Compassionate use of psychedelics
Abstract
Greif, A., & Šurkala, M. (2020). Compassionate use of psychedelics. Medicine, Health Care, and Philosophy.,
Link to full text
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Compassionate use of psychedelics Read More »
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 »
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 »
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
Structure of a Hallucinogen-Activated Gq-Coupled 5-HT 2A Serotonin Receptor Read More »
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
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
Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders Read More »
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
Whole-Brain Models to Explore Altered States of Consciousness from the Bottom Up Read More »
The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA’s effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.
Oeri H. E. (2021). Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy. Journal of psychopharmacology (Oxford, England), 35(5), 512–536. https://doi.org/10.1177/0269881120920420
Ido Hartogsohn on the influence of society on the psychedelic experience Read More »
You founded the first licensed training program for psychedelic therapists. How did this come about ?
The genesis of this program came about in 2014 at a Heffter Research Institute board meeting, where one of the trustees of our college heard the dire need for psychedelic therapists to be trained.
Our university has been training about 250 therapists a year in 6 different programmes for over 30 years. Stan Grof, Ralph Metzner and other psychedelic researchers have been teaching at CIIS for decades. CIIS trustees gave us seed money for a 3-year grant. I was the founder and creator of the programme, and the opportunities for this were very rich.
We wanted to bring in indigenous ways of knowing as well as the approach typically used in the research protocols for both psilocybin and MDMA.
What are the challenges you faced in this process ?
Well, we were creating something in a vacuum. There were no guidelines yet for how to do this, because no-one had done it before. For a year, I consulted with researchers, underground and above-ground therapists, and in related areas such as hospice care centres and emergency rooms, on how to work with people in altered states.
To devise the programme, we drew from anthropology, clinical and transpersonal psychology, psychoanalysis and ceremonial uses. The challenge was to try to integrate all these in the best possible way.
However, we chose to emphasise the research approach for now, because of the need for therapists to be in FDA-approved clinics. This is a compromise we made, but the upside is that now our graduates get hired by these research entities and they’re opening clinics that will be ready to use MDMA and psilocybin in the next couple of years.
Things seem to be progressing quite fast these days. Are you sometimes concerned they may be going too fast?
I’m concerned about the decriminalisation movements in the US. They’re going quicker than I’m comfortable with. The general public is not sufficiently aware of the hazards and the benefits of the use of plant medicines. Even physicians and nurses don’t know enough, and neither do school teachers.
So we’re working on scaling up our programme to include the general public and give them information online for free: interactions with medications, incompatibilities with certain psychological difficulties, how parents can talk to their kids about psychedelics, etc. I’m concerned there might be another backlash like we had in the sixties if these medicines are not used responsibly.
My other concern is that we’re training only 75 people a year, about 300 so far. MAPS has only trained about 250. We need thousands of therapists trained. I’m concerned that when the medicines get rescheduled, there won’t be enough therapists, with resulting insufficient access to the medicines for patients. So we’re looking to scale it up and develop affiliations with other universities.
What have you taken away from this whole adventure so far?
I’ve been delighted to witness the integrity of the therapists and medical doctors wanting to come into this space. They want to see healing happen, they’re concerned about what’s happening on the planet in terms of politics, genocides and global warming.
They know that psychedelics are not the only way for people to heal, of course, but the kind of therapy we can do is augmented tremendously by the use of plant medicines. I see them changing psychiatry and psychology for nothing but the good.
On average, the professionals who apply for the programme have 15 years of licensed practice, so they’re quite experienced in their work. Some were retired medical doctors who reactivated their license in order to do this work. I also witnessed our students building community with each other, creating associations, building salons, and it’s very exciting to see this flourish across the United States, into Canada, South America and the EU. I realised once again how desperate people are for community. And finally, it’s been wonderful to meet the new generation, I’m very happy to pass the hat to younger people.
Dr. Phelps’ talk at ICPR 2020 will be titled: “Training future psychedelic therapists”
Janis Phelps on training the first psychedelic therapists Read More »