Happy Monday!
I recently read a very large study published in The BMJ that provided the strongest signal yet that something tangible may be happening in the brain on GLP-1s.
The study analyzed health records from more than 600,000 U.S. veterans with type 2 diabetes to examine whether GLP-1 drugs influenced addiction risk and addiction outcomes.
The findings were surprising.
And they help explain why so many people report that the urge to chase rewards changes when they start these drugs.
The Largest Human Study Yet
The BMJ study followed 606,434 patients in the Veterans Affairs health system who were being treated for diabetes. Researchers compared people taking GLP-1 receptor agonists with patients SGLT2 inhibitors (like Jardiance).
They tracked whether patients developed substance use disorders related to alcohol, cannabis, cocaine, nicotine, and opioids.
They also looked at outcomes in patients who already had substance use disorders.
What did they find?
People taking GLP-1 drugs had a 14 percent lower risk of developing a substance use disorder overall compared with the other medication group.
When broken down by substance, the reductions looked like this:
Alcohol disorders reduced by 18%
Cannabis disorders reduced by 14%
Cocaine disorders reduced by 20%
Nicotine disorders reduced by 20%
Opioid disorders reduced by 25%
These findings suggest that GLP-1 drugs may be interacting with the biological systems that drive craving itself.
What Happened to People Who Already Had Addiction
The study also looked at patients who already had substance use disorders before starting a GLP-1 drug.
This part of the analysis might be even more interesting.
Among these individuals, starting a GLP-1 medication was associated with significant reductions in severe addiction related outcomes.
Over the three year follow up period the data showed:
31% fewer emergency department visits
26% fewer hospitalizations
39% fewer overdoses
50% lower risk of death related to substance use
When researchers looked at the population level, they estimated that GLP-1 drugs prevented about seven new substance use disorders and twelve serious addiction-related events per 1,000 users during the study period.
In addiction medicine, it is rare to see a single intervention associated with improvements across multiple substances at the same time!
What’s Going on in the Brain
To understand why these drugs might influence addiction, we have to look at where GLP-1 receptors exist in the body.
Most people think of GLP-1 as a gut hormone.
It is released after eating and helps regulate blood sugar, insulin secretion, and satiety.
However, GLP-1 receptors are also found in several brain regions involved in reward processing.
These regions include parts of the mesolimbic system, which is heavily involved in motivation and dopamine signaling.
Addictive substances such as alcohol, nicotine, and opioids stimulate this same reward pathway.
Researchers believe that activating the GLP-1 receptor may dampen the intensity of reward signals in these circuits.
When that signal becomes weaker, the brain experiences less reinforcement from addictive substances.
In practical terms, this may translate into fewer cravings or less compulsion around the behavior.
Some researchers have described this effect as quieting the craving signal that drives addiction across different substances.
Why the Effect Shows Up Across Many Different Substances
One of the most interesting findings in the study was the breadth of the effect.
The reductions appeared across alcohol, nicotine, cannabis, cocaine, and opioids.
In addiction medicine, treatments usually target one specific substance. Nicotine patches help with smoking. Medications like buprenorphine help with opioid addiction. There are very few treatments that appear to influence multiple addictions at once.
The reason GLP-1 drugs might affect several substances is that they may act on the craving pathway itself rather than the substance.
Addictive substances activate the same reward circuits in the brain. They stimulate dopamine release in areas that reinforce behavior.
If GLP-1 signaling reduces activity in this pathway, the brain may experience a weaker drive toward many different rewarding stimuli.
This could explain why people taking these drugs often describe a broader shift in behavior.
Food cravings drop. Alcohol cravings soften. Other compulsive behaviors sometimes change as well.
Important Limitations
Even though this study is very large, it is important to understand what it does and does not prove.
The research is observational.
That means it identifies associations between GLP-1 drugs and addiction outcomes. It does not prove that the drugs directly caused the reduction in addiction risk.
The study population also consisted mostly of older male veterans with type 2 diabetes.
That population may not perfectly represent the broader public.
Researchers also cannot fully account for differences in lifestyle, socioeconomic status, or other factors that might influence addiction risk.
Despite these limitations, the study used a rigorous analysis design, and the results remained consistent across multiple tests.
For now, the findings provide a strong signal that deserves further investigation through randomized clinical trials.
Several groups are already planning studies to test GLP-1 drugs directly as addiction treatments.
My Perspective
For years, people taking GLP-1 peptides have reported that the noise around food becomes quieter.
This study suggests something broader may be happening.
The same signal that quiets food cravings may also reduce the brain’s drive toward other rewarding substances.
If that effect proves true in future trials, it could reshape how we think about addiction treatment.
Addiction medicine has struggled for decades to find medications that influence the core biology of craving across multiple substances.
GLP-1 signaling may represent a new pathway worth exploring.
Sometimes the most interesting discoveries in medicine start as an unexpected side effect.
This may turn out to be one of those moments!
Best,
Hunter Williams
Further Reading
BMJ cohort study on GLP-1 drugs and substance use disorders:
WashU Medicine summary of the study: