the high-risk population of adolescent psychotic inpatients. The strong association between inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide prevention and intervention programs in adolescent-onset schizophrenia.

Adolescent↗
PubMed1993

Effect of freezing on the concentration of drugs of abuse in urine.

Benzoylecgonine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-acid), phencyclidine, codeine, morphine, amphetamine, methamphetamine, and lysergic acid diethylamide were dissolved in urine, stored frozen in plastic tubes at -16 to -18 degrees C, defrosted, transferred to other tubes, and analyzed by gas chromatography/mass spectrometry (GC/MS); no significant loss of compound was observed, except for THC-acid, which showed an average loss of 11%, ranging from 0 to 34% of the total concentration. The loss is attributed to the decrease in solubility of the compound and to adherence to the side of the container during freezing.

Freezing↗
PubMed2001

Effects of Stealth adulterant on immunoassay testing for drugs of abuse.

Stealth is an adulterant advertised as being undetectable by adulteration tests. It has been described as peroxidase and peroxide, which, when added to urine samples, are intended to prevent a positive drug test. Characterization of the effect of Stealth on urine samples and immunoassay results was undertaken to assist in detection of this adulterant. Stealth was added to a number of urine matrices, and various parameters were evaluated including pH, specific gravity, color, creatinine, chloride, urea, blood, glucose, and nitrite. Samples were spiked with THC acid metabolite, benzoylecgonine, morphine, secobarbital, PCP, amphetamine, and lysergic acid diethylamide (LSD) then tested by Roche OnLine and Microgenics CEDIA immunoassay reagents. Results of these analyses showed Stealth did not cause the urine sample to exceed any of the monitored parameters including those routinely used in drug-testing laboratories that would indicate adulteration of a sample. It did, however, cause samples positive for the marijuana metabolite (11-nor-delta9-tetrahydrocannibinol-9-carboxylic acid), LSD, and opiate (morphine) at 125-150% of cutoff to screen negative by immunoassay. Adulterating an authentic positive sample provided by a marijuana user caused that sample to screen negative using these immunoassay reagents as well.

Drug Contamination↗
PubMed1990

Recreational drug use and the risk of primary infertility.

Recreational drug (marijuana, lysergic acid diethylamide or LSD, speed, cocaine, and "other") exposures of women with primary infertility were compared with those of a matched control group of women with proven fertility. Women who reported smoking marijuana had a slightly elevated risk for infertility due to an ovulatory abnormality (RR = 1.7, 95% CI = 1.0 to 3.0). The risk was greatest among women who had used marijuana within one year of trying to become pregnant (RR = 2.1, 95% CI = 1.1 to 4.0). No consistent frequency or duration of use effects could be demonstrated, and the risk was confined to low-frequency users. Risks associated with the use of other drugs were not elevated. The risk of infertility from a tubal abnormality associated with cocaine use was greatly increased (RR = 11.1, 95% CI = 1.7 to 70.8). Our results are consistent with animal studies suggesting that smoking marijuana may cause a transient disruption of ovulatory function. The possibility that cocaine exposure influences the development of tubal infertility needs further investigation.

Adult↗
PubMed1986

Hyperthermia associated with drug intoxication.

Hyperthermia (temperature of at least 40.5 degrees C for at least one hour) associated with drug intoxication was identified in 12 patients over a 5-yr period. Intoxication was due to anticholinergic drugs (tricyclic antidepressants, antipsychotics, antihistamines), CNS stimulants (phencyclidine, cocaine, 3,4-methylene dioxyamphetamine, mescaline, lysergic acid diethylamide), salicylates, or combinations of these. Hyperthermia was present in four patients on admission, but its onset was delayed up to 12 h in the remainder. Outcome of hyperthermic patients was poor: five died and four had severe permanent neurologic sequelae. Clinical signs common to patients who developed hyperthermia were increased muscular activity and absence of sweating. Five patients suffered seizures, and four did not respond to anticonvulsant medication until body temperature was lowered. Cooling did not appear to favorably affect the outcome after body temperature had remained above 40.5 degrees C for a prolonged period. Prevention of death or neurologic sequelae from drug-induced hyperthermia depends upon the recognition of risk factors and the prompt treatment of hyperthermia.

Adolescent↗
PubMed2000

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Adult↗
PubMed1985

Pharmacology of potent and selective S2-serotonergic antagonists.

Ketanserin is the prototype of a new series of serotonergic antagonists that competitively and selectively block 5-hydroxytryptamine (S2) serotonergic receptors. Ketanserin and its analogues antagonize the events mediated by this receptor, i.e., serotonin-induced vasoconstriction, bronchoconstriction, and platelet aggregation, irrespective of whether serotonin acts directly or amplifies the effect of vasoconstrictors or platelet aggregating agents. The antagonism is pure because compounds such as ketanserin are devoid of agonistic activity. The actions of ketanserin are mainly peripheral, whereas other members of the series, e.g., ritanserin, act on the brain and are potent antagonists of lysergic acid diethylamide and other centrally acting serotonomimetic drugs. The different pharmacological profiles of the new S2-serotonergic antagonists and the evidence already available on their clinical effects prompt a further exploration of these agents in a large range of cardiovascular and other diseases.

Animals↗
PubMed2002

Drugs of abuse monitoring in blood for control of driving under the influence of drugs.

Driving under the influence of drugs is an issue of growing concern in the industrialized countries as a risk and a cause for road accidents. In forensic toxicology, the increasing number of samples for determination of drugs in blood is mainly due to zero-tolerance laws in several countries and well-trained police officers who can better recognize drivers under the influence of drugs of abuse. This review describes procedures for detection of the following drugs of abuse in whole blood, plasma, and serum: amphetamine, methamphetamine, 3,4-methylenedioxy methamphetamine (MDMA), N-ethyl-3, 4-methylenedioxyamphetamine (MDEA), 3,4-methylenedioxyamphetamine (MDA), cannabinoids (delta-9-tetrahydrocannabinol [THC], 11-hydroxy-delta-9-THC, 11-nor-9-carboxy-delta-9-THC), cocaine, benzoylecgonine, ecgonine methyl ester, cocaethylene, the opiates (heroin, 6-monoacetylmorphine, morphine, or codeine), and methadone as well as gamma-hydroxybutyric acid (GHB), lysergic acid diethylamide (LSD), phencyclidine (PCP), and psilocybin/psilocin. For many of the analytes, sensitive immunologic methods for screening are available. Gas chromatography-mass spectrometry (GC-MS) is still the state-of-the-art method for confirmatory analysis or for screening and confirmation in one step. Liquid chromatography-mass spectrometry (LC-MS) procedures for such purposes are also included in this review. Basic data about the biosample assayed, internal standard, workup, GC or LC column and mobile phase, detection mode, reference data, and validation data of each procedure are summarized in two tables.

Accidents, Traffic↗