Opioids and Mental Health

Over 30 years ago, pharmaceutical companies assured the medical community that opioids were safe and that patients would not become addicted. With this assurance, healthcare providers began to prescribe them at much higher rates for pain control. This led to widespread misuse and addiction.  

Recommended course: Pain Assessment and Management 

By 2017, the U.S. Department of Health and Human Services declared the opioid crisis to be a public health emergency. They estimate that 10.1 million Americans have misused opioids in the past year. Currently, over 1.6 million have an Opioid Use Disorder (OUD). (HHS, 2022).  

Among the millions of people with OUD, 64% have a mental illness and 27% have a serious mental illness. (NIH, 2023). The medical community estimates that the 7.8 million people with a diagnosed psychiatric disorder receive more than half of the 200 million yearly opioid prescriptions.  

As alarming as this statistic is, it still significantly underestimates the scope of the problem. It does not account for the millions more who abuse nonprescription opioids such as heroin and fentanyl. 

What are opioids?  

Opioids are natural or synthetic substances that bind to opioid receptors in the brain and body and reduce the perception of pain. They also provide euphoric and sedating effects and are highly addictive. At higher doses, opioids can slow breathing and lead to death. Common opioids include codeine, morphine, oxycodone, hydrocodone, methadone, heroin, and fentanyl. 

Fentanyl in particular has received widespread attention due to its powerful effects. With a potency 50 times greater than heroin and 100 times greater than morphine, the Drug Enforcement Agency (DEA) has labeled fentanyl as the most prevalent and most significant synthetic opioid threat to the United States. (DEA, 2023). 

Opioid use disorder 

OUD is defined in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (APA, 2022) as a problematic pattern of opioid use leading to clinically significant impairment or distress and includes at least two of the following:  

  • Taking larger amounts or for longer than intended 
  • Unsuccessful efforts to cut down or control use 
  • Spending a lot of time obtaining, using, or recovering from the drug 
  • Cravings to use 
  • Use causes failure to fulfill role obligations 
  • Continued use despite social or interpersonal problems 
  • Activities given up due to use 
  • Use in hazardous situations 
  • Continued use despite use causing physical or psychological problems 
  • Tolerance for the drug 
  • Withdrawal symptoms or use to avoid withdrawal 

Opioids can lead to physical dependence in a short period of time, in as little as 4-8 weeks. Stopping use can cause strong withdrawal symptoms including pain, chills, cramps, diarrhea, restlessness, anxiety, nausea, vomiting, insomnia, and intense cravings. This creates a powerful motivation to continue using. 

Opioids and mental health 

Estimates of mental health disorders which are concurrent with opioid use vary widely. In general, there tends to be higher rates of depression and anxiety in persons with OUD. 


Symptoms of depression can include intense sadness, hopelessness, irritability, insomnia, loss of interest and motivation, and/or difficulty concentrating. Individuals with clinically significant depression who begin taking opioids are at greater risk of developing OUD.   

Conversely, individuals with OUD are more likely to develop significant depression even after short term use. The underlying mechanism for this association is still not entirely clear, but research suggests that the body’s opioid system is directly involved in the regulation of mood.  

Opioids activate the reward centers in the brain and flood the body with dopamine, the “feel good” neurotransmitter. This initially provides pain relief and a sense of euphoria and energizes the motivation to consume more. Over time, however, the brain gets used to the level of opioids present and begins to adapt by decreasing the amount of dopamine made and by becoming less sensitive to the dopamine that is present.  

Impaired quantity and quality of sleep, decreased concentration, and slowed reaction times emerge. There is a need to take increasing amounts of the drug to achieve an effect. Sensitivity to pleasurable feelings significantly declines. This reset of dopamine at lower levels can persist even after withdrawal and treatment-resistant depression may emerge or worsen. 

While small doses of opioids may improve mood by activating opioid receptors in the body, prolonged use over 30 days saturates these receptors. This increases the risk of developing serious depression by more than 25% compared to opioid use less than 30 days. (Rosoff et al., 2021).  

Studies suggest that individuals with serious depression may reach for opioids for their euphoric effects in order to improve mood, but over a short time opioid use only leads to worsening depression. Even in those without preexisting depression, opioid use over 30 days is associated with increased risk of new-onset depression. (Li et al., 2020). 

Anxiety disorders          

Anxiety disorders are characterized by intense feelings of nervousness and can include symptoms of restlessness, fear, panic, a sense of impending doom, hyperventilation, trembling, sweating, and avoidance behaviors. As with depressive disorders, those with significant anxiety may look to opioids to reduce their symptoms.  

However, opioids are capable of producing anxiety both during and after use and can lead to agitation, paranoia, and insomnia. Anxiety can be extremely intense during withdrawal, providing a strong motivator to keep using. Over 60% of individuals with OUD also have a diagnosable anxiety disorder (Langdon et al., 2020). 

Norepinephrine is both a hormone and a neurotransmitter. It plays a primary role in controlling alertness and blood pressure and is also involved in the body’s flight or fight response. Opioid use inhibits norepinephrine. The brain responds by producing higher levels of norepinephrine in order to bring energy and blood pressure back to baseline.  This higher level of norepinephrine leads to anxiety, jitteriness, insomnia, muscle cramps, and diarrhea as it overstimulates brain regions which are associated with anxiety.  

Similarly, during acute withdrawal from opioids norepinephrine is no longer inhibited and symptoms of anxiety intensify. The short acting opioids including codeine, oxycodone, and heroin cause the most severe levels of anxiety during withdrawal. Even after withdrawal, the disrupted neurotransmitter system may not return to baseline and chronic anxiety continues. 


Approximately 30% of individuals with OUD report suicidal ideation. The number of suicide deaths has increased by 60% over the past several decades. The suicide rate among those with an opioid use disorder is six times higher than the rate of suicide in the general population.  

Recommended course: Suicide Prevention: Identifying and Intervention with the At-Risk Person

In addition, research suggests that 20-30% of deaths labeled as unintentional overdoses may actually have had suicidal intent, indicating that suicide statistics underrepresent the true rate. There are likely multiple reasons for this association. OUD leads to depression and a loss of sensitivity to pleasure. Resulting hopelessness, despair, and negative thought patterns may be underlying contributors to suicidal ideation.  

Another potential hypothesis is that the motivation to live is eroded during opioid addiction and suicidal ideation results in risk-taking behaviors with intentional or unintentional overdose. Regardless of underlying cause, individuals with OUD should be considered a critical high-risk group for suicidal ideation and behavior. (Na et al, 2022). 


Effective treatment requires a multi-pronged approach. Medication-Assisted Treatment is the gold standard for addressing OUD. Medications like buprenorphine, methadone, or naltrexone are used to relieve cravings and withdrawal symptoms and to block the euphoric effects of opioids. Compatible medications to address depression and anxiety may also be prescribed to ease the concurrent mental health symptoms.  

In addition, counseling and behavioral therapies are strong evidence-based components of treatment. Of the numerous therapy approaches, cognitive behavioral therapy has been found to be one of the most effective therapy options for addressing both the mental health and substance abuse issues. 

For further information about mental health, opioid and substance abuse, and treatment options see The Substance Abuse and Mental Health Services Administration website at https://www.samhsa.gov/find-help