Imperial College London

Dr Robin Carhart-Harris

Faculty of MedicineDepartment of Brain Sciences

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7992r.carhart-harris

 
 
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Assistant

 

Miss Bruna Cunha +44 (0)20 7594 7992

 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

85 results found

Nour MM, Evans L, Carhart-Harris RL, 2017, Psychedelics, Personality and Political Perspectives, JOURNAL OF PSYCHOACTIVE DRUGS, Vol: 49, Pages: 182-191, ISSN: 0279-1072

Journal article

Schartner MM, Carhart-Harris RL, Barrett AB, Seth AK, Muthukumaraswamy SDet al., 2017, Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin, Scientific Reports, Vol: 7, ISSN: 2045-2322

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

Journal article

Walpola IC, Nest T, Roseman L, Erritzoe D, Feilding A, Nutt DJ, Carhart-Harris RLet al., 2017, Altered Insula Connectivity under MDMA, Neuropsychopharmacology, Vol: 42, Pages: 2152-2162, ISSN: 0893-133X

Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations–both of which are known to be associated with insular functioning.

Journal article

Nour MM, Carhart-Harris RL, 2017, Psychedelics and the science of self-experience, BRITISH JOURNAL OF PSYCHIATRY, Vol: 210, Pages: 177-179, ISSN: 0007-1250

Journal article

Curran HV, Wall M, Demetriou L, Carhart-Harris R, Fergusson B, Nutt Det al., 2016, Effects of ecstasy on autobiographical memories: implications for MDMA assisted psychotherapy, 29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S145-S145, ISSN: 0924-977X

Conference paper

Nutt D, Carhart-Harris RL, Curran H, 2016, Recent insights into the psychopharmacology of MDMA, 29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S145-S145, ISSN: 0924-977X

Conference paper

Carhart-Harris R, 2016, 5-HT2A agonist drugs as new treatments in psychiatry, 29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S121-S121, ISSN: 0924-977X

Conference paper

Kaelen M, Roseman L, Lorenz R, Simmonds A, Santos-Ribeiro A, Nutt D, Carhart-Harris Ret al., 2016, Effects of LSD and music on brain activity, 29th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S130-S130, ISSN: 0924-977X

Conference paper

Carhart-Harris RL, Nutt DJ, 2016, Question-based Drug Development for psilocybin Reply, LANCET PSYCHIATRY, Vol: 3, Pages: 807-807, ISSN: 2215-0374

Journal article

Family N, Vinson D, Vigliocco G, Kaelen M, Bolstridge M, Nutt DJ, Carhart-Harris RLet al., 2016, Semantic activation in LSD: evidence from picture naming, Language Cognition and Neuroscience, Vol: 31, Pages: 1320-1327, ISSN: 2327-3798

Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity.

Journal article

Nour M, Evans L, Nutt D, Carhart-Harris Ret al., 2016, Ego-dissolution and psychedelics: validation of the Ego-Dissolution Inventory (EDI), Frontiers in Human Neuroscience, Vol: 10, ISSN: 1662-5161

Aims: The experience of a compromised sense of “self”, termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution.Method: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; eight relating to the experience of ego-dissolution (comprising the EDI), and eight relating to the antithetical experience of increased self-assuredness, termed ego-inflation. Items were rated using a visual analog scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine and/or alcohol. They also answered the seven questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings.Results: Six hundred and ninety-one participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics, 377 cocaine, 408 alcohol). Exploratory factor analysis demonstrated that the eight EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to ego-inflation (rho = −0.110), demonstrating discriminant validity. The EDI correlated strongly with the MEQ-derived measure of unitive experience (rho = 0.735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach’s alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho = 0.371), but not for cocaine (rho = 0.115) or alcohol (rho = −0.055). Secondly, the linear regression line relating the subjective intensity of the experience to ego-dissolution was significantly steep

Journal article

Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJet al., 2016, Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study, Lancet Psychiatry, Vol: 3, Pages: 619-627, ISSN: 2215-0374

BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to

Journal article

Lebedev AV, Kaelen M, Lövdén M, Nilsson J, Feilding A, Nutt DJ, Carhart-Harris RLet 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.

Journal article

Roseman L, Sereno MI, Leech R, Kaelen M, Orban C, McGonigle J, Feilding A, Nutt DJ, Carhart-Harris RLet 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.

Journal article

Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, Leech R, Williams LT, Williams TM, Bolstridge M, Sessa B, McGonigle J, Sereno MI, Nichols D, Hellyer PJ, Hobden P, Evans J, Singh KD, Wise RG, Curran HV, Feilding A, Nutt DJet 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.

Journal article

Tagliazucchi E, Roseman L, Kaelen M, Orban C, Muthukumaraswamy SD, Murphy K, Laufs H, Leech R, McGonigle J, Crossley N, Bullmore E, Williams T, Bolstridge M, Feilding A, Nutt DJ, Carhart-Harris Ret al., 2016, Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution, Current Biology, Vol: 26, Pages: 1043-1050, ISSN: 1879-0445

Journal article

Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, Barrett FS, Bolstridge M, Williams T, Williams L, Wall MB, Feilding A, Muthukumaraswamy S, Nutt DJ, Carhart-Harris Ret 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.

Journal article

Terhune DB, Luke DP, Kaelen M, Bolstridge M, Feilding A, Nutt D, Carhart-Harris R, Ward Jet 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.

Journal article

Speth J, Speth C, Kaelen M, Schloerscheidt AM, Feilding A, Nutt DJ, Carhart-Harris RLet 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.

Journal article

Kaelen M, Roseman L, Lebedev A, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, Nutt D, Carhart-Harris Ret 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

Conference paper

Carhart-Harris RL, Kaelen M, Bolstridge M, Williams TM, Williams LT, Underwood R, Feilding A, Nutt DJet al., 2016, The paradoxical psychological effects of lysergic acid diethylamide (LSD), Psychological Medicine, Vol: 46, Pages: 1379-1390, ISSN: 1469-8978

BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.

Journal article

Carhart-Harris R, 2015, Results: Of a Multi-Modal Neuroimaging Study of LSD and a Psilocybin for Treatment-Resistant Depression Clinical Trial, 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP), Publisher: NATURE PUBLISHING GROUP, Pages: S91-S92, ISSN: 0893-133X

Conference paper

Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B, Williams LTJ, Roseman L, Brugger S, De Meer I, Tanner M, Tyacke R, Wolff K, Sethi A, Bloomfield MAP, Williams TM, Bolstridge M, Stewart L, Morgan C, Newbould RD, Feilding A, Curran HV, Nutt DJet al., 2015, The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity, Biological Psychiatry, Vol: 78, Pages: 554-562, ISSN: 1873-2402

BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

Journal article

Curran HV, Carhart-Harris R, Nutt D, Ferguson Bet al., 2015, Effects of MDMA on self-referent encoding and personal memories: implications for its use in PTSD, 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S147-S147, ISSN: 0924-977X

Conference paper

Kaelen M, Barrett FS, Roseman L, Lorenz R, Family N, Bolstridge M, Curran HV, Feilding A, Nutt DJ, Carhart-Harris RLet al., 2015, LSD enhances the emotional response to music., Psychopharmacology, Vol: 232, Pages: 3607-3614, ISSN: 1432-2072

RATIONALE: There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. OBJECTIVES: The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. METHODS: Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). RESULTS: Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". CONCLUSIONS: These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.

Journal article

Lebedev AV, Lövdén M, Rosenthal G, Feilding A, Nutt DJ, Carhart-Harris RLet al., 2015, Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin., Human Brain Mapping, ISSN: 1097-0193

Ego-disturbances have been a topic in schizophrenia research since the earliest clinical descriptions of the disorder. Manifesting as a feeling that one's "self," "ego," or "I" is disintegrating or that the border between one's self and the external world is dissolving, "ego-disintegration" or "dissolution" is also an important feature of the psychedelic experience, such as is produced by psilocybin (a compound found in "magic mushrooms"). Fifteen healthy subjects took part in this placebo-controlled study. Twelve-minute functional MRI scans were acquired on two occasions: subjects received an intravenous infusion of saline on one occasion (placebo) and 2 mg psilocybin on the other. Twenty-two visual analogue scale ratings were completed soon after scanning and the first principal component of these, dominated by items referring to "ego-dissolution", was used as a primary measure of interest in subsequent analyses. Employing methods of connectivity analysis and graph theory, an association was found between psilocybin-induced ego-dissolution and decreased functional connectivity between the medial temporal lobe and high-level cortical regions. Ego-dissolution was also associated with a "disintegration" of the salience network and reduced interhemispheric communication. Addressing baseline brain dynamics as a predictor of drug-response, individuals with lower diversity of executive network nodes were more likely to experience ego-dissolution under psilocybin. These results implicate MTL-cortical decoupling, decreased salience network integrity, and reduced inter-hemispheric communication in psilocybin-induced ego disturbance and suggest that the maintenance of "self"or "ego," as a perceptual phenomenon, may rest on the normal functioning of these systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Journal article

Steeds H, Carhart-Harris RL, Stone JM, 2015, Drug models of schizophrenia., Therapeutic Advances in Psychopharmacology, Vol: 5, Pages: 43-58, ISSN: 2045-1261

Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.

Journal article

Carhart-Harris RL, Kaelen M, Whalley MG, Bolstridge M, Feilding A, Nutt DJet al., 2015, LSD enhances suggestibility in healthy volunteers, PSYCHOPHARMACOLOGY, Vol: 232, Pages: 785-794, ISSN: 0033-3158

Journal article

Petri G, Expert P, Turkheimer F, Carhart-Harris R, Nutt D, Hellyer PJ, Vaccarino Fet al., 2014, Homological scaffolds of brain functional networks, Journal of the Royal Society Interface, Vol: 11, ISSN: 1742-5689

Networks, as efficient representations of complex systems, have appealed toscientists for a long time and now permeate many areas of science, includingneuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198.(doi:10.1038/nrn2618)). Traditionally, the structure of complex networks hasbeen studied through their statistical properties and metrics concerned withnode and link properties, e.g. degree-distribution, node centrality and modularity.Here, we study the characteristics of functional brain networks at themesoscopic level from a novel perspective that highlights the role of inhomogeneitiesin the fabric of functional connections. This can be done by focusingon the features of a set of topological objects—homological cycles—associatedwith the weighted functional network. We leverage the detected topologicalinformation to define the homological scaffolds, a new set of objects designed torepresent compactly the homological features of the correlation network andsimultaneously make their homological properties amenable to networks theoreticalmethods. As a proof of principle, we apply these tools to compare restingstatefunctional brain activity in 15 healthy volunteers after intravenous infusionof placebo and psilocybin—the main psychoactive component of magic mushrooms.The results show that the homological structure of the brain’s functionalpatterns undergoes a dramatic change post-psilocybin, characterized by theappearance of many transient structures of low stability and of a smallnumber of persistent ones that are not observed in the case of placebo.

Journal article

Tagliazucchi E, Carhart-Harris R, Leech R, Nutt D, Chialvo DRet al., 2014, Enhanced Repertoire of Brain Dynamical States During the Psychedelic Experience, HUMAN BRAIN MAPPING, Vol: 35, Pages: 5442-5456, ISSN: 1065-9471

Journal article

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