CBD and the Brain: How it Helps Mental Balance Published on February 4, 2025 by Masha Burelo Index Toggle What is glutamate and why is it so important?What kind of emotions and sensations does glutamate produce?What happens if glutamate is out of control?How does CBD act in the brain?In what conditions can CBD help?CBD and Glutamate on anxietyCannabinoids and Mental Balance: Their Impact on Glutamate RegulationMental Effects of THC on GlutamateMental Effects of CBD on GlutamateTherapeutic potential of CBD for glutamate disordersConclusion The brain functions thanks to constant communication between its nerve cells, something that depends on substances called neurotransmitters. One of the most important of these is glutamate, which is essential for functions such as memory, learning and movement control. However, its dysregulation can lead to serious health problems. In this context, CBD, a non-psychoactive compound derived from the hemp plant, emerges as a promising option to regulate glutamate. In this article, we will explain what glutamate is and how CBD is being investigated in its regulation and promotion of brain health. What is glutamate and why is it so important? Glutamate is an amino acid that neurons use to communicate. Its main function is to activate neurons, a neuronal activation, known as excitatory neurotransmission , which enables processes such as memory, emotions and learning (1). Glutamate is like the “accelerator” of the brain. It activates neurons to process information, making it essential for functions such as memory and learning, control of movement, emotions and sensory perception. Glutamate is the main excitatory neurotransmitter in the brain, a chemical compound involved in the transmission of sensory information, emotions, motor coordination, memory and learning (2, 3, 4). For this reason, it is present in high concentrations in the brain. When there is too much glutamate in the brain, this neurotransmitter can overstimulate neurons and cause damage, known as “excitotoxicity”, which is linked to neurological disorders such as anxiety, stress, or even neurodegenerative diseases such as Alzheimer’s disease. Glutamate is synthesized from the amino acid glutamine (present in food proteins) by the action of the enzyme glutaminase, which converts glutamine to glutamate within neurons. Its chemical formula is C5H9NO4 and it has a molar mass of 14,713 g/mol. What kind of emotions and sensations does glutamate produce? While glutamate does not directly produce specific emotions or sensations, it is essential for brain functions that support emotional and sensory experiences. Its proper functioning is crucial for maintaining cognitive abilities. What happens if glutamate is out of control? Although rare, there is a genetic disorder called glutamate formiminotransferase deficiency that is characterized by a decrease in glutamate (5). In addition, dysregulation of glutamate signaling is implicated in several neurological disorders, including epilepsy, schizophrenia, and neurodegenerative diseases (6). Glutamate is the brain’s main activator: it drives memory, learning and neuronal communication, but its dysregulation can severely affect brain health. How does CBD act in the brain? CBD or cannabidiol, unlike other cannabis compounds such as THC, does not have psychoactive effects. Instead, it interacts with different systems in the brain to help maintain mental balance. Here’s what it does: Glutamate modulation: Helps reduce glutamate “overload”, protecting neurons from damage. Promotes relaxation: It favors the action of another neurotransmitter called GABA, which acts as the brain’s natural “brake”, counteracting the excitation of glutamate and helping the balance between activation and inactivation of brain cells. Neuroprotective effects: By preventing neuronal damage due to excitotoxicity, CBD may be useful and is being investigated for use in conditions such as epilepsy, diseases such as Parkinson’s or Alzheimer’s and other disorders related to brain damage. CBD to Reduce Stress Naturally In what conditions can CBD help? CBD has shown promising results in the treatment of certain forms of epilepsy, especially those resistant to other drugs, such as Dravet syndrome. In addition, its mood-stabilizing and anxiety-reducing properties make it an interesting option for problems related to glutamate imbalance such as anxiety and stress, by helping to calm brain overactivation. Although the effects, safety and proper dosage of CBD are still being researched, studies show that this component of hemp has the potential to improve mental well-being by supporting the chemical balance of the brain. More studies are needed to fully understand how it works and to confirm its effectiveness in different conditions. CBD and Glutamate on anxiety The role of glutamate in anxiety is complex. Anxiety is related to the biology of fear conditioning and involves different brain circuits, including glutamatergic signaling (4). Alterations of the excitatory-inhibitory circuit, involving the inhibitory neurotransmitter GABA and glutamate, are responsible for anxiety disorders. Therefore, different anxiolytic drugs focus on decreasing neuronal excitability, making neurons less reactive to glutamate. CBD for Anxiety Cannabinoids and Mental Balance: Their Impact on Glutamate Regulation The cannabis plant contains numerous compounds called cannabinoids, which can influence the glutamatergic system through various mechanisms. Mental Effects of THC on Glutamate Tetrahydrocannabinol (THC), the psychoactive cannabinoid present in large amounts in marijuana, can modulate glutamate release through activation of endocannabinoid receptors called CB1 receptors in the brain (10). This interaction may alter glutamate signaling in chronic marijuana users (11) and thereby affect cognitive processes. In addition, it has been shown that THC can increase brain glutamate levels, which may be related to high-dose marijuana-induced psychosis (11). Mental Effects of CBD on Glutamate Unlike THC, CBD acts on different areas of the brain, not only on endocannabinoid receptors. The regulation of glutamate through CBD may occur through its binding to another type of receptor, the transient receptor potential vanilloid type 1 or TRPV1 receptors (12). CBD can also increase the action of GABA, a neurotransmitter that promotes the “inactivation” of neurons. CBD can inhibit the effects of glutamate by increasing GABAergic transmission and antagonizing GPR55 receptors located in the basal ganglia of the brain (13). In addition, CBD can improve the chemical balance of the brain by upregulating serotonin. As an agonist of serotonergic receptors, particularly serotonin 5-HT1A receptors, CBD can suppress glutamate and GABA transmission in the prefrontal cortex (14). Cannabinoids, the Happiness Molecules Overall, CBD appears to have a positive impact on the activation and inactivation systems of the brain. The effect of CBD on all these receptors may modulate excitatory and inhibitory pathways in the brain, exerting antipsychotic and antiepileptic effects. By reducing glutamate-induced excitotoxicity, CBD has been shown to have neuroprotective properties, as well as helping to stabilize mood and cognitive function. Glutamate is naturally present in a variety of foods and is responsible for umami flavor, the fifth basic flavor that increases palatability and satiety (7, 8). According to a study by the University of Tokyo (9), some natural sources of glutamate include corn, seaweed, fermented soybeans, milk, fish sauce, asparagus, potatoes, tomatoes, seafood, and chicken. Therapeutic potential of CBD for glutamate disorders CBD can reduce the excessive release of glutamate in the brain, thus protecting neurons, which is particularly important in neurodegenerative diseases. Likewise, CBD’s modulation of neuronal excitation-inhibition makes it a possible treatment for certain types of epilepsy, such as Dravet syndrome (15). CBD may also be effective in the treatment of drug-resistant epilepsy associated with Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis, and temporal lobe epilepsy (16, 17, 18). It is important to mention that CBD does not help all people with epilepsy, as some studies have identified that certain people do not respond to its effects (19). Conclusion Glutamate is a neurotransmitter involved in a variety of brain functions, and its regulation is critical to maintaining neuronal health. CBD offers therapeutic potential to help regulate glutamate and treat medical conditions associated with its dysregulation. Although research on CBD and its impact on neurotransmitters has provided valuable insights, much remains to be discovered. Further studies are needed to fully understand the underlying mechanisms and to determine the efficacy of CBD in various clinical conditions related to glutamate imbalance. Note: This is an informative article with no prescriptive character, it is not intended to prevent, diagnose or treat any disease. Its content can complement, but should never replace, the diagnosis or treatment of any disease or symptom. Cannactiva products are not medicines and are intended for external use. There may be new relevant scientific evidence since the date of publication. Consult with your physician before using CBD. Therapeutic advice should be personalized and depends on professional assessment. References Owen, A. D., & Bird, M. M. (1997). Role of glutamate in the regulation of the outgrowth and motility of neurites from mouse spinal cord neurons in culture. Journal of anatomy, 191 ( Pt 2)(Pt 2), 301-307. https://doi.org/10.1046/j.1469-7580.1997.19120301.x Hassel, Bjørnar & Dingledine, Raymond (2012). Glutamate and Glutamate Receptors. Basic Neurochemistry. 342-366. http://dx.doi.org/10.1016/B978-0-12-374947-5.00017-1 Davis, M., Rainnie, D., & Cassell, M. (1994). 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G., Thiele, E., Whalley, B., & Friedman, D. (2014). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802 . https://doi.org/10.1111/epi.12631. Masha BureloInvestigadora en cannabinoides | Doctoranda en Neurociencia Masha Burelo es Maestra en Ciencias Farmacéuticas e investigadora en neurociencias. Actualmente está realizando su Doctorado en Neurociencia en la Universidad de Aberdeen, [...]