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LSD

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

November 15, 2016 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2Creceptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area—nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT2Creceptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens.

Canal, C. E., & Murnane, K. S. (2016). The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens. Journal of Psychopharmacology, 0269881116677104.
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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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Psychedelics as Medicines: An emerging new paradigm

November 4, 2016 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2Areceptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing anti-inflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after acute effects have resolved. Anti-inflammatory effects may hold promise for efficacy in treatment of inflammation-related non-psychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.

Nichols, D. E., Johnson, M. W., & Nichols, C. D. (2016). Psychedelics as Medicines: An emerging new paradigm. Clinical Pharmacology & Therapeutics. 10.1002/cpt.557
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Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness

November 2, 2016 / LSD, Papers, Psychology, Publications / By /

Abstract

Revisiting the history of postwar LSD (lysergic acid diethylamide) research illuminates how the work of a chemist at the Rockefeller Institute contributed to the development of a biochemical paradigm for mental functioning. Dilworth Wayne Woolley proposed one of the first theories of the biochemistry of mental illness based on empirical evidence. His research with LSD and serotonin had wide-ranging repercussions for pharmacology and fit neatly into the emerging medicalization of mental illness. Reevaluating Woolley’s ideas and the fruits of psychopharmacology leads to possible new approaches toward mental health and illness when considered alongside lessons learned from past research with psychedelic substances, and exemplifies a broader paradigm shift in cultural studies toward a biopsychosocial model that acknowledges the intersections between biology and culture.

Hewitt, K. (2016). Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness. History of Science, 0073275316674724.
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Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging

October 31, 2016 / Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By / , , ,

Abstract

Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: “ayahuasca”, “DMT”, “psilocybin”, “LSD”, “mescaline” crossed one by one with the terms “mri”, “fmri”, “pet”, “spect”, “imaging” and “neuroimaging”. Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT2A receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & Hallak, J. E. (2016). Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging. Neuroscience & Biobehavioral Reviews, 71, 715-728. 10.1016/j.neubiorev.2016.10.026
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Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm

October 29, 2016 / Ayahuasca, DMT, LSD, Mescaline / Cacti, Papers, Psychology, Publications / By / ,

Abstract

The objective of the current chapter is to evaluate the potential utility of classic psychedelics including dimethyltryptamine (found in the Amazonian plant decoction ayahuasca), lysergic acid diethylamide (LSD), mescaline (found in peyote and other psychoactive cacti), and psilocybin (found in certain mushrooms) in addressing rational suicide among the elderly. An overview of the sociopolitical history of classic psychedelics is presented, followed by an examination of empirical findings pertaining to rational suicide. This chapter concludes that classic psychedelics may counteract rational suicide among the elderly by promoting the perception that life is worth living even in the face of great adversity and encourages future study on this important topic.

Hendricks, P. S., & Grob, C. S. (2017). Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm. In Rational Suicide in the Elderly (pp. 203-210). Springer International Publishing. 10.1007/978-3-319-32672-6_14

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Creativity and Psychoactive Substance Use: A Systematic Review

October 20, 2016 / LSD, Papers, Psychology, Publications / By / , ,

Abstract

The role of psychoactive substance use in the research of artistic creation and creativity is a long-standing topic. Ever since the discovery of LSD, researchers have examined the relationship between the effects of chemical substances and the artistic creative process. The goal of the present study was to systematically review all published empirical publications and case reports in refereed journals that focus on the relationship between psychoactive substances and creativity/creative artistic process. A total of 19 studies were identified that met the inclusion and exclusion criteria. Results were difficult to summarize because of the different study questions asked, the diverse methods used, the different samples applied, and the various substances examined. The general results suggest that there is an association between creativity and substance use. However, the studies were unable to show that substance use directly contributed to the growth of creativity or facilitated creative artistic process. It is concluded that specific skills may be subject to change as a consequence of substance use, and consequently may have an effect on the style of creation.

Iszáj, F., Griffiths, M. D., & Demetrovics, Z. (2016). Creativity and Psychoactive Substance Use: A Systematic Review. International Journal of Mental Health and Addiction, 1-15. 10.1007/s11469-016-9709-8

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Ecstatic Landscapes: The Manifestation of Psychedelic Art

October 20, 2016 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Publications / By /

Abstract

“Psychedelic art” can be defined as artwork manifested in the context of the ingestion of LSD-type drugs and related substances. There is a long history of such work dating back to ancient times (picturing mushrooms and other plants with psychedelic effects) as well as more recent anecdotal first-person accounts and various collections of psychological data resulting from experiments and interviews. One such collection includes the studies by Krippner of over 200 artists, writers, and musicians who referred to their artistic productions as “psychedelic” because they had some connection with their occasional or frequent use of these substances. Although there were no commonalities characterizing all of their paintings, films, poems, novels, songs, or other works, several frequent themes were noted following content analysis of the interview reports. The results of this group of studies, as well as those of more structured explorations, attests to the importance of this topic for humanistic psychology with its emphasis upon creativity, human potential, and exploring the wide range of human experience.
Krippner, S. (2016). Ecstatic Landscapes: The Manifestation of Psychedelic Art. Journal of Humanistic Psychology, 0022167816671579.
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Alterations of consciousness and mystical-type experiences after acute LSD in humans

October 7, 2016 / LSD, Papers, Psychology, Publications / By / , ,

Abstract

Rationale: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking.

Methods: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.

Results: On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.

Conclusions: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Liechti, M. E., Dolder, P. C., & Schmid, Y. (2016). Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology, 1-12. 10.1007/s00213-016-4453-0

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Psychedelics in the treatment of unipolar mood disorders: A systematic review

October 1, 2016 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s. They are relatively safe when used in medically controlled environments, with no reported risk of dependence. Here, we present a systematic review of published clinical treatment studies using psychedelics in patients with broadly defined unipolar mood disorder, and consider their place in psychiatry. Whilst all the included studies have methodological shortcomings, of 423 individuals in 19 studies, 335 (79.2%) showed clinician-judged improvement after treatment with psychedelics. A recently completed pilot study in the UK favours the use of psilocybin with psychological support in treatment resistant depressive disorder. The evidence overall strongly suggests that psychedelics should be re-examined in modern clinical trials for their use in unipolar mood disorders and other non-psychotic mental health conditions.

Rucker, J. J., Jelen, L. A., Flynn, S., Frowde, K. D., & Young, A. H. Psychedelics in the Treatment of Unipolar Mood Disorders: A Systematic Review.
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