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Psychology

Protecting the human rights of people who use psychedelics

April 1, 2015 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Summary

In a recent Comment Ben Sessa1 explained how the War on the Drugs worldwide has impeded development of psychiatric treatment with psychedelics such as LSD (lysergic acid diethylamide) and psilocybin (found in magic mushrooms). Prohibition also had negative outcomes for the millions of individuals who find it worthwhile to use psychedelics in various cultural settings outside of those in the clinic.

Krebs, T. S. (2015). Protecting the human rights of people who use psychedelics. The Lancet, 2(4), 294.295. http://dx.doi.org/10.1016/S2215-0366(15)00084-X
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Serotonergic psychedelics temporarily modify information transfer in humans

March 28, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Background: Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.

Methods: here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy (TE), a non-linear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in two experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine (DMT).

Results: the analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. TE analysis showed that frontal sources decreased their influence over central, parietal and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior TE decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior TE correlated with the degree of incapacitation experienced.

Conclusions: these results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.

Alonso, J. F., Romero, S., Mañanas, M. À., & Riba, J. (2015). Serotonergic psychedelics temporarily modify information transfer in humans. International Journal of Neuropsychopharmacology. http://dx.doi.org/10.1093/ijnp/pyv039
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Current knowledge on the neurobiology of classical hallucinogens and their relevance for the treatment of mood and anxiety disorders

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

Abstract

Hallucinogenic substances have been used for millenia. Still, the scientific investigation into the effects and mechanisms of classical hallucinogens in humans has only commenced with the discovery of LSD by Albert Hofmann in 1943. In the 1960’s, there were more than a thousand clinical studies that reported promising therapeutic effects of LSD and psilocybin in psychiatric patients. Only recently, however, the neuropharmacological and neurobiological underpinnings of hallucinogenic drugs have undergone systematic investigations. Despite having different chemical structures, classical hallucinogens produce striking similar subjective and behavioral effects in both animals and humans. Activation of the serotonin 2A (5-HT2A) receptor is a core feature in hallucinogenic pharmacology. Recent neuroimaging studies have begun to elucidate the brain mechanisms underlying hallucinogen-induced changes of thought, perception, and mood. Among the many networks involved in hallucinogen-related states of consciousness, the prefrontal cortex and the limbic regions appear to be especially relevant to the putative antidepressant effects of classical hallucinogens. Furthermore, hallucinogens may foster neuroplastic adaptations within cortico-subcortical brain networks. This appears to be a promising mechanism with regard to future clinical studies into the effects of classical hallucinogens in depression and anxiety.

Kraehenmann, R. (2015). The Effect of Serotonin Receptor Manipulation On Brain Networks and Its Impact On Emotion Regulation. European Psychiatry, 30, 21. http://dx.doi.org/10.1016/S0924-9338(15)30016-X
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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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The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making

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

Abstract

Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.

In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.

The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.

These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.

Preller, K. H., Pokorny, T., Krähenmann, R., Dziobek, I., Stämpfli, P., & Vollenweider, F. X. (2015). The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making. European Psychiatry, 30, 22. http://dx.doi.org/10.1016/S0924-9338(15)30017-1
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MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults

March 25, 2015 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.

Danforth, A. L., Struble, C. M., Yazar-Klosinski, B., & Grob, C. S. (2015). MDMA-Assisted Therapy: A New Treatment Paradigm for Autistic Adults with Social Anxiety. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2015.03.011
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Underground MDMA-, LSD- and 2-CB-assisted individual and group psychotherapy in Zurich: Outcomes, implications and commentary

March 24, 2015 / Anxiety Disorders / PTSD, LSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

Underground psychedelic-assisted psychotherapy has persisted in Europe despite the banning of the substances LSD and MDMA in the 1960s and 1980s, respectively. This article describes the work of a Zurich-based psychotherapist providing individual and group psycholytic psychotherapy, whose practice persisted for several years before she was arrested in 2009. The article provides commentary on the psychopharmacological, moral, ethical and legal issues of this case and discusses these issues in the context of the growing medical research of psychedelic substances as mainstream treatments for psychiatry.

Sessa, B., & Fischer, F. M. (2015). Underground MDMA-, LSD-and 2-CB-assisted individual and group psychotherapy in Zurich: Outcomes, implications and commentary. Drug Science, Policy and Law, 2, 1-8. https://dx.doi.org/10.1177/2050324515578080
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Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

March 20, 2015 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Objectives

Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode.

Methods:

Open-label trial conducted in an inpatient psychiatric unit.

Results:

Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement.<

Conclusions:

These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

Osório, F. D. L., Sanches, R. F., Macedo, L. R., Dos Santos, R. G., Maia-de-Oliveira, J. P., Wichert-Ana, L., … & Hallak, J. E. (2015). Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Revista Brasileira de Psiquiatria, 37(1), 13-20. http://dx.doi.org/10.1590/1516-4446-2014-1496
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A brief survey of drug use and other activities preceding mystical-religious experiences

March 20, 2015 / Anthropology & Sociology, Papers, Psychology, Publications / By /

Abstract

Many people report having had mystical-religious experiences. The prevalence of these experiences has increased over time, which suggests changing cultural factors may contribute the experience. I conducted an online survey of 6,209 adults to determine how common different activities, including drug use, were before the onset of a mystical-religious experience. 19.6% (1,045) reported having had a mystical-religious experience and were asked a follow-up question on their activities before the experience. The most commonly endorsed pre-onset activity categories were: Prayer, meditation, or contemplation (37.2%); Being outdoors in nature (19.6%); and Religious ceremony, practice, or ritual (16.1%). Less commonly, respondents reported fasting (5.7%) or drug use (4.7%). A large percent (35.2%) reported not engaging in any of these activities before their experiences. Psychoactive drugs and nature are precedents to mystical-religious experience that are not selectively associated with traditional religious institutions and deserve additional study.

Baggott MJ. (2015) A brief survey of drug use and other activities preceding mystical-religious experiences Available at: https://github.com/mattbaggott/mysticalsurvey/blob/master/results/Baggott%20mystical%20survey%20March2015.pdf.
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Classic hallucinogens in the treatment of addictions

March 14, 2015 / Ayahuasca, DMT, Iboga / Ibogaine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Bogenschutz, M. P., & Johnson, M. W. (2015). Classic hallucinogens in the treatment of addictions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2015.03.002
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