Understanding Low Mood and GLP-1 Medications
Why Do Some People Experience Low Mood During Weight Loss?
Weight loss, especially rapid weight loss, can sometimes be accompanied by low mood, fatigue, and changes in emotional well-being. Several factors contribute to this, including:
Hormonal fluctuations – Changes in insulin, leptin, and cortisol can impact mood.
Caloric restriction – Reduced food intake can affect neurotransmitter levels such as serotonin and dopamine.
Nutrient deficiencies – Low levels of essential nutrients like vitamin B12, magnesium, and omega-3 fatty acids may contribute to mood disturbances.
Psychological adjustment – As body weight changes, individuals may experience shifts in self-image and emotional processing.
How GLP-1 Medications May Contribute to Low Mood
GLP-1 receptor agonists interact with multiple pathways in the brain, influencing mood regulation. The following mechanisms explain how these medications may contribute to low mood:
1. Impact on Neurotransmitters and Brain Regions
GLP-1 receptors are widely expressed in areas of the brain that regulate mood, including the hypothalamus, amygdala, hippocampus, and prefrontal cortex. Activation of these receptors influences neurotransmitter systems such as:
- Serotonin (5-HT) Pathway: GLP-1 modulates serotonin transmission, which plays a crucial role in mood regulation. Some studies suggest that while GLP-1 may enhance serotonin signaling in some contexts, chronic use could lead to adaptations in receptor sensitivity, potentially causing mood disturbances (Holt et al., 2021, Neuropsychopharmacology).
- Dopamine (DA) Pathway: The mesolimbic dopamine system, which governs reward and motivation, is affected by GLP-1 receptor activation. While GLP-1 drugs can reduce food-seeking behavior, they may also reduce dopamine release in the nucleus accumbens, leading to lower motivation and anhedonia (Reddy et al., 2020, Journal of Neuroscience).
- GABA and Glutamate Balance: GLP-1 modulates gamma-aminobutyric acid (GABA) and glutamate neurotransmission, which influences stress responses and excitability. Disruptions in this balance could contribute to emotional blunting or increased anxiety (Anderberg et al., 2016, Molecular Psychiatry).
2. Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation
GLP-1 receptor activation interacts with the HPA axis, which controls the body's stress response. Some research suggests that chronic GLP-1 activation may lead to:
- Increased cortisol release, associated with stress and low mood.
- Altered CRH (corticotropin-releasing hormone) signaling, impacting energy levels and motivation (Arora et al., 2022, Stress & Hormones Journal).
3. Gut-Brain Axis and Mood Regulation
The gut microbiome plays a crucial role in mental health, with gut-derived short-chain fatty acids (SCFAs) and tryptophan metabolites influencing brain function. Since GLP-1 drugs alter gut motility and microbiome composition, this could affect:
- Serotonin synthesis in the gut, as 90% of the body's serotonin is produced in the intestines.
- Inflammatory cytokine levels, which may contribute to neuroinflammation and depressive symptoms (Cryan et al., 2020, Microbiome Research).
How to Minimise Low Mood While on GLP-1 Therapy
If you’re experiencing low mood while on a GLP-1 medication, consider the following strategies:
1. Optimise Nutrient Intake
Protein: Supports neurotransmitter production; aim for at least 1g of protein per kg of body weight.
B Vitamins: Essential for brain function and energy metabolism; found in eggs, meat, and leafy greens.
Magnesium: Helps regulate mood and stress; found in nuts, seeds, and dark chocolate.
Omega-3 Fatty Acids: Support brain health and reduce inflammation; found in fatty fish, walnuts, and flaxseeds.
2. Consider Supplements
Vitamin D – Low levels are linked to depression, especially in winter months.
Probiotics – May support gut-brain communication and mood stability.
Adaptogens (e.g., Ashwagandha, Rhodiola) – Help manage stress and improve resilience.
3. Maintain Stable Blood Sugar Levels
Avoid prolonged fasting if it worsens mood symptoms.
Include slow-digesting carbohydrates (whole grains, legumes, vegetables) to prevent blood sugar crashes.
4. Engage in Regular Physical Activity
Even light exercise, such as walking or yoga, can boost endorphin levels and improve mood.
Strength training helps regulate insulin and supports metabolic health.
When to Speak to a GP or Mental Health Professional
Seek medical advice if:
- Low mood persists for more than a few weeks
- You experience severe fatigue, anxiety, or loss of interest in activities
- Symptoms interfere with work, relationships, or daily life
- You have suicidal thoughts or worsening depression
A GP may suggest blood tests for vitamin deficiencies, thyroid function, and blood sugar levels to rule out underlying causes. They may also refer you to a mental health professional if additional support is needed.
While GLP-1 medications can be effective for weight loss, they may contribute to low mood in some individuals due to neurotransmitter changes, nutrient deficiencies, and metabolic adjustments. By ensuring balanced nutrition, stable blood sugar levels, and regular exercise, you can support emotional well-being while on GLP-1 therapy. If symptoms persist, seeking medical advice can help identify and address potential underlying issues.
