68 results found
Carhart-Harris R, Lawton G, 2017, Trip advisor, NEW SCIENTIST, Vol: 235, Pages: 42-43, ISSN: 0262-4079
Carhart-Harris RL, Bolstridge M, Day CMJ, et al., 2017, Psilocybin with psychological support for treatment-resistant depression: six-month follow-up., Psychopharmacology (Berl)
RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.
Carhart-Harris RL, Goodwin GM, 2017, The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future, Neuropsychopharmacology, Vol: 42, Pages: 2105-2113, ISSN: 0893-133X
Carhart-Harris RL, Nutt DJ, 2017, Serotonin and brain function: a tale of two receptors, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 31, Pages: 1091-1120, ISSN: 0269-8811
Carhart-Harris RL, Roseman L, Bolstridge M, et al., 2017, Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Erritzoe D, Nutt DJ, Carhart-Harris R, 2017, Concerns regarding conclusions made about LSD-treatments, HISTORY OF PSYCHIATRY, Vol: 28, Pages: 257-258, ISSN: 0957-154X
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
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
Roseman L, Demetriou L, Wall MB, et al., 2017, Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression., Neuropharmacology
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. TRIAL REGISTRATION: ISRCTN, number ISRCTN14426797.
Schartner MM, Carhart-Harris RL, Barrett AB, et al., 2017, Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin, Scientific Reports, Vol: 7, Pages: 46421-46421
Stroud JB, Freeman TP, Leech R, et al., 2017, Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression., Psychopharmacology (Berl)
RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. RESULTS: We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). CONCLUSIONS: Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.
Timmermann C, Spriggs MJ, Kaelen M, et al., 2017, LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm., Neuropharmacology
Under the predictive coding framework, perceptual learning and inference are dependent on the interaction between top-down predictions and bottom-up sensory signals both between and within regions in a network. However, how such feedback and feedforward connections are modulated in the state induced by lysergic acid diethylamide (LSD) is poorly understood. In this study, an auditory oddball paradigm was presented to healthy participants (16 males, 4 female) under LSD and placebo, and brain activity was recorded using magnetoencephalography (MEG). Scalp level Event Related Fields (ERF) revealed reduced neural adaptation to familiar stimuli, and a blunted neural 'surprise' response to novel stimuli in the LSD condition. Dynamic causal modelling revealed that both the presentation of novel stimuli and LSD modulate backward extrinsic connectivity within a task-activated fronto-temporal network, as well as intrinsic connectivity in the primary auditory cortex. These findings show consistencies with those of previous studies of schizophrenia and ketamine but also studies of reduced consciousness - suggesting that rather than being a marker of conscious level per se, backward connectivity may index modulations of perceptual learning common to a variety of altered states of consciousness, perhaps united by a shared altered sensitivity to environmental stimuli. Since recent evidence suggests that the psychedelic state may correspond to a heightened 'level' of consciousness with respect to the normal waking state, our data warrant a re-examination of the top-down hypotheses of conscious level and suggest that several altered states may feature this specific biophysical effector.
Watts R, Day C, Krzanowski J, et al., 2017, Patients' Accounts of Increased "Connectedness" and "Acceptance" After Psilocybin for Treatment-Resistant Depression, JOURNAL OF HUMANISTIC PSYCHOLOGY, Vol: 57, Pages: 520-564, ISSN: 0022-1678
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
Carhart-Harris RL, Bolstridge M, Rucker J, et 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
Carhart-Harris RL, Kaelen M, Bolstridge M, et al., 2016, The paradoxical psychological effects of lysergic acid diethylamide (LSD), PSYCHOLOGICAL MEDICINE, Vol: 46, Pages: 1379-1390, ISSN: 0033-2917
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: 0027-8424
Carhart-Harris RL, Nutt DJ, 2016, Question-based Drug Development for psilocybin Reply, LANCET PSYCHIATRY, Vol: 3, Pages: 807-807, ISSN: 2215-0374
Curran HV, Wall M, Demetriou L, et 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
Family N, Vinson D, Vigliocco G, et al., 2016, Semantic activation in LSD: evidence from picture naming, LANGUAGE COGNITION AND NEUROSCIENCE, Vol: 31, Pages: 1320-1327, ISSN: 2327-3798
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: 0924-977X
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
Kaelen M, Roseman L, Lorenz R, et 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
Lebedev AV, Kaelen M, Lovden M, et al., 2016, LSD-Induced Entropic Brain Activity Predicts Subsequent Personality Change, HUMAN BRAIN MAPPING, Vol: 37, Pages: 3203-3213, ISSN: 1065-9471
Nour MM, Evans L, Nutt D, et al., 2016, Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI), FRONTIERS IN HUMAN NEUROSCIENCE, Vol: 10, ISSN: 1662-5161
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
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: 1065-9471
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: 0269-8811
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