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D. Nutt

Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use

November 15, 2016 / Ayahuasca, Depressive Disorders, Iboga / Ibogaine, Ketamine, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.

Morgan, C., McAndrew, A., Stevens, T., Nutt, D., & Lawn, W. (2017). Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use. Current Opinion in Behavioral Sciences, 13, 71-76. 10.1016/j.cobeha.2016.10.009
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Semantic activation in LSD: evidence from picture naming

August 11, 2016 / LSD, Papers, Psychology, Publications / By / , , , , , ,

Abstract

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.

Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., & Carhart-Harris, R. L. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition and Neuroscience, 1-8. http://dx.doi.org/10.1080/23273798.2016.1217030
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Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI)

May 20, 2016 / Papers, Psychology, Publications / By / , , ,

Abstract

Aims: The experience of a compromised sense of ‘self’, termed ego-dissolution, is a key feature of the psychedelic experience and acute psychosis. 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; 8 relating to the experience of ego-dissolution (comprising the EDI), and 8 relating to the antithetical experience of increased self-assuredness. Items were rated using a visual analogue scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine or alcohol. They also answered the 7 questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings.
Results: 691 participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics. 377 cocaine. 408 alcohol). Exploratory factor analysis demonstrated that the 8 EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to increased self-assuredness (rho= -.110), demonstrating discriminant validity. The EDI correlated strongly with our measure of unitive experience (rho = .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=.371), but not for cocaine (rho=.115) or alcohol (rho=-0.055). Secondly, the linear regression line relating the subjective intensity of the experience to EDI was significantly steeper for psychedelics (unstandardized B coefficient= 0.701) compared with cocaine (0.135) or alcohol (0.144). Finally, a binary support vector machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone.
Conclusions: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis.
Nour, M. M., Evans, L., Nutt, D., & Carhart-Harris, R. L. (2016). Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). Frontiers in Human Neuroscience, 10, 269. http://dx.doi.org/10.3389/fnhum.2016.00269
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LSD-induced entropic brain activity predicts subsequent personality change

May 6, 2016 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

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.

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Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide

March 24, 2016 / Depressive Disorders, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

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.

Speth, J., Speth, C., Kaelen, M., Schloerscheidt, A. M., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide. Journal of psychopharmacology (Oxford, England), 30(4), 344. http://dx.doi.org/10.1177/0269881116628430

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The paradoxical psychological effects of lysergic acid diethylamide (LSD).

February 5, 2016 / LSD, Papers, Psychology, Publications / By / , , , , ,

Abstract

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.

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., … & Nutt, D. J. (2016). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological medicine, 1-12. http://dx.doi.org/10.1017/S0033291715002901

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Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin

May 22, 2015 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , ,

Abstract

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.

Lebedev, A. V., Lövdén, M., Rosenthal, G., Feilding, A., Nutt, D. J., & Carhart‐Harris, R. L. (2015). Finding the self by losing the self: Neural correlates of ego‐dissolution under psilocybin. Human brain mapping. https://dx.doi.org/10.1002/hbm.22833
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5HT2a Receptors – a New Target for Depression?

March 28, 2015 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic drugs psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.

Nutt, D. (2015). 5HT2a Receptors–a New Target for Depression? European Psychiatry, 30, 35. http://dx.doi.org/10.1016/S0924-9338(15)30027-4
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