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LSD

Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD).

June 18, 2019 / LSD, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination of researchers for many years and its rediscovery as an important research tool is evidenced by its clinical use within neuroscientific and therapeutic settings. At the same time, a number of novel LSD analogs have recently emerged as recreational drugs, which makes it necessary to study their analytical and pharmacological properties. One recent addition to this series of LSD analogs is 1-butanoyl-LSD (1B-LSD), a constitutional isomer of 1-propanoyl-6-ethyl-6-nor-lysergic acid diethylamide (1P-ETH-LAD), another LSD analog that was described previously. This study presents a comprehensive analytical characterization of 1B-LSD employing nuclear magnetic resonance spectroscopy (NMR), low- and high-resolution mass spectrometry platforms, gas- and liquid chromatography (GC and LC), and GC-condensed phase and attenuated total reflection infrared spectroscopy analyses. Analytical differentiation of 1B-LSD from 1P-ETH-LAD was straightforward. LSD and other serotonergic hallucinogens induce the head-twitch response (HTR) in rats and mice, which is believed to be mediated largely by 5-HT2A receptor activation. HTR studies were conducted in C57BL/6J mice to assess whether 1B-LSD has LSD-like behavioral effects. 1B-LSD produced a dose-dependent increase in HTR counts, acting with ~14% (ED50  = 976.7 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). This finding suggests that the behavioral effects of 1B-LSD are reminiscent of LSD and other serotonergic hallucinogens. The possibility exists that 1B-LSD serves as a pro-drug for LSD. Further investigations are warranted to confirm whether 1B-LSD produces LSD-like psychoactive effects in humans.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Stratford, A., Elliott, S. P., Dowling, G., … & Halberstadt, A. L. (2019). Return of the lysergamides. Part V: Analytical and behavioural characterization of 1‐butanoyl‐d‐lysergic acid diethylamide (1B‐LSD). Drug testing and analysis., https://doi.org/10.1002/dta.2613
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Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers

June 3, 2019 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

Background
Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as “microdosing,” improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors, and with limited evidence that higher doses of LSD (100-200 μg) positively bias emotion processing. Yet, the effects of such sub-threshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0 – 26μg) on mood and behavior in healthy volunteers under double-blind conditions.
Methods
Healthy young adults (N=20) attended four laboratory sessions during which they received placebo, 6.5μg, 13μg, or 26μg LSD in randomized order at one-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.
Results
LSD produced dose-related subjective effects across the three doses (6.5μg, 13μg, or 26μg). At the highest dose the drug also increased ratings of “vigor” and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected.
Conclusions
Single “microdoses” of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13μg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.
Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., https://doi.org/10.1016/j.biopsych.2019.05.019
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Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

June 3, 2019 / Depressive Disorders, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

BACKGROUND:

Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100-200 μg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0-26 μg) on mood and behavior in healthy volunteers under double-blind conditions.

METHODS:

Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 μg of LSD in randomized order at 1-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.

RESULTS:

LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 μg). At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected.

CONCLUSIONS:

Single microdoses of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 μg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.

Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., 10.1016/j.biopsych.2019.05.019
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Psychedelic drugs-a new era in 
psychiatry?


June 1, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards.

Nutt, D. (2019). Psychedelic drugs—a new era in psychiatry?. Dialogues in clinical neuroscience, 21(2), 139., https://dx.doi.org/10.31887%2FDCNS.2019.21.2%2Fdnutt
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Motives and side-effects of microdosing with psychedelics among users

May 31, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

BACKGROUND:

Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects.

METHODS:

An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, and had experience with microdosing were included in the analyses.

RESULTS:

In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence.

CONCLUSION:

In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Motives and side-effects of microdosing with psychedelics among users. International Journal of Neuropsychopharmacology., 10.1093/ijnp/pyz029

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Psychedelic-assisted therapies: The past, and the need to move forward responsibly.

May 25, 2019 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Recent clinical studies illustrate that psychedelics such as LSD and psilocybin may represent much-needed new treatment options for mood disorders and alcohol and other drug use disorders. More clinical studies are required to confirm the safety and efficacy of psychedelic-assisted therapies, but the cultural stigma that has surrounded psychedelics since the 1960s has hindered research. This problem is amplified in Australia. There has been a complete absence of research into psychedelic therapies, and Australian-based research advocates claim to have encountered a number of barriers. In this commentary, we provide a brief account of the historical stigma associated with psychedelics, and an overview of the contemporary context of research into psychedelic-assisted therapies, including the purported barriers to research in Australia. In light of the complex history of psychedelics, we identify a number of pressing questions relating to the social and legal context that need to be addressed so that clinical studies can proceed. Research is needed to address such questions so that the nature and extent of purported barriers to clinical studies with psychedelics can be properly elucidated, and strategies developed – with practitioners, patients, families and other stakeholders – to responsibly address these barriers. This is important because it will enable Australian researchers to contribute robust evidence about the possible efficacy and safety of psychedelic therapies, and to facilitate local expertise needed to implement psychedelic-assisted therapies, should they prove efficacious.
Gardner, J., Carter, A., O’Brien, K., & Seear, K. (2019). Psychedelic-assisted therapies: The past, and the need to move forward responsibly. International Journal of Drug Policy, 70, 94-98., https://doi.org/10.1016/j.drugpo.2019.05.019
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Cessation and reduction in alcohol consumption and misuse after psychedelic use

May 14, 2019 / LSD, Papers, Psychology, Publications / By / , , , , ,

Abstract

Background:

Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.

Aims:

To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.

Methods:

An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.

Results:

343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.

Conclusions:

Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of Psychopharmacology, 0269881119845793., https://doi.org/10.1177%2F0269881119845793
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Narrative identity, rationality, and microdosing classic psychedelics

May 6, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

BACKGROUND:

Microdosing involves ingesting a small dose of a classic psychedelic (e.g., LSD and psilocybin) at regular intervals for prolonged periods. The practice is said to reduce anxiety, improve mood, and offer several creative and practical benefits to users. Using the narrative identity theoretical framework, our aim was to explore the experiences of those who microdosed classic psychedelics. Specifically, we sought to understand how and why they began microdosing and how they made sense of their actions in the context of their conventional lives.

METHODS:

To understand the experiences of those who microdose classic psychedelics, we rely on data collected from semi-structured interviews with 30 people who had microdosed.

RESULTS:

Participants saw themselves as conventional citizens who microdosed for rational and instrumental purposes. They emphasized the rationality of microdosing by discussing (1) the practicality of their procurement and administration processes, (2) the connection between their microdosing practice and their general awareness in health and wellness, and (3) the benefits of the practice.

CONCLUSION:

Participants described their microdosing in the context of embracing traditional middle-class values. This created social distance between themselves and those who use drugs recreationally. While people who use drugs recreationally typically construct boundaries by distancing themselves from symbolic others (i.e., “crackheads,” “meth heads,” “junkies”), microdosers constructed boundaries by emphasizing connections to conventional citizens who embrace middle-class values. This connection to conventional citizens allows them to normalize their drug use and facilitates persistence.

Webb, M., Copes, H., & Hendricks, P. S. (2019). Narrative identity, rationality, and microdosing classic psychedelics. International Journal of Drug Policy, 70, 33-39., 10.1016/j.drugpo.2019.04.013
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Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects.

April 29, 2019 / LSD, Neuroscience, Papers, Pharmacology & Chemistry / By / , , , , ,

Abstract

AIMS:

The aim of the present study was to characterize the pharmacokinetics and exposure-subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients.

METHOD:

LSD (100 μg) was administered in 27 healthy subjects using a placebo-controlled, double-blind, cross-over design. Plasma levels of LSD, nor-LSD, and 2-oxo-3-hydroxy-LSD (O-H-LSD) and subjective drug effects were assessed up to 11.5 hours.

RESULTS:

First-order elimination kinetics were observed for LSD. Geometric mean maximum concentration (Cmax ) values (range) of 1.7 (1.0-2.9) ng/mL were reached at a tmax (range) of 1.7 (1.0-3.4) hours after drug administration. The plasma half-life (t1/2 ) was 3.6 (2.4-7.3) hours. The AUC∞ was 13 (7.1-28) ng·h/mL. No differences in these pharmacokinetic parameters were found between male and female subjects. Plasma O-H-LSD but not nor-LSD (< 0.01 ng/mL) concentrations could be quantified in all subjects. Geometric mean O-H-LSD Cmax values (range) of 0.11 (0.07-0.19) ng/mL were reached at a tmax (range) of 5 (3.2-8) hours. The t1/2 and AUC∞ values of O-H-LSD were 5.2 (2.6-21) hours and 1.7 (0.85-4.3) ng·h/mL, respectively. The subjective effects of LSD lasted (mean ± SD) for 8.5 ± 2.0 hours (range: 5.3-12.8 h), and peak effects were reached 2.5 ± 0.6 hours (range 1.6-4.3 h) after drug administration. EC50 values were 1.0 ± 0.5 ng/mL and 1.9 ± 1.0 ng/mL for “good” and “bad” subjective drug effects, respectively.

CONCLUSION:

The present study characterized the pharmacokinetics of LSD and its main metabolite O-H-LSD. The subjective effects of LSD were closely associated with changes in plasma concentrations over time.

Holze, F., Duthaler, U., Vizeli, P., Müller, F., Borgwardt, S., & Liechti, M. E. (2019). Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects. British journal of clinical pharmacology., 10.1111/bcp.13918
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Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature.

April 26, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans.
METHODS:
Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included.
RESULTS:
Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated.
CONCLUSIONS:
Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.
Rocha, J. M., Osório, F. L., Crippa, J. A. S., Bouso, J. C., Rossi, G. N., Hallak, J. E., & dos Santos, R. G. (2019). Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature. Therapeutic advances in psychopharmacology, 9, 2045125319845774., https://doi.org/10.1177/2045125319845774
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