The World Health Organization has designated 10th October as World Mental Health Day. In Flanders, this date marks the pinnacle of a ten-day period dedicated to mental health. What does this have to do with party drugs? More than you might think, explains VUB Professor Dimitri De Bundel. "Further research is still needed, but substances like MDMA and psilocybin could potentially be used in the future to treat mental health conditions."
Domestic violence, sexual abuse, serious traffic accidents, war trauma: post-traumatic stress disorder (PTSD) can have many causes. And serious consequences. PTSD sufferers relive traumatic events through flashbacks, experience feelings of guilt or shame, have difficulty sleeping, suffer from nightmares, or may suddenly have unprovoked outbursts of anger. The standard approach is psychotherapy, possibly combined with medication. These are usually conventional antidepressants, the so-called selective serotonin reuptake inhibitors (SSRIs). This works for many PTSD patients, but not for everyone, says Dimitri De Bundel. "For about a third of patients, treatment with psychotherapy and antidepressants is ineffective. And in recent decades, there haven't been many new medications for PTSD on the market. This is why alternative or complementary therapies have long been sought. Non-invasive brain stimulation with magnetic pulses or electrical currents is one avenue of research. Psychedelics are another. In recent years, Nature Medicine has published promising articles on MDMA-assisted psychotherapy for the treatment of PTSD."
The idea of using MDMA therapeutically is not new.
Dimitri De Bundel: "The molecule was first synthesised in 1912. In the 1970s, it was experimented with as a support for psychotherapy. In the 1980s, MDMA became popular in the club scene as the active ingredient in the party drug ecstasy. Over the past 15 years, research into its therapeutic potential has resumed."
What is MDMA and what does it do?
"MDMA is an amphetamine derivative with psychedelic properties that acts on serotonin, noradrenaline, and dopamine transporters in the brain. Its effects vary. Many users experience altered states of consciousness and a sense of euphoria. Additionally, the drug can induce feelings of empathy and connection, likely because it also stimulates the release of the 'cuddle hormone', oxytocin."
"One theory is that under the influence of MDMA, people look at themselves and others with more compassion and openness"
And how does that help in treating PTSD?
"Some studies have shown positive effects, but we don't yet fully understand the mechanism. It's too early to make broad claims. One theory is that people under the influence of MDMA are more compassionate and open towards themselves and others. This could, for example, strengthen the bond of trust with a therapist, making it easier to talk about painful issues."
MDMA also affects the amygdala in the brain?
"The amygdala is a brain region involved in processing emotions. MDMA might amplify positive emotions and make negative memories less distressing. This effect of MDMA is associated with changes in activity in the amygdala and other parts of the brain. It could assist in processing traumatic experiences."
Dimitri De Bundel
How is MDMA thought to be used in treating post-traumatic stress disorder?
"It's referred to as MDMA-assisted psychotherapy. After preparatory therapy sessions, the patient takes a dose of MDMA. Two trained therapists guide the patient in recalling and processing traumatic memories, while also monitoring cardiovascular and other side effects. Following the initial MDMA session, three therapy sessions are held—so-called integration sessions—to discuss and process the memories and emotions that emerged. This cycle is repeated three times, totalling three experimental sessions with MDMA and nine integration sessions over about three months. It's quite intensive."
What was the structure of the studies?
"One study involved 91 patients with severe, chronic PTSD who had not responded well to conventional therapy. The patients were divided into a group receiving MDMA-assisted psychotherapy and a placebo psychotherapy control group. Just over 30% of patients in the MDMA-assisted group went into remission, meaning they no longer met the criteria for PTSD. The percentage of 'responders'—those who benefited—was even 80%. In the placebo group, those figures were much lower: 5% went into remission, and 50% felt some improvement. A second study with 104 patients with moderate to severe PTSD found that 46% of the MDMA group went into remission, compared to 20% in the placebo group."
Has the MDMA approach been compared with the standard treatment, i.e., therapy and/or antidepressants?
"Not yet, and that's a point of criticism. Ideally, you'd want to prove that the new treatment is more effective than what's currently available and that the costs don't become significantly higher. More research will be needed before the US FDA or its European counterpart, the EMA, can approve the treatment."
MDMA isn't the only psychedelic being explored as a potential aid in psychotherapy. Psilocybin is thought to help with depression.
"Psilocybin is the active ingredient in magic mushrooms. In a clinical study, psilocybin performed as well as escitalopram, a selective serotonin reuptake inhibitor, in treating long-term moderate to severe depression, potentially with fewer side effects. This isn't surprising, as psilocybin involved only two doses spread over three weeks, whereas antidepressants are taken daily for extended periods."
How does that work?
Does the active ingredient truly alter the brain, or does the psychedelic experience itself help lift people out of depression? "That's still up for debate. Brain scans do show long-term changes in brain network activity. But whether this is responsible for the antidepressant effect? One idea is that a psychedelic experience temporarily frees people from entrenched patterns like obsessive rumination, a negative self-image, or depressive thoughts. This state should then be reinforced with psychotherapy."
"The EU has just awarded 6.5 million euros for research into treating psychological distress in terminal illnesses using psilocybin"
In your lab, you use mouse models to study what happens in the brain. Can mice, like humans, hallucinate?
"When you administer psilocybin to mice, you definitely see an effect on the activity of brain cells. A few years ago, we published a study on the effects of a synthetic psychedelic, dimethoxy-4-iodoamphetamine. When we administered it, we observed an effect on the serotonin 2A receptors in the amygdala in the mice. The result was that the animals no longer displayed fear. But how they experience that? And whether they, like humans, see or feel strange things under the influence of psychedelics? That's hard to know."
Are you planning any follow-up research?
"The EU has just awarded 6.5 million euros for research into treating psychological distress in terminal illnesses using psilocybin. We are going to investigate something else: the effect of psilocybin on neuroinflammatory processes and neurogenesis—meaning the formation of new nerve cells. The hope is that psilocybin or its derivatives could play a role in treating neurodegenerative conditions such as Alzheimer’s disease."
Does a researcher need to use psychedelics themselves to understand what they’re talking about?
"I don't think so. Out of curiosity, I once participated in a truffle retreat. Interesting, but it doesn't help to understand the scientific mechanisms."
Who is Dimitri De Bundel?
Dimitri De Bundel is an associate professor at the Faculty of Medicine and Pharmacy at the Vrije Universiteit Brussel. He graduated as a pharmacist, earned a PhD in Pharmaceutical Sciences at VUB, and completed postdoctoral training at the Karolinska Institutet in Sweden and the Institut GĂ©nomique Fonctionelle in France. Dimitri is a member of the Experimental Pharmacology research group.
*This is a machine translation. We apologize for any inaccuracies.