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Psychedelic Science: Remedies for Repeating History

Updated: Mar 18

Note: Guests of The Psychedelic Blog do not endorse, support, or otherwise advocate on behalf of any particular treatment approach for mental illnesses unless stated otherwise. The views expressed during this interview do not necessarily reflect the opinions or endorsement of The Psychedelic Blog. Readers should always consult with qualified healthcare professionals and conduct their own research before considering any treatment options. The blog and its authors are not responsible for any decisions made based on the information provided.

"To be hopeful and optimistic about psychedelic drugs and their potential is one thing; to be messianic is another."

- Robert Masters and Jean Houston, The Varieties of Psychedelic Experience


Robert Benz: Drs. Eiko I. Fried and Michiel van Elk may have wanted to place the above words of caution on billboards in every corner of the planet. Instead, they saved the 1966 admonition, by Masters and Houston, for the very end of their paper, History Repeating: A Roadmap to Address Common Problems in Psychedelic Science. Whether this display of supreme restraint was a kind of poetic genius or not, I couldn't resist amplifying the quote in a blown-up headline with emboldened font. There, that's better.


The Old Testament tells the story of Moses. He was a shepherd when he encountered a burning bush through which God instructed him to lead the Israelites out of bondage from Egypt to the Promised Land. Psychedelic history also has transformative figures. Dr. Timothy Leary, for example, was a well-respected Harvard University researcher and lecturer in clinical psychology when he encountered his own burning bush, LSD. And, while Moses carried the Lord´s Ten Commandments on engraved stone tablets, Leary had only Three commandments which were printed on flyers and distributed wherever he went: Turn on, Tune in, Drop out.


Those are the words that encouraged a generation to explore altered states of consciousness through psychedelic substances like LSD, psilocybin, and mescaline. Young people were asked to detach from societal norms and disengage from mainstream institutions. While Leary's messages were, in fact, liberating for their audience, they posed a worrisome threat to the establishment. Amidst a combustible backdrop, including the Vietnam War, the Civil Rights Movement, and the Beatles, Leary ignited a countercultural revolution that would effectively derail the progression of global psychedelics studies. Certainly, Leary wasn't the sole instigator, but he symbolized a turning point where potential treatments for various mental illnesses and substance use disorders escaped the lab. Subsequently, the establishment freaked out and then they responded. Psychedelics became Schedule 1 drugs and the research was silenced.


Today, the once-muted voices of psychedelic advocates are gradually intensifying their calls to make the substances available to help address the growing mental health crisis and to permit psychonauts to, once more, explore the mind without facing legal repercussions. Even louder than those voices, however, are the grinding gears of capital with grand visions of profits. The stakes are very high and the tension is building. Yes, you might call it combustible. Let's meet our guest, Dr. Michael van Elk.


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Dr. Michiel van Elk

"I think there's a risk that every person working in this field, including myself, is enthusiastic about psychedelics because of personal experiences, positive personal experiences."

- Dr. Michiel van Elk

 

Michiel van Elk is an Associate Professor at the unit Cognitive Psychology of the Institute of Psychology, at Leiden University. As head of the Psychedelic, Religious, Spiritual, and Mystical (PRSM) Lab, his research focuses on religious and spiritual experiences, and altered states of consciousness (ASCs), as induced through meditation, sensory deprivation, psychedelics and other means. By using a variety of different techniques, including self-report measures, interviews, expectancy manipulations, neuroimaging tools, psychophysiological techniques, and pharmacological challenges he aims to understand how ASCs come about, the effects they have on our behavior and well-being, and the philosophical implications of ASCs for our views on the self and reality.

 

Robert: Welcome, Michiel. Congratulations to you and Dr. Fried on this work, titled History Repeating, A Roadmap to Address Common Problems in Psychedelic Science. The paper implies that modern psychedelic studies lack a structured approach. What led you to the conclusion about the lack of quality and scientific rigor in modern psychedelic studies?


MvE: It was, basically, the key publications that came out just over the last five years. We've been accused, after writing the paper, of cherry-picking bad examples of specific studies that lacked proper control conditions, etc. But we really did our best to also look at the more high-profile studies. There, the somewhat disappointing conclusion is that even high-profile studies often lacked scientific rigor. That was evident in terms of statistical reporting, adhering to the pre-registered study protocol, including transparent reporting of breaking blinds information, including transparent reporting of conflicts of interest, and also lack of long-term follow-up measurements. So, in many of the studies that I've seen come out in the past years, these are still recurrent problems. But the field seems to be slowly improving. Still, overall, there's much to be gained from applying a more rigorous approach to studying psychedelic therapy.


Robert: You categorize problems in your study by easy problems, moderate problems, and hard problems. Let's talk for a second about conflicts of interest, which is one of the easy ones. What are your primary concerns about conflicts of interest in psychedelic research?


MvE: Well, the main risk is bias. That somehow, if there's a conflict of interest, there's an increased bias, or risk for bias, for reporting positive outcomes, and in the reporting of negative outcomes or adverse or serious adverse events. In the paper, we refer to review papers that have basically pointed out that studies, which had a conflict of interest, had a 5x higher likelihood of finding significant effects than studies without a conflict of interest. And, specifically in the field of psychedelic therapy, there's a risk for bias because of the huge investments that have been made by pharmaceutical companies who want to prove that these medicines work. Even for a nonprofit organization like MAPS, they have their agenda, for bringing MDMA therapy to society. That's really their primary aim. It's a kind of political aim, and there's a risk that the science is being used as a vehicle for achieving that aim.


Specifically, in the field of psychedelic science, I think there's a risk that every person working in this field, including myself, is enthusiastic about psychedelics because of positive personal experiences. And that's not a problem at all, but it might bring in motivated efforts for implicitly trying to prove that these medicines work effectively, whereas the data might not be that favorable. So, I think that's the main problem we try to address in this paper.


Robert: Is there a precedent for studies being done where so many of the researchers have personal experience with the substances being studied? I imagine cannabis might be one?


MvE: Well, I often make parallels with mindfulness-based interventions (MBI) that have followed the same trajectory and that have resulted in the field of contemplative science.


Whenever you go to a mindfulness scientific conference, you're surrounded by people who are meditation enthusiasts. Based on personal positive experiences with meditation, many researchers became interested in the topic. We have seen a similar hype in the field of mindfulness as we currently see with psychedelics. The mindfulness hype was peaking around 10 years ago when we saw more and more stories coming out that evidence-based approaches showed that MBIs were helping people with depression, anxiety, OCD, addiction, etc. Those trials actually suffered from similar problems as the trials that we see with psychedelics, including a lack of a proper control group, but also conflicts of interest, and, as a consequence, selective reporting of results. So, only now, we gradually see more and more nuance in the literature about mindfulness, pointing out that, for a group of people, MBIs can actually be detrimental and can lead to psychotic episodes or dissociation. In that sense, the field of psychedelic research appears already quite careful, and we see in the current literature, especially over the last year, an increased awareness of the risk potential of adverse effects.

Several important papers have come out, including both qualitative and quantitative data, pointing out that, under certain circumstances, people might actually become more suicidal following psilocybin therapy or there may be increased risk for abuse in the therapy room. These are very real risks that we should take that seriously. So, I think, especially because of the history of these fields, everyone is already super aware of the potential problems. I have reason to be more optimistic compared to other fields where very similar problems occurred.


Robert: Is the control group issue in psychedelic studies particularly difficult because of the nature of psychedelics?


MvE: Not particularly. I think with any intervention, be it cognitive-behavioral therapy (CBT), antidepressants, or MBIs, you have the same problem that, as soon as you apply the intervention, it will become immediately obvious to the participants what therapy they've been assigned to. As soon as you're doing something to someone, they will figure out what it is you're doing, or they try to figure it out. Then you have the breaking blinds problem. ("Breaking blinds", "breaking the blind" or "unblinding" refers to revealing the treatment that a participant is receiving. In a double-blind study, neither the participants nor the researchers know who is receiving the treatment and who is receiving a placebo. This is done to eliminate bias in the results.)


What is actually quite promising is that, in psychedelic therapy, you have a good way to control for the breaking blind problem. For instance, in Chicago, Harriet De Wit is setting up a study where they inform people that they may receive one of four substances, thereby increasing the uncertainty about what people will be treated with. Also, at Johns Hopkins, they are conducting more and more studies where they apply multiple dosing regimes to different groups of people. You can still expect that higher doses will be associated with a stronger dose-response relationship, thereby reducing the risk of the breaking blinds problem. It will be more difficult for people to figure out if they received 10 mg versus 15 mg of psilocybin, as the dosage is quite close. So there are quite elegant solutions for this. But, as we point out in the paper, those solutions are costly in terms of money. You need a lot of funding to be able to add all of these control conditions, but also costly in terms of all the infrastructure you need to do these things: multiple centers, therapists need to be trained, etc.


Robert: Your study highlights the issue of small sample sizes. How do you determine the ideal sample size for your studies to ensure meaningful and reliable results?


MvE: There are different tools available for doing this. The conventional way that people go about determining their sample size is a by conducting a power analysis. There are different software packages available that you can use for this where you basically specify your effect size of interest. Based on that, you can infer how many participants you need to be able to detect such an effect. Over the past 10 years, more and more tools have become available that are even more fine-grained for conducting a power analysis, including simulation studies where you simulate your expected data. If you expect, for instance, a mean difference between two mean groups and a certain standard deviation for different groups then, based on that simulated data, you can estimate how many participants you need to recruit to show a specific effect of interest. Online tools are available that can help you with this too.


"In my perspective, the future of psychedelic therapy may involve finding a niche for specific patient profiles that respond exceptionally well to these treatments."

- Michiel van Elk


Robert: Can you articulate your biggest concerns regarding psychedelic research, particularly in light of the challenges highlighted in your study?


MvE: Certainly, my foremost concern revolves around the potential for the hype surrounding psychedelics to create unrealistic expectations. Many colleagues and I, working in the field of psychedelic science, frequently encounter individuals in distress, individuals suffering from various mental disorders, as well as family members desperately seeking guidance on how to access psychedelic therapy. It's crucial to emphasize repeatedly that these substances are not yet widely available for therapeutic use, especially in regulated, above-ground therapy settings. There's a risk that people might invest all their hopes in this specific treatment modality.


In my perspective, the future of psychedelic therapy may involve finding a niche for specific patient profiles that respond exceptionally well to these treatments. We might be able to identify individuals based on their specific symptoms, predisposing factors, and the likelihood of benefiting from psychedelic therapy. However, I believe it's overly simplistic to conclude that within the next 10 or 20 years, every person suffering from a major depressive disorder, for instance, will universally benefit from psychedelic therapy.


Depression, for example, is an incredibly heterogeneous condition with various symptom presentations that can co-occur. Each depressed patient is unique, as is the case with individuals dealing with post-traumatic stress disorder (PTSD). While there may be some commonalities, there are also significant differences among them. Therefore, we need to scrutinize these distinctions, both at a theoretical level and through more rigorous research, to determine who stands to benefit most from psychedelic therapy. It's entirely possible that other patients may derive more benefit from established therapeutic approaches such as SSRIs (selective serotonin reuptake inhibitors or antidepressant drugs), CBT, or other tools already available in the therapists' arsenal.


Robert: Michiel, I like hearing your vision of where psychedelic-assisted therapies are heading. I wanted to go back for a moment and ask about the public exuberance around the potential of psychedelic-assisted. Do you think people are looking at this as an all-or-nothing proposition where psychedelics become the next preferred therapeutic tool and SSRIs are out? Or, if psychedelics are not successful, we'll go back to what we're using?


MvE: Well, I think it depends on who you ask. Many psychiatrists still see the benefits of their classical tool kit, including SSRIs and all of the pharmacological medicines that they already have. Then they see the potential for psychedelics next to this because these existing medications have many side effects and disadvantages, and maybe psychedelics can improve there.


Robert With all of the factors moving in one direction: we talked about the huge investments being made in psychedelic research, the media building high expectations, the growing desperation of people who have mental disorders that are highly resilient to existing treatments… does this sometimes feel like a runaway train that can't be stopped, or is there still time to establish some of the safety measures you propose?


MvE: No. I think that if you talk to the people in the field, you will witness a very high conscientiousness and openness to learn about how we can improve on the research design and quality. I am continuously in contact with people setting up these types of trials, and they're very open to suggestions that we make in the paper. But they also repeatedly point out that many of these things, for instance, reporting of safety, is already part of the medical ethical protocols and is already there. There are already a lot of checks and balances in the system. So, we're not there yet, but I am indeed optimistic that we can improve.


I think that maybe we need to take a step back and think more carefully about, if those substances are to be of benefit, then how exactly does this work? What is the process and what is the profile of patients that might benefit from these substances? I'm more hopeful about the results of MDMA therapy for PTSD. If you look at the most recent phase 3 studies that came out a couple of weeks ago, those results actually look quite good; patients really improve. And they improved more in the MDMA-assisted psychotherapy condition than the control condition. What I found really apparent, and is also apparent in previous studies with MDMA-assisted psychotherapy, is that the control groups also show dramatic improvement of symptoms. That's probably related to the fact that they are immersed with very intense psychotherapy where they spent hours and hours with their therapist and, even if they get a placebo, they still benefit a lot from that attention; this helps them to improve the relationship, improves their trust, makes them more open and more able to accept their emotions.


So, it's important to keep an eye out on the fact that the explanatory mechanism is still probably very much related to interpersonal trust and the psychotherapeutic approach in what we call in clinical psychology, common factors. Common factors underlie the experimental group and the control group and contribute to why people feel better. That's important to keep in mind. And, there's something else that intrigues me that we didn't spell out in the paper. If there's any prospect for psilocybin therapy to be specifically useful, I think it's primarily for people who cope with existential-related concerns. For instance, end-of-life anxiety.


If you look at end-of-life anxiety studies that have been conducted, for example, by Roland Griffiths,* who was the first to look into this topic, the results are good and promising. It seems that psilocybin therapy can cure people who suffer from depression related to fear of death. From a psychological point of view, when people are coping with their own existential threat but have their basic structure in place - a social network, safety, an income, etc.- their life should be okay. But, when your worldview changes in the face of this existential threat and you develop depression, I think that psychedelics can bring insight and can be of benefit. Especially compared to other types of depression that may be more grounded in acute symptoms like sleep deprivation, alcohol abuse, lack of physical exercise. Psychedelics in and of themselves are not going to help treat the depression symptoms. That requires an intense program of coaching, CBT, habits change, etc. In the end, psychedelics might find their niche in mental health care, but always as part and parcel of a bigger toolkit of interventions that we can throw at people to help them and cure them.


* Thanks to Dr. Roland Redmond Griffiths (July 19, 1946 - October 16, 2023) for sharing your life and hints for improving our own.


Robert: The paper discusses the lack of standardized training for therapists involved in psychedelics. How do you ensure that therapists involved in your studies possess the necessary skills and qualifications to provide effective and ethical psychedelic-assisted psychotherapy?


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Michiel doing a TED Talk

"I am indeed optimistic that we can improve."

- Dr. Michiel van Elk


MvE: I think the best practice someone can get is guiding people through psychedelic experiences. To provide this skill in a standardized way is really challenging. A psychiatrist or psychologist can be formally trained by MAPS and then participate in a clinical trial to have a first-person experiential session with MDMA. This is very costly, time-consuming, and they still get very limited experience.


I’m always impressed when I talk to retreat facilitators and organizers. They sit on this wealth of knowledge for tens of years in dealing with all types of problems that you can think of. How do you translate that knowledge into clinical practice? I think that’s the Holy Grail. In the paper we talked about how people applying psychedelic therapy need to be licensed. They need to have their training and education in place for knowing how to deal with those that are very vulnerable. They need to know how to deal with serious adverse events and a professional training, for instance, studying psychology can help you prepare better for this. That's the more formal part, but the hands-on part is a different challenge.


Something else that you see happening, of course, is looking at other methods for inducing altered states. For some of the MAPS trainings that have been conducted in Europe, it was not possible for the therapists to have an experiential session with MDMA themselves, but then they engaged in breathwork, for instance, and that also helps them to experience and learn to deal with a person being in an altered state of mind. So, there are different ways this can be done and they need to be explored more.


Robert: I was looking at a project being implemented in Colombia which provided psychotherapy for women that were victims of violence in two conflict areas. Understanding that the need is so great to treat and support victims of trauma in Colombia, the project sought to train survivors, who had successfully gone through therapy, to be LPCWs (lay psychosocial community workers) believing that others from the community could be helpful especially considering the dearth of mental health care workers in these areas. If psychedelic-assisted therapies are approved for use on a wider scale, is this a viable means for fulfilling what is bound to be a tremendous need for support?


MvE: No, I think it’s going to be hard mostly for legal purposes. I think it will take a long time before these substances are approved in countries like Colombia. Then if they are approved, it's still only in a very limited context.


We need to think globally about how we prepare for that situation. We need international training programs that will prepare people from all backgrounds and cultures to be able to work with these substances.


Robert: No doubt. Transparency regarding funding sources is crucial. Can you elaborate on how you disclose and manage potential conflicts of interest within your research team to uphold the credibility of your findings?


MvE: Yes, we’re in a somewhat fortunate situation that we receive funding from the Netherlands Organization for Scientific Research. That gives us a lot of freedom and also independence, so there are no strings attached to that funding. There’s not an agenda whatsoever for showing that psychedelics work. Whenever we publish, we acknowledge the funding but we’re not bound to reporting certain findings or whatever.


Simply reporting that a study has been funded is already a starting point. Sometimes those COIs are hidden behind the paywalls and should be made more easily accessible so that everyone can read.


I’ve also started thinking more and more about being even more transparent about other conflicts of interests that could come into play. Like personal disclosures that could bias the results. A topic that I find really intriguing is self-experimentation among psychedelic researchers. It’s a topic that at conferences or workshops is discussed all the time. Everyone talks about their own personal experiences, and everyone in the field has a lot of experience with taking psychedelics. But it’s never discussed within the context of a research paper. Why is that? It’s even considered not done because it may bring bias or people might be afraid of being the next Timothy Leary. At the same time, it would be important to share some of that information, specifically if it might bear relevance to the research design of the study (e.g., how was the feasibility of the study piloted) or the framing of the results.


So, it might be interesting to consider simply including not just COI statements but a personal disclosure statement about prior experiences and prior beliefs that people hold. At least it may be relevant for outcomes of a certain study. So I think we can be even more transparent and also be more creative in thinking about what factors we want to include in the reporting of our studies.


Robert: What came first, your psychedelic research or your experience with psychedelics?


MvE: For me, my experience with psychedelics came first. But my interest in this topic follows naturally from my previous research interests, which were more on the topics of religion and spirituality. So psychedelics fit naturally with that interest.


Thinking of that and personal disclosures, a weird example that came to mind from the field of religion and spirituality was research on faith healing. There’s a lot of research on remote intercessory prayer (praying to your deity of choice on behalf of someone else's health), trying to see if you pray for an experimental group and do not pray for a control group, if the experimental group fares better. These studies have even been conducted as randomized control trials. But some of these studies disclosed belief systems of the authors by, for instance, saying that they would like to thank God for healing the experimental group. That is a clear example of bias that should indeed be disclosed.


Robert: Thank you so much, Michiel, for taking the time to speak with us. This has been excellent. You're a calming voice amongst the clamor surrounding psychedelic science. Hopefully, the practical words of wisdom from professionals like you can help us better interpret the hype from wannabe messiahs.


If you enjoyed this blog article, please consider sharing it with a friend. Interested in writing a blog article? Contact robert@thepsychedelicblog.com.



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