Effects of Meditation on Dopamine, Glutamate and GABA Among Long-term Skilled Meditators in Sri Lanka

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Thambyrajah, Sunesha Arella Perera, Shiroma M. Handunnetti, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7561502/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives Studying the effects of meditation on neurotransmitters will shed light on the neurobiological basis and correlated neuroplastic changes. The current study aimed at comparing dopamine, glutamate, and GABA levels in blood in a group of long-term-skilled meditators with a one-on-one matched control group to explore the association of Buddhist meditation practices on these three neurotransmitters in one cohort. Methods A comparative analytical laboratory-based study was conducted on long-term skilled meditators (n = 30) and a non-meditator control (n = 30) group. Venous blood was collected from each participant to determine the neurotransmitter concentration. The neurotransmitter levels in blood were obtained using enzymatic immunoassay (ELISA). Results There was no significant difference in socio demographic factors and habits between the long-term-skilled meditators (LTSM, age = 42.23 years ± 8.99) compared to controls (age = 42.2 ± 9.04). GABA levels were significantly higher in LTSM’s with a mean concentration of 67.92 ng/ml (± 2.39 SE) compared to 61.21 ng/ml (± 1.37 SE) in the controls (p = 0.006). Similarly, the dopamine levels were also significantly higher in the LTSM compared to controls (LTSM, 134.8 ng/ml ± 18.2; Controls 94.7 ng/ml ± 15.5, p = 0.019). Glutamate levels were significantly lower in LTSM’s compared to controls. (LTSM, 6.0 ug/ml ± 0.49; controls, 7.3 ug/ml ± 0.54, p = 0.008). Conclusions Meditation alters the levels of neurotransmitters in blood. Further research is needed to determine the potential use of meditation as a therapeutic tool to treat neurological and neuropsychiatric disorders which involve the imbalance of key neurotransmitters. Meditation Glutamate GABA Dopamine Neurotransmitters Figures Figure 1 Figure 2 Introduction Known for its ability to calm and ease the mind and body, meditation, a complex mental exercise, has been shown to influence emotions, cognition, sensory perception and hormonal control (Daube and Jakobsche, 2015; Jindal et al., 2013; Kasala et al., 2014; Guglietti et al., 2012). Although many forms of meditation exist, some shared fundamental concepts include controlling breath and clearing one’s mind from any distractions (Daube and Jakobsche, 2015). Interestingly, meditation has been shown to have the ability to advance health and overall well-being (Yi-Yuan et al., 2020). Over time, meditation has also become a useful therapeutic tool in treating various medical and psychological conditions, particularly, stress-related physical and mental disorders (Jindal et al., 2013). Additionally, meditation is also being used as an adjuvant therapy due to its favourable outcomes (Kasala et al., 2014, Vithanage et al., 2024). Meditation has positively impacted individuals by influencing physiological pathways such as neurotransmission, immune and neuroendocrine regulation, affecting neurochemicals such that it could contribute to lowering stress levels and improving relaxation, as well as posing prospective advantages in combating oxidative stress (Kasala et al., 2014; Thambyrajah et al., 2022; Thambyrajah et al., 2023). The imbalances in dopamine, GABA and glutamate are implicated in the pathogenesis of neuropsychiatric illnesses. The evidence from research suggests that meditation has a significant impact on the neurotransmitter systems of dopamine, glutamate, and gamma-aminobutyric acid (GABA), each playing a unique role in the cognitive and emotional benefits of meditation (Tolahunase et al. (2018); Guglietti et al., 2012; Kasala et al., 2014; Aggarwal, 2020). Regulating these neurotransmitters via meditation may contribute to improved mental health, particularly in conditions characterized by neurotransmitter imbalances, such as anxiety, depression, and stress-related disorders. Further research is needed to explore these effects across different types of meditation practices and in diverse populations to emphasize the therapeutic potential of meditation across different settings. Gamma-aminobutyric acid ( GABA) is the most important inhibitory neurotransmitter in the central nervous system (La paz et al., 2021). Further, GABA plays an important role in the modulation of cortical excitability and neural plasticity (Guglietti et al., 2012). The broad distribution of GABAergic cells suggests that this inhibitory neurotransmitter plays a role in numerous functions within the central nervous system (CNS) (La Paz et al., 2021). Apart from regulating primordial functions such as mood and sleep, an increase in GABA also improves overall concentration of individuals, by specifically suppressing the activity of the visual cortex and posterior superior parietal lobule, allowing meditators to ignore certain stimuli while focusing on others (Guglietti et al., 2012; La Paz et al., 2021. There are significant differences in cortical silent period (CSP) protocol which is a measure of GABA B related cortical inhibition when comparing those with psychiatric conditions and healthy controls (Azargive, 2015). Interestingly, among the neurochemical changes observed as a result of meditation, an increase in GABA has been one such change. The process of meditation, via influencing the brain areas such as the prefrontal cortex as well as parts of the thalamus have indicated an increase in production and delivery of the inhibitory neurotransmitter GABA (Guglietti et al., 2012; Kasala et al., 2014). Dopamine , another important neurotransmitter, plays a crucial role in reward, motivation, and the regulation of mood. Dopamine levels are affected in psychiatric and neurodegenerative disorders, where for instance, in depressed patients a functional deficit of synaptic dopamine has been revealed. Previous research has shown that meditation can significantly increase dopamine levels (Kjaer et al., 2002; Kasala et al., 2014). Moreover, Tolahunase et al. (2018) reported that meditation-based interventions, such as mindfulness and yoga, can enhance dopamine release, improve mood and alleviate depressive symptoms. Further, a related study by Sharma et al., (2016) suggested that mindfulness meditation may enhance dopamine function, contributing to improved cognitive and emotional regulation in neuropsychiatric conditions. Glutamate , the brain's primary excitatory neurotransmitter, is essential for synaptic plasticity, learning, and memory. A dysfunction in the glutamatergic system has been linked to various conditions such as schizophrenia and depression where there is a lower glutamate metabolism in these cases (Yi-Yuan et al., 2020). Meditation has been shown to affect glutamate levels, thereby contributing to cognitive and neuroprotective effects. Aggarwal (2020) discusses the role of meditation in regulating glutamate neurotransmission, emphasizing its importance in stress management and cognitive health. Additionally, Mehta and Gangadhar (2019) explored how yoga practices balance the excitation-inhibition equilibrium by modulating glutamate and GABA levels, providing therapeutic benefits for individuals with psychiatric disorders. Deshpande and Babu (2019) further highlight the potential of meditation in modulating glutamate activity, which is crucial for maintaining neuronal health and preventing excitotoxicity in neurodegenerative and psychiatric disorders. Additionally, brain metabolism has been changed by integrative body mind training such that there was a significant increase in glutamate metabolism which could potentially make conditions such as depression better (Yi-Yuan et al., 2020). Although previous studies have explored effect of meditation on changes of individual neurotransmitters, the possible effects of meditation on the changes of these three neurotransmitters together in one cohort has not been addressed. Studying the effects of meditation on these important neurotransmitters will shed light on the neurobiological basis and correlated plastic changes of the neurotransmitter systems. The current study compared dopamine, glutamate, and GABA levels in blood in a group of long-term skilled mediators with a one-on-one matched control group to explore the association of long-term Buddhist meditation practices on these three neurotransmitter systems in one cohort. Methods Study design A comparative analytical lab-based study was conducted on long-term Vipassana meditators and a non-meditator control group. Participants Initially a total of 114 meditators were recruited for the present study and assessed for eligibility based on the inclusion and exclusion criteria (Fig. 1 ). The study finally comprised a total sample size of 60 participants, with 30 individuals assigned to the meditator group and 30 to the control group. Long-term meditators were recruited from the International Vipassana Meditation Centre and Siyane Vipassana Meditation Centre in Sri Lanka. The meditators attending the centre were screened using a validated intake interview (Outschoorn et al, 2022). The interview was conducted until 30 meditators were eligible for the study and were considered skilled meditators. Thirty age, gender and education level matched participants who had never practiced any form of meditation were recruited as controls. Participants who were having autoimmune diseases, noncommunicable diseases, mental illness, neuropsychiatric disorders and those who were on medications that affect neurotransmitter levels were excluded from the study. Monks, pregnant women, smokers and those who participated in other stress management techniques such as guided imagery, breath focus, yoga, Sudarshan kriya and tai chi were also excluded from this study. Data collection All participants (from both long-term-skilled meditator and control groups) were requested to fill a questionnaire prepared to collect data on their age, gender, educational level, marital status, body mass index, sleeping hours, working hours, healthy habits, alcohol consumption, type of diet and exercise hours per day. Procedure Participants were also requested to fast for 12 hours and to get sufficient and undisturbed rest during the night before the day of sample collection. Venous blood (10ml) was collected between 08.00–09.00 h, into EDTA tubes. Plasma was separated after incubating the blood sample for 1 h at 37°C and for 2 h at 4°C followed by centrifugation at 900 g for 10 min at 4 ºC. Plasma was separated and stored at -20 ºC until used for assays. Quality control samples at two levels were analysed in each run to assess the performance of the assay. The neurotransmitter levels in blood were analysed using an enzymatic immunoassay kit (ELISA Fast Track, LDN, Nordhorn, Germany). Data analysis Statistical Package for the Social Sciences/ Statistical Product and Service Solutions (SPSS) Version 28 was used for all statistical analyses. The Shapiro-Wilk test was used for testing the normality of the data distribution. Statistical significance was defined as p < 0.05 at a confidence interval of 95%. Since the data for GABA were normally distributed, independent t tests were used to determine if participants who meditated had different concentrations of each neurotransmitter compared to the controls. Means are shown with standard error. For dopamine and glutamate, since the data was non-normally distributed Mann-Whitney U tests were run to determine the effect of meditation on dopamine and glutamate concentration. A Pearson correlation test was performed to determine if there was a relationship between the three neurotransmitters in those who meditated and in the control group respectively. Further, an additional Pearson correlation test was performed to see if the time spent meditating influenced the increase, decrease or constant level of each neurotransmitter. Results Socio demographic factors and habits were taken into consideration to ensure there was no significant difference in factors such as age, BMI, and gender between long term skilled meditators and non-meditators which may have thereby influenced the neurotransmitter levels (Table 1 ). Table 1 Socio demographic factors and habits of skilled meditators and non-meditators. Variable Skilled Meditators Non-meditators Gender Ratio (% Females) 17/30 (57%) 17/30 (57%) Marital Status (% Married) 19/30 (63%) 14/30 (47%) Age (Mean, SD) 42.23 ± 8.99 42.2 ± 9.04 Body Mass Index (Mean, SD) 23.32 ± 2.99 24.03 ± 3.23 Exercise hours per week (Mean, SD) 1.27 ± 1.68 1.32 ± 1.56 Sleeping hours (Mean, SD) 6.27 ± 1.99 6.22 ± 1.31 Neurotransmitter Levels in Meditators and Non-Meditators GABA levels were significantly higher in long-term skilled meditators with a mean concentration of 67.92 ng/ml (± 2.39 SE) compared to 61.21 ng/ml (± 1.37 SE) in the controls (t 46.12 = 2.44, p = 0.006) (Fig. 2 (a)). Dopamine levels were also significantly higher in long-term skilled meditators with a mean concentration of 134.8 ng/ml (± 18.2 SE) compared to 94.7 ng/ml (± 15.5 SE) in the controls (p = 0.019) (Fig. 2 (b)) Glutamate levels were significantly lower in long-term skilled meditators with a mean concentration of 6.0 µg/ml (± 0.49 SE) compared to 7.3 µg/ml (± 0.54 SE) in the controls (p = 0.008) (Fig. 2 (c)). Association Between Dopamine, Glutamate and GABA in Meditators and Non-Meditators In meditators the correlation between dopamine and GABA (r = 0.067; p = 0.169), dopamine and glutamate (r = 0.024; p = 0.418) and glutamate and GABA (r = 0.031; p = 0.351) was weak and non-significant. In non-meditators the correlation between dopamine and GABA (r = 0.007; p = 0.664), dopamine and glutamate (r = 0.0003; p = 0.923) and glutamate and GABA (r = 0.017; p = 0.493) was weak and non- significant. Association Between Dopamine, Glutamate, GABA and the Total Time Spent Meditating The correlation between dopamine and the total time spent meditating (r = 0.067; p = 0 .726), GABA and the total time spent meditating (r = 0.076; p = 0.690), and glutamate and the total time spent meditating (r = 0.255; p = 0.174) was weak and non-significant. This suggests that there is little to no relationship between either of the neurotransmitters and the time spent meditating across a lifetime. Discussion The current study aimed at comparing blood dopamine, glutamate, and GABA levels in a group of long-term-skilled meditators with a one-on-one matched control group to explore the association of Buddhist meditation practices with these three neurotransmitter levels in one cohort. GABA : The results showed that there was an increase in the levels of GABA in those who are skilled meditators compared to the control participants. The finding of increased GABA levels in skilled meditators is in line with a study carried out by Guglietti et al. (2013) where they found that meditation increases GABAergic cortical inhibition which results from an increase in GABA, which in turn has shown to positively affect emotional regulation as well as cognitive functioning. Further, given that the stimulation of the prefrontal cortex (PFC) results in the reticular nucleus of the thalamus being excited (Newberg and Iverson, 2003) which in turn produces GABA. It has been found that increased activity in the PFC in meditators correlates with an increase in GABA (Krishnakumar et al., 2015). In addition to the positive effects of an increase in GABA resulting from meditation, increased activation of brain regions such as the PFC enhances problem solving and decision making. Particularly, the activation of the anterior PFC which moderates social behaviour as well as controls cognitive behavior is a said to be a major benefit of meditation (Jindal et al., 2013). Although GABA receptors are found throughout the brain, a reduction of GABA in certain areas result in specific disorders (Krishnakumar et al., 2015). A reduction in GABA activity is associated with higher levels of anxiety (Krishnakumar et al., 2015). Interestingly, meditation has shown to result in an increase in GABA levels in many regions of the brain (Jindal et al.,2013) which means that meditation could potentially be used to treat certain conditions which might otherwise require multiple treatments depending on the region of the brain affected in the illness or disorder. Dopamine : the results of the present study also showed significantly higher levels of dopamine in meditators compared to the control participants which is supported by previous findings which yielded similar results following various forms of meditation (Tolahunase et al., 2018; Sharma et al., 2016; Kjaer et al., 2002). Dopamine plays multiple key roles in brain function including learning, reward and motor control functions (Ko and Strafella, 2012). Further, it is also a neurotransmitter which when not available at right concentrations, causes multiple neurological and neuropsychiatric disorders including diseases such as schizophrenia as well as addiction behaviors (Franco et al., 2021). Looking at meditation from the lens of having the potential to be a therapeutic tool, given that for instance in a disease like Parkinson disease, where dopamine reduction results from the loss of dopamine neurons, a key point to consider then would be if meditation could really do anything to relieve the key symptoms of someone with Parkinsonism given that the absence of dopamine neurons would completely wipe out the possible production of dopamine as a whole. Hence, given that most dopamine related diseases occur involving both dopamine neurons and dopamine receptors it would be worth looking at how meditation might affect symptoms of individuals with diseases such as Parkinson disease. Research shows that there are reduced levels of dopamine in those with social phobia resulting from anxiety disorders (Schneier et al., 2000). Further, a significant number of those with Parkinson disease have shown to suffer with anxiety disorders (Walsh and Bennett, 2000). Taking both findings into consideration, comparing symptoms of anxiety disorders from both groups of individuals upon meditation could potentially shed light on how the levels of dopamine might be influenced because of meditation. Although dopamine levels in the substantia nigra may drastically reduce, provided there are dopamine neurons elsewhere which could be stimulated to produce dopamine, perhaps there could be a possibility of dealing with certain symptoms which are caused by just a reduction in dopamine rather than the specific location such as the substantia nigra. Another important factor to take into consideration is the greater presence of dopamine in the periphery, particularly the gut, compared to its presence in the central nervous system. Additionally, given that intestinal cells and enteric neurons may also accumulate and release dopamine, it remains in question if upon meditation, an increase in dopamine in the gut might then influence the dopamine link between the gut and inflammation (Franco et al., 2021). Apart from its potential therapeutic benefits, meditation could potentially be used to enhance learning and reward behaviors, which are a few of the many behaviors’ dopamine influences. Glutamate : the results of the present study showed significantly lower levels of glutamate in long-term skilled meditators compared to the control participants. Apart from being classed as the main excitatory neurotransmitter in the mammalian brain, glutamate plays a crucial role in learning and mood among other factors (Pal, 2021). The finding of this study is in line with a study which used magnetic resonance spectroscopy to quantify glutamine and glutamate in the brain which revealed statistically significant reduced glutamate levels in the left thalamus in a long-term Zen meditator group compared to a non-meditator group that may reflect decreased function of neurons (Fayed et al., 2013). Higher glutamate levels can in fact be quite harmful to the brain where it has the potential to induce excitotoxicity which can ultimately lead to neuronal death (Nicosia, 2024). Further, it important to take into consideration that the glutamate concentration obtained in this study was from venous blood which indicates glutamate concentration in the periphery. This is not representative of the glutamate levels in the brain due to the gradient of glutamate between the blood and brain cells being maintained by the blood brain barrier (Gruenbaum, 2022). Additionally, although the mean concentration of glutamate in controls was significantly higher, it falls well within the normal of range of 40- 60 μM (Bai and Zhou, 2017) which therefore is no need for concern. For future studies an alternative method could be used to detect glutamate levels such as that used in the study carried out by Tang et al. (2020) where they used non-invasive spectroscopy to detect increased glutamate metabolism following meditation. The present study also aimed to examine associations between the neurotransmitters GABA, dopamine and glutamate as well as the relationship between these neurotransmitters and the total time spent meditating. The fact that these correlations yielded weak, non-significant interactions could be a result of some limitations which include, the small sample size, which may have been underpowered to detect minute but meaningful effects. Additionally, self- reported meditation time could have been prone to recall bias. Hence, future studies could incorporate larger sample sizes, longitudinal designs or potentially incorporating a repeated measuring of tests. Overall, the results of the present study supported by previous research, points to the fact that the benefits of meditation could be vast where it has the potential to not only influence everyday behaviors such as learning but also has the potential to be used as a therapeutic tool. Importantly, this study highlights the profound influence the mindfulness can exert on the brain, offering a glimpse into how mental processes may manifest in neurobiological function through changes in neurotransmitter levels and how they can be used in preventive medicine. Additionally, through this study it has been made clear that meditation is capable of altering the levels of multiple neurotransmitters without major side effects unlike how most drugs used to treat various neurodegenerative conditions, whilst aiming to rectify the levels of just a single neurotransmitter would also result in undesirable side effects (Snyder et al., 2015). In conclusion, this study which is the first of kind where three key neurotransmitters were looked at in one cohort has laid the foundation for some potentially promising results which meditation might reveal in the future. Declarations Author Contribution Funding Data availability The data used to support the findings in this study are available from the corresponding author upon request. Declarations Ethics approval and consent to participate Ethics approval for the study was obtained from the Ethics Review Committee, …..Informed written consent was obtained from the eligible participants before data and sample collection. Conflict of Interest The authors declare no competing interests. Disclaimer The funder played no role in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. References Aggarwal, A. (2020). Hypothalamo-Pituitary-Adrenal axis and Brain during Stress, Yoga and Meditation: A review. International Journal of Health and Clinical Research, 3(9), 96–103. Bai, W., & Zhou, Y.-G. (2017). Homeostasis of the Intraparenchymal-Blood Glutamate Concentration Gradient: Maintenance, Imbalance, and Regulation. Frontiers in Molecular Neuroscience, 10. https://doi.org/10.3389/fnmol.2017.00400 Daube, W. C., & Jakobsche, C. E. (2015). 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We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7561502","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":516202837,"identity":"d880ec51-955c-4562-8058-df1bf5cd82d0","order_by":0,"name":"James C. 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1","display":"","copyAsset":false,"role":"figure","size":63309,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart depicting the process of sample recruitment followed in the present study.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7561502/v1/f01d073fcfc1620099a03efa.png"},{"id":91842814,"identity":"3e5b8dbf-8801-4457-8275-edd01661f95a","added_by":"auto","created_at":"2025-09-22 10:02:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31528,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the concentrations of neurotransmitters between long-term skilled meditators and non-meditator control participants.\u003c/p\u003e\n\u003cp\u003eComparison of the concentrations of three neurotransmitters, GABA(a), dopamine (b) and glutamate (c) between long-term skilled meditators and non-meditator control participants. (GABA p= 0.006; Dopamine p=0.019; Glutamate p= 0.008)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7561502/v1/23c62dded096c48afef4e88f.png"},{"id":91847713,"identity":"3d830356-0a59-4236-b1a3-8dfe61b1bdfb","added_by":"auto","created_at":"2025-09-22 10:26:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":633657,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7561502/v1/eaa41286-8423-4d5c-bd38-cf6bdfcbd827.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Meditation on Dopamine, Glutamate and GABA Among Long-term Skilled Meditators in Sri Lanka","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKnown for its ability to calm and ease the mind and body, meditation, a complex mental exercise, has been shown to influence emotions, cognition, sensory perception and hormonal control (Daube and Jakobsche, 2015; Jindal et al., 2013; Kasala et al., 2014; Guglietti et al., 2012). Although many forms of meditation exist, some shared fundamental concepts include controlling breath and clearing one\u0026rsquo;s mind from any distractions (Daube and Jakobsche, 2015). Interestingly, meditation has been shown to have the ability to advance health and overall well-being (Yi-Yuan et al., 2020). Over time, meditation has also become a useful therapeutic tool in treating various medical and psychological conditions, particularly, stress-related physical and mental disorders (Jindal et al., 2013). Additionally, meditation is also being used as an adjuvant therapy due to its favourable outcomes (Kasala et al., 2014, Vithanage et al., 2024). Meditation has positively impacted individuals by influencing physiological pathways such as neurotransmission, immune and neuroendocrine regulation, affecting neurochemicals such that it could contribute to lowering stress levels and improving relaxation, as well as posing prospective advantages in combating oxidative stress (Kasala et al., 2014; Thambyrajah et al., 2022; Thambyrajah et al., 2023). The imbalances in dopamine, GABA and glutamate are implicated in the pathogenesis of neuropsychiatric illnesses. The evidence from research suggests that meditation has a significant impact on the neurotransmitter systems of dopamine, glutamate, and gamma-aminobutyric acid (GABA), each playing a unique role in the cognitive and emotional benefits of meditation (Tolahunase et al. (2018); Guglietti et al., 2012; Kasala et al., 2014; Aggarwal, 2020). Regulating these neurotransmitters via meditation may contribute to improved mental health, particularly in conditions characterized by neurotransmitter imbalances, such as anxiety, depression, and stress-related disorders. Further research is needed to explore these effects across different types of meditation practices and in diverse populations to emphasize the therapeutic potential of meditation across different settings.\u003c/p\u003e\u003cp\u003e\u003cb\u003eGamma-aminobutyric acid\u003c/b\u003e (\u003cb\u003eGABA)\u003c/b\u003e is the most important inhibitory neurotransmitter in the central nervous system (La paz et al., 2021). Further, GABA plays an important role in the modulation of cortical excitability and neural plasticity (Guglietti et al., 2012). The broad distribution of GABAergic cells suggests that this inhibitory neurotransmitter plays a role in numerous functions within the central nervous system (CNS) (La Paz et al., 2021). Apart from regulating primordial functions such as mood and sleep, an increase in GABA also improves overall concentration of individuals, by specifically suppressing the activity of the visual cortex and posterior superior parietal lobule, allowing meditators to ignore certain stimuli while focusing on others (Guglietti et al., 2012; La Paz et al., 2021. There are significant differences in cortical silent period (CSP) protocol which is a measure of GABA B related cortical inhibition when comparing those with psychiatric conditions and healthy controls (Azargive, 2015). Interestingly, among the neurochemical changes observed as a result of meditation, an increase in GABA has been one such change. The process of meditation, via influencing the brain areas such as the prefrontal cortex as well as parts of the thalamus have indicated an increase in production and delivery of the inhibitory neurotransmitter GABA (Guglietti et al., 2012; Kasala et al., 2014).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDopamine\u003c/b\u003e, another important neurotransmitter, plays a crucial role in reward, motivation, and the regulation of mood. Dopamine levels are affected in psychiatric and neurodegenerative disorders, where for instance, in depressed patients a functional deficit of synaptic dopamine has been revealed. Previous research has shown that meditation can significantly increase dopamine levels (Kjaer et al., 2002; Kasala et al., 2014). Moreover, Tolahunase et al. (2018) reported that meditation-based interventions, such as mindfulness and yoga, can enhance dopamine release, improve mood and alleviate depressive symptoms. Further, a related study by Sharma et al., (2016) suggested that mindfulness meditation may enhance dopamine function, contributing to improved cognitive and emotional regulation in neuropsychiatric conditions.\u003c/p\u003e\u003cp\u003e\u003cb\u003eGlutamate\u003c/b\u003e, the brain's primary excitatory neurotransmitter, is essential for synaptic plasticity, learning, and memory. A dysfunction in the glutamatergic system has been linked to various conditions such as schizophrenia and depression where there is a lower glutamate metabolism in these cases (Yi-Yuan et al., 2020). Meditation has been shown to affect glutamate levels, thereby contributing to cognitive and neuroprotective effects. Aggarwal (2020) discusses the role of meditation in regulating glutamate neurotransmission, emphasizing its importance in stress management and cognitive health. Additionally, Mehta and Gangadhar (2019) explored how yoga practices balance the excitation-inhibition equilibrium by modulating glutamate and GABA levels, providing therapeutic benefits for individuals with psychiatric disorders. Deshpande and Babu (2019) further highlight the potential of meditation in modulating glutamate activity, which is crucial for maintaining neuronal health and preventing excitotoxicity in neurodegenerative and psychiatric disorders. Additionally, brain metabolism has been changed by integrative body mind training such that there was a significant increase in glutamate metabolism which could potentially make conditions such as depression better (Yi-Yuan et al., 2020).\u003c/p\u003e\u003cp\u003eAlthough previous studies have explored effect of meditation on changes of individual neurotransmitters, the possible effects of meditation on the changes of these three neurotransmitters together in one cohort has not been addressed. Studying the effects of meditation on these important neurotransmitters will shed light on the neurobiological basis and correlated plastic changes of the neurotransmitter systems. The current study compared dopamine, glutamate, and GABA levels in blood in a group of long-term skilled mediators with a one-on-one matched control group to explore the association of long-term Buddhist meditation practices on these three neurotransmitter systems in one cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eA comparative analytical lab-based study was conducted on long-term Vipassana meditators and a non-meditator control group.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eInitially a total of 114 meditators were recruited for the present study and assessed for eligibility based on the inclusion and exclusion criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The study finally comprised a total sample size of 60 participants, with 30 individuals assigned to the meditator group and 30 to the control group. Long-term meditators were recruited from the International Vipassana Meditation Centre and Siyane Vipassana Meditation Centre in Sri Lanka. The meditators attending the centre were screened using a validated intake interview (Outschoorn et al, 2022). The interview was conducted until 30 meditators were eligible for the study and were considered skilled meditators. Thirty age, gender and education level matched participants who had never practiced any form of meditation were recruited as controls. Participants who were having autoimmune diseases, noncommunicable diseases, mental illness, neuropsychiatric disorders and those who were on medications that affect neurotransmitter levels were excluded from the study. Monks, pregnant women, smokers and those who participated in other stress management techniques such as guided imagery, breath focus, yoga, Sudarshan kriya and tai chi were also excluded from this study.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eAll participants (from both long-term-skilled meditator and control groups) were requested to fill a questionnaire prepared to collect data on their age, gender, educational level, marital status, body mass index, sleeping hours, working hours, healthy habits, alcohol consumption, type of diet and exercise hours per day.\u003c/p\u003e\n\u003ch3\u003eProcedure\u003c/h3\u003e\n\u003cp\u003eParticipants were also requested to fast for 12 hours and to get sufficient and undisturbed rest during the night before the day of sample collection. Venous blood (10ml) was collected between 08.00\u0026ndash;09.00 h, into EDTA tubes. Plasma was separated after incubating the blood sample for 1 h at 37\u0026deg;C and for 2 h at 4\u0026deg;C followed by centrifugation at 900\u003cem\u003eg\u003c/em\u003e for 10 min at 4 \u0026ordm;C. Plasma was separated and stored at -20 \u0026ordm;C until used for assays. Quality control samples at two levels were analysed in each run to assess the performance of the assay. The neurotransmitter levels in blood were analysed using an enzymatic immunoassay kit (ELISA Fast Track, LDN, Nordhorn, Germany).\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eData analysis\u003c/h2\u003e\u003cp\u003eStatistical Package for the Social Sciences/ Statistical Product and Service Solutions (SPSS) Version 28 was used for all statistical analyses. The Shapiro-Wilk test was used for testing the normality of the data distribution. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 at a confidence interval of 95%. Since the data for GABA were normally distributed, independent t tests were used to determine if participants who meditated had different concentrations of each neurotransmitter compared to the controls. Means are shown with standard error. For dopamine and glutamate, since the data was non-normally distributed Mann-Whitney U tests were run to determine the effect of meditation on dopamine and glutamate concentration. A Pearson correlation test was performed to determine if there was a relationship between the three neurotransmitters in those who meditated and in the control group respectively. Further, an additional Pearson correlation test was performed to see if the time spent meditating influenced the increase, decrease or constant level of each neurotransmitter.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eSocio demographic factors and habits were taken into consideration to ensure there was no significant difference in factors such as age, BMI, and gender between long term skilled meditators and non-meditators which may have thereby influenced the neurotransmitter levels (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSocio demographic factors and habits of skilled meditators and non-meditators.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSkilled Meditators\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-meditators\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender Ratio (% Females)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17/30 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17/30 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarital Status (% Married)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19/30 (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14/30 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (Mean, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.23\u0026thinsp;\u0026plusmn;\u0026thinsp;8.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index (Mean, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.32\u0026thinsp;\u0026plusmn;\u0026thinsp;2.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExercise hours per week (Mean, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSleeping hours (Mean, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNeurotransmitter Levels in Meditators and Non-Meditators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGABA\u003c/em\u003e levels were significantly higher in long-term skilled meditators with a mean concentration of 67.92 ng/ml (\u0026plusmn;\u0026thinsp;2.39 SE) compared to 61.21 ng/ml (\u0026plusmn;\u0026thinsp;1.37 SE) in the controls (t \u003csub\u003e46.12\u003c/sub\u003e = 2.44, p\u0026thinsp;=\u0026thinsp;0.006) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (a)).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDopamine\u003c/em\u003e levels were also significantly higher in long-term skilled meditators with a mean concentration of 134.8 ng/ml (\u0026plusmn;\u0026thinsp;18.2 SE) compared to 94.7 ng/ml (\u0026plusmn;\u0026thinsp;15.5 SE) in the controls (p\u0026thinsp;=\u0026thinsp;0.019) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (b))\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGlutamate\u003c/em\u003e levels were significantly lower in long-term skilled meditators with a mean concentration of 6.0 \u0026micro;g/ml (\u0026plusmn;\u0026thinsp;0.49 SE) compared to 7.3 \u0026micro;g/ml (\u0026plusmn;\u0026thinsp;0.54 SE) in the controls (p\u0026thinsp;=\u0026thinsp;0.008) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (c)).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation Between Dopamine, Glutamate and GABA in Meditators and Non-Meditators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn meditators the correlation between dopamine and GABA (r\u0026thinsp;=\u0026thinsp;0.067; p\u0026thinsp;=\u0026thinsp;0.169), dopamine and glutamate (r\u0026thinsp;=\u0026thinsp;0.024; p\u0026thinsp;=\u0026thinsp;0.418) and glutamate and GABA (r\u0026thinsp;=\u0026thinsp;0.031; p\u0026thinsp;=\u0026thinsp;0.351) was weak and non-significant.\u003c/p\u003e\n\u003cp\u003eIn non-meditators the correlation between dopamine and GABA (r\u0026thinsp;=\u0026thinsp;0.007; p\u0026thinsp;=\u0026thinsp;0.664), dopamine and glutamate (r\u0026thinsp;=\u0026thinsp;0.0003; p\u0026thinsp;=\u0026thinsp;0.923) and glutamate and GABA (r\u0026thinsp;=\u0026thinsp;0.017; p\u0026thinsp;=\u0026thinsp;0.493) was weak and non- significant.\u003c/p\u003e\n\u003ch3\u003eAssociation Between Dopamine, Glutamate, GABA and the Total Time Spent Meditating\u003c/h3\u003e\n\u003cp\u003eThe correlation between dopamine and the total time spent meditating (r\u0026thinsp;=\u0026thinsp;0.067; p\u0026thinsp;=\u0026thinsp;0 .726), GABA and the total time spent meditating (r\u0026thinsp;=\u0026thinsp;0.076; p\u0026thinsp;=\u0026thinsp;0.690), and glutamate and the total time spent meditating (r\u0026thinsp;=\u0026thinsp;0.255; p\u0026thinsp;=\u0026thinsp;0.174) was weak and non-significant. This suggests that there is little to no relationship between either of the neurotransmitters and the time spent meditating across a lifetime.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u0026nbsp;The current study aimed at comparing blood dopamine, glutamate, and GABA levels in a group of long-term-skilled meditators with a one-on-one matched control group to explore the association of Buddhist meditation practices with these three neurotransmitter levels in one cohort.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003cstrong\u003eGABA\u003c/strong\u003e\u003c/em\u003e: The results showed that there was an increase in the levels of GABA in those who are skilled meditators compared to the control participants. The finding of increased GABA levels in skilled meditators is in line with a study carried out by Guglietti et al. (2013) where they found that meditation increases GABAergic cortical inhibition which results from an\u003cbr\u003e\u0026nbsp;increase in GABA, which in turn has shown to positively affect emotional regulation as well as cognitive functioning. Further, given that the stimulation of the prefrontal cortex (PFC) results in the reticular nucleus of the thalamus being excited (Newberg and Iverson, 2003) which in turn produces GABA. It has been found that increased activity in the PFC in\u003cbr\u003e\u0026nbsp;meditators correlates with an increase in GABA (Krishnakumar et al., 2015). In addition to the positive effects of an increase in GABA resulting from meditation, increased activation of brain regions such as the PFC enhances problem solving and decision making. Particularly, the activation of the anterior PFC which moderates social behaviour as well as controls cognitive behavior is a said to be a major benefit of meditation (Jindal et al., 2013).\u003cbr\u003e\u0026nbsp;Although GABA receptors are found throughout the brain, a reduction of GABA in certain areas result in specific disorders (Krishnakumar et al., 2015). A reduction in GABA activity is associated with higher levels of anxiety (Krishnakumar et al., 2015). Interestingly, meditation has shown to result in an increase in GABA levels in many regions of the brain (Jindal et al.,2013) which means that meditation could potentially be used to treat certain conditions which\u003cbr\u003e\u0026nbsp;might otherwise require multiple treatments depending on the region of the brain affected in the illness or disorder.\u003cbr\u003e\u003cem\u003e\u0026nbsp; \u003cstrong\u003eDopamine\u003c/strong\u003e\u003c/em\u003e: the results of the present study also showed significantly higher levels of dopamine in meditators compared to the control participants which is supported by previous\u003cbr\u003e\u0026nbsp;findings which yielded similar results following various forms of meditation (Tolahunase et \u0026nbsp;al., 2018; Sharma et al., 2016; Kjaer et al., 2002). Dopamine plays multiple key roles in brain function including learning, reward and motor control functions (Ko and Strafella, 2012). Further, it is also a neurotransmitter which when not available at right concentrations, causes multiple neurological and neuropsychiatric disorders including diseases such as schizophrenia as well as addiction behaviors (Franco et al., 2021). Looking at meditation \u0026nbsp;from the lens of having the potential to be a therapeutic tool, given that for instance in a disease like Parkinson disease, where dopamine reduction results from the loss of dopamine\u003cbr\u003e\u0026nbsp;neurons, a key point to consider then would be if meditation could really do anything to relieve the key symptoms of someone with Parkinsonism given that the absence of dopamine neurons would completely wipe out the possible production of dopamine as a whole. Hence, given that most dopamine related diseases occur involving both dopamine neurons and dopamine receptors it would be worth looking at how meditation might affect symptoms of\u003cbr\u003e\u0026nbsp;individuals with diseases such as Parkinson disease. Research shows that there are reduced levels of dopamine in those with social phobia resulting from anxiety disorders (Schneier et al., 2000). Further, a significant number of those with Parkinson disease have shown to suffer with anxiety disorders (Walsh and Bennett, 2000). Taking both findings into consideration, comparing symptoms of anxiety disorders from both groups of individuals upon meditation could potentially shed light on how the levels of dopamine might be influenced because of meditation. Although dopamine levels in the substantia nigra may drastically reduce,\u003cbr\u003e\u0026nbsp;provided there are dopamine neurons elsewhere which could be stimulated to produce\u003cbr\u003e\u0026nbsp;dopamine, perhaps there could be a possibility of dealing with certain symptoms which are caused by just a reduction in dopamine rather than the specific location such as the substantia nigra. Another important factor to take into consideration is the greater presence of dopamine in the periphery, particularly the gut, compared to its presence in the central nervous system. Additionally, given that intestinal cells and enteric neurons may also accumulate and release dopamine, it remains in question if upon meditation, an increase in dopamine in the gut might then influence the dopamine link between the gut and inflammation (Franco et al., 2021). Apart from its potential therapeutic benefits, meditation could potentially be used to enhance learning and reward behaviors, which are a few of the many behaviors\u0026rsquo; \u0026nbsp;dopamine influences.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eGlutamate\u003c/em\u003e\u003c/strong\u003e: the results of the present study showed significantly lower levels of\u003cbr\u003e\u0026nbsp;glutamate in long-term skilled meditators compared to the control participants. Apart from being classed as the main excitatory neurotransmitter in the mammalian brain, glutamate plays a crucial role in learning and mood among other factors (Pal, 2021). The finding of this study is in line with a study which used magnetic resonance spectroscopy to quantify glutamine and glutamate in the brain which revealed statistically significant reduced glutamate levels in the left thalamus in a long-term Zen meditator group compared to a non-meditator group that may reflect decreased function of neurons (Fayed et al., 2013). \u0026nbsp;Higher glutamate levels can in fact be quite harmful to the brain where it has the potential to induce excitotoxicity which can ultimately lead to neuronal death (Nicosia, 2024). Further, it important to take into consideration that the glutamate concentration obtained in this study was from venous blood which indicates glutamate concentration in the periphery. This is not representative of the glutamate levels in the brain due to the gradient of glutamate between the blood and brain cells being maintained by the blood brain barrier (Gruenbaum, 2022). Additionally, although the mean concentration of glutamate in controls was significantly higher, it falls well within the normal of range of 40- 60 \u0026mu;M (Bai and Zhou, 2017) which therefore is no need for concern. For future studies an alternative method could be used to detect glutamate levels such as that used in the study carried out by Tang et al. (2020) where they used non-invasive spectroscopy to detect increased glutamate metabolism following meditation.\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; The present study also aimed to examine associations between the neurotransmitters GABA,\u003cbr\u003e\u0026nbsp;dopamine and glutamate as well as the relationship between these neurotransmitters and the total time spent meditating. The fact that these correlations yielded weak, non-significant interactions could be a result of some limitations which include, the small sample size, which may have been underpowered to detect minute but meaningful effects. Additionally, self- reported meditation time could have been prone to recall bias. Hence, future studies could incorporate larger sample sizes, longitudinal designs or potentially incorporating a repeated measuring of tests.\u003cbr\u003e\u0026nbsp; \u0026nbsp; Overall, the results of the present study supported by previous research, points to the fact that the benefits of meditation could be vast where it has the potential to not only influence everyday behaviors such as learning but also has the potential to be used as a therapeutic tool. Importantly, this study highlights the profound influence the mindfulness can exert on the\u003cbr\u003e\u0026nbsp;brain, offering a glimpse into how mental processes may manifest in neurobiological function through changes in neurotransmitter levels and how they can be used in preventive medicine. Additionally, through this study it has been made clear that meditation is capable of altering the levels of multiple neurotransmitters without major side effects unlike how most drugs used to treat various neurodegenerative conditions, whilst aiming to rectify the levels of just a single neurotransmitter would also result in undesirable side effects (Snyder et al., 2015). In conclusion, this study which is the first of kind where three key neurotransmitters were looked at in one cohort has laid the foundation for some potentially promising results which meditation might reveal in the future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eThe data used to support the findings in this study are available from the corresponding author upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003eEthics approval for the study was obtained from the Ethics Review Committee, …..Informed written consent was obtained from the eligible participants before data and sample collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclaimer\u0026nbsp;\u003c/strong\u003eThe funder played no role in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAggarwal, A. 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Application of Biomedical Engineering in Neuroscience, 401\u0026ndash;413. https://doi.org/10.1007/978-981 13-7142-4_20\u003c/li\u003e\n\u003cli\u003eFayed, N., Lopez del Hoyo, Y., Andres, E., Serrano-Blanco, A., Bell\u0026oacute;n, J., Aguilar, K., Cebolla, A. and Garcia-Campayo, J., (2013. Brain changes in long-term zen meditators using proton magnetic resonance spectroscopy and diffusion tensor imaging: a controlled study. \u003cem\u003ePLoS One\u003c/em\u003e, \u003cem\u003e8\u003c/em\u003e(3), p.e58476. https://doi.org/10.1097/wnr.0000000000001527\u003c/li\u003e\n\u003cli\u003eFranco, R., Reyes-Resina, I., \u0026amp; Navarro, G. (2021). Dopamine in Health and Disease: Much\u003cbr\u003e More Than a Neurotransmitter. Biomedicines, 9(2), 109.\u003cbr\u003e https://doi.org/10.3390/biomedicines9020109\u003c/li\u003e\n\u003cli\u003eGruenbaum, B. F., Zlotnik, A., Fleidervish, I. A., Frenkel, A., \u0026amp; Boyko, M. (2022).\u003cbr\u003e Glutamate Neurotoxicity and Destruction of the Blood\u0026ndash;Brain Barrier: Key Pathways\u003cbr\u003e for the Development of Neuropsychiatric Consequences of TBI and Their Potential\u003cbr\u003e Treatment Strategies. International Journal of Molecular Sciences, 23(17), 9628\u0026ndash;\u003cbr\u003e 9628. https://doi.org/10.3390/ijms23179628\u003c/li\u003e\n\u003cli\u003eGuglietti, C. L., Daskalakis, Z. J., Radhu, N., Fitzgerald, P. B., \u0026amp; Ritvo, P. (2013). Meditation- Related Increases in GABAB Modulated Cortical Inhibition. Brain Stimulation, 6(3), 397\u0026ndash; 402. https://doi.org/10.1016/j.brs.2012.08.005 Jindal, \u003c/li\u003e\n\u003cli\u003eV., Gupta, S., \u0026amp; Das, R. (2013). Molecular Mechanisms of Meditation. Molecular Neurobiology, 48(3), 808\u0026ndash;811. https://doi.org/10.1007/s12035-013-8468-9\u003c/li\u003e\n\u003cli\u003eKasala, E. R., Bodduluru, L. N., Maneti, Y., \u0026amp; Thipparaboina, R. (2014). Effect of meditation on neurophysiological changes in stress mediated depression. Complementary Therapies in Clinical Practice, 20(1), 74\u0026ndash;80. https://doi.org/10.1016/j.ctcp.2013.10.001\u003c/li\u003e\n\u003cli\u003eKjaer, T. W., Bertelsen, C., Piccini, P., Brooks, D., Alving, J., \u0026amp; Lou, H. C. (2002). Increased dopamine tone during meditation-induced change of consciousness. Cognitive Brain Research, 13(2), 255\u0026ndash;259. https://doi.org/10.1016/s0926 6410(01)00106-9 \u003c/li\u003e\n\u003cli\u003eKo, J. H., \u0026amp; Strafella, A. P. (2012). Dopaminergic Neurotransmission in the Human Brain:\u003cbr\u003e New Lessons from Perturbation and Imaging. The Neuroscientist: A Review Journal\u003cbr\u003e Bringing Neurobiology, Neurology and Psychiatry, 18(2), 149\u0026ndash;168.\u003cbr\u003e https://doi.org/10.1177/1073858411401413\u003c/li\u003e\n\u003cli\u003eKrishnakumar, D., Hamblin, M. R., \u0026amp; Lakshmanan, S. (2015). Meditation and Yoga can Modulate Brain Mechanisms that affect Behavior and Anxiety-A Modern Scientific Perspective. Ancient Science, 2(1), 13\u0026ndash;19. https://doi.org/10.14259/as.v2i1.171 \u003c/li\u003e\n\u003cli\u003eMehta, U. M., \u0026amp; Gangadhar, B. N. (2019). Yoga: Balancing the excitation-inhibition equilibrium in psychiatric disorders. Progress in Brain Research, 244, 387\u0026ndash;413. https://doi.org/10.1016/bs.pbr.2018.10.024\u003c/li\u003e\n\u003cli\u003eNewberg, A. B., \u0026amp; Iversen, J. (2003). The neural basis of the complex mental task of meditation: neurotransmitter and neurochemical considerations. Medical Hypotheses, 61(2), 282\u0026ndash;291. https://doi.org/10.1016/s0306-9877(03)00175-0 \u003c/li\u003e\n\u003cli\u003eNicosia, N., Giovenzana, M., Misztak, P., Mingardi, J., \u0026amp; Musazzi, L. (2024). Glutamate-\u003cbr\u003e Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental\u003cbr\u003e and Adult Mental Disorders. International Journal of Molecular Sciences, 25(12),\u003cbr\u003e 6521. https://doi.org/10.3390/ijms25126521\u003c/li\u003e\n\u003cli\u003eOchoa-de la Paz, L. D., Gulias-Cañizo, R., D ́Abril Ruíz-Leyja, E., Sánchez-Castillo, H., \u0026amp; Parodí, J. (2021). The role of GABA neurotransmitter in the human central nervous system, physiology, and pathophysiology. Revista Mexicana de Neurociencia, 22(2). https://doi.org/10.24875/rmn.20000050\u003c/li\u003e\n\u003cli\u003ePal, M. M. (2021). Glutamate: The Master Neurotransmitter and Its Implications in Chronic\u003cbr\u003e Stress and Mood Disorders. Frontiers in Human Neuroscience, 15(15).\u003cbr\u003e https://doi.org/10.3389/fnhum.2021.722323\u003c/li\u003e\n\u003cli\u003eSaam Azargive. (2015). The Acute GABAergic Effects of Mindfulness Meditation in the Motor Cortex of University Students.\u003c/li\u003e\n\u003cli\u003eSchneier, F. R. (2000). Low Dopamine D2 Receptor Binding Potential in Social Phobia. American Journal of Psychiatry, 157(3), 457\u0026ndash;459. https://doi.org/10.1176/appi.ajp.157.3.457\u003c/li\u003e\n\u003cli\u003eSharma, K., Davis, T., \u0026amp; Coulthard, E. (2016). Enhancing attention in neurodegenerative diseases: current therapies and future directions. Translational Neuroscience, 7(1). https://doi.org/10.1515/tnsci-2016-0016 \u003c/li\u003e\n\u003cli\u003eSnyder, G. L., Vanover, K. E., Zhu, H., Miller, D. B., O\u0026rsquo;Callaghan, J. P., Tomesch, J., Li, P., Zhang, Q., Krishnan, V., Hendrick, J. P., Nestler, E. J., Davis, R. E., Wennogle, L. P., \u0026amp; Mates, S. (2014). FuncSonal profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology, 232(3), 605\u0026ndash;621. h[ps://doi.org/10.1007/s00213- 014-3704-1 \u003c/li\u003e\n\u003cli\u003eTang, Y.-Y., Askari, P., \u0026amp; Choi, C. (2020). Brief mindfulness training increased glutamate metabolism in the anterior cingulate cortex. NeuroReport, 31(16), 1142 1145. https://doi.org/10.1097/wnr.0000000000001527\u003c/li\u003e\n\u003cli\u003eThambyrajah, J., Dilanthi, H., Handunnetti, S., \u0026amp; Dissanayake, D. (2023). Serum melatonin and serotonin levels in long-term skilled meditators. \u003cem\u003eEXPLORE\u003c/em\u003e, \u003cem\u003e19\u003c/em\u003e(5). https://doi.org/10.1016/j.explore.2023.03.006\u003c/li\u003e\n\u003cli\u003eThambyrajah, J. C., Handunnetti, S. M., Dilanthi, H. W., \u0026amp; Dissanayake, D. W. N. (2022). Higher Serum Antioxidant Capacity Levels and Its Association with Serum NOx Levels Among Long-term Experienced Meditators in Sri Lanka. \u003cem\u003eMindfulness\u003c/em\u003e. https://doi.org/10.1007/s12671-022-01840-8\u003c/li\u003e\n\u003cli\u003eTolahunase, M. R., Sagar, R., Faiq, M., \u0026amp; Dada, R. (2018). Yoga- and meditation based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: A randomized controlled trial. Restorative Neurology and Neuroscience, 36(3), 423\u0026ndash;442. https://doi.org/10.3233/rnn-170810 Walsh, K. (2001). Parkinson\u0026rsquo;s disease and anxiety. Postgraduate Medical Journal, 77(904), 89\u0026ndash;93. https://doi.org/10.1136/pmj.77.904.89\u003c/li\u003e\n\u003cli\u003eVithanage, K., Dissanayake, D., \u0026amp; Chang, T. (2024). Randomized control clinical trial to assess the effect of meditation on selected clinical outcomes in patients with Parkinson\u0026rsquo;s disease. \u003cem\u003eCeylon Journal of Medical Science\u003c/em\u003e, \u003cem\u003e61\u003c/em\u003e(1), 38\u0026ndash;47. https://doi.org/10.4038/cjms.v61i1.5072\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Meditation, Glutamate, GABA, Dopamine, Neurotransmitters","lastPublishedDoi":"10.21203/rs.3.rs-7561502/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7561502/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjectives\u003c/b\u003e\u003c/p\u003e\u003cp\u003eStudying the effects of meditation on neurotransmitters will shed light on the neurobiological basis and correlated neuroplastic changes. The current study aimed at comparing dopamine, glutamate, and GABA levels in blood in a group of long-term-skilled meditators with a one-on-one matched control group to explore the association of Buddhist meditation practices on these three neurotransmitters in one cohort.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA comparative analytical laboratory-based study was conducted on long-term skilled meditators (n\u0026thinsp;=\u0026thinsp;30) and a non-meditator control (n\u0026thinsp;=\u0026thinsp;30) group. Venous blood was collected from each participant to determine the neurotransmitter concentration. The neurotransmitter levels in blood were obtained using enzymatic immunoassay (ELISA).\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere was no significant difference in socio demographic factors and habits between the long-term-skilled meditators (LTSM, age\u0026thinsp;=\u0026thinsp;42.23 years\u0026thinsp;\u0026plusmn;\u0026thinsp;8.99) compared to controls (age\u0026thinsp;=\u0026thinsp;42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.04). GABA levels were significantly higher in LTSM\u0026rsquo;s with a mean concentration of 67.92 ng/ml (\u0026plusmn;\u0026thinsp;2.39 SE) compared to 61.21 ng/ml (\u0026plusmn;\u0026thinsp;1.37 SE) in the controls (p\u0026thinsp;=\u0026thinsp;0.006). Similarly, the dopamine levels were also significantly higher in the LTSM compared to controls (LTSM, 134.8 ng/ml\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2; Controls 94.7 ng/ml\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5, p\u0026thinsp;=\u0026thinsp;0.019). Glutamate levels were significantly lower in LTSM\u0026rsquo;s compared to controls. (LTSM, 6.0 ug/ml\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49; controls, 7.3 ug/ml\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54, p\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMeditation alters the levels of neurotransmitters in blood. Further research is needed to determine the potential use of meditation as a therapeutic tool to treat neurological and neuropsychiatric disorders which involve the imbalance of key neurotransmitters.\u003c/p\u003e","manuscriptTitle":"Effects of Meditation on Dopamine, Glutamate and GABA Among Long-term Skilled Meditators in Sri Lanka","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 10:02:37","doi":"10.21203/rs.3.rs-7561502/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1d951464-d495-4f0b-ac50-8018369ae7c9","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T07:56:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 10:02:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7561502","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7561502","identity":"rs-7561502","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}