GLP-1RAs: Do They Have a Role in Psychiatry?

We have all seen the commercials for GLP-1s. Ozempic and Wegovy have clearly helped many with their ability to manage type 2 diabetes and weight loss. But what if I told you GLP-1RAs have a place in psychiatry. I know this sounds weird, but research is growing and shows great promise with improvement in many different areas of psychiatry. Research has unveiled the potential for GLP-1 receptor agonists to treat a growing range of psychiatric and neurological conditions.

Mental healthcare has a wave of improvement on the way. Between curbing addictive cravings to possibly managing mood disorders to offering neuroprotective benefits, GLP-1Ras are the way making way. GLP-1RAs were originally designed for metabolic pathways but have revealed a great connection between the gut, metabolism, and the brain. The research may be growing still but it is promising.

Understanding GLP-1 Receptor Agonists: The Basics

Before we can see how GLP-1RAs play a role in psychiatry we must understand how they work.

What Are GLP-1RAs?

GLP-1 receptor agonists are medications that mimic the action of the natural hormone GLP-1. The GLP-1 hormone is produced in the gut and released in response to food intake. It plays an important role in regulating blood sugar levels, which is why these drugs were initially developed for type 2 diabetes.

How They Work in the Body

When a GLP-1RA is administered, it binds to and activates GLP-1 receptors throughout the body. This activation triggers several effects:

• It stimulates the pancreas to release insulin, which helps lower blood sugar.
• It suppresses the release of glucagon, another hormone that raises blood sugar.
• It slows down gastric emptying, making you feel full for longer and reducing appetite.

FDA-Approved Uses vs. Emerging Applications

Currently, drugs like semaglutide (Ozempic, Wegovy, Rybelsus) and liraglutide (Victoza, Saxenda) are FDA-approved for managing type 2 diabetes and chronic weight management. But the recent discovery of GLP-1 receptors in the brain has created a pathway for research on the “off-label” use in psychiatry and neurology. This new research is desperately needed for both psychiatry and neurology.

The Brain-Gut Connection: GLP-1RAs’ Role in Psychiatry

A powerful connection in the body is the one between the gut and the brain. Now let’s talk about how strong of a player is GLP-1 in this connection.

GLP-1 Receptors in the Brain

GLP-1 receptors are not just in the gut and pancreas; they are also found in critical areas of the brain associated with appetite, reward, mood, and cognition. The GLP-1 receptors can be found in the hypothalamus, hippocampus, and parts of the brain’s reward circuitry. By working on these receptors, GLP-1RAs can influence so much more than just appetite control.

Emerging Psychiatric Applications

Because of the widespread presence of GLP-1 receptors in the brain is why researchers are exploring GLP-1RAs with multiple psychiatric conditions. Compelling evidence has emerged showing a connection between GLP-1RAs and improving addiction. There is also promising evidence in the way of mood disorders and neurodegenerative diseases.

The evidence for using GLP-1RAs in new ways is coming from a mix of preclinical animal studies, case reports, observational data, and an increasing number of clinical trials. Most of this research is still in early stages but is showing great promise for new “off label” uses in the world of psychiatry. The consistency in findings has created much excitement throughout the medical community.

Addiction and Craving Reduction: Rewiring the Reward System

With as much excitement for off-label use of GLP-1RAs, it appears the most exciting finding may be in the treatment of substance use disorders.

The Science Behind Addiction and GLP-1

We know that addiction is driven by a dysregulated brain reward system. Science shows us that the use of substances creates a surge of dopamine in the reward system. This creates a powerful sense of pleasure that ultimately reinforces the use of the substance. Preclinical studies are showing that GLP-1RAs can decrease the “high” from addictive substances and therefore decrease cravings that lead to using the substance again.

Substance Use Disorders: Clinical Evidence

Here’s a look at the evidence for specific substance use disorders:

• Alcohol Use Disorders: There are multiple studies showing a reduction in alcohol consumption in animals with the use of GLP-1RAs. Early human trial and case reports are mirroring these findings as well. Many patients are reporting a decrease in the desire to use alcohol while on GLP-1RAs.
• Stimulant Use Disorders: Animal models suggest that GLP-1RAs can decrease self-administration of stimulants like cocaine and amphetamines. Human research in this area is still developing but holds promise.
• Nicotine Dependence: Just as in other substances, preclinical data is showing GLP-1RAs can reduce nicotine-seeking behaviors. Anecdotal reports suggest GLP-1RAs may also help with quitting smoking altogether.
• Opioid Use Disorders: Unfortunately, evidence in this area is limited but some animal studies are showing hope. Some studies indicate GLP-1RAs may help in reducing opioid self-administration and withdrawal symptoms.

While there have been some formal studies, the informal reports from patients and clinicians have created great interest in this area. Many patients taking GLP-1RAs for weight loss have reported a reduction in cravings for alcohol, nicotine, and behavioral addictions like compulsive shopping and gambling. These informal reports show great promise in the off-label use of GLP-1RAs.

Neuropsychiatric and Mood Effects: A Complex Picture

GLP-1RAs have a complex impact on mood. Studies show great promise and the need for caution.

Depression and Anxiety: Mixed but Promising Results

There has been some research on GLP-1RAs showing they may have antidepressant and anti-anxiety effects. This comes from the possible reduction in neuroinflammation and the promotion of the birth of new brain cells. While research has shown positive prospects, other reports have linked GLP-1RAs to mood changes that include depression and suicidal ideation. With these mixed results things remain unclear but more research will help us better understand how to use GLP-1RAs off-label for depression and anxiety effectively.

Bipolar Disorder and Mood Stabilization

There are few studies around the off-label use of GLP-1RAs for bipolar disorder but the limited research is intriguing. GLP-1RAs improve metabolic health and this can be particularly helpful in bipolar disorder as patients often have a higher risk of metabolic syndrome. Some researchers are even saying that the neuroprotective and anti-inflammatory aspects of GLP-1RAs may contribute to mood stabilization.

Safety Considerations in Mental Health

With the lack of formal information and the concern of how GLP-1RAs may affect mood it is incredibly important for providers to be vigilant. Those with a history of depression, bipolar disorder, or suicidality should be monitored closely when starting a GLP-1RA. If you are starting a GLP-1RA, it is important to tell your provider of any significant mood changes, and they should be addressed quickly.

Neuroprotection and Alzheimer’s Disease: Guarding the Aging Brain

One thing many are excited about is the potential for GLP-1RAs to help in the prevention and treatment of neurodegenerative diseases.

Alzheimer’s Disease and Cognitive Decline

With Alzheimer’s Disease, GLP-1RAs can improve insulin sensitivity, reduce neuroinflammation, and clear away the amyloid-beta plaques and tau tangles that are hallmarks of the disease. There are many clinical trials currently working to find if GLP-1RAs can slow cognitive decline in early Alzheimer’s.

Parkinson’s Disease Applications

Just as in Alzheimer’s disease, GLP-1RAs are being looked at for treatment of Parkinson’s disease. GLP-1RAs seem to protect dopamine producing neurons which are the cells lost in Parkinson’s. GLP-1RAs are showing great promise in improving motor symptoms in early clinical trials.

Mechanisms of Neuroprotection

The neuroprotective effects of GLP-1RAs are thought to stem from several mechanisms, including:

• Reducing inflammation in the brain.
• Protecting neurons from cell death.
• Promoting the growth of new neurons and synapses.
• Improving the brain’s energy metabolism.

Cardiovascular and Anti-inflammatory Benefits

The benefits of GLP-1RAs extend beyond the brain, offering systemic health improvements that are also relevant to psychiatric care.

Cardiovascular Protection

GLP-1RAs have shown that they can reduce heart attacks and strokes. This aspect of GLP-1RAs can be of great benefit to those with psychiatric conditions who often have a higher risk of heart disease. This is often due to lifestyle factors, medication side effects, and the stress brought on by psychiatric illnesses.

Anti-inflammatory Properties

Chronic inflammation is a common factor in many psychiatric disorders, including depression. GLP-1RAs have strong anti-inflammatory effects throughout the body and brain. This may contribute to their therapeutic potential in mental health.

Clinical Considerations and Future Directions

As excitement and research grows, it’s important to look at the use of GLP-1RAs in psychiatry with both optimism and caution. Any time we use medications off label there are benefits and consequences that should be weighed before use.

Off-Label Use: Critical Considerations

Using GLP-1RAs for psychiatric conditions is considered off-label use. Due to the lack of evidence in their effectiveness and their potential to increase unwanted effects it is important that the patient and provider discuss the use in detail. The provider must obtain informed consent from the patient, and it is important that the provider monitors the patient’s use of the GLP-1RA closely to manage any adverse effects.

Integration with Standard Psychiatric Care

At this time, it is important that we do not use GLP-1RAs as a replacement for established psychiatric treatments. GLP-1RAs are going to be utilized best when used in addition to current psychiatric treatments. GLP-1RAs should be integrated into psychiatry with a comprehensive treatment plan.

Charting a New Path in Mental Health

GLP-1RAs are bridging the gap between metabolic and mental health. While the transition from diabetes drug to psychiatric treatment is still building the potential is undeniable. These medications offer new ways to treat psychiatric conditions in a way that we couldn’t see before. This new and building research could provide much hope for those with addiction, mood disorders, and neurodegenerative diseases. The key is to balance hope with caution. The evidence for addiction treatment is strong and should be considered in specific situations. For mood disorders and neurodegenerative diseases research is coming. As we continue to learn, GLP-1RAs could become a huge part of psychiatry in a holistic approach, and approach that sees the profound connection between the body and the mind.

Important Disclaimers and Resources

This blog is not medical advice; it is only for informational purposes. Using GLP-1RAs to treat psychiatric disorders or neurodegenerative disorders is not approved, so it is important that you only think about it after talking to a qualified healthcare professional who can weigh the pros and cons with you.

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