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Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges

August 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Substance Use Disorder / By / , , , , ,

Abstract

Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances.
Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000.
Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA).
Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.
Majić, T., Jungaberle, H., Schmidt, T. T., Zeuch, A., Hermle, L., & Gallinat, J. (2017). Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges. Fortschritte der Neurologie-Psychiatrie, 85(7), 383. 10.1055/s-0043-103085
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Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

July 26, 2017 / Ayahuasca, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

The potential of psychedelic drugs in the treatment of mental health problems is increasingly being recognized. However, relatively little thrust has been given to the suggestion that individuals without any mental health problems may benefit from using psychedelic drugs, and that they may have a right to do so. This review considers contemporary research into the use of psychedelic drugs in healthy individuals, including neurobiological and subjective effects. In line with findings suggesting positive effects in the treatment of mental health problems, such research highlights the potential of psychedelic drugs for the enhancement of wellbeing even in healthy individuals. The relatively low risk associated with usage does not appear to align with stringent drug laws that impose heavy penalties for their use. Some policy implications, and suggestions for future research, are considered.
Elsey, J. W. (2017). Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy. Drug Science, Policy and Law, 3, 2050324517723232.
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Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways

July 5, 2017 / LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers / By / ,

Abstract

The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic effects of LSD and the observations that LSD and the endogenous ligand serotonin share chemical and pharmacological profiles led to the suggestion that biogenic amines like serotonin were involved in the psychosis of mental disorders such as schizophrenia. Although they bind other G protein-coupled receptor (GPCR) subtypes, studies indicate that several effects of hallucinogens involve agonist activity at the serotonin 5-HT2Areceptor. In this chapter, we review recent advances in understanding hallucinogen drug action through characterization of structure, neuroanatomical location, and function of the 5-HT2A receptor.
López-Giménez, J. F., & González-Maeso, J. (2017). Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. 10.1007/7854_2017_478
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The Effects of Hallucinogens on Gene Expression

July 5, 2017 / LSD, Neuroscience, Papers / By / ,

Abstract

The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.
Martin, D. A., & Nichols, C. D. (2017). The Effects of Hallucinogens on Gene Expression. 10.1007/7854_2017_479
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LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark

July 5, 2017 / LSD, Papers, Psychology / By /

Abstract

BACKGROUND:
New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s.
AIMS:
The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients.
METHODS:
The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material.
RESULTS:
LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients.
CONCLUSIONS:
Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.
Larsen, J. K. (2017). LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark. Nordic Journal of Psychiatry, 1-7. 10.1080/08039488.2017.1336251
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LSD experiments by the United States Army

July 1, 2017 / Humanities & Art, LSD, Papers / By /

Abstract

Extensive LSD testing was conducted by the US Army at Edgewood Arsenal and other locations from 1955 to 1967. A number of different reports have been produced describing the health effects of this testing, including the Veterans Health Initiative Report in 2003. By and large, these reports gloss over and minimize the short and long-term side effects and complications of this testing. However, the reports themselves document frequent, severe complications of the LSD. These side effects were regarded by the Army as having been directly caused by the LSD exposure. In view of the current resurgence of interest in hallucinogens within psychiatry, the sanitized version of the effects of LSD exposure on US soldiers needs to be replaced with a more accurate account.
Ross, C. A. (2017). LSD experiments by the United States Army. History of Psychiatry, 0957154X17717678.
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Self unbound: ego dissolution in psychedelic experience

June 30, 2017 / LSD, Mushrooms / Psilocybin, Papers, Philosophy & Religious Studies, Psychology, Publications / By / ,

Abstract

Users of psychedelic drugs often report that their sense of being a self or ‘I’ distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such ‘ego dissolution’ experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as resulting from the integrated functioning of hierarchical predictive models which posit the existence of a stable and unchanging entity to which representations are bound. Combining recent work on the ‘integrative self’ and the phenomenon of self-binding with predictive processing principles yields an explanation of ego dissolution according to which self-representation is a useful Cartesian fiction: an ultimately false representation of a simple and enduring substance to which attributes are bound which serves to integrate and unify cognitive processing across levels and domains. The self-model is not a mere narrative posit, as some have suggested; it has a more robust and ubiquitous cognitive function than that. But this does not mean, as others have claimed, that the self-model has the right attributes to qualify as a self. It performs some of the right kinds of functions, but it is not the right kind of entity. Ego dissolution experiences reveal that the self-model plays an important binding function in cognitive processing, but the self does not exist.
Letheby, C., & Gerrans, P. (2017). Self unbound: ego dissolution in psychedelic experience. Neuroscience of Consciousness, 3(1). 10.1093/nc/nix016
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Self unbound: ego dissolution in psychedelic experience.

June 30, 2017 / LSD, Papers, Psychology / By / ,

Abstract

Users of psychedelic drugs often report that their sense of being a self or ‘I’ distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such ‘ego dissolution’ experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as resulting from the integrated functioning of hierarchical predictive models which posit the existence of a stable and unchanging entity to which representations are bound. Combining recent work on the ‘integrative self’ and the phenomenon of self-binding with predictive processing principles yields an explanation of ego dissolution according to which self-representation is a useful Cartesian fiction: an ultimately false representation of a simple and enduring substance to which attributes are bound which serves to integrate and unify cognitive processing across levels and domains. The self-model is not a mere narrative posit, as some have suggested; it has a more robust and ubiquitous cognitive function than that. But this does not mean, as others have claimed, that the self-model has the right attributes to qualify as a self. It performs some of the right kinds of functions, but it is not the right kind of entity. Ego dissolution experiences reveal that the self-model plays an important binding function in cognitive processing, but the self does not exist.
Letheby, C., & Gerrans, P. (2017). Self unbound: ego dissolution in psychedelic experience. Neuroscience of consciousness, 2017(1), nix016., 10.1093/nc/nix016
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A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

June 28, 2017 / LSD, Neuroscience, Papers / By / , , , ,

Abstract

Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo. Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans.
Dolder, P. C., Grünblatt, E., Müller, F., Borgwardt, S. J., & Liechti, M. E. (2017). A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects. Frontiers in Pharmacology, 8. 10.3389/fphar.2017.00423
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