Publications
1392 results found
Maron E, Near J, Wallis G, et al., 2016, A pilot study of the effect of short-term escitalopram treatment on brain metabolites and gamma-oscillations in healthy subjects, Journal of Psychopharmacology, Vol: 30, Pages: 579-580, ISSN: 1461-7285
Freeman TP, Pope RA, Wall MB, et al., 2016, Dissociable effects of cannabinoids on anticipatory and consummatory reward processing, 30th World Congress of the International-College-of-Neuropsychopharmacology (CINP), Publisher: OXFORD UNIV PRESS, Pages: 155-156, ISSN: 1461-1457
Nutt D, 2016, Imaging the 5-HT system in anxiety disorders, Australian and New Zealand Journal of Psychiatry, Vol: 50, Pages: 88-88, ISSN: 1440-1614
Sharma AN, Arango C, Coghill D, et al., 2016, BAP Position Statement: Off-label prescribing of psychotropic medication to children and adolescents, Journal of Psychopharmacology, Vol: 30, Pages: 416-421, ISSN: 1461-7285
Tang SP, Mirzaei N, Coello C, et al., 2016, EVALUATION OF [11C]PBR28 PET IMAGING TO DETECT CHANGES IN MICROGLIAL ACTIVATION IN MOUSE MODELS OF ALZHEIMER'S DISEASE, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 654-655, ISSN: 0271-678X
Lebedev AV, Kaelen M, Lövdén M, et al., 2016, LSD-induced entropic brain activity predicts subsequent personality change, Human Brain Mapping, Vol: 37, Pages: 3203-3213, ISSN: 1097-0193
Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
Kuhn CM, Zepf FD, Nutt D, et al., 2016, TRANSLATIONAL INSIGHTS INTO ANXIETY AND BEHAVIOURAL INHIBITION, AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, Vol: 50, Pages: 86-86, ISSN: 0004-8674
Nutt D, 2016, ADDICTION PSYCHIATRY: HOW CAN BRAIN RESEARCH EMPOWER NEW TREATMENTS?, AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, Vol: 50, Pages: 4-4, ISSN: 0004-8674
Nutt D, Hood S, Bassett D, et al., 2016, INTERNATIONAL MASTERS OF AFFECTIVE NEUROSCIENCES, AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, Vol: 50, Pages: 99-99, ISSN: 0004-8674
Hood SD, Hince D, Davies SJC, et al., 2016, TRYPTOPHAN DEPLETION ENHANCES CARDIOVASCULAR RESPONSES TO STRESS IN RECOVERED PATIENTS WITH ANXIETY DISORDERS, AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, Vol: 50, Pages: 88-88, ISSN: 0004-8674
Nutt DJ, Blier P, 2016, Neuroscience-based Nomenclature (NbN) for Journal of Psychopharmacology, Journal of Psychopharmacology, Vol: 30, Pages: 413-415, ISSN: 1461-7285
Nutt D, 2016, History and philosophy of the international masters of affective neurosciences, Australian and New Zealand Journal of Psychiatry, Vol: 50, Pages: 99-99, ISSN: 1440-1614
Limbrick-Oldfield E, Mick I, Cocks R, et al., 2016, Neural Substrates of Cue Reactivity and Craving in Gambling Disorder, Publisher: ELSEVIER SCIENCE INC, Pages: 341S-341S, ISSN: 0006-3223
Roseman L, Sereno MI, Leech R, et al., 2016, LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion, Human Brain Mapping, Vol: 37, Pages: 3031-3040, ISSN: 1097-0193
The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
Carhart-Harris RL, Muthukumaraswamy S, Roseman L, et al., 2016, Neural correlates of the LSD experience revealed by multimodal neuroimaging, Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: 4853-4858, ISSN: 1091-6490
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
Tagliazucchi E, Roseman L, Kaelen M, et al., 2016, Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution, Current Biology, Vol: 26, Pages: 1043-1050, ISSN: 1879-0445
Myers JF, Nutt DJ, Lingford-Hughes AR, 2016, γ-aminobutyric acid as a metabolite: Interpreting magnetic resonance spectroscopy experiments., Journal of Psychopharmacology, Vol: 30, Pages: 422-427, ISSN: 1461-7285
The current rise in the prevalence of magnetic resonance spectroscopy experiments to measure γ-aminobutyric acid in the living human brain is an exciting and productive area of research. As research spreads into clinical populations and cognitive research, it is important to fully understand the source of the magnetic resonance spectroscopy signal and apply appropriate interpretation to the results of the experiments. γ-aminobutyric acid is present in the brain not only as a neurotransmitter, but also in high intracellular concentrations, both as a transmitter precursor and a metabolite. γ-aminobutyric acid concentrations measured by magnetic resonance spectroscopy are not necessarily implicated in neurotransmission and therefore may reflect a very different brain activity to that commonly suggested. In this perspective, we examine some of the considerations to be taken in the interpretation of any γ-aminobutyric acid signal measured by magnetic resonance spectroscopy.
Mick I, Myers J, Ramos AC, et al., 2016, Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers, 3rd International Conference on Behavioral Addictions, Publisher: Akadémiai Kiadó, Pages: 30-30, ISSN: 2063-5303
Kaelen M, Roseman L, Kahan J, et al., 2016, LSD modulates music-induced imagery via changes in parahippocampal connectivity, European Neuropsychopharmacology, Vol: 26, Pages: 1099-1109, ISSN: 1873-7862
Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.
Terhune DB, Luke DP, Kaelen M, et al., 2016, A placebo-controlled investigation of synaesthesia-like experiences under LSD, Neuropsychologia, Vol: 88, Pages: 28-34, ISSN: 1873-3514
The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia.
Werb D, Kazatchkine M, Kerr T, et al., 2016, A call to reprioritise metrics to evaluate illicit drug policy, Lancet, Vol: 387, Pages: 1371-1371, ISSN: 1474-547X
Speth J, Speth C, Kaelen M, et al., 2016, Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide, Journal of Psychopharmacology, Vol: 30, Pages: 344-353, ISSN: 1461-7285
This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug’s subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one’s past, likely mediated by DMN functioning, is symptomatic.
Taylor P, Nutt D, Curran V, et al., 2016, Ketamine-the real perspective, LANCET, Vol: 387, Pages: 1271-1272, ISSN: 0140-6736
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Nutt DJ, Phillips LD, Balfour D, et al., 2016, E-cigarettes are less harmful than smoking., Lancet, Vol: 387, Pages: 1160-1162
Nutt DJ, Phillips LD, Balfour D, et al., 2016, E-cigarettes are less harmful than smoking, LANCET, Vol: 387, Pages: 1160-1162, ISSN: 0140-6736
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- Citations: 41
Mirzaei N, Tang SP, Ashworth S, et al., 2016, In vivo imaging of microglial activation by positron emission tomography with [11 C]PBR28 in the 5XFAD model of Alzheimer's disease, GLIA, ISSN: 0894-1491
Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [11C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [11C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [11C]PBR28 in 6-month-old 5XFAD mice and in wild-type controls. Autoradiography with [3H]PBR28 was carried out in the same brains to further confirm the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co-localization of TSPO with microglia. PET imaging revealed that brain uptake of [11C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [3H]PBR28, measured by autoradiography, was enriched in cortical and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 and amyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPO demonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post-mortem AD brains. The data provided support of the suitability of [11C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD
Nahar LK, Cordero R, Nutt D, et al., 2016, Validated method for the quantification of baclofen in human plasma using solid-phase extraction and liquid chromatography–tandem mass spectrometry, Journal of Analytical Toxicology, Vol: 40, Pages: 117-123, ISSN: 0146-4760
A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupoleliquid chromatography–tandem mass spectrometry (LC–MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r2 > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthymale volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability.
Kaelen M, Roseman L, Lebedev A, et al., 2016, Effects of LSD and music on brain activity, ECNP Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S80-S81, ISSN: 0924-977X
Taylor EM, Murphy A, Boyapati V, et al., 2016, Impulsivity in abstinent alcohol and polydrug dependence: a multidimensional approach, Psychopharmacology, Vol: 233, Pages: 1487-1499, ISSN: 1432-2072
Lingford-Hughes A, Myers J, Watson B, et al., 2016, Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism, Neuroimage, Vol: 132, Pages: 1-7, ISSN: 1095-9572
The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised inaddiction. Using the α1/α5 benzodiazepine receptor PET radioligand [ 23 11C]Ro15 4513, we previously showed reducedbinding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that 24reduced [ 25 11C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampusand positive relationship with memory was a consequence of chronic alcohol abuse. To examine this 26further we assessed [ 27 11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysisto estimate contributions of α1 and α5 subtypes to [ 28 11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependentgroups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [ 29 11C]Ro154513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in 30[ 31 11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy controlgroup. There was no relationship between [ 32 11C]Ro15 4513 binding in the hippocampus with memory. Wefound that reduced [ 33 11C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependentgroup. This was also seen in an alcohol-dependent group where an association between memory 34performance and [ 35 11C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reducedα5 levels in the nucleus accumbens are associated with addiction since we have now shown this in depen- 36dence to two pharmacologically different substances, alcohol and opiates.
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