Liliana Galindo, 40, compares psychedelic therapies for mental health to surgery. “It’s a paradigm shift. Before, we used to administer daily medication, focused on treating symptoms that sometimes caused side effects and are expected to be taken for years. This type of therapy requires a significant initial investment because, in addition to the medication, you need a therapist, a psychiatrist, and a nurse — all working together — but over a short period, maybe about three months, to provide intensive treatment that seeks to address the root cause of the illness.”
Galindo’s experience shows that the effort is worth it. “In many cases, there is complete improvement,” she says. Galindo continues the analogy: “In surgery, anesthesia is used to tolerate the physical pain, the surgeon intervenes and cleans the wound, and then the body heals. Here, we use a substance to open and tolerate the emotional pain, to see the wound, process it, and then the person continues to improve, like in a postoperative period.”
Psychedelic drugs are back in fashion in medicine, after decades of being sidelined due to the bad reputation and illegality brought about by their recreational use and association with counterculture. In 2019, the use of esketamine, an analog of ketamine, was approved to treat severe depression, and in recent years a growing number of studies have showed the potential of MDMA, or ecstasy, for post-traumatic stress disorder, and psilocybin, the active ingredient in hallucinogenic mushrooms, for depression.
Galindo, who is an assistant professor of psychiatry at the University of Cambridge, a psychiatrist at the Cambridgeshire and Peterborough NHS Foundation Trust, and founder of the Cambridge Psychedelic Research Group, visited Madrid a few days ago to participate in Psymposium, a forum that promotes scientific and ethical progress in mental health, neuroscience, and psychedelic research.
The researcher, who began her career in Spain alongside Magí Farré and Víctor Pérez-Sola at the Hospital del Mar in Barcelona, speaks about substances that represent a paradigm shift in the pharmacological treatment of mental health — and in the very understanding of the mind — but which will also require a new way of designing studies to measure their true effectiveness.
Question. Does the fact that many of these substances have been used for fun affect expectations about them or the possibilities of using them?
Answer. Humans have used substances as tools to achieve different states of consciousness for thousands of years. In the Americas, many Indigenous communities have used psychedelic substances, such as ayahuasca. Some people use them for spiritual reasons and others for recreational reasons, but the medical model has fundamental differences. It is done in a supervised manner, with a substance whose properties are precisely known and in the right amount, because we already know that the dose makes the poison — or, in this case, the remedy.
Q. How does it work?
A. In general, the person must have three types of sessions. Preparatory sessions in which they meet with a therapist, establish a series of goals, and learn about the person’s past, in order to understand the context and be able to make a decision.
Information should also be provided on what to do if the patient feels anxious or has memories that cause significant distress. During these preparation sessions, they can practice exercises to calm themselves during these moments.
After these preparation sessions, comes the session in which the substance is administered, which must happen in the company of a therapist. This can’t be just any therapist, but someone trained in these interventions, which are quite different from those of conventional psychotherapy. Here, the therapist doesn’t intervene as much as in other conventional sessions; they’re more like a co-pilot, supporting the person, who is the one who decides which path to take.
In the case of post-traumatic stress disorder, for example, the patient is helped to connect with those traumatic memories to revisit and process them, and that is something the person does alone.
And after that session come the integration sessions, which are usually done the day after. These sessions are key because, with psychedelics, it has been shown that one of the reasons they work is neuroplasticity. They can create changes at the inflammatory and neuronal levels, and even in dendritic connections, and these changes appear to be key in memory reconsolidation. It’s important to take advantage of this window of greater neuroplasticity after taking the substance so the person can process what happened during the four, six, or more hours — depending on the substance, that the experience may have lasted — in order to make sense of what happened. In this case, also with a supportive therapist.
Q. What do these substances do in the brain to give them these potential beneficial effects?
A. In the case of empathogens, like MDMA, they have structures that are sometimes quite similar to those of serotonin or dopamine. On the one hand, they increase serotonin, dopamine, aand norepinephrine, and produce feelings of well-being and connection. But they also seem to produce an increase in oxytocin. And this oxytocin, which is the attachment molecule, plays a very important role in the reprocessing of traumatic experiences.
If you think about oxytocin, one of the times it’s secreted a lot is around childbirth and during breastfeeding, when the whole bonding process takes place. But it also helps overcome many of the memories and traumas surrounding labor and birth. It can be traumatic at times, but we still do it more than once, twice, or three times. There’s a point in that reconciliation of memories where oxytocin plays an important role.
Q. What about classic psychedelics, like psilocybin?
A. The specific action is on one of the serotonin receptors, which are the 5HT2A. This serotonergic action changes our brain connections, performing a kind of reset to previous cognitive patterns.
There are many mental illnesses that involve rigid cognitive patterns: rumination, when we feel anxious and go over the same thing in circles; in depression, we have an idea or conviction that something is wrong, circular thoughts that are difficult to escape; we also see this in obsessive-compulsive disorder or eating disorders, with very circular beliefs about the body.
These substances seem to reset those ideas, and changes are seen fairly quickly, like after psilocybin sessions, where a broader therapeutic range has been observed. It has shown significant improvements in treatment-resistant depression, and even in OCD and eating disorders, there is preliminary evidence suggesting they can improve.
Q. If psychedelics facilitate plasticity in the brain, just as they help to undo the rigid thought patterns that cause depression, can they also create new problems?
A. Of course, this needs to be investigated. Side effects have been seen, especially when doses are not supervised or the setting is not appropriate. In controlled settings, it seems safe. But we need to better understand what doses, for whom, and how.
Q. Now that psychedelics are becoming more accepted and even trendy, there’s sometimes a perception that they’re harmless. What risks need to be monitored with these substances?
A. They’re not harmless, but neither are psychedelics, nor any treatment. It all depends on the dose, who takes it, and how it’s taken. The biggest danger, and what has given many of these substances a bad reputation, is that they’ve existed in an illegal market, where people believe they’re taking things they’re not. That’s why, in clinical settings, the first thing monitored is the dose. There’s no option to increase it because “it feels good.”
And, of course, the fact that not all psychedelics are good for everything and everyone, even though they have enormous therapeutic potential.
Much of the focus of research now is trying to understand, of all the substances that appear to have therapeutic potential, which types of people will benefit and which won’t. We need to understand the contraindications and which people might benefit, for example, from therapy with MDMA, psilocybin, or ayahuasca. They’re completely different.
Part of the research is trying to understand how the effects of substances change personal history, the illness we’re treating, even family history, whether there are other members who have had mental illnesses or have previously had adverse reactions to substances of this type.
Q. You also work on psychosis — on detecting in advance those at risk, to prevent or reduce its effects.
A. Psychosis refers to when someone experiences changes in their perception of reality. A person begins to have an idea that becomes so strong that, in a way, our brain tries to process all the information it receives as confirmation of that idea, or tries to associate it with that idea and relate unrelated things. And suddenly, it’s as if that idea steals all our energy, all our attention in life. That belief begins to be the most important thing. It’s usually associated with a very strong fear, what we call paranoia.
There are different types of content: the person may believe they’re being followed, or that they have a power, a superpower, or that they’re on a mission, but suddenly they begin to see that everything is connected to that idea. Whether it’s: “I’m being followed,” “my neighbor is an alien,” whatever the idea may be.
These are what we call delusions. Separately, other people may experience what we call hallucinations. The most common is hearing voices or things that aren’t there. Some people can also see things, but this is less common. In addition to these changes in perception and information processing, they are accompanied by enormous fear.
Q. What else is known?
A. In most cases, it begins before age 20 and is more common in men. We also know that there’s a second peak of psychosis presentation that usually occurs in women around hormonal changes during menopause. This isn’t talked about much, and there’s still a lot of stigma attached to it, but it exists.
What we know is that when people are experiencing these changes, the most important thing is to be able to detect them early. At that moment, an inflammatory process is creating changes in the brain that can lead to long-term cognitive or memory changes.
Q. Can you intervene?
A. Worldwide, the first early intervention model was developed in Australia. For at least three years, the person will be seen very frequently, almost weekly, by doctors, psychologists, and occupational therapists; they work with the family, the school, and the workplace. Everything is focused on helping the person return to their life as it was before they became ill.
What has been seen is that, if this change is achieved in the first three years, and above all, most importantly, if the person manages to recognize this episode as something abnormal, understand why it is better to continue treatment, detect early symptoms of relapse (each person has their own), and return to their previous functioning, the disease can be prevented from deteriorating in the medium or long term.
We used to believe there was no way to stop the progression of psychosis, or that everyone would necessarily end up severely deteriorating in a mental hospital. We now know that’s not the case. But we must act early and work hard on treatment and education for the individual and their family.
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