
There is a complex relationship between opioids and depression.
Initially, opioids provide temporary relief from the symptoms of depression — symptoms that include feelings of sadness and hopelessness. This happens because opioids stimulate the release of neurotransmitters like dopamine and serotonin, both of which are associated with feeling good physically and mentally.[1]
However, this effect is only short-term. Over time, a higher and higher dose of opioids is needed to achieve that same relief from depression. Eventually, the drugs don’t help the problem at all.
Additionally, long-term use of opioids can worsen symptoms of depression, putting people at risk even more so than using high doses of opioids irregularly.[2]
In some cases, opioid use disorders (OUD) can contribute to the development of a depressive disorder even if no signs were present prior to the use of opioids. This is because opioids can disrupt the normal functioning of the brain and alter the balance of neurotransmitters.
The reasons for using opioids can also impact mental health symptoms. For example, people who use opioids to manage chronic pain may be at an increased risk for developing depression due to the limitations caused by their ongoing pain. This can be exacerbated by opioid use and the isolation that it brings with it.
Research has also found that people with depression may be more vulnerable to the addictive effects of opioids. That temporary relief from depression symptoms can be a compelling reason to keep using the drugs, and over time, dependence and then OUD can develop.
The relationship between opioids and depression is complex and not yet fully understood, but research suggests that long-term opioid use can alter the brain's chemical balance and lead to the development of depression.[3]
One of the ways opioids can contribute to depression is by altering the levels of neurotransmitters in the brain. Opioids work by binding to specific receptors in the brain and spinal cord, which can increase the release of neurotransmitters like dopamine and serotonin.[4] These neurotransmitters are associated with feelings of pleasure, reward, and well-being, providing a mood boost that can range from pleasant to euphoric.
However, over time, the brain can become desensitized to the effects of opioids, which can lead to a decrease in the levels of the “feel good” neurotransmitters released in response to the opioids binding to the receptors. This can result in a state of dysphoria, or feelings of unease, dissatisfaction, and sadness, which can contribute to the development of depression.
Additionally, chronic pain itself can be a risk factor for the development of depression on its own. People who use opioids to manage chronic pain may be at an increased risk for both depression and opioid use disorder due to the combination of triggers.
To add to the risk, opioid use can disrupt the body's natural sleep/wake cycle, which can lead to sleep disturbances and fatigue. Low energy and lethargy that comes with a lack of restorative sleep are also associated with depression.
For many people, taking opioids nonmedically is their attempt to manage symptoms of depression. They may not have access to appropriate mental health care or may not find that traditional therapies are working or working quickly enough. Because of this, they may take the drugs as a way to manage the symptoms on their own.
Even with no history of substance misuse, self-medication rates are high among people struggling with depression.[10] This use is always nonmedical use. Without the supervision of a physician, it is easy to misuse the substances, take more than is safe, and avoid taking medications that are actually proven to treat symptoms of depression.
In other cases, opioid use disorder comes first. People who misuse painkillers or street drugs like heroin may find themselves experiencing symptoms of depression after long-term use. This can be due to a number of factors, including these:
It can be difficult to identify depression that is induced by opioids, because it shares many symptoms with major depressive disorder.
However, the signs that indicate depression that may be exacerbated or caused by misuse of opioids include the following:
Additionally, there will usually be the signs of depression that come with grief, trauma, and major depressive disorder, including low mood, lack of energy, and changes in sleeping and eating patterns.
Opioid use disorder and depression are both serious medical conditions that require appropriate treatment when they occur individually or on their own, but when they co-occur at the same time, it is essential to seek treatment that addresses both problems fully.
Some treatment options that can address both OUD and depression simultaneously include the following:
If you or someone you love is attempting to treat a depression disorder by self-medicating with opioids or if opioid misuse has triggered depression, treatment is available. With comprehensive care that addresses opioid use disorder and depression simultaneously, you can achieve recovery on all fronts.
Reach out to us here at Bicycle Health to learn how we can help. We offer Medication for Addiction Treatment (MAT) to effectively manage opioid use disorder, and therapy to address co-occurring disorders like depression.

Peter Manza, PhD received his BA in Psychology and Biology from the University of Rochester and his PhD in Integrative Neuroscience at Stony Brook University. He is currently working as a research scientist in Washington, DC. His research focuses on the role of the brain dopamine system in substance use disorders and in aging. He also studies brain function in obesity and eating disorders.
Our science-backed approach boasts 95% of patients reporting no withdrawal symptoms at 7 days. We can help you achieve easier days and a happier future.
Get Startedor book an enrollment call