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Can we confidently use ketamine as a clinical treatment for depression?

January 1, 2018 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By /

Abstract

Findings from several proof-of-concept, double-blinded, placebo-controlled studies have shown rapid and large antidepressant effects in patients with major depression after a single dose of ketamine.1 These data are remarkable in the rapidity of therapeutic effects, with remission within 24 h (though relapse often occurs within days), the high degree of antidepressant potency in cohorts with moderate-to-high treatment resistance, and the consistency of findings between studies. Given that ketamine is readily available in many countries as an approved anaesthetic drug, it is not surprising that there has been enthusiasm for the use of ketamine to treat depression.
Loo, C. (2018). Can we confidently use ketamine as a clinical treatment for depression?. The Lancet Psychiatry, 5(1), 11-12. 10.1016/S2215-0366(17)30480-7
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Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

January 1, 2018 / Depression, Mushrooms / Psilocybin, Papers, Personal development, Personality, Philosophy, Psychiatry, Psychotherapy, Publications / By / ,

Abstract

RATIONALE:
Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations.
AIM:
Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD).
METHODS:
This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively.
RESULTS:
Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects.
CONCLUSIONS:
This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.
Lyons, T., & Carhart-Harris, R. L. (2018). Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression. Journal of Psychopharmacology, 0269881117748902.
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Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

December 27, 2017 / Depression, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , ,

Abstract

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.
Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. L. (2017). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology. 10.1016/j.neuropharm.2017.12.041
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Psychiatry & the psychedelic drugs. Past, present & future.

December 25, 2017 / Cacti / Mescaline, LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychosis, Psychotherapy, Publications, Sociology / By / , ,

Abstract

The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called ‘psychoneurotic’ disorders sometimes benefited considerably from their tendency to ‘loosen’ otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting. Pre-prohibition studies in this area were sub-optimal, although a recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. The incidence of serious adverse events appears to be low. Since 2006, there have been several pilot trials and randomised controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders. These have provided encouraging results that provide initial evidence of safety and efficacy, however the regulatory and legal hurdles to licensing psychedelics as medicines are formidable. This paper summarises clinical trials using psychedelics pre and post prohibition, discusses the methodological challenges of performing good quality trials in this area and considers a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry.
Rucker, J. J., Iliff, J., & Nutt, D. J. (2017). Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 10.1016/j.neuropharm.2017.12.040
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Psychiatry & the psychedelic drugs. Past, present & future.

December 25, 2017 / Cacti / Mescaline, LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychosis, Psychotherapy, Publications, Sociology / By / , ,

Abstract

The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called ‘psychoneurotic’ disorders sometimes benefited considerably from their tendency to ‘loosen’ otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting. Pre-prohibition studies in this area were sub-optimal, although a recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. The incidence of serious adverse events appears to be low. Since 2006, there have been several pilot trials and randomised controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders. These have provided encouraging results that provide initial evidence of safety and efficacy, however the regulatory and legal hurdles to licensing psychedelics as medicines are formidable. This paper summarises clinical trials using psychedelics pre and post prohibition, discusses the methodological challenges of performing good quality trials in this area and considers a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry.
Rucker, J. J., Iliff, J., & Nutt, D. J. (2017). Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 10.1016/j.neuropharm.2017.12.040
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Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

December 20, 2017 / Anxiety disorders / PTSD, Depression, Mushrooms / Psilocybin, Mystical experiences, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , ,

Abstract

Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.
Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest.
Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).
Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.
Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2017). Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Frontiers in Pharmacology, 8, 974. 10.3389/fphar.2017.00974
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Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD

December 15, 2017 / LSD, Neuroscience, Other subjects, Papers, Psychology, Publications / By / , , , , ,

Abstract

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ‘connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.
Atasoy, S., Roseman, L., Kaelen, M., Kringelbach, M. L., Deco, G., & Carhart-Harris, R. L. (2017). Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Scientific reports, 7(1), 17661. 10.1038/s41598-017-17546-0
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Breaking the cycle of opioid use disorder with Ibogaine

December 7, 2017 / Iboga / Ibogaine, Neuroscience, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications, Substance Use Disorder / By /

Abstract

Ibogaine is an indole alkaloid that comes from the root of the West African shrub Tabernanthe iboga. Ibogaine has been used for centuries in spiritual celebrations, coming of age rituals, and healings among the Babongo and Mitsogo people of West Central Africa. In Africa today, approximately 2–3 million members of the Bwiti religion scattered in groups throughout the countries of the Gabon, Zaire, and the Cameroun take large doses for the “Bwiti initiation ritual”—a powerful “rebirth” ceremony that group members typically undergo before the commencement of their teenage years.
The discovery that ibogaine eliminates the signs and symptoms of opioid withdrawal and diminishes craving for opioids was first made in the 1960s by a group of self-treating individuals with heroin use disorder; a single oral dose administration of ibogaine was associated with a disruption of five addicted individual’s use of opiates for up to 6 months . An underground railroad of individuals in recovery helping others with addictions arose, using ibogaine to help people break their cycle of addiction to heroin, cocaine, and alcohol. Ibogaine is thought to enable individuals with opioid use disorder to transition to abstinence and establish a substance-free recovery through an ibogaine-induced experience that has personal meaning and/or other benefits. Ibogaine’s long-lasting metabolite noribogaine may reset brain circuits to block the intractable cravings and desire to use opioids that set the addiction relapse cycle into motion.
C. Mash, D. (2017). Breaking the cycle of opioid use disorder with Ibogaine. The American Journal of Drug and Alcohol Abuse, 1-3. 10.1080/00952990.2017.1357184
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Influence of Environmental Factors and Cultural Methods on the Content of N,N‑Dimethyltryptamine in Psychotria viridis (Rubiaceae)

December 6, 2017 / Ayahuasca, DMT, Ethnobotany, Indigenous use, Papers, Publications / By / , , , , , ,

Abstract

Psychotria viridis is one of the species that produces N,N-dimethyltryptamine. Its decoction together with other species, such as Banisteriopsis caapi, produces ayahuasca, a beverage used for ritualistic and medicinal purposes. The goal of this study was to understand how environmental factors and cultivation methods influenced the content of N,N-dimethyltryptamine in P. viridis. Over all four seasons, leaf samples were collected from 25 different locations in 14 Brazilian states, and Federal District. Environmental parameters, micro and macronutrients, plant characteristics, information on farming methods were correlated with N,N-dimethyltryptamine content, determined by gas chromatography coupled to mass spectrometry (GC-MS). Greatest effects on the N,N-dimethyltryptamine amount were associated with seasonality, altitude, latitude and biome type. A positive correlation between N and Mg content and N,N-dimethyltryptamine levels was statistically established. By regression analysis, the adequate foliar nutrient levels that would result in the concentration of N,N-dimethyltryptamine in cultivated plants similar to that of Amazonian P. viridis were equated.

Cavalcante, A. D., Cardoso, G. A., de Oliveira, F. L., Bearzoti, E., Okuma, A. A., Duartee, L. P., & Vieira-Filhof, S. A. Influence of Environmental Factors and Cultural Methods on the Content of N, N‑Dimethyltryptamine in Psychotria viridis (Rubiaceae).
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