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LSD

Lysergic Acid Diethylamide and mystical experiences

Abstract

The term psychedelic (“mind-manifesting”) was coined by British psychiatrist Humphry Osmond in 1956 to refer to a unique class of mind-altering chemicals with distinctive effects that set them apart from other drugs with hallucinogenic properties. Some psychedelics come from natural sources that have been traditionally featured in religious, ritual, and healing practices of indigenous cultures of the Americas (Anderson, 1980; Hofmann, 1983; Salak, 2007; Smith, 2000); such drugs include mescaline (from peyote and San Pedro cacti), psilocybin and psilocin (from Psilocybe mushrooms), and dimethyltryptamine or DMT (from the leaves of Psychotria viridis). Many other psychedelics have partly or wholly synthetic origins. The most potent psychedelic agent yet discovered is the semisynthetic ergot derivative lysergic acid diethylamide (LSD), which has distinctive effects at the microscopic dose of 25 μg; a typical psychedelic dose ranges from 50 to 200 μg. There are also a number of purely synthetic psychedelics, many of which are chemically related to both amphetamine and mescaline (Shulgin & Shulgin, 1991). One of the most potent of these is dimethoxymethylamphetamine, or DOM, which was known as “STP” when introduced to the hippie subculture of San Francisco in the late 1960s. More familiar today is methylenedioxymethamphetamine (MDMA, ecstasy), which has only mild or partial psychedelic effects as opposed to full psychedelics such as LSD, psilocybin, and mescaline; MDMA is thus sometimes described as an “entactogen,” meaning “touch within” (Bravo, 2001; Smith, 2000), as opposed to full psychedelics or “entheogens,” meaning “God within.” A newer, extremely potent synthetic psychedelic, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][(2-methoxyphenyl)methyl] ethanamine (2CI-NBOMe, or “N-Bomb”), was invented in 2003 and is useful as a laboratory tool to map brain serotonin receptors (Ettrup et al., 2010). The threshold dose is several hundred micrograms, making this psychedelic second in potency only to LSD. Media reports indicate that 2CI-NBOMe has been sold to drug users on pieces of blotter paper, like LSD, and often misrepresented as the latter drug. Unfortunately 2CI-NBOMe has a much lower therapeutic index than LSD, hence several highly publicized deaths appear to have been caused by this drug (e.g., Hastings, 2013; Poklis et al., 2014) and, in some cases, possibly misattributed to LSD. Some of the deaths resulted from drug-induced seizures, whereas in other cases the individuals killed themselves accidentally or purposefully in a drug-induced psychotic or delirious state. By contrast, fatal reactions are extremely uncommon with the “classic” psychedelics LSD, psilocybin, and mescaline.

Lyvers, M. (2016). Lysergic Acid Diethylamide and mystical experiences. 10.1016/B978-0-12-800212-4.00078-9
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The Entheogen Reformation

Abstract

In addition to promising leads for treating PTSD, addictions, depression, and death anxiety, 21st Century research at medical schools finds that with careful screening, insightful attention to the variables of set, setting, and dosage, psychedelic drug administration often facilitates significant spiritual experiences, meaningfulness, altruism, well-being, and similar prospiritual effects. This article calls for theologians, professors of religious studies, philosophy, sociology, and psychology to update their courses. It challenges leaders of religious organizations, ‘‘How can your institution incorporate these practices and benefit from them?’’

Roberts, T. B. (2016). THE ENTHEOGEN REFORMATION. Association for Transpersonal Psychology, 26.

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Psychedelic Psychotherapy Insights From 25 Years of Research

Abstract

Presented at a conference titled “Psychedelic Science 2013,” highlighting the resumption of investigations with psychedelic substances (i.e., psilocybin, DMT, LSD, MDMA, etc.) in the United States and Europe after a dormant period of more than two decades, the author presents insights and perspectives gleaned from his 25 years of clinical research experience. After acknowledging the vastness and potential significance of this research frontier, the article focuses on the “cartography of inner space”; the unique therapeutic potential of transcendental states of consciousness; the entelechy of the interpersonally grounded psyche; the importance of integration in drug-free therapy sessions; the roles of expectation, religious education and faith; the role of music; and future research directions.

Richards, W. A. (2016). Psychedelic Psychotherapy Insights From 25 Years of Research. Journal of Humanistic Psychology, 0022167816670996.
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The Resurrection Of Psychedelic Psychiatry And Its Role In Addiction Treatment

Abstract

Psychedelic psychiatry, a field which was previously popular between 1950-1970, has recently received a renewed interest as several recent studies have highlighted the potential role of hallucinogens in the treatment of addictions and various mental illnesses. This paper looks at evidence supporting the use of LSD, ibogaine and ayahuasca to treat various addictions and discusses the barriers to further exploration of the therapeutic potential of psychedelic substances.

Skocylas, R. (2016). The resurrection of psychedelic psychiatry and its role in addiction treatment. UBC Medical Journal, 8(1).
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The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors

Abstract

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT1 and 5-HT2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5–20 μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT2A and D2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30–120 μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D2 receptor antagonist haloperidol (50 μg/kg, i.v.) and by the 5-HT1A receptor antagonist WAY-100,635 (500 μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR1) antagonist EPPTB (5 mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT1A, D2 and TAAR1 receptors.

De Gregorio, D., Posa, L., Ochoa-Sanchez, R., McLaughlin, R., Maione, S., Comai, S., & Gobbi, G. (2016). The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT 1A, D 2 and TAAR 1 receptors. Pharmacological Research, 113, 81-91. http://dx.doi.org/10.1016/j.phrs.2016.08.022
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The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

Abstract

Developing methods for improving creativity is of broad interest. Classic psychedelics may enhance creativity; however, the underlying mechanisms of action are unknown. This study was designed to assess whether a relationship exists between naturalistic classic psychedelic use and heightened creative problem-solving ability and if so, whether this is mediated by lifetime mystical experience. Participants (N = 68) completed a survey battery assessing lifetime mystical experience and circumstances surrounding the most memorable experience. They were then administered a functional fixedness task in which faster completion times indicate greater creative problem-solving ability. Participants reporting classic psychedelic use concurrent with mystical experience (n = 11) exhibited significantly faster times on the functional fixedness task (Cohen’s d = –.87; large effect) and significantly greater lifetime mystical experience (Cohen’s d = .93; large effect) than participants not reporting classic psychedelic use concurrent with mystical experience. However, lifetime mystical experience was unrelated to completion times on the functional fixedness task (standardized β = –.06), and was therefore not a significant mediator. Classic psychedelic use may increase creativity independent of its effects on mystical experience. Maximizing the likelihood of mystical experience may need not be a goal of psychedelic interventions designed to boost creativity.

Sweat, N. W., Bates, L. W., & Hendricks, P. S. (2016). The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving. Journal of Psychoactive Drugs, 1-7. 10.1080/02791072.2016.1234090
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Semantic activation in LSD: evidence from picture naming

Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity.

Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., & Carhart-Harris, R. L. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition and Neuroscience, 1-8. http://dx.doi.org/10.1080/23273798.2016.1217030
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Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century

Abstract

Henry Knowles Beecher, an icon of human research ethics, and Timothy Francis Leary, a guru of the counterculture, are bound together in history by the synthetic hallucinogen lysergic acid diethylamide (LSD). Both were associated with Harvard University during a critical period in their careers and of drastic social change. To all appearances the first was a paragon of the establishment and a constructive if complex hero, the second a rebel and a criminal, a rogue and a scoundrel. Although there is no evidence they ever met, Beecher’s indirect struggle with Leary over control of the 20th century’s most celebrated psychedelic was at the very heart of his views about the legitimate, responsible investigator. That struggle also proves to be a revealing bellwether of the increasingly formalized scrutiny of human experiments that was then taking shape.

Moreno, J. D. (2016). Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century. Perspectives in Biology and Medicine, 59(1), 107-121. 10.1353/pbm.2016.0019

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Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Abstract

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

Tófoli, L. F., & de Araujo, D. B. (2016). Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics. International Review of Neurobiology. 10.1016/bs.irn.2016.06.005
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From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide

Abstract

Among the psychedelic drugs that enjoyed a period of popularity in psychiatric research during the 1950s and 1960s, lysergic acid diethylamide (LSD) is the most prominent one. Psychiatrists of that time had seen LSD not only as a tool for psychotherapy but also as a potential therapeutic for anxiety, depression, alcohol abuse, autism, and even schizophrenia. When it became a quasi-religious epitome of the Hippie counterculture in the mid 1960s, and cases of what we now call hallucinogen persisting perception disorder and acute psychotic “flashbacks” mounted, authorities moved to make LSD illegal. Although research was never actually forbidden, the field almost completely dried out until the early 2010s. Using today’s tools of molecular pharmacology, functional imaging, and neuronal network theory, neuropsychiatry is now resurrecting LSD research-with implications that leave us with many medical and ethical questions. Few people are aware that this is a repurposed compound, originally developed in an effort to synthesize a new analeptic. On top of all potential LSD might have in psychiatry, it also serves as a reminder of the unexpected potential that discarded early-stage compounds can have.

Mucke, H. A. (2016). From Psychiatry to Flower Power and Back Again: The Amazing Story of Lysergic Acid Diethylamide. ASSAY and Drug Development Technologies. 10.1089/adt.2016.747.

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