Alcohol, opioids, methamphetamine, and benzodiazepines carry the strongest documented links to suicidal behavior. CDC toxicology data from 2022 found that among suicide decedents who were tested, 40% had alcohol in their system, 21% tested positive for opioids, 20% for benzodiazepines, and nearly 29% for cannabis. These numbers reflect what was present at the time of death, but the relationship between substance use and suicide runs deeper than intoxication alone.
Alcohol
Alcohol is the single substance most consistently found in the bodies of people who die by suicide. Among decedents tested for blood alcohol in 2022, roughly four in ten were positive, and nearly two-thirds of those had levels at or above the legal driving limit of 0.08 g/dL. That level of intoxication significantly impairs judgment and lowers inhibition.
The risk extends beyond acute intoxication. People with alcohol dependence have roughly twice the odds of attempting suicide compared to people without an alcohol use disorder, even after accounting for co-occurring mood disorders. Chronic heavy drinking physically changes the brain in ways that overlap with the neurobiology seen in suicide attempters: reduced gray matter in the prefrontal cortex (the area responsible for decision-making and impulse control), disrupted serotonin signaling, and a hyperactive stress response system. These overlapping changes help explain why alcohol problems and suicidal behavior so frequently co-occur.
Opioids
Opioid use disorder carries an extraordinarily high lifetime rate of suicide attempts. In a study of patients receiving opioid addiction treatment in Norway, 41% had attempted suicide at least once, with rates slightly higher among women (46%) than men (39%). That is many times higher than the general population rate.
Like alcohol, chronic opioid use damages the prefrontal cortex, reducing the brain’s capacity for impulse control and emotional regulation. People with opioid use disorder show lower gray matter volume, weakened connections between brain regions involved in decision-making, and impaired serotonin function. These changes make it harder to manage distress and easier to act on suicidal thoughts. Opioids also carry the added danger of being a readily available lethal means: overdose is one of the most common methods of suicide attempt among people who use them.
Methamphetamine and Stimulants
Methamphetamine use shows a distinctive and somewhat counterintuitive pattern. Users are actually less likely than non-users to report suicidal thoughts in the abstract. But they are far more likely to make a concrete plan (twice the odds) or to attempt suicide (nearly three times the odds). In other words, methamphetamine appears to push people past the thinking stage directly into action.
This pattern follows a dose-response curve. Light users (once or twice a month) have about 1.8 times the odds of suicidal behavior compared to non-users. Daily users face 3.2 times the odds. Chronic methamphetamine use damages the brain’s dopamine and serotonin pathways and causes neurotoxic effects in regions governing impulse control and emotional regulation. The result is a rapid transition from distress to suicidal action, with fewer of the internal brakes that might otherwise slow someone down. Cocaine, the other major stimulant, was found in about 7.5% of tested suicide decedents in 2022, a lower rate but still notable given that cocaine use is less prevalent than alcohol or opioid use in the general population.
Benzodiazepines
Benzodiazepines (drugs like diazepam, alprazolam, and clonazepam, commonly prescribed for anxiety and insomnia) showed up in 20% of suicide decedents tested in 2022. A large study of over one million veterans with PTSD found that those prescribed benzodiazepines had 2.74 times the risk of dying by suicide and 1.85 times the risk of attempting suicide compared to matched veterans not prescribed these drugs.
These medications lower inhibition in a similar way to alcohol, which may partially explain the elevated risk. They can also cause rebound anxiety and depressive symptoms between doses or during withdrawal, creating cycles of emotional instability. The combination of reduced impulse control while intoxicated and worsened mood during withdrawal creates a particularly dangerous pattern.
Cannabis
Cannabis carries a more modest but still meaningful association. Among adolescents hospitalized for psychiatric reasons, cannabis use disorder was linked to 40% higher odds of suicide attempts after adjusting for other factors. In the 2022 CDC data, cannabis was present in about 29% of suicide decedents who were tested for it. The relationship is less dramatic than with alcohol or opioids, but heavy, disordered cannabis use, particularly during adolescence when the brain is still developing, is a consistent risk factor.
Why Multiple Substances Multiply the Risk
Using more than one substance at a time amplifies risk far beyond what any single drug produces on its own. Adolescents who used multiple substances were 3.8 times more likely to have suicidal thoughts, 3.5 times more likely to make a plan, and 4.6 times more likely to attempt suicide compared to those who used no substances. Polysubstance use accounted for about 14% of the overall variation in youth suicidality, a substantial share for a single risk factor.
This makes intuitive sense. Combining alcohol with benzodiazepines, for example, compounds the disinhibition and cognitive impairment of each drug. Mixing stimulants with depressants creates volatile emotional swings. Each additional substance adds another layer of impaired judgment, emotional dysregulation, or neurological damage.
How Substances Increase Risk
Substances drive suicidal behavior through several overlapping mechanisms. The most immediate is disinhibition: alcohol, benzodiazepines, and stimulants all reduce the brain’s ability to put the brakes on impulsive actions. A person who might otherwise resist acting on a suicidal thought becomes more likely to follow through while intoxicated.
Chronic use produces longer-term changes. Heavy use of alcohol, opioids, and methamphetamine all reduce gray matter in the prefrontal cortex, the brain region most critical for weighing consequences and controlling impulses. They disrupt serotonin signaling, which is closely tied to mood regulation. And they dysregulate the body’s stress response system, leaving people more reactive to emotional pain and less equipped to cope with it.
Withdrawal adds another layer of danger. As substances leave the body, rebound depression, anxiety, and agitation can surge. A protracted withdrawal phase, sometimes lasting weeks or months, can produce persistent depressive symptoms and suicidal thoughts even after acute withdrawal has resolved. This means the period after someone stops using a substance can be just as dangerous as the period of active use, particularly without proper support.
Finally, substance use disorders erode the social and financial stability that protects against suicide. Job loss, relationship breakdown, legal problems, and isolation are both consequences of addiction and independent risk factors for suicidal behavior. The substance use and the life disruption it causes reinforce each other in a cycle that becomes progressively harder to interrupt.