OPEN Foundation

Menu
Search
Close this search box.

LSD

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey.

January 22, 2020 / Anthropology & Sociology, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).

Aims: The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.

Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.

Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.

Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Garcia-Romeu, A., Davis, A. K., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2020). Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Frontiers in psychiatry, 10, 955; 10.3389/fpsyt.2019.00955
Link to full text

Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials.

January 21, 2020 / Depressive Disorders, LSD, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.
Fuentes, J. J., Fonseca, F., Elices, M., Farre, M., & Torrens, M. (2019). Therapeutic use of LSD in psychiatry: A systematic review of randomized-controlled clinical trials. Frontiers in Psychiatry, 10, 943., https://doi.org/10.3389/fpsyt.2019.00943
Link to full text
 

A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

January 13, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry, 31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
Link to full text

Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species

January 7, 2020 / DMT, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 41 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT2A agonists in humans.

Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J., & Brandt, S. D. (2020). Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology, 107933., 10.1016/j.neuropharm.2019.107933
Link to full text

Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity.

December 20, 2019 / Anxiety Disorders / PTSD, LSD, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

BACKGROUND:
The practice of “microdosing,” or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.
METHODS:
The present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed.
RESULTS:
LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.
CONCLUSIONS:
These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug’s purported antidepressant effect.

Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Bershad, A. K., Preller, K. H., Lee, R., Keedy, S., Wren-Jarvis, J., Bremmer, M. P., & de Wit, H. (2019). Preliminary report on the effects of a low dose of LSD on resting state amygdalar functional connectivity. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging., https://doi.org/10.1016/j.bpsc.2019.12.007
Link to full text

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.

December 18, 2019 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.
OBJECTIVE:
This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.
METHODS:
This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).
RESULTS:
Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment.
CONCLUSIONS:
Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).
Family, N., Maillet, E. L., Williams, L. T., Krediet, E., Carhart-Harris, R. L., Williams, T. M., … & Raz, S. (2019). Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers. Psychopharmacology, 1-13., https://doi.org/10.1007/s00213-019-05417-7
Link to full text

Decreased directed functional connectivity in the psychedelic state.

December 17, 2019 / Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2019). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 116462., https://doi.org/10.1016/j.neuroimage.2019.116462
Link to full text

From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner.

December 16, 2019 / Anxiety Disorders / PTSD, Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 1 week before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: The frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and was dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.
Kettner, H., Gandy, S., Haijen, E. C., & Carhart-Harris, R. L. (2019). From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner. International Journal of Environmental Research and Public Health, 16(24), 5147., https://doi.org/10.3390/ijerph16245147
Link to full text
 

Neurotrophic mechanisms of psychedelic therapy

December 12, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Psychedelic drugs, often referred to as hallucinogens, are quite distinct from other classes of psychotropic drugs. Although the subjective and behavioral effects they induce are quite dramatic, they possess little addictive potential when compared to nicotine, alcohol or opiates. Since the discovery of ketamine antidepressant effects, there has been growing interest for these molecules. Serotonergic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) are gaining attention as potential treatments for depression and addiction, similarly to 3,4-methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD), and ibogaine for addiction. Although they possess distinct pharmacological profiles, their kinetics of action are quite similar: the therapeutic effects are felt within the hours following administration, and last well beyond drug elimination by the organism. This strongly suggests the induction of neurogenic and plastic mechanisms, including the involvement of trophic factors. This review will explore the literature dealing with the effects of psychedelics on neurotrophins, as well as the plastic adaptations that they induce, in an attempt to understand their surprising therapeutic potential. We will show that although ketamine and serotonergic psychedelics have affinity for very different receptors (NMDA, 5-HT2A), they ultimately initiate similar plastic adaptations in the prefrontal cortex through the involvement of the brain-derived neurotrophic factor (BDNF). We will see that although MDMA uses the same receptors as serotonergic psychedelics to alleviate PTSD symptoms, its effect on BDNF levels seem paradoxical and quite different. Finally, we show how ibogaine could exert its anti-addictive properties through a completely different neurotrophic factor than other psychedelic drugs, the glial cell line-derived neurotrophic factor (GDNF). While the current literature concerning the psychiatric applications of psychedelic therapy is encouraging, it remains to be determined whether their benefits could be obtained without their psychotomimetic effects, or concerns over potential toxicity.
Corne, R., & Mongeau, R. (2019). Neurotrophic mechanisms of psychedelic therapy. Biologie aujourd’hui, 213(3-4), 121., https://doi.org/10.1051/jbio/2019015
Link to full text

 

interested in becoming a trained psychedelic-assisted therapist?

Management of Psychedelic-Related Complications - Online Event - Nov 20th

REGISTER NOW