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K. Kuypers

’Psychedelic professors’ on the rise as universities expand courses on psychedelics

If you attended university or college and didn’t have an option to take a course on psychedelics – that was because they were practically nonexistent until very recently. Up to the beginning of this century, getting educated about psychedelics meant researching on your own, learning from elders, attending the few conferences that existed, reading available journal articles and books, or maybe joining secret psychedelic societies (in person or on the internet).

But today we are simultaneously experiencing a rise in international psychedelic research and an international acceptance of this field as a genuine, revived field of science. As a result, there is an emergence of university courses. And not just in a few places, but in some very prominent universities.

The psychedelic professors

The relative novelty of this educational endeavor spiked our interest: What are the types of courses offered? How are they organized and taught? What type of students are taking them? And what are the biggest challenges in teaching about psychedelics? We’ve interviewed three professors of current psychedelic courses at prominent research universities, who can rightfully call themselves psychedelic professors: Kim Kuypers (Maastricht, NL), Gianni Glick (Stanford University CA, USA), and Brian Pace (Ohio State University, OH) 

Kim Kuypers, PhD, is an Associate Professor of Psychology and Neuroscience at Maastricht University in the Netherlands. Dr. Kuypers focuses on “Me We Biology”, trying to understand the biology of mental well-being. She researches psychedelics and their effects on cognition, creativity, hormones, and the mechanisms underlying these effects. Dr. Kuypers will be a speaker at this year’s ICPR conference

Giancarlo “Gianni” Glick, MD, is a 3rd-year psychiatry resident at Stanford whose psychiatric focus is on the interdependence of emotional and physical well-being for his patients. He is also the organizer of the Stanford Psychedelic Science Group.  

Brian Pace, PhD, is an affiliate scholar with the Centre for Psychedelic Drug Research and Education in the College of Social Work and a lecturer in the Department of Plant Pathology at The Ohio State University. Trained as an evolutionary ecologist, Brian studied agroecology, climate change, and ethnobotany. He is the Politics and Ecology Editor at the 501c3 psychedelic watchdog Psymposia and is currently a part of the team organizing Psychedemia, an interdisciplinary psychedelics conference scheduled for August of 2022 at Ohio State.

Here is what they teach, how they teach it, and why it is important they do it. 

Q: Which courses on psychedelics do you teach?

A: Kuypers (Maastricht) “Psychedelic Medicine” is an 8-week long elective course for third-year bachelor’s students which is housed in Maastricht’s department of psychology. I also teach a first-year elective course in the same department, called “Drugs in the Brain”. This is for first-year students and is only 4 weeks long. This helps to serve as good preparation for those who will take the psychedelics class. 

A: Glick (Stanford) “Introduction to Psychedelic Medicine” is a 10-week course, housed in the department of psychiatry at Stanford Medical School. This semester we have 187 students enrolled. It is an elective course and the make-up is about 70% undergraduates and the rest are graduates of all kinds. We also have many auditors ranging from neuroscience postdocs to attending psychiatrists. This makes for a huge range of expertise and familiarity with psychiatry. 

A: Pace (Ohio State) “Psychedelic Studies: Neurobiology, Plants, Fungi, and Society” is a 14-week/one-semester course and it is through the Department of Plant Pathology. The course is for undergraduate bachelor’s students, without any prerequisites, but I frequently have graduate students as well. The majority are third and fourth-year students. There is also a new course being taught in our department called “Psychedelic Bioethics,” taught by my colleague, Dr. Neşe Devenot.  

Kim Kuypers teaches “Psychedelic Medicine” at Maastricht University to third-year bachelor’s students. She is also a speaker at ICPR 2022.

Q: What are the key learning outcomes for your students?

A: Kuypers (Maastricht) I want the students to know about the rich history of psychedelics and to be educated on both the positive and negative aspects of these substances. I place a major focus on how to properly read a scientific article: reviewing the research methodology, analyzing the results, and having a critical mind about it.  I see this course as really the first way of getting the students acquainted with psychedelics and from here they should be able to navigate the future research that comes out with a better eye, and maybe also be inclined to get into the research and/or work in psychedelic-assisted therapies themselves. 

A: Glick (Stanford) This question keeps me up at night, but I hope for a good cause – there are so many decisions about what to present, how to engage, what sequence of information makes the most sense. Ultimately, I want to prepare students to critically interact with everything they hear in the media and in the scientific literature about psychedelics. This course covers the foundational principles, history, and context for these students to then ask more questions and hopefully contribute to the field of psychedelics, themselves. I think one of the first questions we try to ask is: What does it even mean to call psychedelics medicines? And in doing so understand that we are applying a particular frame to it, specific to this pre-FDA-approval moment in time and space. While it’s nicer pedagogically to stay focused on psychedelics as a medicine, we also tell them that psychedelics can be many other things: sacraments, recreation, and so on. But for this course, we focus on them as medicines.

A: Pace (Ohio State) As the instructor of a course on psychedelics it is my job to prepare students to engage intellectually, become better communicators, and to have better conversations around a controversial topic that is rapidly taking center stage. Frankly, there are a lot of grifters in the psychedelic space, people who are attempting to own the space, and so part of my responsibility is to provide students with tools to critically evaluate psychedelic science and health claims, the job market they may enter, and to hopefully have these students make informed choices.

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Q: What is the greatest challenge in teaching your course on psychedelics? 

A: Kuypers (Maastricht) I haven’t had too many difficulties in teaching this material. I did have an incident where I was teaching about animal research that was done with MDMA to investigate neuronal death, and in doing these studies I discussed the methodology which included decapitation to further look at their brains. As a result of saying so I had a student who left the room because they could not bear to hear this type of work. Though not directly related to in-class learning itself, I have had emails sent to me from parents of children who have abused drugs who question whether I am being too positive about these compounds, even going so far as calling me the devil. But in the 4 years of teaching this course, I have not faced many challenges from students. 

A: Glick (Stanford) Trying to figure out – what are the first principles of psychedelic medicine?  Where do you start?  How to strike a balance between asking big, zoomed-out, philosophical questions of human life and suffering (which I think is what this is really about), while staying in close contact with the data, the practice of medicine, counterpoints to my own views, and a sober take on all of this. How to teach students a kind of big picture schema that new ideas and facts and questions can fit into.

A: Pace (Ohio State) Psychedelics are inherently interdisciplinary. I’m not a psychiatrist. I’m not a social theorist. I’m not a political scientist. Yet these topics are as necessary to address as botanical, mycological, or neurochemical considerations–even though more broadly they may exceed the scope of my expertise. This can be challenging at times, but manageable. What is truly challenging is that issues like colonialism, addiction, and traumatic experiences are discussed in my course, and the reality is that some of the mental health distress faced globally is experienced personally by some of my students. Real injustice never gets easier to talk about, especially with those who are directly impacted by it.

One early psychedelic professor is Dr. Neşe Devenot – now an Affiliate Scholar at the Center for Psychedelic Drug Research and Education at Ohio State University.
She advocated for Psychedelic Studies courses for years, formally so in an essay in 2011 entitled “A Declaration of Psychedelic Studies”. Her first class, “Poetic Vision and the Psychedelic Experience,” ran from 2011 to 2012. A later class called Drug Wars had a focus on psychedelics and featured guest lectures from Matt Johnson and others working in the field. Her “Higher Dimensions in Literature” class in 2014 read McKenna and Castaneda. She went on to teach Psychedelic Studies at the University of Puget Sound from 2015 – 2018.

Q: What pedagogical tools do you use in your course? 

A: Kuypers (Maastricht) For both the “Psychedelic Medicine” 8-week course and the 4-week “Drugs of the Mind” course I use Problem Based Learning (PBL). This pedagogy works by bringing real-world problems to the class which functions as vehicles for students to have to look up things they don’t know, synthesize an answer based on their research and these problems are generally guided, often providing one part of a problem at a time.  An example of the last PBL assignment was a problem evaluating the positive and negative of the field of psychedelic medicine. In terms of course materials, I developed a course manual and we also use recent research articles for the “Psychedelic Medicine” course. In the 1st year course “Drugs of the Mind” course we use David Nutt’s “Drugs Without the Hot Air”.  I do most of the lectures but some of my colleagues help as well. We have a limited amount of time in these courses so we provide additional resources online for students to read and watch on their own. 

A: Glick (Stanford) Two years ago the course started as a lecture series, with a different speaker each week presenting on their area of expertise.  We updated the second iteration (last year) to have a more coherent through-line and progression of topics, with added small group discussion. And this year we tried to improve that further, so we spent the first third laying the foundational principles, the second third hearing from serious experts in the field (Brian Anderson, Jennifer Mitchell, Robin Carhart-Harris), and the final third weaving everything together.  The best session is always the last one when students give 5-minute presentations to the class on any topics or psychedelics subgenres they found interesting.  This year they taught us about psychedelics in China, the Eleusinian mysteries, research in psychotic disorders, and a bunch more.

A: Pace (Ohio State) This is a lecture-based course accompanied by reading articles and watching videos that conclude with 30-minute discussions each class. Since it is a course goal is to get students to have better, evidence-based conversations around psychedelics, students write weekly reading reflections showing that they are considering the material and reflecting on how they feel, and how these topics may connect to their life. Students also do presentations which are evaluated in part by peer review. From day one I am walking students through difficult, yet respectful conversations; you can’t understand psychedelics without touching on topics like consciousness, perception, religious experiences, and criminalization. 

Q: What do you believe is the ROLE of university courses in the psychedelic renaissance? 

A: Kuypers (Maastricht) It is incredibly important to have these available. I get requests from therapists and psychiatrists who did not get these types of courses in the curriculum of their educational training. Some of them also tell me of the cost for psychedelic-assisted therapy training from private institutions that can cost upwards of 20,000-25,000 Euros, which is crazy. Instead, this type of education should be embedded within all levels of university education from bachelor’s, graduate, and medical education. We definitely need psychedelic-assisted training for therapists in the universities (instead of the private organizations). 

A: Glick (Stanford) Similarly to how Johns Hopkins, NYU, and UCLA have stewarded the research through this kind of rigorous academic environment, there is this similar way that universities may offer a credible education, with a kind of peer review process, with a set of checks and balances where you can’t just teach anything. Secondly, doctors should know about this. For medical students and psychiatry residents to be competent about medicines their patients are in some cases already using and that may soon become legal, this should be part of the curriculum.

A: Pace (Ohio State) Psychedelics were abandoned by institutions following the Controlled Substances act in 1970. The new-agey, cultish stuff we see around psychedelics now, with tuning your chakras and merging souls or whatever: that is our fault. That’s an abdication of the responsibility to investigate interesting questions and to chase down data: to find out how things work.  So where we are now is a very timid and late re-entry to the subject, more so for education than research.  Psychedelic research didn’t end when the universities and governments abandoned it. It continued in the underground. The role of the university courses on psychedelics is to identify and evaluate high-quality information on the topic. We have a lot of catching up to do and I think that should be done with humility.

Addendum: The author of this article, Dr. Joey Lichter, is a volunteer for OPEN and ICPR, but also a chemistry professor who teaches a course titled “The Psychedelic Renaissance” at Florida International University in Miami, FL USA, thereby also qualifying as another psychedelic professor.

Spontaneous and deliberate creative cognition during and after psilocybin exposure

Abstract

Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking. Acutely, psilocybin increased ratings of (spontaneous) creative insights, while decreasing (deliberate) task-based creativity. Seven days after psilocybin, number of novel ideas increased. Furthermore, we utilized an ultrahigh field multimodal brain imaging approach, and found that acute and persisting effects were predicted by within- and between-network connectivity of the default mode network. Findings add some support to historical claims that psychedelics can influence aspects of the creative process, potentially indicating them as a tool to investigate creativity and subsequent underlying neural mechanisms. Trial NL6007; psilocybin as a tool for enhanced cognitive flexibility; https://www.trialregister.nl/trial/6007 .

Mason, N. L., Kuypers, K., Reckweg, J. T., Müller, F., Tse, D., Da Rios, B., Toennes, S. W., Stiers, P., Feilding, A., & Ramaekers, J. G. (2021). Spontaneous and deliberate creative cognition during and after psilocybin exposure. Translational psychiatry, 11(1), 209. https://doi.org/10.1038/s41398-021-01335-5

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A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

Abstract

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.

Uthaug, M. V., Mason, N. L., Toennes, S. W., Reckweg, J. T., de Sousa Fernandes Perna, E. B., Kuypers, K., van Oorsouw, K., Riba, J., & Ramaekers, J. G. (2021). A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats. Psychopharmacology, 238(7), 1899–1910. https://doi.org/10.1007/s00213-021-05817-8

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Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Abstract

“Microdoses” of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of “under the influence” and “good drug effect” compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of “under the influence,” “good drug effects,” and “bad drug effects.” LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.

Holze, F., Liechti, M. E., Hutten, N., Mason, N. L., Dolder, P. C., Theunissen, E. L., Duthaler, U., Feilding, A., Ramaekers, J. G., & Kuypers, K. (2021). Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants. Clinical pharmacology and therapeutics, 109(3), 658–666. https://doi.org/10.1002/cpt.2057

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Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study

Abstract

There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was to determine the minimal dose of LSD needed to affect mood and cognition. A placebo-controlled within-subject study including 24 healthy participants, was conducted to assess the acute effects of three LSD doses (5, 10, and 20 mcg) on measures of cognition, mood, and subjective experience, up until 6 h after administration. Cognition and subjective experience were assessed using the Psychomotor Vigilance Task, Digit Symbol Substitution Test, Cognitive Control Task, Profile of Mood States, and 5-Dimensional Altered States of Consciousness rating scale. LSD showed positive effects in the majority of observations by increasing positive mood (20 mcg), friendliness (5, 20 mcg), arousal (5 mcg), and decreasing attentional lapses (5, 20 mcg). Negative effects manifested as an increase in confusion (20 mcg) and anxiety (5, 20 mcg). Psychedelic-induced changes in waking consciousness were also present (10, 20 mcg). Overall, the present study demonstrated selective, beneficial effects of low doses of LSD on mood and cognition in the majority of observations. The minimal LSD dose at which subjective and performance effects are notable is 5 mcg and the most apparent effects were visible after 20 mcg.

Hutten, N., Mason, N. L., Dolder, P. C., Theunissen, E. L., Holze, F., Liechti, M. E., Feilding, A., Ramaekers, J. G., & Kuypers, K. (2020). Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 41, 81–91. https://doi.org/10.1016/j.euroneuro.2020.10.002

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Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

Abstract

Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on circulating BDNF levels in healthy volunteers. Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA. The findings demonstrated an increase in BDNF blood plasma levels at 4 h (5 μg) and 6 h (5 and 20 μg) compared to that for the placebo. The finding that LSD acutely increases BDNF levels warrants studies in patient populations.

Hutten, N., Mason, N. L., Dolder, P. C., Theunissen, E. L., Holze, F., Liechti, M. E., Varghese, N., Eckert, A., Feilding, A., Ramaekers, J. G., & Kuypers, K. (2020). Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers. ACS pharmacology & translational science, 4(2), 461–466. https://doi.org/10.1021/acsptsci.0c00099

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The therapeutic potential of microdosing psychedelics in depression

Abstract

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10-20 mcg) and psilocybin (<1-3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

Kuypers K. (2020). The therapeutic potential of microdosing psychedelics in depression. Therapeutic advances in psychopharmacology, 10, 2045125320950567. https://doi.org/10.1177/2045125320950567

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A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers

Abstract

Background: Lysergic acid diethylamide (LSD) is an ergot alkaloid derivative with psychedelic properties that has been implicated in the management of persistent pain. Clinical studies in the 1960s and 1970s have demonstrated profound analgesic effects of full doses of LSD in terminally ill patients, but this line of research evaporated after LSD was scheduled worldwide.

Aim: The present clinical study is the first to revisit the potential of LSD as an analgesic, and at dose levels which are not expected to produce profound mind-altering effects.

Methods: Twenty-four healthy volunteers received single doses of 5, 10 and 20 µg LSD as well as placebo on separate occasions. A Cold Pressor Test was administered at 1.5 and 5 h after treatment administration to assess pain tolerance to experimentally evoked pain. Ratings of dissociation and psychiatric symptoms as well as assessments of vital signs were included to monitor mental status as well as safety during treatments.

Results: LSD 20 µg significantly increased the time that participants were able to tolerate exposure to cold (3°C) water and decreased their subjective levels of experienced pain and unpleasantness. LSD elevated mean blood pressure within the normal range and slightly increased ratings of dissociation, anxiety and somatization.

Conclusion: The present study provides evidence of a protracted analgesic effect of LSD at a dose that is low enough to avoid a psychedelic experience. The present data warrant further research into the analgesic effects of low doses of LSD in patient populations.

Ramaekers, J. G., Hutten, N., Mason, N. L., Dolder, P., Theunissen, E. L., Holze, F., … & Kuypers, K. P. (2020). A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers. Journal of Psychopharmacology, 0269881120940937; 10.1177/0269881120940937
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Microdosing with psychedelics: what do we know?

Abstract

The repeated use of small doses of psychedelics such as psilocybin and lsd over a period of time (microdosing, md) has gained popularity and scientific attention in recent years. Retrospective reports from users suggest clinical potential.<br/> AIM: To answer the question whether md with psychedelics could theoretically provide symptom relief for people with psychiatric disorders. <br/> METHOD: Investigate what the current evidence is about the effects of md with psychedelics on the behavioral level, psychological functioning and mental well-being. A search for relevant articles in PubMed and Medline databases (on January 10, 2020), which resulted in a total of 28 hits. After de-duplication, removal of irrelevant and addition of relevant articles, 23 articles were included.<br/> RESULTS: Most of the knowledge we have so far comes from uncontrolled online questionnaire studies in which users report retrospectively or keep diaries of the effects they experience during md. According to users, it leads to positive effects on mood, concentration, focus and productivity. Negative effects, including physical discomfort and increased fear, also seem to occur. The limited number of experimental studies in healthy people revealed that md has subtle effects on cognitive processes and brain connectivity.<br/> CONCLUSION: The findings of experimental studies in combination with the reports from users give cause for further investigation into the clinical potential of low-dose psychedelics in combating certain symptoms. More placebo-controlled studies are needed to provide clarity for who (age, diagnosis) md can be effective and for which (cognitive, emotional) processes.
Kuypers, K. P. C. (2020). Microdosing with psychedelics: what do we know?. Tijdschrift Voor Psychiatrie62(8), 669-676., https://pubmed.ncbi.nlm.nih.gov/32816295/

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Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

Abstract

There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

Mason, N. L., Kuypers, K. P. C., Müller, F., Reckweg, J., Tse, D. H. Y., Toennes, S. W., … & Ramaekers, J. G. (2020). Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology, 1-11., https://doi.org/10.1038/s41386-020-0718-8
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