Overuse of medication for chronic migraines can lead to medication overuse headaches, a paradoxical condition in which the medications intended to relieve migraines actually contribute to their persistence. Mindfulness-based interventions (MBIs) have shown some efficacy as a non-pharmacological adjunctive treatment for migraines and may help reduce reliance on medication.
Recent studies have advanced knowledge of how mindfulness may influence the biology underlying migraine headaches. One study found MBIs can alter functional connectivity between the brain’s salience network, insula, and sensorimotor facial area—regions associated with pain perception and appraisal.
Other studies suggest MBIs may affect serotonin transporter (5-HTT) gene epigenetics or help normalize serotonin levels. These findings are relevant because serotonin and dopamine play key roles in migraine pathophysiology. However, no studies had previously examined the relationship between changes in brain functional connectivity and changes in neurotransmitter system activity.
Fedeli et al. [Cephalgia] investigated changes in brain functional connectivity associated with serotonin, dopamine, and norepinephrine receptors in chronic migraine patients with medication overuse headaches who participated in a mindfulness training or control group.
The researchers randomly assigned 34 Italian chronic migraine headache patients with medication overuse headaches (average age=50 years; 88% female) to either a treatment as usual (TAU) control or TAU+MBI. The control condition involved withdrawal from overused medications, prescription of antidepressant or neuromodulator medications, and education on healthy lifestyle.
The MBI consisted of six weekly 90-minute guided sessions involving body scan and attention to breath and bodily sensations. From the third session onward, MBI participants were instructed to engage in audio recording-guided home practice 7 to 10 minutes daily.
Patients underwent resting state fMRI brain scans at baseline and one year follow-up. Neurotransmitter-specific functional connectivity maps were generated using open-source PET scan data from healthy participants to approximate serotonin, dopamine, and norepinephrine receptor systems.
At one-year follow-up, both treatment groups showed significant clinical improvement, but the TAU+MBI group improved significantly more than TAU. The TAU group had a reduced average headache frequency from 19 to 11 per month compared to a change from 20 to 8 per month in the TAU+MBI group.
At baseline, there were no group differences in neurotransmitter systems. After one year, the TAU+MBI group exhibited a larger increase in connectivity in serotonergic systems in the caudate and accumbens nuclei than the TAU group. Additionally, the TAU+MBI group displayed a relatively greater degree of increased functional connectivity in dopaminergic systems in the right insular cortex compared to the TAU group. However, these brain changes were not significantly correlated with the degree of clinical improvement.
The early pilot study suggests that a mindfulness training program can be associated with reduced headache frequency in patients with medication overuse headaches and can correlate with brain connectivity in serotonin and dopamine receptor systems. These systems are involved in processes such as pain perception, reward, addiction, and emotional regulation.
Nevertheless, the study should be considered preliminary due to its small sample size and reliance on neurotransmitter receptor maps derived from healthy individuals rather than direct PET scans of the study participants themselves.
Reference:
Fedeli, D., Ciullo, G., Demichelis, G., Medina Carrion, J. P., Bruzzone, M. G., Ciusani, E., Erbetta, A., Ferraro, S., Grisoli, M., Guastafierro, E., Montisano, D. A., D’Amico, D., Raggi, A., Nigri, A., & Grazzi, L. (2025). Neurotransmitter-related functional connectivity changes in serotonin and dopamine systems after mindfulness in medication overuse headache. Cephalalgia.
Link to study
