OPEN Foundation

Menu

Author name: OPEN Foundation

The Science and Folklore of DMT

/ DMT /

Being one of the most powerful psychedelics we know, it is not strange that DMT has become the subject of numerous speculations over the years. Theories linking this molecule to the pineal gland, to dreams or near-death experiences have circulated persistently among users and researchers – yet the scientific evidence just doesn’t seem to be there. 

It has been established that DMT occurs in many organisms endogenously, like plants, animals and humans. Besides that, much has yet to become established science in the academic world. Is DMT synthesized in the pineal gland? If so, what is its function? Is it involved in generating dreams or normal consciousness? Is it behind so-called near-death experiences?

We approached researcher Enzo Tagliazucchi to help us bring some clarity and a scientific perspective to these questions. Tagliazucchi is a neuroscientist and professor at the University of Buenos Aires. He will be speaking about his research and the first Electroencephalography (EEG) study of DMT in naturalistic settings at ICPR 2020.

This is the first part of a three-part interview series with Prof. Enzo Tagliazucchi

OPEN Foundation: Twenty years ago, Rick Strassman popularized DMT as the “Spirit Molecule”. In his popular book, he made the claim that this psychedelic compound is endogenously synthesized in the human pineal gland. What led him to this hypothesis?

Enzo Tagliazucchi: It would not be strange if DMT would actually be synthesized in the pineal gland because melatonin, a molecule that is pretty similar in its structure compared to DMT, is released there. All the necessary enzymes in the corresponding metabolic pathway are present in the pineal gland. You have all these coincidences that seem to suggest that it is a natural process that is creating the molecule, and that this process can take place in the pineal gland.

Strassman was, in fact,  interested in melatonin research at first and then came across DMT. From there, he started to convince himself that it was synthesized in the pineal gland and started wondering about its function. People have been trying to find a role for DMT from the moment it became obvious that it is an endogenous molecule, for instance, some have the hypothesis that DMT is actually a neurotransmitter still without a known receptor (the sigma receptor was considered as a candidate for some time but eventually it was abandoned). Of course, whatever the function was, they conjectured, it had to be something related to the phenomenology of the psychedelic state.

In his investigations, Strassman came across these really strange experiences reported by his research participants, which he actually describes as a kind of shock for him. Confronted with this bizarre information, he hypothesized that DMT is present in the brain to signal certain important moments in life, and that these moments are experienced as strange DMT-like experiences, such as birth and death. This is why he coined the popular phrase “the spirit molecule” in reference to DMT.

Last year, a research team from the University of Michigan led by Jimo Borjigin reported concentrations of DMT in rats’ brains to be similar to that of other neurotransmitters like serotonin during induced experimental cardiac arrest. What are the implications of these findings and what do we know about the endogenous levels of DMT in the human brain?

Recently there was some controversy because of this paper, in which Strassman was actually co-author, showing in an animal model that you can find large amounts of DMT produced near the moment of death.

David Nichols tried to refute this hypothesis years ago arguing that even if DMT is actually synthesized in the pineal gland, you will never get sufficiently high concentrations of endogenous DMT to ever produce a psychedelic-like experience. That was the end for a while, and then came this article which Strassman and others took as evidence to support his theory.

David Nichols again published a rebuttal arguing that the finding of high amounts of DMT is not really conclusive because at that critical moment you get a massive release of several neurotransmitters. If you have twice the usual concentration of DMT, then you also have twice the usual concentration of serotonin. And since serotonin is competing with DMT and it has a higher affinity for all serotonin receptor sub-types, then why would you get an endogenous DMT trip considering these difficulties in binding to serotonin receptors?

I think if I had to bet money, I would say that there is DMT in the pineal gland. It is a very simple tryptamine and you have a lot of different possible pathways to get it. All the chemicals you need for the synthesis of DMT can be found in the pineal gland. I would even bet that when you have hypoxia or if there is a critical injury in the brain, there is a spike in DMT concentration. But at such a moment, you have spikes of several neurotransmitters. However, if somebody finds a high spike of DMT alone, that would be a remarkable finding.

I think that more research is needed because it is really strange that DMT is in the brain. People should keep doing this research and should keep asking: Why is DMT there? What does it do? What receptors does it bind to? What is its role? These questions are important, even if the findings so far have been, for the most part, negative.

We don’t really have any proof at all that Strassman’s theories are more than attractive hypotheses. Something valuable about Strassman’s work is that it made a lot of people think for the first time about the possibility of endogenously triggered altered states of consciousness. Unfortunately, I think there is yet nothing to the claim that DMT is behind these experiences.

It seems that Borjigin’s research has been welcomed by DMT enthusiasts who link this molecule to dreams and normal consciousness. If it is present in the human brain at significant levels, could DMT be considered a neurotransmitter playing a role in generating ordinary consciousness or in dreaming, as it has been claimed?

The challenge is to find DMT in a sufficiently high concentration to produce such effects. You would need around 25 mg of DMT being produced in a short period of time for something like that to happen in your consciousness and, apparently, there is no way that can happen. The endogenous concentrations are in the microgram range, below the active levels by orders of magnitude. The reason why it can’t happen is not only because researchers have not found such high levels, it is because essentially the metabolic pathways do not seem to be able to support that massive biosynthesis.

Similarly, it does not seem that DMT is produced with a sufficiently high concentration to be involved in dreaming, and so on. I do not think it is even needed to explain the phenomenology of dreaming. We understand more or less the neurochemistry of dreaming and serotonin, in fact, tends to be blocked during REM sleep. So the neurochemistry does not seem to suggest at all that 5-HT2A receptor activation by any molecule, let alone one in such small quantities, is responsible for dreaming. This does not preclude, of course, that the phenomenology of dreaming and psychedelic states are very similar. You might get to the same effect following different routes.

If it is in the concentrations it is suspected to be in, there is no way it can influence consciousness. That is the current state of knowledge.

See Enzo’s talk titled The neural and psychological correlates of inhaled N,N-dimethyltryptamine (DMT) in natural and ceremonial settings at ICPR2020.

The Science and Folklore of DMT Read More »

How psychedelics can cause ‘the overview effect’

/ Uncategorized /

Neuroscientist Robin Carhart-Harris (PhD) studies the brain effects of LSD, psilocybin and MDMA. He is currently the head of the Centre for Psychedelic Research, at the Faculty of Medicine, Imperial College London. At ICPR 2016, he held a talk on the heels of his landmark imaging studies of brains on psychedelics. The findings of the team that Carhart-Harris is a part of were a sensation far beyond academics and psychonauts. Pictures of the studies went viral and were printed in newspapers around the world, reaching mainstream attention for psychedelic science.
In this short highlight from our previous convention, dr. Carhart-Harris speaks of treating depression with psychedelics. The findings from their study suggest that the higher the dose, the higher the chance of ego-dissolution, which correlated with lower depression symptoms.
In his talk, he compares the idea of ego-dissolution to the “overview” effect experienced by astronauts: “when you listen to astronauts talking about this experience they often say that they are left with a memory, they cannot forget that experience, that wonder, that awe that they experienced. I think in terms of the psychological mechanisms, this can explain what happens when the prison house of the ego dissolves away and then you have that broader sense of connectedness with other people and with the cosmos as a whole”.

Robin Carhart-Harris’ full talk from 2016 can be watched on the OPEN Foundation Youtube channel

How psychedelics can cause ‘the overview effect’ Read More »

What microdosing did for the perception of psychedelics

/ Microdosing, Publications /

Over the past decade, the phenomenon of ‘microdosing’ has had outsized implications for the perception of psychedelics. Before this phenomenon, narratives around psychedelics always assumed a large dose and a full psychedelic experience. After the popularization of the concept of microdosing, the idea that psychedelics could be taken in small quantities -as a cognitive enhancer- became more prevalent and accepted. Ever since, they’ve been hailed as valuable tools for enhancing various aspects of cognition, creativity, emotion and neuroplasticity.
This article takes notes from Aleksi Hupli’s upcoming PhD dissertation in Sociology at the University of Tampere called: Smarter with Drugs. Cognitive enhancement drugs from users’ perspectives. In it, he partly explores why psychedelic microdosing should be included in the pharmacological neuroenhancement discussion and debate.
Albert Hofmann – the discoverer of the psychoactive properties of LSD – already mentioned in an interview with High Times in 1976 that “very small doses, perhaps 25 micrograms, could be useful as a euphoriant or antidepressant” (Horowitz 1976). The current renaissance of psychedelic microdosing research is usually accredited to Dr. James Fadiman, who dedicated a small chapter to describe experiences with “sub-perceptual doses” in The Psychedelic Explorer’s Guide, published in 2011. Prior to Fadiman, we have to go back to early research done in the 1950s and 60s – especially by the US military – on low doses of LSD. These studies were reviewed by another ICPR2020 speaker, Dr. Torsten Passie (MD) and partly republished in his book The Science of Microdosing Psychedelics (2019), arguably one of the most comprehensive publications on the issue of microdosing to date.
The “very small dose” of 25 micrograms mentioned by Hofmann is not technically considered a microdose or “sub-perceptual dose” as described by Fadiman (2011). As the “common” recreational dose of LSD ranges from 50 to 150 micrograms (Passie et al. 2008), and in contemporary clinical settings from 20 to 200 micrograms, it is still fairly unclear what a “microdose” really is compared to a very low dose or “minidose” (Kuypers et al. 2019; Passie 2019, p. 9-10). According to Fadiman, Hofmann called microdosing “an under-researched area” (Fadiman 2011, p. 211; see also Passie 2019, p. 23-25) and it did take over 45 years for the topic to be picked up by modern mainstream media and research.
Not accepted yet
Some psychedelic researchers remain sceptical about microdosing (e.g. Nichols, Roseman & Timmerman 2018, p. 83) while others acknowledge that “This role of psychedelics as cognitive enhancers is certainly an area in need of more research” (Sessa 2017, p. 276). It is important to note that ‘microdosing’ has several different meanings: for instance, in pharmacokinetic studies, microdosing is being used as a method in novel drug toxicology research. In addition, microdosing is also used as a novel technology in agriculture as a method of distributing plant nutrition (Passie 2019, p. 4).
Lack of research did not prevent a certain “media-hype” from developing, as there were plenty of media reports around the topic of microdosing. These reports described microdosing as a “Revolutionary Way of Using Psychedelics” (High Existence 2014) and, in a “brief history of microdosing” written by Vice in 2015, stated that “while the idea hasn’t yet catapulted itself into the mainstream, it’s getting there”. The following years indeed saw more mainstream media outlets writing about how LSD microdosing “became the hot new business trip” (Rolling Stone 2015) and “the new job enhancer” (Forbes 2015). Microdosing was affiliated with work productivity as a “new brain booster” (The Times 2017) especially in the technology hub Silicon Valley located in California (Wired 2016; Huffington Post 2017; also Mishra 2018; Hupli 2019). These media reports usually included mainly positive reports from people practicing or experimenting with psychedelic microdosing despite that for a long time there was indeed a lack of published research available, as still remains the case.
The definition on Microdosing
In their comprehensive overview of the current literature Kim Kuypers and colleagues, many of whom are presenting at ICPR2020, state: “the term ‘microdosing’ appears to consist of three components: 1) The use of a low dose below the perceptual threshold that does not impair ‘normal’ functioning of an individual. 2) A procedure that includes multiple dosing sessions. 3) The intention to improve well-being and enhance cognitive and/or emotional processes” (Kuypers et al. 2019). Thus, firstly, the dose should be low enough so it does not at least impair “normal” functioning, and in the publication the authors offer a table which includes varying doses (Microdose, Very low Dose, Low dose, Medium dose, High dose) of varying psychedelic compounds (psilocin, LSD, DMT and Ibogaine) that have been studied both in preclinical and clinical research. The authors write that “These doses are approximate values” which were presented as “Per kilogram dose values” which had been “converted to values for a 70-kg person” (Kuypers et al. 2019, p. 3), thus their applicability to ‘real-life settings’ requires careful consideration.
The second component of microdosing according to Kuypers et al., included a procedure with multiple dosing sessions for which there is no unified protocol. This multiple dosing of psychedelic compounds, which is something that usually does not take place with higher doses, is one of the issues that has raised concerns of potential cardiovascular risks associated with nearly daily activation of serotonin receptors with potent partial serotonergic agonists like LSD and psilocin (Kuypers et al. 2019;  Nichols, Roseman & Timmerman 2018, p. 83; Passie 2019). Kuypers et al. (2019, p. 8) conclude that “the possible effects and implications of microdosing remain largely unknown.” While online forums have a vast database of reported effects, from Youtube (Hupli et al. 2019a) to Reddit (Lea, Amada & Jungaberle 2019), according to Kuypers et al. (2019) “the true amount of active substance in these is unknown”. From a research and public health perspective this is, of course, problematic to say the least.
The third component of microdosing described by Kuypers et al., “having an intention to improve well-being and enhance cognitive and/or emotional processes”, is indeed something that users often seem to have when they practice psychedelic microdosing (e.g. Lea et al. 2020; Fadiman & Korb 2019; Hutten et al. 2019; Polito & Stevenson 2019). However, “while in these anecdotal reports the user deliberately ingests a substance for a reason, expecting positive effects, it is difficult to distinguish between expectation ‘placebo’ effects and the effect of a microdose.” (Kuypers et al. 2019, p. 8). From user’ perspectives, however, there is ‘an effect’, whether due to pharmacology or the excitement of doing some thing, even something illegal, but at least something that might improve one’s life-situation which is more than understandable.
Thus, this trend begs for more research on the topic to distinguish “the actual from the imaginary effects of microdosing” (Passie 2019, p. 46), not only for therapy but also for pharmacological neuroenhancement. According to a recent review of psychedelic microdosing, focusing specifically on its potential as a cognitive enhancer, Rifkin, Maraver and Colzato (2020, p. 9, italics added) “conclude that microdosing psychedelics is a promising means for enhancing various aspects of cognition, creativity, and emotion recognition, and that they may be valuable tools to augment cognitive flexibility and neuroplasticity.” However, they also acknowledge that “These findings imply that psychedelics should not be treated as a uniform class of drugs, particularly with respect to microdosing. Various psychedelics, with their distinct receptor affinities, will almost certainly prove to be better for cognitive enhancement in small doses than others.”
Although some users experience also unwanted effects, psychedelic microdosing is more often claimed to bring relief for such conditions such as depression and ADHD (Fadiman & Korb 2019; Lea et al. 2020), which were already mentioned by Albert Hofmann for what ‘very small doses of LSD’ could be useful for, decades ago. The vast list of effects psychedelic microdosing is claimed to produce, now confirmed by an increasing amount of user and preclinical studies (Polito & Stevenson 2019; Hutten et al. 2019; Rifkin, Maraver & Colzato 2020) with some clinical ones completed (Yanakieva et al. 2019; Ramaekers et al. 2020) and others underway (MindMed Press Release 2020; see also Hupli et al 2019a; Wired 2019) require further attention in this field (Hupli 2019).
Fadiman together with Sophia Korb will present some unexpected results from their crowd-sourced research at ICPR2020.
Written by Aleksi Hupli as part of his upcoming PhD Dissertation in Sociology at the University of Tampere titled Smarter with Drugs. Cognitive enhancement drugs from users’ perspectives.
References:
Fadiman, J. (2011). The psychedelic explorer´s guide. Safe, therapeutic and sacred journeys. Park Street Press
Fadiman, J. & S. Korb (2019). Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. Journal of Psychoactive Drugs, 51(2), 118-122.
Horowitz, M. (1976). Interview with Albert Hofmann. Available at: https://hightimes.com/culture/albert-hofmann-lsd-interview/
Hupli A., M. Berning, A. Zhuparris & J. Fadiman (2019a). Descriptive assemblage of psychedelic microdosing: netnographic study of Youtube™ videos and on-going research projects. Performance Enhancement & Health, 6,( 3–4), 129-138.
Hupli, A. (2019). ECR Spotlight: Psychedelic Microdosing – From Silicon Valley Hype towards Placebo-Controlled Science. In HED Matters, Vol 2, Issue 2. Available at: https://humanenhancementdrugs.com/wp-content/uploads/HED-Matters-Issue-3.pdf
Hutten, N., Mason, N., Dolder, P. & K. Kuypers (2019). Motives and Side-Effects of Microdosing With Psychedelics Among Users. International Journal of Neuropsychopharmacology, 22(7), 426–434.
Kuypers, K., Ng, L., Erritzoe, D., Knudsen, G.M., Nichols, C.D., Nichols, D.E., Pani, L. Soula, A. & D. Nutt (2019). Microdosing psychedelics: More questions than answers? An overview and suggestions for future research, Journal of Psychopharmacology, 33(9), 1039-1057.
Lea, T., Amada N. & H. Jungaberle (2020). Psychedelic Microdosing: A Subreddit Analysis. Journal of Psychoactive Drugs, 52, 101 – 112.
Lea, T., Amada, N., Jungaberle, H., Schecke, H., Scherbaum, N. & M. Klein M (2020). Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders. Psychopharmacology, 237,1521 -1532.
Mishra, S. (2018). Microdosing at Work: Reworking Bodies and Chemicals. Essay part of an online supplement to the Openings collection on “Chemo-Ethnography” edited by Nicholas Shapiro and Eben Kirksey in the November 2017 issue of Cultural Anthropology. Available at: https://culanth.org/fieldsights/1307-microdosing-at-work-reworking-bodies-and-chemicals
Nichols, D., Roseman, L. & C. Timmermann (2018). Psychedelics: from pharmacology to phenomenology. An interview with David Nichols. ALIUS Bulletin, 2, 75-85.
Passie, T., Halpern, J.H., Stichtenoth, D.O., Emrich, H.M. & A. Hintzen (2008). The pharmacology of lysergic acid diethylamide: A review. CNS Neuroscience & Therapeutics, 14, 295–314.
Passie, T. (2019). The Science of Microdosing Psychedelics. Psychedelic Press.
Polito, V. & R.J. Stevenson (2019). A systematic study of microdosing psychedelics. PLoS ONE, 14(2): e0211023
Ramaekers JG, Hutten N, Mason NL, et al. A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers. Journal of Psychopharmacology. August 2020. doi:10.1177/0269881120940937
Rifkin, B. D., Maraver, M. J. & L. S. Colzato (2020). Microdosing psychedelics as cognitive and emotional enhancers. Psychology of Consciousness: Theory, Research, and Practice. Advance online publication. https://doi.org/10.1037/cns0000213
Sessa, B. (2017). Psychedelic renaissance. Reassessing the role of psychedelic drugs in 21st century psychiatry and society. 2nd edition. Muswell Hill Press.
Yanakieva, S., Polychroni, N., Family, N., Williams L.T.J., Luke D.P. & D.B. Terhune (2018). The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial. Psychopharmacology,  236(4), 1159-1170.

What microdosing did for the perception of psychedelics Read More »

Compassionate use of psychedelics

/ MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. When talking about psychedelics, we mean specifically two substances: psilocybin and MDMA. When administered under supportive conditions and in conjunction with psychotherapy, therapies assisted by these substances show promising results. However, given the publicly controversial nature of psychedelics, compassionate psychedelic psychotherapy calls for ethical justification. We thus review the safety and efficacy of psilocybin- and MDMA-assisted therapies and claim that it can be rational for some patients to try psychedelic therapy. We think it can be rational despite the uncertainty of outcomes associated with compassionate use as an unproven treatment regime, as the expected value of psychedelic psychotherapy can be assessed and can outweigh the expected value of routine care, palliative care, or no care at all. Furthermore, we respond to the objection that psychedelic psychotherapy is morally impermissible because it is epistemically harmful. We argue that given the current level of understanding of psychedelics, this objection is unsubstantiated for a number of reasons, but mainly because there is no experimental evidence to suggest that epistemic harm actually takes place.
Greif, A., & Šurkala, M. (2020). Compassionate use of psychedelics. Medicine, Health Care, and Philosophy.,
Link to full text

Compassionate use of psychedelics Read More »

Matthew Jonhson: psychedelics are brain plasticity-inducing

/ Neuroscience, Papers, Publications /

MatthewJohnson
Matthew Johnson is associate director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University – a center created last year. Johnson is one of the world’s leading researchers in psychedelic science. The Open Foundation asked him to reflect on some hot topics in psychedelic science today – like the mystical experience, business players entering psychedelic research and new avenues of clinical research.
In September of 2019, Johns Hopkins launched its Center for Psychedelic and Consciousness Research. Just a few months earlier, Imperial College in London had started its own Centre for Psychedelic Research. The creation of the Hopkins center seemed like a ‘response’, in a way. Is there some rivalry we need to know about?
The seeds were being sown long before we were aware of the Imperial center, so I wouldn’t say so. There’s far more room for synergy and collaboration than for rivalry in this field. Of course, you always like to be the first to publish a paper on a given subject, that’s just human. But in the big picture, it’s really great that there are two large, very credible centers in the world, and the hope is that it’s going to keep growing. There’s even a third center in South Carolina now, with Michael Mithoefer and others.
What’s the added value of dedicated centers for psychedelic research?
The center is a term used in academics to mean a certain level of funding that allows for an increased concentration and focus on a research area. Functionally, the important thing is that it’s dramatically increasing the throughput of our work on psychedelics.
Your group at Hopkins seems to place a good deal of emphasis on the mystical experience and considers it the mechanism of action for therapeutic outcomes of psychedelic therapy, whereas Imperial focuses more on imagery and neuroscience. Where does this focus on the mystical experience come from?
I think there’s a focus on the biology and the neuroscience at both sites. I’m conducting a study with 80 people on smoking cessation where subjects are undergoing fMRI with a variety of tasks before and after the experience. Fred Barrett in our group is a neuroscientist, and he’s conducting a number of studies right now. In terms of the psychology, the Imperial group has used more of a Freudian model and we have focused more on the mystical experience, but I think empirically we’re likely talking about the same thing. The term ‘ego loss’ has a high correlation to the mystical experience of unity. The focus on mystical experience dates back to William James, and I see it as continuing a thread of interest in this kind of experience that human beings, around the world and throughout time, have consistently reported. It seems that psychedelics prompt those types of experiences, so that interest is far larger than the therapeutic use of psychedelics, which in itself is very important. It taps into the idea that these can be tools for understanding the biology and the very nature of these extraordinary human experiences, and their ability – however occasioned – to prompt behavior change.
The Hopkins Center is set to research interesting new indications: anorexia, distress associated with Alzheimer’s, and aftercare for Lyme disease.
We have started the first two. We’re actively recruiting for the anorexia treatment study, and we’ve actually run participants through that study, but not enough to discern any results yet. We’re also actively recruiting for the mood within Alzheimer’s disease study. We have the funding for the other study, on post-treatment Lyme disease syndrome, as it’s come to be known, and we’re preparing the regulation to be able to conduct it. We should be starting it within a few months.
What exactly is the aim regarding Alzheimer’s?
The primary aim is clearly the mood of patients, through the lens of cancer research, where the focus is not on treating the disease, but the psychological suffering that so often comes with it, and the existential distress that is also there with dementia. But we’re also going to look at the cognitive outcomes, because there are some interesting animal studies that suggest that there are potential positive cognitive effects of these compounds. Also because having a profound psychological reorientation, where you have reductions in depression, might in itself lead to improved cognition and slow the disease process. We’re not holding our breath that we’ll see something there, but it’s worth a look.
Both the center in Baltimore and the one in London are funded by private donors: do you understand the concerns of people who are wary of the increasing interference of big business with psychedelic research?
There are many opinions out there, so I’m not sure what the concerns exactly are. The Center is funded through a non-profit model and it’s 100 % philanthropy, so I think it’s unrelated to any concerns about business involvement in this area.
Well, people like Tim Ferriss raise some questions. He’s an investor, and investors are known to seek some kind of return on their investments. Some people are quite suspicious of that.
At the surface level I can understand the concerns, if people don’t know the details. From knowing the details, I can say that if his goal was to have a financial return on investment, he’s done a very poor job at setting things up. However, he’s been very clear that the goal was to leverage the growth of an area and the advancement of science.
Humans are interested in leaving a legacy, and being known for having had an impact, so that may be relevant to anybody who makes an investment in an area with a hope for its growth. I think he wants to see this area take off, and a lot of people look to him as someone who sees what’s coming in the future. I also think this has already been an advantage in terms of people paying attention to this area.
Are you concerned that, once legal, psychedelic therapy might turn into big business? The business press is already touting psychedelic therapy as the next big cash cow.
If we’re on to something – and I think we are – then this will happen. There are niches to fill. So the real questions become: What are the actions of any particular entity? Are they operating ethically or unethically? The commercialization of psychedelics raises concerns about the potential for bad actors, but there can be bad actors in pure non-profit and in pure academia. The potential on the monetary side is obviously increased once you introduce a business model. So I think there’s a rationale for increased concern about bad actors. But the fact that business is jumping into this is not a bad thing in itself. It’s a 100 % expected outcome, and overall it’s a good thing. We just have to keep our eyes on the way people are operating.
The title of your ICPR talk will be: “Psychedelics as behavior change agents.” What can we expect?
I want this to be a big-picture presentation that draws from multiple lines of evidence. Not about the treatment of this or that disorder, or this or that effect, but really drawing across all that. The overall point is that psychedelics can occasion behavior change. They seem to be powerful ways to induce mental and behavioral plasticity. We have a whole lot more to figure out on the biology of that and how to most properly leverage psychedelics towards those aims. There’s also a lot to figure out about so-called ‘integration’, but it’s probably that people are left in a state of increased neuroplasticity, which can depend on many mechanisms. So I’d like to present the basic argument that, in the broadest sense, these are plasticity-inducing agents.

Matthew Jonhson: psychedelics are brain plasticity-inducing Read More »

Anonymous donation on Reddit ‘changed everything’ for MDMA research

/ MDMA /

When MAPS founder Rick Doblin was in Amsterdam for our event on MDMA research, he sat down with journalist Thijs Roes for a wide-ranging conversation. One of the topics they touched upon, was how recent MAPS funding had gotten off the ground.

In 2017, MAPS was a much smaller organisation. With no help from any government and no large funds available to them, MAPS had to get by on relatively small donations. Until an anonymous Reddit user called Pine suddenly announced that he had millions of dollars available to support causes that would otherwise be overlooked. She (or he) had bought bitcoins for an incredibly low price, and had had an epiphany while on Ketamine-therapy: the best way to live life was to help other people, and give as much the newly gained wealth away.

“MDMA-assisted psychotherapy will be a gift to the world from the psychedelic and cryptocurrency communities,” Rick Doblin wrote earlier. And in the interview he says the grant “changed everything for us”. Pine ended up giving $5 million dollars to make MDMA-assisted therapy a reality. MAPS is now in phase 3 studies to get MDMA approved and legal for clinical therapy.

Rick Doblin will be speaking at icpr-conference.com – the leading scientific psychedelic conference of Europe, held from September 22 until 24.

Anonymous donation on Reddit ‘changed everything’ for MDMA research Read More »

Structure of a Hallucinogen-Activated Gq-Coupled 5-HT 2A Serotonin Receptor

/ LSD, Neuroscience, Papers, Pharmacology & Chemistry / Leave a Comment / / , , , , , , , , , , , ,

Abstract

Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions-both therapeutic and hallucinogenic-are not understood, although activation of the 5-HT2A serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH-a prototypical hallucinogen-in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders.

Kim, K., Che, T., Panova, O., DiBerto, J. F., Lyu, J., Krumm, B. E., Wacker, D., Robertson, M. J., Seven, A. B., Nichols, D. E., Shoichet, B. K., Skiniotis, G., & Roth, B. L. (2020). Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor. Cell, 182(6), 1574–1588.e19. https://doi.org/10.1016/j.cell.2020.08.024

Link to full text

Structure of a Hallucinogen-Activated Gq-Coupled 5-HT 2A Serotonin Receptor Read More »

Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin

/ Anxiety Disorders / PTSD, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / / , , , ,

Abstract

The aim of this systematic review was to examine the efficacy of MDMA, ketamine, LSD, and psilocybin for the treatment of posttraumatic stress disorder (PTSD). A search of four databases for English language, peer-reviewed literature published from inception to 18th October 2019 yielded 2,959 records, 34 of which were screened on full-text. Observational studies and RCTs which tested the efficacy of MDMA, ketamine, LSD, or psilocybin for reducing PTSD symptoms in adults, and reported changes to PTSD diagnosis or symptomatology, were included. Nine trials (five ketamine and four MDMA) met inclusion criteria. Trials were rated on a quality and bias checklist and GRADE was used to rank the evidence. The evidence for ketamine as a stand-alone treatment for comorbid PTSD and depression was ranked “very low”, and the evidence for ketamine in combination with psychotherapy as a PTSD treatment was ranked “low”. The evidence for MDMA in combination with psychotherapy as a PTSD treatment was ranked “moderate”.

Varker, T., Watson, L., Gibson, K., Forbes, D., & O’Donnell, M. L. (2021). Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin. Journal of psychoactive drugs, 53(1), 85–95. https://doi.org/10.1080/02791072.2020.1817639

Link to full text

Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin Read More »

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

/ Neuroscience, Papers / Leave a Comment / / ,

Abstract

Renewed interest in the use of psychedelics in the treatment of psychiatric disorders warrants a better understanding of the neurobiological mechanisms underlying the effects of these substances. After a hiatus of about 50 years, state-of-the art studies have recently begun to close important knowledge gaps by elucidating the mechanisms of action of psychedelics with regard to their effects on receptor subsystems, systems-level brain activity and connectivity, and cognitive and emotional processing. In addition, functional studies have shown that changes in self-experience, emotional processing and social cognition may contribute to the potential therapeutic effects of psychedelics. These discoveries provide a scientific road map for the investigation and application of psychedelic substances in psychiatry.

Vollenweider, F. X., & Preller, K. H. (2020). Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nature reviews. Neuroscience, 21(11), 611–624. https://doi.org/10.1038/s41583-020-0367-2

Link to full text

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders Read More »

Whole-Brain Models to Explore Altered States of Consciousness from the Bottom Up

/ Neuroscience, Papers / Leave a Comment / / , , , , , ,

Abstract

The scope of human consciousness includes states departing from what most of us experience as ordinary wakefulness. These altered states of consciousness constitute a prime opportunity to study how global changes in brain activity relate to different varieties of subjective experience. We consider the problem of explaining how global signatures of altered consciousness arise from the interplay between large-scale connectivity and local dynamical rules that can be traced to known properties of neural tissue. For this purpose, we advocate a research program aimed at bridging the gap between bottom-up generative models of whole-brain activity and the top-down signatures proposed by theories of consciousness. Throughout this paper, we define altered states of consciousness, discuss relevant signatures of consciousness observed in brain activity, and introduce whole-brain models to explore the biophysics of altered consciousness from the bottom-up. We discuss the potential of our proposal in view of the current state of the art, give specific examples of how this research agenda might play out, and emphasize how a systematic investigation of altered states of consciousness via bottom-up modeling may help us better understand the biophysical, informational, and dynamical underpinnings of consciousness.

Cofré, R., Herzog, R., Mediano, P., Piccinini, J., Rosas, F. E., Sanz Perl, Y., & Tagliazucchi, E. (2020). Whole-Brain Models to Explore Altered States of Consciousness from the Bottom Up. Brain sciences, 10(9), 626. https://doi.org/10.3390/brainsci10090626

Link to full text

Whole-Brain Models to Explore Altered States of Consciousness from the Bottom Up Read More »

Online Community Meet-up with Leor Roseman - Online Event - April 23

REGISTER NOW