OPEN Foundation

OPEN Foundation

Salvinorin A Does Not Affect Seizure Threshold in Mice

Abstract

The κ-opioid receptor has recently gained attention as a new molecular target in the treatment of many psychiatric and neurological disorders including epilepsy. Salvinorin A is a potent plant-derived hallucinogen that acts as a highly selective κ-opioid receptor agonist. It has unique structure and pharmacological properties, but its influence on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of salvinorin A on seizure thresholds in three acute seizure tests in mice. We also examined its effect on muscular strength and motor coordination. The obtained results showed that salvinorin A (0.1-10 mg/kg, i.p.) did not significantly affect the thresholds for the first myoclonic twitch, generalized clonic seizure, or forelimb tonus in the intravenous pentylenetetrazole seizure threshold test in mice. Likewise, it failed to affect the thresholds for tonic hindlimb extension and psychomotor seizures in the maximal electroshock- and 6 Hz-induced seizure threshold tests, respectively. Moreover, no changes in motor coordination (assessed in the chimney test) or muscular strength (assessed in the grip-strength test) were observed. This is a preliminary report only, and further studies are warranted to better characterize the effects of salvinorin A on seizure and epilepsy.

Socała, K., Doboszewska, U., & Wlaź, P. (2020). Salvinorin A Does Not Affect Seizure Threshold in Mice. Molecules (Basel, Switzerland), 25(5), 1204. https://doi.org/10.3390/molecules25051204

Link to full text

Natural Psychoplastogens As Antidepressant Agents

Abstract

Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.

Benko, J., & Vranková, S. (2020). Natural Psychoplastogens As Antidepressant Agents. Molecules25(5), 1172., https://doi.org/10.3390/molecules25051172
Link to full text

Europe’s psychedelic science renaissance has started


The Old World has had its own remarkable history concerning psychedelic research – it was after all the continent where Albert Hofmann first discovered LSD and where Dutch professor Jan Bastiaans treated the trauma of Holocaust survivors with the same substance for many decades.
Now, the psychedelic wave has washed ashore again in Europe, and we’re here to witness it first-hand. In this piece, we have attempted to give the most complete overview of the current wave of psychedelic science that’s happening on the European continent.
The past decade has seen a new wave of academic research into psychedelics – a fledgling but true renaissance of this scientific frontier. Currently, phase 2 trials are underway for the study of MDMA-assisted psychotherapy in the treatment of PTSD in Europe, psilocybin studies are underway in more than one nation, and multiple academic hubs facilitate growth of the field.
Below we summarize the experimental psychedelic studies in the fields of (clinical) psychology, psychiatry and neuroscience in Europe. Many of these studies are still young, and will take years to complete. Still, this decade will likely harbor historic moments in moving psychedelics into the mainstream in Europe – because psychedelics science has only just started scratching the surface of what’s possible.

Research hubs

  • Imperial College in London
  • The University of Basel
  • University of Zurich – the latter being an official study site of the Heffter Research Institute.

In addition to the research carried out at these universities, two multi-site trials – sponsored by the non-profit organisation MAPS (mdma) and the for-profit Compass Pathways (psilocybin) – are underway in Europe, thereby involving various academic treatment centers in Europe in psychedelics research.
There are a few main research hubs in Europe where most of the psychedelics research is concentrated. At these locations, multiple studies below are performed.

Experimental research

Below we summarize the current European research into three psychedelic substances: LSD, psilocybin or mdma3.
Experimental research can be broken down into two basic categories. The first are the clinical trials, in which psychedelics are administered to patient populations. The other is neurobiological research, in which the effect of psychedelics on healthy participants are studied.
Of course, the field of psychedelic research is much broader and includes naturalistic, historical and qualitative research methods such as used in the social sciences and humanities. For lack of a central registry in which such studies are enlisted, it is harder to keep track of ongoing non-experimental (social scientific) research.
Clinical Studies 👩‍🏫First, let’s look at all the clinical studies that are going on.

LSD studies in Switzerland

“LSD is a Baseler product,” said Matthias Liechti to the Guardian about the most famous product from Basel, Switzerland. Liechti – a professor in clinical pharmacology at University Hospital Basel and speaker at ICPR 2020 – studies the effects of LSD on the human mind and body. “It’s tied to Basel’s history as a centre of pharmacology and innovation.”
How fitting that almost all research with LSD is taking place in the substance’s ‘place of birth’, Basel.

  • LSD as Treatment for Cluster HeadacheUniversity Hospital Basel
    Cluster headaches are the most painful and debilitating form of headache, for which available medication often does not work sufficiently. LSD has been reported to abort cluster headache attacks and to decrease their frequency. Headed by lead investigator Professor Matthias Liechti and conducted by Yasmin Schmid, MD, this double-blind, placebo-controlled crossover study will administer LSD (or a placebo) to 30 patients suffering from cluster headaches. They will receive three doses of 100 micrograms within a three week period.
  • LSD Therapy for Major DepressionUniversity Hospital Basel.
    This study will test the efficacy of LSD therapy in patients with Major Depressive Disorder and is recruiting 60 patients. The treatment group will undergo two sessions with LSD (100 & 200 μg) and the control group will undergo two sessions with an active placebo (25 μg and 50 μg LSD). This study is lead by Prof. Dr. med. Stefan Borgwardt and has just started recruiting. It is estimated to be completed by the summer of 2023.
  • LSD Treatment for Anxiety in Severe Somatic DiseasesUniversity Hospital  Basel 
    In this study, 40 patients with an Anxiety Disorder will be given a single dose of LSD. Due to its cross-over within-subjects design, all patients will receive both a placebo dose and an active dose: 200 μg LSD. This study is a collaboration between University Hospital Basel and the private practice of Peter Gasser, MD, who is also the study’s principal investigator.


Imperial College in London has recently founded the world’s first Centre for Psychedelics Research

Psilocybin studies in Europe

About a third of all experimental studies with psilocybin are happening in Europe. All of the European psychedelic research hubs – University of Zurich, University Hospital Basel and Imperial College London – are currently involved in clinical or neurobiological research with psilocybin. Europe also hosts 11 of the 21 sites of the clinical study on psilocybin therapy for treatment resistant depression – for which its sponsor Compass Pathways was granted a breakthrough therapy status by the FDA in 2018.
Clinical studies with patients:

  • Psilocybin vs Escitalopram for Major Depressive DisorderImperial College, London 
    This study is recruiting 50 patients suffering from depression in order to compare the efficacy and mechanisms of action of psilocybin with the SSRI Escitalopram. Principal investigator of this study is Professor David Nutt.
  • Clinical and Mechanistic Effects of Psilocybin in Alcohol Addicted Patients – University of Zurich
    This study will test the efficacy of psilocybin for treating alcohol use disorder and study its underlying neurobiological mechanisms in a randomized, placebo controlled, double blind study. 60 participants are recruited for this study. Six weeks after undergoing a withdrawal treatment, they will either receive a single dose of placebo or a single dose of psilocybin (25 mg, orally). Dr. Katrin Peller is the principal investigator in this study.
  • The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression. This is a multi-site clinical trial with 21 study locations in North America and Europe, sponsored by the (for profit) organization Compass Pathways. The following European sites are involved in this study:

Enhed for Psykiatrisk Forskning, Psykiatrien i Aalborg – Aalborg, Denmark
Tallaght University Hospital – Dublin, Ireland
Groningen University Medical Centre – Groningen, the Netherlands
Leiden University Medical Centre – Leiden, the Netherlands
Utrecht University Medical Centre – Utrecht, the Netherlands
Hospital de Dia Numancia – Barcelona, Spain
Institute Hospital del Mar of Medical Research (IMIM) – Barcelona, Spain
Clinical Research and Imaging Centre – Bristol, United Kingdom
Wolfson Research Centre, Campus for Ageing and Vitality – Newcastle Upon Tyne, United Kingdom
Kings College London, Institute of Psychiatry, Psychology and Neurology – London, United Kingdom
Greater Manchester Mental Health Foundation Trust – Manchester, United Kingdom

MDMA studies by MAPS
The Multidisciplinary Association for Psychedelics Studies from the United States -and headed by Rick Doblin- is planning phase 2 and phase 3 clinical trials to develop MDMA-assisted psychotherapy into an approved treatment for PTSD. In order to conduct part of these trials in Europe, MAPS has created a European-based subsidiary.
Six study sites in five European countries are involved in the “Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study”:

  • Czechia – NUDZ – National Institute of Mental Health, Klecany
  • Norway – Sykehuset Østfold Hf, DPS Norder, Moss
  • Netherlands
    • Maastricht University, Dept of Neuropsychology and Psychopharmacology – Maastricht
    • Stichting Centrum ’45/Arq – Oestgeest
  • Portugal – Fundação de Anna de Sommer Champalimaud, Lisbon
  • United Kingdom – University Hospital of Wales – Research Facility, Cardiff

The University of Bristol and Imperial College London are collaborating in an ongoing study on mdma as a treatment for alcoholism. The “Bristol Imperial MDMA in Alcoholism Study (BIMA)” is an open label within-subject feasibility study in 20 patients with Alcohol Use Disorder who have recently undergone detoxification. The study is conducted by Ben Sessa, MD and its principal investigator is Professor David Nutt.

🧠 Studies into the psychedelic state itself

LSD AND PSILOCYBIN

  • Direct Comparison of Altered States of Consciousness Induced by LSD and PsilocybinUniversity Hospital Basel
    Both LSD and psilocybin are used as pharmacological tools in neuroscience. However, there are no modern studies comparing these two substances directly within the same clinical study and using validated psychometric tools. In this study the researchers will compare the acute effects of LSD, psilocybin and placebo. 30 Healthy participants will be administered various dosages of these psychedelics, the effects of which will be measured with various assessment tools.The study is conducted by Friederike Holze and Professor Matthias Liechti.

  • Comparative Acute Effects of LSD, Psilocybin and Mescaline  –University Hospital Basel
    This study compares the acute effects of LSD, psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design. In four separate sessions, the 25 healthy participants will receive 100 μg LSD, 20 mg psilocybin, 300 mg mescaline and a placebo. Professor Matthias E. Liechti is the principal investigator in all three of the above psilocybin studies taking place in Basel.
  • Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the SelfUniversity of Zurich
    In terms of the number of participants in a single study, this is currently the largest experimental study with psilocybin in Europe. 140 Healthy participants are divided into 4 groups, each with it’s own double-blind, placebo-controlled setup. One of the groups consists of long-term and short-term meditators during a 5-day group retreat. The aim of the study is to identify neural signatures, behavioral and phenomenological expressions of self-related processes.
  • Characterization of Altered Waking States of Consciousness in Healthy Humans – University of Zurich
    This study uses a combination of transcranial magnetic stimulation (TMS) and high density electroencephalography (hd-EEG) to measure the level of consciousness in a pharmacologically altered waking state of consciousness (induced by psilocybin).Lead investigator Professor Franz X. Vollenweider and his team are recruiting 25 healthy participants for this study.

MDMA and fear

  • University Hospital Basel is currently recruiting healthy participants for a study called “The Effect of MDMA (Serotonin Release) on Fear Extinction”. Fear extinction is a psychological process that plays a crucial role in treating disorders such as PTSD. Although MDMA has been shown to enhance the extinction of fear in animals, no data exists on the effect of MDMA on fear extinction in humans. The lead investigator in this study is Professor Matthias E. Liechti, MD.

Should you be interested in contributing to science by participating in a clinical/neuroimaging study: most of these studies are still recruiting. Look them up on this website to study their inclusion and exclusion criteria and to find out more.
This overview only covers the research that has been registered at clinicaltrials.gov and is therefore not exhaustive. Do you know of other ongoing experimental studies in Europe, feel free to reach out to us!

1 The FDA (Food and Drug Administration in the US) granted the label ‘breakthrough therapy’ to mdma-assisted psychotherapy for PTSD (sponsored by MAPS) in 2017. In 2018 the treatment of depression with psilocybin (sponsored by Compass Pathways) was granted the breakthrough therapy status, followed by a designation for the research by Usona in 2019, also for the treatment of major depression with psilocybin assisted therapy.
2 Of course there are other psychedelics, but for the scope of this article we focus on the most popular substances for clinical research. We also focus on trials that induce psychedelic effects – unlike for example many ketamine trials where sub-psychedelic dosages are used.

Can MDMA help to treat addiction? Q&A with Ben Sessa

Until now, MDMA has mostly been studied in the context of treating PTSD and helping with autism. Psychiatrist Ben Sessa is now conducting the world’s first clinical study using MDMA-assisted psychotherapy to treat alcohol addiction, at the University of Bristol. According to him MDMA can be effective to treat addiction issues, because it “brings a particular emphasis on empathy and connection with the positive, loving part of the self, and that’s why it’s good for trauma.”
You often say that 2/3 of people with addictions have been traumatised or abused. Do you think there is addiction without trauma?
It depends on how you define trauma. There’s what I call ‘big T trauma’ and ‘little t trauma’. Not all people with addictions have suffered severe physical or sexual abuse. But if you ask people what was their experience of childhood, a vast majority of them will say it was cold: they didn’t feel loved or wanted, their parents weren’t really there for them. Those experiences fit in with what you’d call emotional abuse. Most people don’t recognise it as such, but they’re left feeling somewhat empty by it. It’s the most common factor in people with addictions.
Given this knowledge about where addiction comes from, why are most conventional treatments largely unsuccessful?
It’s a very difficult illness to treat, because of the availability of drugs and alcohol, the problem of social deprivation and poverty, homelessness and poor housing, racism, exclusion, poor education, lack of childcare, etc. If I had a magic wand and could instantly cure an addiction patient, but then sent them back to their dire home situation with transgenerational lack of hope, poverty and exclusion, they’re just going to pick up their addiction again. So it’s a very multidisciplinary problem with multiple factors that cause and maintain it, and we need to address all those factors.
Why then do psychedelics seem to do better in the treatment of addictions than conventional treatments?
Because underlying addiction, and many if not most chronic mental disorders, is rigidity. Stuck rigid mental narratives about self and the world, which arise early in life as a results of early experiences, in other words, the very core building blocks of our personality, which stay with us for life. The majority of mental health treatments, and certainly all the medicines we use, like SSRI’s, don’t do anything to those narratives, they just paper over the cracks and treat the overlying symptoms. In my experience, psychedelics are the best new form of pharmacology that we’ve come across that has the potential to actually tackle those narratives and allows people to build them up in a new, more positive way.
You’re currently conducting a study with MDMA to treat alcohol addiction. This is the first time MDMA is used for that indication. Why did you choose MDMA over psilocybin?
I was always interested in doing an MDMA study. Five years ago, I was in communication with MAPS about an MDMA/PTSD study. But then I got an offer from a rich benefactor which allowed me to do whatever I wanted. As I was working in addictions at the time, I decided to branch away from PTSD. I was acutely aware of alcoholism as being the number one addiction problem with a massive clinical and personal burden, and a very difficult one to treat. I also liked the fact that no-one else had ever suggested MDMA for addiction. Since trauma appears to be a big part of addictions, and MDMA has been shown to work in trauma treatment, it seemed to make sense that MDMA could work for addictions.
Do you think MDMA therapy and psilocybin therapy share the same paradigm?
They clearly have massive overlaps and similarities, for instance the fact of using a non-ordinary state of consciousness as an augmentation of psychotherapy. People would argue that MDMA isn’t a psychedelic, or at least not a classic one. However, I do think it fits into the same paradigm and I consider it a psychedelic psychotherapy tool. There are clearly also some big differences. With MDMA, you don’t get the ego dissolution that occurs on high doses of classic psychedelics. What you do get is a particular emphasis on empathy and connection with the positive, loving part of the self, and that’s why it’s good for trauma. The barrier to addressing trauma for many patients is this brick wall they hit, that prevents them from believing that they are worthy, after often spending decades believing they’re not. MDMA has this greater capacity than psilocybin to put you in a predominantly loving and warm state.
Where’s your MDMA/alcohol study at right now?
We have 14 participants, we finished dosing at the beginning of December, and we’re following everyone up to 9 months from the date of initial detox, so that will be until June. We’re assessing and analysing the data, and we’re writing the papers, which will be published in the first half of this year. This is a safety and tolerability study, with no placebo control group, which is what you have to do when using a new drug in a new condition for the first time. Obviously, we’re also looking at the subjects’ drinking behaviour and maintenance of abstinence and we’ll report on that, and the results look extremely promising. With conventional therapy, about 80% of patients go back to drinking in the next few months, and so far we have about 17% of people who went back to drinking again.
In his talk at ICPR 2020, Ben Sessa will elaborate on his MDMA/alcohol study and sketch future perspectives of psychedelic therapy research.

Alicia Danforth on ethical challenges in psychedelic medicine

Alicia Danforth, PhD, is a licensed clinical psychologist and researcher and has participated in three major studies on psychedelic-assisted therapy, the latest of which is still unpublished. She began her work in clinical research with psychedelic medicines as a coordinator and co-facilitator on the pilot study of psilocybin treatment for existential anxiety related to advanced cancer. More recently, she was an investigator for the first study of MDMA-assisted therapy for the treatment of social anxiety in autistic adults.
Your first study with psychedelics was about end-of-life anxiety, the second one was about social anxiety, and this latest one also has to do with anxiety to some extent. Is there a thread regarding anxiety in your research work?
I didn’t set out to go that way. The first study had to do with anxiety facing the end of life, yes. But to be candid, social anxiety wasn’t the initial focus of the autism research. I had made the false assumption that autistic individuals lack empathy, which isn’t more than an outdated cliché that I mistakenly took at face value. My initial thinking was that MDMA is an empathogen, so it might help this population experience empathy.
Once I started interviewing autistic adults for my dissertation, I found out that they were quite empathic in many domains of empathy, and they told me what they were struggling with is social anxiety. The desire to connect was there, but the ability to read social cues and to know how to integrate into a group conversation or initiate a friendship is what they needed help with. That’s how working with social anxiety as an indication came about.
So with hindsight, yes, you could say that anxiety is a thread that has run through most of the clinical work that I’ve been involved with. Anxiety disorders are the most common mental health diagnoses in the United States, and they have been a good match so far with psychedelics-assisted therapy.
Your latest research with psychedelics is about psychological distress in long-term AIDS/HIV survivors. Can you tell us more about this new study?
I want to clarify that I’m not one of the investigators on this study, I’m a lead clinician. I co-facilitated the therapy groups and the psilocybin treatment sessions. Dr. Brian Anderson initiated this study at UCSF. San Francisco has been a hub of HIV medicine, and Brian became aware that there’s an underserved population of long-term survivors who acquired the HIV virus back in the 1980’s or early 1990’s. As a result of losing so many of their friends and because of the impact of HIV on their lives and on the community, they were living with a high degree of demoralization.
Dr. Anderson wanted to explore if treatment with psilocybin-assisted therapy could help improve overall quality of life and reduce anxiety and depression symptoms. The first phase has been completed, the data are analyzed, and a manuscript has been prepared. All I can say right now is that the outcomes were encouraging.
One way in which this study was very innovative is that we worked with a group therapy model, where the participants prepared as a group, and then each one had an individual psilocybin-assisted therapy session, and they came back together to do their integration work as a group. We’re frequently asked if everyone took the psilocybin all together, and they did not. I don’t think we’re quite there yet, but I couldn’t help but wonder what that might be like someday.
At the upcoming ICPR 2020 conference in April, you’ll speak about ethical challenges within psychedelic medicine. Can you explain its importance?
It’s no secret that psychedelics present unique challenges when it comes to ethical considerations and boundaries. These substances place people in profound altered states of consciousness, and with that shift can come increased suggestibility and vulnerability. We’re working with such novel treatment paradigms that we need novel approaches to how the individuals who are entrusted with the roles of therapist or guide should be vetted, trained, and supervised.
Could you elaborate?
Well, it became very apparent to me that there are certain personality types that are drawn to situations in which they’re in close proximity to people who are vulnerable and open. They seek to manipulate and have a very unhealthy relationship with power. Back in the 60’s and early 70’s, when people were working with these substances in controlled and uncontrolled settings, there were problems with individuals who would transgress boundaries. And today, we’re plunging headlong into a new era where billions of dollars are accruing to throw money at this enterprise; there’s such a rush to do it quickly.
But, we don’t have the structures in place to keep the participants in research settings -and eventually customers in commercial settings- safe from abuses of power. So, I’ve started proposing that we need to look at other medical professions where they have to accommodate similar levels of vulnerability, such as anesthesiologists, pediatricians and gerontologists. We need to agree on which methods we’re going to have to employ to train and supervise peers. We don’t have a good system for winnowing out individuals who seek to do this work who have clinically significant narcissistic traits or psychopathy. How are we going to gatekeep? If we don’t talk about this responsibility and address it, we’re at risk of running into trouble again.
Alicia Danforth’s talk at ICPR 2020 will be entitled: “Getting Our House in Order: Advancing the Ethics of Psychedelic Medicine and Psychotherapy from Storming to Norming

Psilocybin Therapeutic Research: The Present and Future Paradigm

Abstract

Psilocybin, an active component in “magic mushroom”, may have the potential to meet the therapeutic needs for a number of indications without the addictiveness and overdose risk of other mind-altering drugs, such as cocaine, heroin, alcohol, methamphetamine, and so forth. The need for new therapies is urgent because addiction, overdose, and suicide deaths have risen throughout the United States and around the world. Anecdotal and contemporary pharmacological reports have provided some indication about the therapeutic use of psilocybin for the treatment of mental health disorders such as major depressive disorder and addiction disorders. In this Viewpoint, I summarize the current state of psilocybin therapeutic research and attempt to provide some insight into future directions on which the scientific community may wish to focus.

Kargbo, R. B. (2020). Psilocybin Therapeutic Research: The Present and Future Paradigm. ACS Medicinal Chemistry Letters11(4), 399-402.; 10.1021/acsmedchemlett.0c00048

Link to full text

Psychedelics and Dying Care: A Historical Look at the Relationship Between Psychedelics and Palliative Care

Abstract

This article examines the historical relationship between psychedelics and palliative care. Historians have contributed to a growing field of studies about how psychedelics have been used in the past, but much of that scholarship focused on interrogating questions of legitimacy or proving that psychedelics had therapeutic potential. Palliative care had not yet developed as medical sub-specialty, more often leaving dying care on the margins of modern, pharmaceutical-based treatments. As psychedelic researchers in the 1950s began exploring different applications for psychoactive substances such as LSD and mescaline, however, dying care came into clearer focus as a potential avenue for psychedelics. Before that application gained momentum in clinical or philosophical discussions, psychedelics were criminalized and some of those early discussions were lost. This article looks back at historical discussions about LSD’s potential for easing the anxiety associated with dying, and considers how those early conversations might offer insights into today’s more articulated discussions about psychedelics in palliative care.
Dyck, E. (2019). Psychedelics and dying care: A historical look at the relationship between psychedelics and palliative care. Journal of psychoactive drugs51(2), 102-107., https://doi.org/10.1080/02791072.2019.1581308
Link to full text

Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities.

Abstract

RATIONALE:
Microdosing psychedelics – the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin – is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers.
OBJECTIVES:
To examine the practices and demographics of a population of psychedelic microdosers – including their psychiatric diagnoses, prescription medications, and recreational substance use patterns – to develop a foundation on which to conduct future clinical research.
METHODS:
Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use.
RESULTS:
Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI: 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI: 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI: 2.7-10.8)).
CONCLUSIONS:
Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.
Rosenbaum, D., Weissman, C., Anderson, T., Petranker, R., Dinh-Williams, L. A., Hui, K., & Hapke, E. (2020). Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. Journal of Psychopharmacology, 0269881120908004., https://doi.org/10.1177/0269881120908004
Link to full text
 

Self-reported negative outcomes of psilocybin users: A quantitative textual analysis

Abstract

Psilocybin, a substance mainly found in mushrooms of the genus psilocybe, has been historically used for ritualistic, recreational and, more recently, medicinal purposes. The scientific literature suggests low toxicity, low risk of addiction, overdose, or other causes of injury commonly caused by substances of abuse, with growing interest in the use of this substance for conditions such as treatment-resistant depression. However, the presence of negative outcomes linked to psilocybin use is not clear yet. The objective of this study is to investigate the negative effects of psilocybin consumption, according to the users’ own perception through self-reports extracted from an online platform. 346 reports were analyzed with the assistance of the IRAMUTEQ textual analysis software, adopting the procedures of Descending Hierarchical Classification, Correspondence Factor Analysis and Specificities Analysis. The text segments were grouped in 4 main clusters, describing thinking distortions, emergencies, perceptual alterations and the administration of the substance. Bad trips were more frequent in female users, being associated with thinking distortions. The use of multiple doses of psilocybin in the same session or its combination with other substances was linked to the occurrence of long-term negative outcomes, while the use of mushrooms in single high doses was linked to medical emergencies. These results can be useful for a better understanding of the effects of psilocybin use, guiding harm-reduction initiatives.

 
Bienemann, B., Ruschel, N. S., Campos, M. L., Negreiros, M. A., & Mograbi, D. C. (2020). Self-reported negative outcomes of psilocybin users: A quantitative textual analysis. Plos one15(2), e0229067., https://doi.org/10.1371/journal.pone.0229067
Link to full text

Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks

Abstract

Background: Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24 hours after a single session with the psychedelic ayahuasca.
Methods: We leveraged task-free functional magnetic resonance imaging data 1 day before and 1 day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects.
Results: Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks 1 day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience default mode network connectivity correlated with altered affect scores.
Conclusion: These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.

Pasquini, L., Palhano-Fontes, F., & de Araujo, D. B. (2019). Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. medRxiv, 19007542., https://doi.org/10.1177/0269881120909409
Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Indigenous Talk: Fulni-ô Culture & Jurema - Online Event - Dec 12th