Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Rickli, Anna; Moning, Olivier D.; Hoener, Marius C.; Liechti, Matthias E.

doi:10.1016/j.euroneuro.2016.05.001

Cited by 271 publications

(302 citation statements)

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“…Specifically, MDMA mainly induces the transporter-mediated release of serotonin (Hysek et al 2012) and stimulates oxytocin secretion Ramos et al 2013), which has been implicated in the prosocial effects of MDMA (Ramos et al 2013). Additionally, the serotonin receptor agonist LSD (Rickli et al 2016) stimulated oxytocin secretion (Schmid et al 2015a), produced prosocial effects, and enhanced emotional empathy in the MET (Dolder et al 2016). In contrast to MDMA and LSD and our prediction, the present study found that alcohol did not change oxytocin levels in 30 female and 30 male participants at a low dose (0.27 g/kg) as similarly shown for a high dose of alcohol (0.8 g/kg) in seven male subjects (Bershad et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images

et al. 2016

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Rationale: Social cognition influences social interactions. Alcohol reportedly facilitates social interactions. However, the acute effects of alcohol on social cognition are relatively poorly studied. Methods: We investigated the effects of alcoholic or non-alcoholic beer on emotion recognition, empathy, and sexual arousal using the dynamic face emotion recognition task (FERT), Multifaceted Empathy Test (MET), and Sexual Arousal Task (SAT) in a double-blind, random-order, cross-over study in 60 healthy social drinkers. We also assessed subjective effects using visual analog scales (VASs), BACs, and plasma oxytocin levels. Results: Alcohol increased VAS ratings of stimulated, happy, talkative, open, and want to be with others. The subjective effects of alcohol were greater in participants with higher trait inhibitedness. Alcohol facilitated the recognition of happy faces on the FERT and enhanced emotional empathy for positive stimuli on the MET, particularly in participants with low trait empathy. Pictures of explicit sexual content were rated as less pleasant than neutral pictures after non-alcoholic beer but not after alcoholic beer. Explicit sexual pictures were rated as more pleasant after alcoholic beer compared with non-alcoholic beer, particularly in women. Alcohol did not alter the levels of circulating oxytocin. Conclusions: Alcohol biased emotion recognition toward better decoding of positive emotions and increased emotional concern for positive stimuli. No support was found for a modulatory role of oxytocin. Alcohol also facilitated the viewing of sexual images, consistent with disinhibition, but it did not actually enhance sexual arousal. These effects of alcohol on social cognition likely enhance sociability.

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Section: Discussionmentioning

confidence: 99%

Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images

et al. 2016

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“…Additionally, there is much interest in its therapeutic potential (Baumeister et al 2014; Davenport 2016; Gasser et al 2014; Gasser et al 2015; Krebs and Johansen 2012; Kupferschmidt 2014). Only one modern study has tested the therapeutic effects of LSD in patients (Gasser et al 2014), whereas several clinical trials have recently evaluated the therapeutic potential of psilocybin (Bogenschutz et al 2015; Carhart-Harris et al 2016a; Garcia-Romeu et al 2015; Griffiths 2016; Grob et al 2011; Guss 2016), a similar serotonergic hallucinogen (Rickli et al 2016). A series of studies showed that psilocybin acutely induced mystical experiences in healthy subjects and patients (Garcia-Romeu et al 2015; Griffiths et al 2008; Griffiths et al 2011; Griffiths et al 2006; MacLean et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Alterations of consciousness and mystical-type experiences after acute LSD in humans

2016

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RationaleLysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking.MethodsWe conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.ResultsOn the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.ConclusionsMystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-016-4453-0) contains supplementary material, which is available to authorized users.

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“…Psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives including ergometrine, dihydroergotamine, and LSD, as well as the antiparkinsonian agents bromocriptine and lisuride, display agonistic activity at the rat [59] and mouse [51] TAAR 1 receptor expressed on HEK-293 cells. Simmler et al showed that LSD has relatively high affinity for TAAR 1 in rat but lower in mice and humans [137], for the first time, our laboratory showed that the injection of EPPTB (5 mg/kg, i.v.…”

Section: In the Deep Of The Mechanism: Who Are The Players?mentioning

confidence: 99%

“…The inference was that modulators of serotonin receptors might be useful in the treatment of schizophrenia [45,46]. Multiple lines of evidence indicate that LSD acts through the serotonergic system, binding the 5-HT 2A receptor as a partial agonist, even at human cloned 5-HT 2A receptor [47,48,49,50,51], and the 5-HT 1A receptor as an agonist/partial agonist [52,53]. However, studies have also pointed out the involvement of the dopaminergic [50,54] and glutamatergic [55] systems in LSD’s mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

Gregorio

Comai

Posa

et al. 2016

IJMS

104

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d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1 receptors.

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Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Abstract: The present study investigated interactions between the novel psychoactive

Cited by 271 publications

References 73 publications

Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images

Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images

Alterations of consciousness and mystical-type experiences after acute LSD in humans

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

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