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LSD

Dreams and psychedelics: neurophenomenological comparison and therapeutic implications

June 18, 2017 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. However, the mechanisms of therapeutic action are still not fully explained. Given that an altered state of consciousness is a common denominator that characterizes all classical psychedelics and given that both rapid eye movement sleep (REMS) and psychedelics modulate perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body, in the present article, these two states of consciousness are systematically compared, and therapeutically relevant conclusions are drawn based on available evidence.
Kraehenmann, R. (2017). Dreams and psychedelics: neurophenomenological comparison and therapeutic implications. Current neuropharmacology. 10.2174/1573413713666170619092629
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Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

June 5, 2017 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as “research chemicals” or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, HPLC diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans.
Brandt, S. D., Kavanagh, P. V., Twamley, B., Westphal, F., Elliott, S. P., Wallach, J., … & Halberstadt, A. L. (2017). Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775). Drug Testing and Analysis. 10.1002/dta.2222
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Lifetime experience with (classic) psychedelics predicts pro-environmental behavior through an increase in nature relatedness

June 1, 2017 / LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

In a large-scale ( N = 1487) general population online study, we investigated the relationship between past experience with classic psychedelic substances (e.g. LSD, psilocybin, mescaline), nature relatedness, and ecological behavior (e.g. saving water, recycling). Using structural equation modeling we found that experience with classic psychedelics uniquely predicted self-reported engagement in pro-environmental behaviors, and that this relationship was statistically explained by people’s degree of self-identification with nature. Our model controlled for experiences with other classes of psychoactive substances (cannabis, dissociatives, empathogens, popular legal drugs) as well as common personality traits that usually predict drug consumption and/or nature relatedness (openness to experience, conscientiousness, conservatism). Although correlational in nature, results suggest that lifetime experience with psychedelics in particular may indeed contribute to people’s pro-environmental behavior by changing their self-construal in terms of an incorporation of the natural world, regardless of core personality traits or general propensity to consume mind-altering substances. Thereby, the present research adds to the contemporary literature on the beneficial effects of psychedelic substance use on mental wellbeing, hinting at a novel area for future research investigating their potentially positive effects on a societal level. Limitations of the present research and future directions are discussed.
Forstmann, M., & Sagioglou, C. (2017). Lifetime experience with (classic) psychedelics predicts pro-environmental behavior through an increase in nature relatedness. Journal of Psychopharmacology, 0269881117714049.
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Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial

May 26, 2017 / LSD, Papers, Pharmacology & Chemistry, Publications / By / , ,

Abstract

BACKGROUND:
Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide (LAE), lysergic acid ethyl-2-hydroxyethylamide (LEO), 2-oxo-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD, should be identified.
METHODS:
Separation of LSD and its metabolites was achieved on a reversed phase chromatography column after turbulent-flow online extraction. For the identification and quantification, a triple-stage quadrupole LC-MS/MS instrument was used.
RESULTS:
The validation data showed slight matrix effects for LSD, iso-LSD, O-H-LSD, or nor-LSD. Mean intraday and interday accuracy and precision were 105%/4.81% and 105%/4.35% for LSD, 98.7%/5.75% and 99.4%/7.21% for iso-LSD, 106%/4.54% and 99.4%/7.21% for O-H-LSD, and 107%/5.82% and 102%/5.88% for nor-LSD, respectively. The limit of quantification was 0.05 ng/mL for LSD, iso-LSD, and nor-LSD and 0.1 ng/mL for O-H-LSD. The limit of detection was 0.01 ng/mL for all compounds.
CONCLUSION:
The method described herein was accurate, precise, and the calibration range within the range of expected plasma concentrations. LSD was quantified in the plasma samples of the 24 subjects of the clinical trial, whereas iso-LSD, O-H-LSD, nor-LSD, LAE, LEO, 13/14-hydroxy-LSD, and 2-oxo-LSD could only sporadically be detected but were too low for quantification.
Dolder, P. C., Liechti, M. E., & Rentsch, K. M. (2017). Development and validation of an LC‐MS/MS method to quantify lysergic acid diethylamide (LSD), iso‐LSD, 2‐oxo‐3‐hydroxy‐LSD, and nor‐LSD and identify novel metabolites in plasma samples in a controlled clinical trial. Journal of Clinical Laboratory Analysis. 10.1002/jcla.22265
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Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

May 23, 2017 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Philosophy & Religious Studies, Psychology, Publications / By /

Abstract

There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED.
Millière, R. (2017). Looking For The Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution. Frontiers in Human Neuroscience, 11. 10.3389/fnhum.2017.00245
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Therapeutic Applications of Classic Hallucinogens

May 18, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.
Bogenschutz, M. P., & Ross, S. (2016). Therapeutic applications of classic hallucinogens. 10.1007/7854_2016_464
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Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile

May 18, 2017 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
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Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile

May 18, 2017 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
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“Too Hot to Handle”: LSD, Medical Activism, and the Spring Grove Studies

May 1, 2017 / Humanities & Art, LSD, Papers, Publications / By /

Abstract

In the early 1950s, medical researchers across the United States began investigating the use of the hallucinogenic drug lysergic acid diethylamide (LSD) as a facilitating agent in psychotherapy. Despite great promise, crisis struck this young field when, in the early 1960s, the federal government began tightening regulations on LSD—this being a result of public and political anxieties about increasing recreational use of the drug, as well as changing clinical trial standards. Scholars maintain that psychedelic researchers unilaterally responded to the crisis by abandoning the field, fearing that their continued association with the drug would wreak havoc on their careers and personal lives. However, a close examination of the proceedings at the Spring Grove State Hospital, located in Catonsville, Maryland, tells a different story. Drawing on archival material from Purdue’s Psychoactive Substances Research Collection, this thesis explores the Spring Grove research team’s effort to midwife a more favorable view of this defamed drug. In doing so, this analysis provides a new perspective on psychedelic researchers’ response to the LSD crisis.
Haslem, L. N. (2017). ” Too Hot to Handle”: LSD, Medical Activism, and the Spring Grove Studies.
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"Too Hot to Handle": LSD, Medical Activism, and the Spring Grove Studies

May 1, 2017 / Humanities & Art, LSD, Papers, Publications / By /

Abstract

In the early 1950s, medical researchers across the United States began investigating the use of the hallucinogenic drug lysergic acid diethylamide (LSD) as a facilitating agent in psychotherapy. Despite great promise, crisis struck this young field when, in the early 1960s, the federal government began tightening regulations on LSD—this being a result of public and political anxieties about increasing recreational use of the drug, as well as changing clinical trial standards. Scholars maintain that psychedelic researchers unilaterally responded to the crisis by abandoning the field, fearing that their continued association with the drug would wreak havoc on their careers and personal lives. However, a close examination of the proceedings at the Spring Grove State Hospital, located in Catonsville, Maryland, tells a different story. Drawing on archival material from Purdue’s Psychoactive Substances Research Collection, this thesis explores the Spring Grove research team’s effort to midwife a more favorable view of this defamed drug. In doing so, this analysis provides a new perspective on psychedelic researchers’ response to the LSD crisis.
Haslem, L. N. (2017). ” Too Hot to Handle”: LSD, Medical Activism, and the Spring Grove Studies.
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