Cognitive impairment, dementia, Alzheimer’s and psychedelics: 5 Questions for researcher Albert Garcia-Romeu
Garcia-Romeu discusses the potential of psilocybin to address issues associated with cognitive decline, and noteworthy preliminary observations from his research.
Currently, researchers are investigating psilocybin’s potential in treating a variety of conditions, including depression, anxiety, alcohol use disorder, and obsessive-compulsive disorder. While the drug’s mechanism of action is not yet fully understood, some researchers have posited that psychedelics could stimulate neural growth, and improve the brain’s ability to adapt and form new connections — which could, in turn, be a potential treatment for people experiencing cognitive impairment, including dementia.
Studies with animals, like octopuses and rodents, suggest psychedelics might induce neuroplasticity, the brain’s ability to adapt and grow. Still, research in humans investigating the link between cognitive decline and psychedelics is in its infancy. Albert Garcia-Romeu, an assistant professor at Johns Hopkins School of Medicine, is running a clinical trial using psilocybin to treat depression in people with mild cognitive impairment and early-stage Alzheimer's disease. The Microdose spoke with Garcia-Romeu about the potential of psilocybin to address issues associated with cognitive decline, and noteworthy preliminary observations from his research.
When people experience neurodegenerative disease, what is happening physiologically — and what are the existing treatments to address that?
Over time, people experience physical decline; for the most part, as you get older, things start to break down, and the same goes for the brain and for cognitive processes. You start to see forgetfulness, or people aren’t on the same ability to function on the cognitive level they were able to in earlier adulthood. There's a natural level of decline that's happening over time but some people develop mild cognitive impairment, where there's a level of memory and cognitive functioning problems that start to impact people's ability to engage in the activities in daily life. They might forget to turn the stove off after they finish cooking, misplace things, forget names, and have trouble remembering words. As that gets worse, it can progress to some form of dementia, and there's a whole plethora of forms of dementia and related conditions. Alzheimer's disease is one most people have heard of, and we know that is related to the accumulation of tau tangles and beta amyloid plaques in the brain. The actual nuts and bolts of how that works is still quite mysterious. What we know about it, and our ability to do anything about it, is very limited.
Some medications to treat Alzheimer’s were approved in the 90s, but they didn't do much. Two have been approved in the last few years; one is associated with severe brain bleeds, and for the other, members of an FDA advisory committee consulted about the drug resigned after it was approved. The cost of these drugs are in the realm of $30,000 to $60,000 a year, and their overall “benefits” are questionable. Yet we’re facing a huge public health issue; modern medicine has allowed people to live longer and as people get older, the more Alzheimer's disease or dementia is popping up. In many cases it’s more than just forgetting people's names or remembering words; people can go into much more severe decline, including personality changes, complete inability to function, and ultimately death.
You’re studying how psilocybin can treat depression in people with mild cognitive impairment. Does depression occur as a result of these cognitive difficulties or is there some other physiological phenomenon that might be at the root of both cognitive impairment and depression?
That's a great question, and we don't really know the answer. Anywhere from a third to about a half of people that are diagnosed with some sort of dementia are also dealing with some kind of neuropsychiatric issue or mood and anxiety conditions. Those are pretty common overlapping factors and the exact directionality is not 100% clear.
There seems to be some sort of chicken or egg question at hand. For instance, people who have had incidents of major depression before they get older seem to be more likely to develop Alzheimer's or related dementia later on, so it's possible that your 20s, 30s or 40s might be setting the stage in your brain for later decline.
But then, there's also the possibility that decline in itself is demoralizing or depressing. Often that comes with its own set of existential questions and problems that people have to deal with because you're not going to know exactly what's going to happen when you find out that you're having these problems. Worst case scenario, it could be pretty bad. And given that we don't have a lot of good treatments for it, cognitive decline can set off other psychological issues where people feel concerned, anxious or depressed about that diagnosis.
There’s a lot of excitement about the potential for psychedelics to reopen critical periods, or improve neuroplasticity. If psilocybin is an effective treatment for cognitive decline, what would success look like? For instance, do we expect it could slow or stop the trajectory of decline, or even reverse decline?
If you were lucky, you would see improved quality of life and general well-being. But we're talking about just putting the brakes on the process of decline, not stopping it or reversing it. You have to really think about all this in context: when you look at Alzheimer's disease and when beta amyloid plaques start forming, in most cases you're seeing that happen as early as ten or more years before people have any sort of cognitive impairment. Your brain is building up toxic plaques for years and years before anything even happens. So the idea that the possibility that something you do after you've experienced a decades-long process of cognitive decline could reverse things? I would say that’s overly optimistic.
That's also borne out by the treatments out there now, the new and controversial antibody treatments I mentioned earlier. Those are the best drugs that have ever been found for treating Alzheimer's disease, and even then, many people experience severe side effects while the benefits are very modest. In those cases the benefits are not an improvement in cognitive function, per se; it’s more a lessening of the decline. People are so desperate for anything that could help that they'll try it.
I have personally treated about a dozen people with mild cognitive impairment or early stages of Alzheimer's with psilocybin, and I have seen how challenging their situation is. It’s not just what they're dealing with from the cognitive decline standpoint, but all the other psychosocial factors that they're struggling with. There's a loss of social connectedness. Their friends are dying, their spouses are dying or dead. They're no longer working, so many feel a loss of purpose. They can no longer drive or physically do the things they once did. When you look at all that, I think the best you can really hope for would be some kind of low level enhancement of quality of life, and potentially some improvement in mood or cognitive function.
Are there special considerations for the ethics of recruiting participants with cognitive decline for psychedelic studies, or in the logistics of giving these participants psychedelics?
There's a whole area around this; dementia is a disease model people have been studying for years and years. We have safety measures in place to make sure participants understand what they're consenting to, like quizzes or other types of testing to assess their level of comprehension. For instance, we might use validated measures like the Montreal Cognitive Assessment or the Mini-Mental State Exams, and if participants score below a certain cut-off, that indicates a moderate or severe cognitive impairment that might suggest they’re not fit to provide informed consent on their own. Still, there's lots of work done with folks who have more severe forms of dementia or cognitive impairment, and in those cases, a care partner — a family member, spouse, someone who’s closely involved in their care and treatment — might be a part of the consent process. We actually involve care partners in our study as well, because we're also examining how psilocybin treatment impacts the quality of life of participants’ care partners. After all, they are also dealing with their own set of issues that come along with taking care of a loved one who's experiencing cognitive decline.
On the logistics side, the biggest thing is increased fall risk. This is common with older adults across the board regardless of cognitive function, and in general, with psychedelics, it's possible that people can lose their balance and become disoriented. So when older people with cognitive impairment are under the influence of psilocybin, they can become more uncoordinated than usual. They can have visual perceptual disturbances, which can make it harder to navigate the world. So that's something we're extra careful with. Like when participants need to go to the bathroom, a facilitator needs to go with them and make sure that they're able to get in there, then get back to the couch.
Your trial is still in progress, but is there anything surprising you’ve noticed about the data you’ve collected so far?
I've done around 140 dosing sessions with a wide range of groups, from priests to people with alcohol dependance. You almost never hear somebody say, “I don't remember what happened.” Sometimes people say that there are parts of the day that were a little scrambled or they have a hard time remembering clearly. But the most interesting thing I've noted in this study is that the majority of participants have come back after their dosing session and said they don't remember what happened. That's very unusual. And I think it speaks to potential differences in outcome for this group compared to others we have studied, like people with major depression. It’s possible that difference in memory and experience influence the drug’s effects.
Another thing that’s surprised me is how hard it's been to get people into the study. We've been working on recruitment for a couple of years now, and COVID didn't do anybody any favors, but we’ve had difficulty getting people into the lab for the study. People over 60 are more likely to have mild cognitive impairment or an Alzheimer's diagnosis, and that population also seems less aware of the work that we're doing and less enthusiastic about it. There seems to be a sizable generation gap in terms of public perceptions of psychedelics; in one recent poll, 55 percent of millennials said they are interested in trying psychedelic treatments for mental health issues, but only 10 percent of Baby Boomers. By and large, the people who have participated in our study have been connected to us because their adult children, mostly millennials, read about what we're doing and encouraged their parents to participate.
This interview has been edited and condensed for clarity and length.
