Substance/Medication-Induced Psychotic Disorder
When prescription medications, recreational drugs, or excessive alcohol provoke psychotic symptoms, the condition is diagnosed as Substance/Medication-Induced Psychotic Disorder. Anyone with an established mental health problem, or who is prone to psychosis, is at a higher risk of developing a psychotic disorder from overintoxication, abuse of, or withdrawal from a legal or illegal substance. Nevertheless, the propensity to develop psychosis seems to be a function of the severity and chronicity of substance use.
In substance/medication-induced psychotic disorder, the psychotic symptoms are considered a physiological consequence of a drug of abuse, a medication, or toxin exposure and cease after removal of the agent. That distinguishes them from primary, or autonomous, psychotic disorder, arising from an enduring malfunction in the operations of the brain.
The landscape of substance-induced psychotic disorder is changing rapidly, faster than medical science can keep up with. That is largely the result of the constant introduction of powerful new synthetic agents, often manufactured illicitly, that target with surgical precision specific populations and subpopulations of brain receptors in neurotransmitter systems involved in producing drug “highs.”
As with any other psychotic conditions, the primary symptoms of Substance/Medication-Induced Psychotic Disorder are hallucinations and delusions that are more severe than what may be considered routine symptoms of intoxication or withdrawal, and that cause distress. Signs of psychosis include:
- unusual and suspicious beliefs
- delusions of persecution that are unlikely to be true, such as "people are out to get me" or "people are spying on me"
- hallucinations, or hearing or seeing things that aren't actually there
These symptoms are considered the “positive symptoms” of psychosis—they are abnormal by their very presence. In addition, there are a number of “negative symptoms” of psychosis, so-called because they reflect the absence of normal behaviors. These include:
- diminished emotional expression
- lack of motivation
- poor thinking, inferred from poverty of speech
Psychosis is often marked by other physical and psychological symptoms. These may include:
- aggressive behavior
- mood swings, typically ranging from euphoria to deep fear
- suicidal thoughts
Symptoms of Substance/Medication-Induced Psychotic Disorder are generally acute, lasting only until the substance or medication is cleared from the body. In some cases, however, depending on the type of substance or medication involved, psychotic symptoms may continue for up to several weeks.
A major dilemma that clinicians face is how to distinguish substance-induced psychosis from primary psychotic illness or from a psychotic illness with comorbid substance use. It matters to the approach to treatment.
The symptoms of drug psychosis typically appear suddenly and intensely and include paranoia; hallucinations, possibly violent in nature; and delusions, sometimes about being pursued for drug use. Speech becomes disorganized and incoherent. Those experiencing transient psychosis may, while experiencing delusions, attempt to act on such delusions and engage in dangerous behavior.
The symptoms can be distressing and terrifying to those who have them— they don’t know what is real and what is not—and may be accompanied by thoughts of suicide. In this altered state of reality perception, people can be withdrawn or agitated, and they may become aggressive, threatening harm to others as well as self. Amphetamines, cocaine, and cannabis are the most common precipitants among drugs of abuse, but prescribed medications such as steroids are also known to precipitate a psychotic episode.
An affected person may speak very rapidly and string together words and sentences that make little outside sense. They may reveal thoughts and perceptions that bear little relation to current reality, strike out at others, or refuse to eat or drink.
While the onset of substance-induced psychosis is typically dramatic, it can also emerge more slowly with subtle shifts in behavior. That does not make them of any less concern. Substance-induced psychosis should be regarded as needing emergency medical intervention.
The symptoms of substance-induced psychosis and primary psychosis can be so floridly similar that psychiatric emergency clinicians struggle to distinguish which patients are which. In theory, one distinguishing feature is timing. By definition, the substance-induced disorder develops in minutes or hours after taking the offending substance or during withdrawal from it after a period of heavy use. Its onset is typically sudden, and it resolves after use of the substance is stopped and leaves the system.
In practice, however, things are not always so clear-cut. People often abuse more than one drug, prolonging the duration of hallucinations and other symptoms. And many people at high risk of a psychotic disorder consume substances of abuse. Statistics vary, but data indicate that up to 50 percent of people seeking medical attention for a first psychotic episode are using one or more substances.
Studies that attempt to identify factors that distinguish substance-induced psychosis from primary psychosis suggest several subtle discriminators, none of them invariable or definitive:
Those with primary psychosis
• tend to be younger
• have higher baseline scores of “unusual content of thought” when administered the Brief Psychiatric Rating Scale, a diagnostic assessment tool
• have higher rates of parental mental illness.
Those with substance-induced psychosis
• are less likely to have a family history of psychotic disorders
• have hallucinations that tend to be more visual
• have significantly higher rates of substance use disorder, with chronic, heavy use
• have more depressive symptoms and more anxiety
• have higher rates of suicidal ideation.
Drug-induced psychosis is a transient condition with an abrupt onset that typically resolves on its own in hours or days. Schizophrenia is a chronic brain disorder characterized by recurring episodes of psychosis. According to the Diagnostic and Statistical Manual of Mental Disorders, “schizophrenia lasts for at least six months and includes at least one month of active-phase symptoms,” such as hallucinations, delusions, disorganized speech, and extremely disorganized or catatonic behavior.
The DSM states that up to a quarter of individuals presenting with a first episode of psychosis in different settings are reported to have substance/medication-induced psychotic disorder. There may be no difference between schizophrenia-based, or primary, psychosis and drug-induced psychosis in regard to the initial signs and symptoms; that is why frontline clinicians have a hard time distinguishing the two. The main difference is the trigger of an episode and its duration. Substance-induced psychosis is always provoked by a drug of some kind, or withdrawal from it. In schizophrenia, psychotic episodes can be triggered by stress. And substance-induced psychosis typically resolves in hours or days as the drug is metabolized and eliminated from the body.
An episode of drug-induced psychosis can be as short as a few hours, extend for a couple of days, or, rarely, persist for several weeks. In general, how long a substance-induced psychosis lasts depends on the type of substance used and, to a lesser degree, for how long the substance has been used.
• Methamphetamine-induced psychosis can be intense but usually lasts only for a few hours while the acute intoxication lasts. It can also occur during withdrawal from chronic meth use and last up to a week.
• Opiates are nervous system depressants and, when stopped after long-term use, can have rebound effects that include psychotic symptoms—opiate withdrawal psychosis. The condition is transient and lasts until the drug is completely cleared from a person’s system.
• Alcohol, when used over a very long period of time, can stimulate a transient psychosis that lasts for the amount of time that that it takes for the substance to be metabolized and leave the system. Alcohol can also induce psychosis during withdrawal after a long period of chronic use. It can develop within 24 hours after heavy alcohol use stops and can last for several days.
• Cannabis, or marijuana, is increasingly linked to psychotic episodes because of breeding practices that deliberately increase the potency of the marijuana plant and the manufacture of highly potent synthetic cannabis. Cannabis psychosis typically lasts as long as the intoxication lasts, which may be up to two days. But cannabis-induced psychosis markedly increases the risk for primary psychotic disorders such as schizophrenia and the mania associated with bipolar disorder.
Enduring symptoms of psychosis following an episode of substance provoked psychosis may indicate conversion to a primary mental health disorder.
A family history of schizophrenia has been identified as a marker of vulnerability to psychotic response to substance use. In addition, early use of such drugs creates vulnerability, as does heavy use of them, particularly over a long period of time.
Increasingly however, drugs are changing. There are new substances of abuse being synthesized regularly, largely in illicit laboratories around the world, that by the nature of their chemical makeup increase the potential for psychotic response. They tend to be particularly powerful and affect receptors for neurotransmitters known to be involved in the production of psychotic symptoms; they also often have toxic effects. Synthetic cannabinoids are a well-established example, and reports indicate that they are far more likely than plant marijuana to cause not just transient psychosis but chronic psychosis. While many such drugs are banned by the FDA, new variants are continually being developed that elude the prohibitions.
Marijuana, too, has been changing—significant because marijuana use it at historically high levels among high school and college students. As a result of plant breeding, the marijuana sold today has a significantly higher content of THC (tetrahydrocannabinol), the psychoactive compound that is responsible for the marijuana high, than it did just a few years ago. The more potent the dose, the greater the risk of provoking a psychotic episode, especially among the young—who, studies show, increasingly believe that marijuana is risk-free.
There is evidence suggesting that substance use and development of a psychotic episode may share a common underlying risk factor. Studies show that the majority of patients having a first episode of primary psychosis—62 percent—have a current substance use problem, while 74 percent have had one sometime in their life. Alcohol, nicotine, and cannabis are the substances most commonly abused by people with psychotic disorders. It is possible that such people are drawn to drugs as a way to self-medicate emerging psychiatric symptoms.
Substance/Medication-Induced Psychotic Disorder can occur with the use of, or during withdrawal from, alcohol, recreational drugs, and even prescription medications such as opioids and sedatives/hypnotics. Other substances that can trigger a psychotic event include cocaine, amphetamines, phencyclidine (PCP), and alcohol. More than half of methamphetamine users have experienced short- or long-term psychosis. Studies have found that chronic use of cannabis, especially when started at a young age, can also induce psychosis.
There is very good converging evidence from multiple types of studies of multiple populations that cannabis use can precipitate acute, short-term psychosis, especially in chronic users and heavy users, the majority of whom are young males. While the incidence is relatively low, and the symptoms may vary widely in severity, the large and growing number of cannabis users—hundreds of millions worldwide, including 15.3 percent of the U.S. population each year—and the increasing potency of cannabis products, as well as the development and illicit use of powerful synthetic cannabinoids (often called “spice”), make cannabis-induced psychosis a substantial clinical problem.
In fact, medical experts voice surprise that the growing use of cannabis has led to decreased perceptions of its harmfulness at the very time when its ability to induce psychosis has become clinically problematic. The psychotic features of cannabis are directly related to the content of tetrahydrocannabinol (THC) in the cannabis—and the THC content of cannabis is rapidly rising. The cannabis content of today’s marijuana is many times greater than that of the marijuana available a generation ago.
Synthetic cannabis appears to be more psychotogenic than natural cannabis and is particularly associated with psychosis and paranoia. Persecutory delusions are common, along with anxiety. People often experience depersonalization/derealization, a condition in which they feel disconnected from their body, their surroundings, or both. Studies show that natural, plant-based cannabis contains an antipsychotic compound, cannabidiol (CBD) that is neuroprotective and acts in opposition to the THC known to cause the marijuana high.
The psychosis induced by cannabis may arise in minutes, when inhaled, or hours, when ingested, after cannabis use, and it may persist for days. What is becoming increasingly clear is that an unusually high proportion of those who develop an episode of cannabis-induced psychosis—close to 50 percent—later develop the psychotic disorder schizophrenia or bipolar disorder. More than half of them do so within 3.1 years.
Studies show that of all substances, cannabis has the highest rate of conversion from substance-induced psychosis to schizophrenia or bipolar disorder. The high rate of conversion may, in fact, be an undercount, given the advent of synthetic cannabinoids and their documented capacity to provoke psychosis, even after a single dose; such drugs have a powerful appeal—they are undetectable by conventional urine drug screens
Adding to clinical concern is the well-established fact that people with emerging psychosis often self-medicate their symptoms with cannabis. It can be challenging for those providing care to distinguish which patients are experiencing a true psychotic break and which are experiencing transient cannabis-induced psychotic disorder.
The high rate of conversion of cannabis-induced psychosis to schizophrenia may reflect the widespread use of cannabis among young people. It is thought that cannabis use has the capacity to particularly affect developing brains in such a way as to lay the foundation for future psychoses. Cannabis use may also interact with genetic vulnerability to schizophrenia in complex ways. For example, studies show that genetic risk for schizophrenia slightly elevates the likelihood of cannabis use, while cannabis use ups the risk of schizophrenia in those genetically predisposed to the disorder. Cannabis may enduringly alter the activity of genes coding for enzymes involved in the breakdown of the neurotransmitter dopamine.
Because of the risk of conversion to a primary psychotic disorder, people experiencing a transient cannabis-induced psychosis should be periodically monitored for the development of schizophrenia or bipolar disorder.
Some prescribed medications and many psychoactive agents used medicinally or illicitly can cause an acute short-term psychosis. Among prescribed medications, the perhaps best known are steroids, widely prescribed short-term and long-term to suppress inflammatory and immune processes. Steroids can induce a number of psychiatric symptoms, including mania, depression and anxiety, as well as psychosis, and reports indicate that up to 5 percent of patients treated with corticosteroids experience such reactions. Steroid-induced psychosis is relatively rare, marked by delusions, hallucinations, or both, and resolves with a reduction in drug dosage and administration of an antipsychotic agent.
Among psychoactive drugs, most notable are stimulants, such as amphetamines and cocaine, and hallucinogens. Studies show that approximately 40 percent of those who chronically use the potent amphetamine analog methamphetamine experience acute psychosis. The number is especially concerning as methamphetamine use has been rising around the world. Users of crystallized meth are especially likely to experience drug-induced psychosis.
Prominent symptoms are auditory, visual, and tactile hallucinations—patients may feel that bugs are crawling all over them—as well as persecutory delusions, particularly relating to drug use. Amphetamine-type stimulants are the most widely used type of illicit drug worldwide after cannabis, easy and cost-effective to manufacture in clandestine laboratories. In the U.S., meth use is twice as common in rural areas than in urban areas. The frequency of psychotic symptoms among chronic meth users is thought to explain their high rate of encounters with the criminal justice system; a high proportion of meth users experiencing paranoia purchase a weapon, use a weapon, or assault others. Meth-induced psychosis is usually transient and resolves as drug levels diminish and intoxication recedes..
As with methamphetamine, frequent high-dose cocaine use poses the risk of substance-induced psychosis. Studies indicate that more than half of cocaine users experience transient psychotic symptoms, such as paranoia, suspiciousness, and hallucinations., particularly auditory ones. Studies report that the higher the cocaine dose, the greater the severity of psychotic symptoms. And the younger the age at which a person uses cocaine, the greater the vulnerability to psychotic symptoms.
It is the very nature of hallucinogens such as LSD to alter perception and create hallucinations, and reportedly up to 27 percent of those using hallucinogens experience transient episodes of psychosis. But hallucinogen-induced psychosis does not appear to pose the risk of conversion to schizophrenia. Studies find no link between lifetime use of psychedelics and increased rate of any mental health outcomes. Nor have reports emerged of prolonged psychosis from recent trials of psilocybin, LSD or other hallucinogens. In fact, specific hallucinogens are under study, in combination with psychotherapy, for their ability to alleviate mental disorders.
Cannabis, or marijuana, is on the rise as a major provocateur of substance-induced psychosis, due to the increasing potency of plant marijuana and the manufacture of synthetic cannabis. Cannabis-induced psychosis is especially associated with depersonalization/derealization, a condition in which people feel disconnected from their body, their surroundings, or both.
Of all the psychoactive agents that can induce transient psychosis, alcohol appears to be the best known but not the most likely. Acute psychosis, characterized by hallucinations, paranoia, and fear, can manifest during acute intoxication, during withdrawal, or as a consequence of long-term heavy alcohol use.
Use of opioid drugs such as heroin is not typically associated with psychotic symptoms, but such drugs can precipitate hallucinations and delusions, along with irritability, especially upon abrupt stoppage after chronic use. Psychotic symptoms may emerge during the withdrawal period a few days after stopping drug use and continue for several weeks. Withdrawal from heavy, chronic use is often accomplished most safely in a supervised setting in which patients can be closely monitored through the earliest stages of addiction recovery.
With many drugs, the experience of substance/medication-induced psychosis is associated with increased risk of later developing a primary psychotic condition such as schizophrenia. Cannabis, methamphetamines, and cocaine are among the most widely abused drugs, and all are associated with development of schizophrenia or bipolar disorder months or years after a transient experience of substance-induced psychotic symptoms. Their capacity to generate effects similar to those seen in a psychotic state earns them the label “psychotomimetic” agents.
Medical scientists debate what causes the “conversion” of transient psychotic symptoms into a more enduring psychiatric disorder. There’s some evidence that it occurs in those with a family history of mental illness, suggesting that the transient symptoms activate a genetic predisposition. People with early psychotic symptoms are also known to frequently abuse psychotomimetic drugs.
But other factors play a role in the conversion of transient psychosis into primary psychosis. For example, it is known that the conversion is more likely to occur in those of younger age at the time of transient psychosis or who start chronic use of a psychoactive substance at a younger age. Research documents that the human brain is still developing well in to the 20s, during which it may be especially vulnerable to permanent disruption. Substance use, and especially cannabis use, occurs primarily among the young.
Chronicity of usage and amount of substance consumed are also linked to conversion to schizophrenia. All told, the evidence suggests that there are both factors within people and properties of psychoactive substances that make them neurotoxic, able to indelibly alter brain function.
Clinical experts are concerned that the variety of substances capable of provoking a psychotic episode is increasing in such a way to significantly amplify the risk of primary psychosis. The ease and profitability of illicit manufacture of drugs is leading to the steady development of new synthetic variants of psychoactive agents that are many times more powerful than the parent agent; synthetic cannabinoids and synthetic opioids (such as fentanyl) have made headlines for their behavioral effects. Both the short- and long-term effects of such drugs on the brain are largely unknown—but that hasn’t stopped such drugs from having, as one study puts it, “rapidly entered into the common pool of abusers' habits.”
Substance/medication-induced psychosis incidents are often seen in hospital emergency rooms and mental health crisis intervention centers. Since patients with mental health disorders can also have medication overuse or substance abuse problems, the frontline clinician must first determine whether psychotic symptoms are due to a condition such as schizophrenia or to bipolar disorder or to the substance itself.
In practice, clinicians often struggle to distinguish a substance-induced psychosis from a primary psychotic illness or a psychotic illness with comorbid substance use. The distinction matters for indicating the best course of treatment.
There is no specific treatment to counteract a substance/medication-induced psychotic disorder. In general, but depending on the type of substance that triggered the psychotic event, treatment of a transient substance-induced psychotic episode typically consists of monitoring the patient in a calm, quiet environment. A dose of an antipsychotic agent such as haloperidol or anti-anxiety medication such as a benzodiazepine may be administered to reduce symptoms, especially in the case of psychosis due to amphetamines or other dopamine-stimulating drugs.
Recovery from transient substance-induced psychosis is the rule. The psychosis typically resolves in hours or a few days.
However, substance-induced psychosis can trigger or unmask a primary psychosis, particularly in those with a family history of psychiatric problems and those who start substance use early. Episodes of primary psychosis can last for months. Further, psychosis is itself neurotoxic, setting off inflammatory and other changes that damage nerve cells. For example, researchers have noted significant reductions in the levels of an important nerve growth factor, BDNF (brain-derived neurotrophic factor), in persons with substance-induced psychosis. Such changes suggest diminished neuroplasticity and resilience of brain cells and make a strong case for prompt medical attention to substance-induced psychosis.
There is no one specific treatment for drug-induced psychosis, and it is not always necessary to give a person medication to counteract the psychosis. The first order of care usually involves stopping the drug that triggered the psychosis, then monitoring the person in a safe and calm environment. That is often all that is needed, especially when the triggering substance is a hallucinogen.
If the person is agitated, an anti-anxiety agent may be given. In cases of psychosis triggered by use of an amphetamine-related substance, which stimulates the release of dopamine in the brain, an antipsychotic medication such as haloperidol may be given to alleviate the acute psychotic symptoms.
Once the psychosis has passed, those who are chronic drug users are often advised to begin treatment for substance use disorder. In situations where the psychosis is triggered by a prescription drug used to manage a medical condition, patient and doctor need to find an alternative treatment.
A significant body of evidence ties primary psychotic episodes to lasting disturbances in brain structure and function. Researchers document shrinkage in certain brain regions and loss of connectivity, resulting in alterations of processing speed, among other changes. Little is known about the long-term consequences of a transient episode of psychosis, except that it is a significant stress to the system.
Evidence indicates that most people experiencing a transient substance-induced psychosis suffer no lasting damage. There is some evidence, however, that use of substances at a young age or for a long period of time can alter brain function in ways that increase the likelihood of developing such chronic conditions as schizophrenia and bipolar disorder. There is little research into long-term harm to brain structure or function from highly potent synthetic substances manufactured illicitly and widely distributed, but concern is warranted.
What is known is that an episode of substance-induced psychosis can also unmask an underlying vulnerability to schizophrenia. The substance that triggers the psychosis does not directly cause schizophrenia; it activates a predisposition, typically in those with a family history of mental illness, perhaps by altering the function of one or more gene variants.
There are immediate dangers and longer-term dangers if an episode of substance-induced psychosis is not attended to. In the short term, the psychosis may carry the immediate risk of harm to the person or others. The delusions are real to the people experiencing them, and there is the possibility they may act on them. In addition, the changes in perception can be extremely distressing to a person, making suicide a risk.
Substance-induced psychosis typically resolves within hours or days. Nevertheless, there is some evidence that use of the triggering substance—particularly the case with powerful synthetic drugs— can indelibly alter brain structure or function and create ongoing psychiatric problems. Further, substance use itself may signal an emerging primary psychosis that needs ongoing treatment. And transient episodes of psychosis can convert to primary psychosis within months or years. Because it is impossible to know at the outset whether an episode will be a one-time event, periodic monitoring or follow-up is considered advisable.
If the psychosis unmasks an underlying mental health disorder or precipitates the development of schizophrenia or bipolar disorder, psychiatric treatment is especially urgent. There is evidence that psychosis can itself be neurotoxic, damaging to nerve cells; that makes the duration of untreated psychosis an important factor in prognosis. Studies show that the shorter the time between a first psychotic episode and administration of treatment, the better the long-term outlook for people with the disorder.
Although drug-induced psychotic symptoms can be short-lived, they can be terrifying and dangerous. They carry the immediate risk of self-harm, including suicide, as well as the risk of harm to others.
Experts agree that drug-induced psychosis is best regarded as a medical emergency. If it is not possible to get a person to seek help on their own, it is worth making the effort to get them to an emergency room. As a last resort, it may be necessary to call the police as a way to get help. Medication may be in order for some symptoms.
At the very least, care is required for communicating with a person in a psychotic state. It can be tempting to dismiss the thoughts of the person experiencing psychosis, but those thoughts are very real to that person and may drive their behavior.
Here is some general advice for engaging with anyone in a psychotic state:
• Let the person speak without interruption at their own pace
• When addressing the person , use short sentences, in a calm, non-threatening voice
• Do not judge, contradict, or try to demonstrate the falsity of the person’s beliefs and experiences
• Listen and be supportive of the person’s feelings
• Do not get angry and do not take any statements personally
• Empathize with the person’s experience
• Treat the person with respect
• Understand that the person may be terrified of what they are experiencing
• Ask how you can be of help, but accept that they may not want to talk.