OPEN Foundation

Menu
Search
Close this search box.

LSD

Psychedelic medicine: The biology underlying the persisting psychedelic effects.

February 11, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Psychedelic substances have regained interest as therapeutic agents in the treatment of stress-related disorders. The effects seem to be of persisting nature even after a single dose. Also in lower than ‘regular’ recreational doses, so-called micro-doses, without the typical effects on consciousness, users report beneficial effects on cognitive processes and well-being. The exact neurobiological mechanism underlying these persisting effects is not clear. While previous research has mainly focused on the central nervous system including the immune system and the neuroendocrine system, I propose a central role for sleep and the microbiome in the effects of regular and low doses of psychedelics respectively. It will be explained why this is hypothesized and studies to test this idea proposed. It is concluded that while these studies are needed to understand the biology underlying psychedelic medicine, it is also important to approach it in a holistic way, including all the above mentioned biological processes psychedelics are known to affect, and explore the role of other substance-related factors like route of administration and form, and factors like diet and lifestyle which are part of the psychedelic experience.

Kuypers, K. P. C. (2019). Psychedelic medicine: The biology underlying the persisting psychedelic effects. Medical hypotheses, 125, 21-24., https://doi.org/10.1016/j.mehy.2019.02.029
Link to full text

Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats

January 10, 2019 / Depressive Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

The prototype 5-HT2A receptor agonist hallucinogens LSD, mescaline, and psilocybin are classified as Schedule 1 drugs of abuse by the U.S. Drug Enforcement Administration. Accumulating clinical evidence has also suggested that acute or repeated “microdosing” with these drugs may have utility for treatment of some mental health disorders, including drug abuse and depression. The goal of the present study was to evaluate LSD, mescaline, and psilocybin effects on intracranial self-stimulation (ICSS), a procedure that has been used to evaluate abuse-related effects of other classes of abused drugs. Effects of repeated LSD were also examined to evaluate potential changes in its own effects on ICSS or changes in effects produced by the abused psychostimulant methamphetamine or the prodepressant kappa opioid receptor (KOR) agonist U69,593. Male Sprague-Dawley rats were implanted with microelectrodes targeting the medial forebrain bundle and trained to respond under a “frequency-rate” ICSS procedure, in which many drugs of abuse increase (or “facilitate”) ICSS. In acute dose-effect and time-course studies, evidence for abuse-related ICSS facilitation was weak and inconsistent; the predominant effect of all 3 drugs was dose- and time-dependent ICSS depression. Repeated LSD treatment failed to alter either its own ICSS depressant effects or the abuse-related effects of methamphetamine; however, repeated LSD did attenuate ICSS depression by U69,593. These results extend those of previous preclinical studies to suggest weak expression of abuse-related effects by 5-HT2A agonist hallucinogens and provide supportive evidence for therapeutic effects of repeated LSD dosing to attenuate KOR-mediated depressant effects but not abuse potential of psychostimulants.

Sakloth, F., Leggett, E., Moerke, M. J., Townsend, E. A., Banks, M. L., & Negus, S. S. (2019). Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats. Experimental and clinical psychopharmacology., 10.1037/pha0000253.
Link to full text

Microdosing psychedelics: personality, mental health, and creativity differences in microdosers

January 2, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:

Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.

OBJECTIVES:

This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.

METHODS:

In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.

RESULTS:

Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.

CONCLUSIONS:

These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2018). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 1-10., 10.1007/s00213-018-5106-2
Link to full text

Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

January 2, 2019 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:
Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.
OBJECTIVES:
This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.
METHODS:
In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.
RESULTS:
Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.
CONCLUSIONS:
These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2019). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 236(2), 731-740., https://doi.org/10.1007/s00213-018-5106-2
Link to full text

Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics

September 10, 2024 / Anxiety Disorders / PTSD, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Scienitific Discipline / By / , , ,

Abstract

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are 5HT2AR agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. We also review neuroimaging studies that suggest neurobiological mechanisms of psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Finally, we provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies which have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2018). Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics. Pharmacology & therapeutics., 10.1016/j.pharmthera.2018.11.010

 
Link to full text

 

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial.

November 26, 2018 / LSD, Papers, Psychology, Publications / By / , , , , ,

Abstract

RATIONALE:
Previous research demonstrating that lysergic acid diethylamide (LSD) produces alterations in time perception has implications for its impact on conscious states and a range of psychological functions that necessitate precise interval timing. However, interpretation of this research is hindered by methodological limitations and an inability to dissociate direct neurochemical effects on interval timing from indirect effects attributable to altered states of consciousness.
METHODS:
We conducted a randomised, double-blind, placebo-controlled study contrasting oral administration of placebo with three microdoses of LSD (5, 10, and 20 μg) in older adults. Subjective drug effects were regularly recorded and interval timing was assessed using a temporal reproduction task spanning subsecond and suprasecond intervals.
RESULTS:
LSD conditions were not associated with any robust changes in self-report indices of perception, mentation, or concentration. LSD reliably produced over-reproduction of temporal intervals of 2000 ms and longer with these effects most pronounced in the 10 μg dose condition. Hierarchical regression analyses indicated that LSD-mediated over-reproduction was independent of marginal differences in self-reported drug effects across conditions.
Yanakieva, S., Polychroni, N., Family, N., Williams, L. T., Luke, D. P., & Terhune, D. B. (2018). The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial. Psychopharmacology, 1-12., 10.1007/s00213-018-5119-x
Link to full text

Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

November 13, 2018 / Humanities & Art, LSD, Mushrooms / Psilocybin, Neuroscience, Psychology / By / ,

Abstract

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Garcia-Romeu, A., & Richards, W. A. (2018). Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. International Review of Psychiatry, 30(4), 291-316., 10.1080/09540261.2018.1486289.
Link to full text

Predicting Responses to Psychedelics: A Prospective Study

November 2, 2018 / Ayahuasca, DMT, Iboga / Ibogaine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively. Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a “mystical-type experience” had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., “challenging experience” and “visual effects”, did not influence the change in well-being after the psychedelic experience. Having “clear intentions” for the experience was conducive to mystical-type experiences. Having a positive “set” as well as having the experience with intentions related to “recreation” were both found to decrease the likelihood of having a challenging experience. The baseline trait “absorption” and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed that baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.

Haijen, E. C. H. M., Kaelen, M., Roseman, L., Timmermann, C., Russ, S., Nutt, D., & Carhart-Harris, R. L. (2018). Predicting responses to psychedelics: a prospective study. Frontiers in pharmacology, 9, 897., 10.3389/fphar.2018.00897
Link to full text

Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition.

October 25, 2018 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

The search for the universal laws of human brain function is still on-going but progress is being made. Here we describe the novel concepts of connectome harmonics and connectome-harmonic decomposition, which can be used to characterize the brain activity associated with any mental state. We use this new frequency-specific language to describe the brain activity elicited by psilocybin and LSD and find remarkably similar effects in terms of increases in total energy and power, as well as frequency-specific energy changes and repertoire expansion. In addition, we find enhanced signatures of criticality suggesting that the brain dynamics tune toward criticality in both psychedelic elicited states. Overall, our findings provide new evidence for the remarkable ability of psychedelics to change the spatiotemporal dynamics of the human brain.
Atasoy, S., Vohryzek, J., Deco, G., Carhart-Harris, R. L., & Kringelbach, M. L. (2018). Common neural signatures of psychedelics: Frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition. Progress in brain research, 242, 97-120., 10.1016/bs.pbr.2018.08.009
Link to full text

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

October 25, 2018 / LSD, Papers, Publications / By / , , , , , ,

Abstract

BACKGROUND:

Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown.

METHODS:

We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.

FINDINGS:

LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans.

CONCLUSION:

Together, these results strongly implicate the 5-HT2A receptor in LSD’s neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics.

Preller, K. H., Burt, J. B., Ji, J. L., Schleifer, C. H., Adkinson, B. D., Stämpfli, P., … & Vollenweider, F. X. (2018). Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife, 7, e35082., 10.7554/eLife.35082

Link to full text

interested in becoming a trained psychedelic-assisted therapist?

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

REGISTER NOW