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The case of a patient who developed catatonia one week following Lysergic Acid Diethylamide (LSD) ingestion is presented. The psychosis developed two days after the intake. The catatonic syndrome resolved dramatically following one treatment of electroconvulsive therapy (ECT). This is perhaps the first case report of catatonia following the use of LSD. The need for a diagnostic category of organic catatonia is highlighted.
As revealed in earlier studies, the antinocifensive effect of morphine is brought about, among other things, with involvement of serotoninergic transmission mechanisms. In this context the role of the serotoninergic raphe-hippocampus system has been studied in this paper. Topical microinjections of serotonin into the dorsal hippocampus increased morphine analgesia in a dose-dependent fashion, while application into the striatum had no effect. Morphine injections into the median raphe nucleus in relatively low doses exert an antinocifensive effect which is inhibitable by methysergide. Lysergic acid diethylamide administered into the median raphe nucleus also abolished the effect of morphine in a dose-dependent manner. The results in connection with literature data lend support to the presumed integrative function of the serotoninergic raphe-hippocampus system in the mechanism of antinocifensive action of morphine.
An assay has been developed for quantitative determination of lysergic acid diethylamide (LSD) and a major metabolite of LSD in human urine at concentrations as low as 10 pg/mL. In most LSD-positive urine samples the metabolite, 2-oxo-3-hydroxy-LSD, is present at higher concentrations than LSD and can be detected for a longer time than LSD after ingestion of the drug. Urine samples are extracted using Varian Bond Elut Certify extraction cartridges. Confirmatory identification is accomplished by trimethylsilylation of LSD and 2-oxo-3-hydroxy-LSD, followed by gas chromatography-tandem mass spectrometry analysis using positive ion chemical ionization and selected reaction monitoring. Commercially available lysergic acid methylpropylamide and 2-oxo-3-hydroxy-LAMPA are used as internal standards. With selected reaction monitoring, both compounds gave linear calibration curves from 10 pg/mL to 5000 pg/mL. Forty-nine human urine samples that had previously been shown to contain LSD were reanalyzed by the new method. These samples showed an average LSD concentration of 357 pg/mL and an average 2-oxo-3-hydroxy-LSD concentration of 3470 pg/mL. Additional experiments using clinical samples in which two subjects were dosed with LSD support the conclusion that analysis for 2-oxo-3-hydroxy-LSD can permit identification of LSD users for a longer period following ingestion than analysis for the parent drug.
A serotonin (5-HT)-mediated phosphoinositide hydrolysis response was characterized in fibroblasts cultured from rabbit choroid plexus. 5-HT elicited a maximum 8-fold increase in [3H]inositol-phosphate ([3H]IP) formation, while the partial agonists, (+)-lysergic acid diethylamide and (-)-1-(4-bromo-2,5-dimethyoxyphenyl)-2-aminopropane caused 2- and 5-fold increases, respectively. Mianserin, ketanserin, and spiperone were equipotent at blocking the 5-HT-mediated response. Thus, agonist and antagonist profiles indicate interactions with 5-HT2 receptors.
In differential outcomes procedures, the correlation of unique reinforcers with distinct discriminative stimuli can decrease the amount of time needed for response acquisition and improve terminal accuracy of responding. The drug discrimination assay is widely used to categorize psychoactive drugs as similar or dissimilar and to describe underlying neurochemical changes associated with drug administration. Because the drug discrimination assay relies heavily upon initial response acquisition and continuing terminal accuracy, a procedure successful at shortening acquisition time and improving terminal accuracy would be beneficial. The present studies examined differences in acquisition of drug stimulus control between rats exposed to differential outcome procedures and rats exposed to the outcomes, in a non-systematic way, in two experiments. The first experiment examined acquisition of control by (+/-)-3,4-methylenedioxymethamphetamine (MDMA), D-amphetamine and saline; the second examined control by MDMA, (+)-lysergic acid diethylamide (LSD) and saline. Neither initial acquisition nor terminal accuracy was influenced by differential outcomes in either experiment. Although the differential outcome effect has been demonstrated in many situations, it does not appear to be useful in the drug discrimination assay. Possible reasons for the lack of an observed effect are discussed.
Rhesus monkeys, previously trained to avoid electric shock, pressed a lever to extinguish a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the onset of the light. Each response when the light was on terminated the light for a 1-minute time-out period (avoidance); a response during the infusion terminated the infusion (escape). Under these conditions the monkeys tolerated a high number of saline infusions. Saline was replaced by different doses of chlorpromazine, lysergic acid diethylamide (LSD) and pentobarbital each for six successive daily 2-hour sessions. Infusions of chlorpromazine (5.0-20 mug/kg/infusion) or LSD (1.0-2.5 mug/kg/infusion) generated and maintained avoidance/escape behavior, whereas most of the infusions of pentobarbital (10-100 mu/kg/infusion) were tolerated. In rhesus monkeys with no previous drug experience, chlorpromazine and LSD, but not pentobartital, have negative reinforcing properties.
In order to describe the interaction of morphine and 5-hydroxytryptamine (5-HT) in the raphe-hippocampus system we tested the influence on the antinocifensive effect of topic administrations of morphine and serotonergic substances into the dorsal hippocampus and the median raphe nucleus in rats. 5-HT administered into the dorsal hippocampus increased the morphine analgesia. Lysergic acid diethylamide injected into the raphe nucleus antagonized the morphine effect. Morphine given into the raphe nucleus was highly effective, while its injection into the striatum was ineffective. The effect of the intrahippocampal morphine was antagonized by methysergide. The results indicate the important role of the serotonergic raphe-hippocampus system in the mechanism of the morphine analgesia.
Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.
The two beta-adrenoceptor agonists salbutamol and clenbuterol have been shown to be effective antidepressant drugs. Flerobuterol, a new beta-adrenoceptor agonist, exhibits antidepressant activity in animal models. Given the long-standing notion that the serotonergic (5-HT) system might be involved in the etiology and/or the therapeutics of affective disorders and that this class of adrenergic agents can alter factors regulating 5-HT transmission, the effects of acute and repeated administrations of flerobuterol on the 5-HT system were studied. Acute administration of flerobuterol (up to 2 mg/kg, IV) did not modify the firing rate of dorsal raphe 5-HT neurons. However, the sustained administration of flerobuterol for two days (0.5 mg/kg/day, SC. delivered by an osmotic minipump) produced a marked decrease of the firing rate of 5-HT neurons. The reversal of this effect of flerobuterol by the somatodendritic 5-HT autoreceptor antagonist spiperone suggests that this decrease in the firing activity of 5-HT neurons in rats treated for 2 days with flerobuterol resulted from an enhanced synaptic availability of 5-HT. This initial decrease in firing activity of 5-HT neurons was followed by a progressive recovery to normal after 14 days of treatment with flerobuterol. At this point in time, the effect of intravenous lysergic acid diethylamide on the firing of 5-HT neurons was attenuated, indicating that the somatodendritic 5-HT autoreceptors had desensitized. The effectiveness of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of dorsal hippocampus pyramidal neurons was markedly enhanced in rats treated with flerobuterol for 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Tolerance and cross-tolerance relationships between lysergic acid diethylamide (LSD) and 5-hydroxytryptophan (5-HTP) were studied in rats trained on an operant task. The results demonstrated that behavioral tolerance to both compounds occur in the rat and that asymmetrical cross-tolerance relationships exist; that is, animals tolerant to 5-HTP were cross-tolerant to LSD, but animals tolerant to LSD were not cross-tolerant to 5-HTP.
The effects of picrotoxin (0.75 and 1.5 mg/kg), an antagonist of GABA mediated chloride ion conductance changes, were examined on the acquisition and performance of a bidirectional active avoidance (BAA) response and on locomotor activity. Treatment with this agent disrupted both the acquisition and performance of this task and decreased locomotor activity. This picrotoxin-induced suppression of BAA was reversed by pretreatment with diazepam (2 mg/kg), d-amphetamine (d-AMP, 2.0 mg/kg) and lysergic acid diethylamide (LSD, 10 micrograms/kg) and was reversed partially by cinanserin (5 mg/kg) and methysergide (5 mg/kg). Picrotoxin-induced activity decreases in locomotor activity were antagonized by d-AMP, were partially reversed by LSD but were not reversed by methysergide. It is proposed that picrotoxin disrupts bidirectional active avoidance behavior by increasing the response suppressive effects of aversive stimuli and by inducing a general depression of motility.
The serotonin (5-HT) agonists, D-lysergic acid diethylamide (LSD) and 5-methoxytryptamine (5-Me-O-T), dose dependently inhibited the K+-evoked outflow of [3H]5-HT from preloaded rat hippocampal slices in vitro, indicating activation of the 5-HT autoreceptor. However, this effect was abolished in slices pretreated with pertussis toxin. It is thus concluded that the 5-HT autoreceptor in the hippocampus is coupled to G proteins.
The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.
The inhibitory effects of microiontophoretically-applied serotonin (5-HT) and 6-chloro-2[1-piperazinyl]pyrazine (MK-212) were examined on spontaneously firing somatosensory cerebral cortical neurons and dorsal raphe neurons in rats anesthetized with chloral hydrate. On cortical neurons, MK-212 caused only weak and variable inhibition of extracellularly recorded neuronal activity, compared to the effects of 5-HT. However, on raphe cells, MK-212 exerted potent inhibitory effects, equivalent to those observed with 5-HT. In contrast to the inhibitory actions of D-lysergic acid diethylamide (LSD) and 5-HT at presumed 5-HT autoreceptors, MK-212 did not affect the in vitro release of [3H]5-HT from slices of rat hypothalamus stimulated by methiothepin. These findings, coupled with previously reported behavioral, biochemical and electrophysiological effects of MK-212 may indicate that this novel serotonergic agonist uniquely discriminates between subsets of serotonergic receptors in the CNS.
Infertility, permanent or temporary, resulting from drug-induced injury is an important clinical problem. Many common used drugs are potentially toxic to gonads. It is well-known that estrogens are toxic to the male genital system, but androgens may also produce infertility. Anovulation may also be a consequence of exposure to sex steroids. Cimetidine regularly produces hypospermia in men; phenytoin does so occasionally. Marijuana has been shown to be a gonadal toxin, while the effects of lysergic acid diethylamide (LSD) remain controversial. The most significant group of drugs that may injure the gonads is the cancer chemotherapeutic agents, of which the alkylating agents are the worst offenders. Prediction of infertility induced by these agents may be possible based on the duration of therapy and the patient's age and sex.
Ten naive male albino rats were trained to press a bar under a variable-interval 30-sec schedule with water as the reinforcer in two experiments. This behavior was disrupted by chlorpromazine in Experiment I (two rats) and by lysergic acid diethylamide (LSD) in both Experiment I (two rats) and Experiment II (six rats). The administration of the drug was paired with an originally neutral white light. After several pairings with either drug, the light also depressed behavior. When the light was no longer paired with drug, the depression effect extinguished much faster than is usually observed in conditioned suppression studies.
Burst-firing activity of neuron R 15 in the abdominal ganglion of Aplysia californica is inhibited by dopamine (DA) (50-500 microM). By using voltage clamp analysis of agonist-induced reduction of inward current and bath application of pharmacological agents, the agonist and antagonist specificity of the receptor mediating burst-firing inhibition in this cell was studied. The phenethylamine compounds DA, epinine, (-)-norepinephrine, (+)-norepinephrine, (-)-epinephrine, (+)-epinephrine and (-)-phenylephrine are active at similar concentrations. DA analogs 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene HBr and 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene HBr are active, whereas apomorphine, piribedil, (3,4-dihydroxyphenylamino)-2-imidazoline HCl and RU 24213 are inactive. DA-mediated inhibition of burst-firing is not antagonized by neuroleptics or certain adrenergic antagonists. Antagonism is seen with dihydroergotamine, lysergic acid diethylamide, ergonovine and other ergot alkaloids and the complex nature of this antagonism is discussed in detail. The specificity of this receptor for agonists and antagonists is compared to DA and adrenergic receptors from mammalian and other invertebrate tissues. We conclude that this DA-sensitive receptor mediating burst-firing inhibition of cell R 15 in Aplysia californica is very different from DA and adrenergic receptors.
Two adolescents with a long history of abuse of lysergic acid diethylamide (LSD) and symptoms consistent with major depressive disorder, on initiation of antidepressant therapy with selective serotonin reuptake inhibitor agents, had the new onset or worsening of LSD flashback syndrome. The similarity in neuroreceptor physiology for both LSD and serotonin suggests that the LSD flashback syndrome may be induced by these drugs in patients with a history of LSD abuse.