1. Overview — Substance-Induced Psychosis (SIPD)

Substance-Induced Psychosis (SIPD), whose full name in DSM-5-TR is Substance/Medication-Induced Psychotic Disorder, is a condition in which delusions or hallucinations arise from the direct influence of chemicals, whether they are illicit drugs, stimulants, misused medications, certain prescribed drugs, or even some forms of environmental toxins. This is not a primary psychotic illness like schizophrenia that gradually develops over time, but rather a state of psychosis that is “triggered” by an external substance that acutely disrupts brain mechanisms.

In terms of the overall picture, SIPD is considered one of the most frequently misdiagnosed psychotic presentations in clinical practice, because the clinical picture is almost indistinguishable from schizophrenia. The key difference, however, lies in the timing of onset in direct relation to substance use. To confirm the diagnosis, clinicians must use a combination of history-taking, physical examination, urine/blood toxicology screens, and careful observation of the time course after substance cessation.

The core of this condition rests on three major points:

There are genuine psychotic symptoms. It is not just intoxication, not just confusion or being “out of it”, but a level of disturbance where the person actually “experiences” or “believes” things that are not real, such as hearing people speaking when no one is there, or believing that someone is following them or trying to harm them despite the absence of any evidence.

Symptoms emerge immediately after using a substance, or during intoxication/withdrawal, especially with substances that have a strong potential to destabilize dopamine and glutamate systems, such as high-THC cannabis, amphetamines, cocaine, or hallucinogens.

The symptoms cannot be better explained by a pre-existing primary psychotic disorder such as schizophrenia — meaning the clinician must be confident that the main cause is the substance, not an underlying brain illness that was already there.

A classic example frequently seen in clinical settings is Cannabis-Induced Psychosis (CIP), which has been increasing worldwide following cannabis legalization in many countries. High-THC cannabis, in particular, can trigger psychosis in individuals with no prior history of psychotic illness. The risk becomes markedly higher in those who start using at a young age, use frequently, use heavily, or have a family history of schizophrenia or other psychotic disorders.

Another group often encountered is psychosis resulting from amphetamine / methamphetamine, where symptoms are typically severe: intense agitation, extreme anxiety, marked paranoia, seeing people who are “after them” or hearing commanding voices. In contrast, alcohol-related psychosis often emerges during withdrawal in chronic users, and in some cases it progresses to full-blown visual hallucinosis.

From a prognostic standpoint, SIPD is a phenomenon that warrants close and longer-term follow-up than most people assume. While many symptoms may subside within hours to days after the substance’s effects wear off, in some individuals the symptoms do not resolve after cessation, and a pattern of illness resembling schizophrenia gradually becomes increasingly evident. Meta-analytic research indicates that about 32% of individuals who have experienced Substance-Induced Psychosis will later develop schizophrenia or bipolar disorder in the long term, and the highest rates are in Cannabis-Induced Psychosis, where nearly half (~47%) may transform into a chronic psychotic disorder.

Therefore, SIPD is not simply “you got high and tripped out, you’ll be fine later”. It is one of the “warning windows” that the brain may have an underlying vulnerability. Once triggered by psychoactive substances, psychosis can surface rapidly — like flipping a shortcut switch in an abnormal brain circuit. Without serious and sustained follow-up, one may miss the golden window for treating first-episode psychosis.

Ultimately, the most important point is this: SIPD is not just about “having hallucinations”. It is an intersection of chemicals, brain mechanisms, genetics, and environment, working together in a complex way. This gives the condition high clinical importance and explains why clinicians often choose to follow patients in this group for more than 6–12 months, to determine whether their symptoms are truly substance-induced or whether they represent a chronic psychotic disorder that has been triggered and unmasked by substance use.

2. Core Symptoms — The central features of Substance-Induced Psychosis

The core ideas of this section can be broken into three layers:

The “appearance” of the symptoms looks like any other psychosis – if you look only at the patient while they are acutely psychotic, you can hardly tell whether it is schizophrenia or substance-induced.

The key difference lies in the “timing” and “relationship to the substance” – symptoms usually peak during intoxication/withdrawal or shortly after substance use.

The severity goes beyond simple intoxication – it is not just being high, dreamy, or overexcited; it reaches a point where perception, reality testing, and the ability to function in daily life are truly disrupted.

2.1 Core axis: Delusions

Delusions in Substance-Induced Psychosis often follow patterns similar to those in schizophrenia, but they frequently carry the “flavor” of the substance-use context, such as themes involving police, drugs, criminal groups, surveillance, etc.

Key characteristics:

They are beliefs that are clearly false in relation to reality, yet the person holds onto them very rigidly.
No amount of reasoning can make the person “let go” of these beliefs.
They generate fear, anger, and intense paranoia, at a level that clearly changes the person’s behavior.

Common types:

Persecutory / Paranoid Delusions

The standard theme is “someone is trying to kill me / arrest me / set me up”.

Examples:

Believing the police are wiretapping their phone because they use drugs.
Believing neighbors are collaborating with a drug gang to plan an attack or arrest.
Seeing a black car passing by the house → interpreting it as “they’re surveilling me”.

The difference from ordinary suspicion, where some insight remains, is that in true delusion the patient never asks, “Am I overthinking this?”. They believe it completely.

Grandiose Delusions

Seen in some cases, especially where stimulants/hallucinogens are used, alongside an underlying personality with unstable self-esteem or in cases with abnormally elevated mood (mania-like).

Frequently encountered content includes:

“I understand the entire universe now.”
“I am the chosen one / I have psychic powers / I can communicate with God or aliens.”

Sometimes the delusion is linked directly to substance effects, such as:

“When I used LSD, I understood the ultimate truth of the world; it’s like God gave me a special mission.”

Referential Delusions / Ideas of Reference

The person believes that certain signals or messages in TV shows, songs, social media, or from people passing by are “sent specifically to them.”

For example:

Turning on the TV and hearing a line that resembles their private thoughts → believing the program is talking about them or hypnotizing them.
Seeing people laughing in a café → interpreting it as “they’re laughing at me.”

In the context of substance-related states, this often co-occurs with intoxication from cannabis or amphetamines.

Key point:
Delusions in SIPD may remit after the substance’s effects wear off. However, while the episode is active, the person believes the delusion 100%, and that is precisely why it can be so dangerous for behavior and safety.

2.2 Core axis: Hallucinations

Hallucinations in SIPD are perceptions that arise subjectively (seeing / hearing / feeling) despite no external stimulus being present, and the level of realism is often “as seamless as real life”, not just vague images or mild imaginings.

Common types:

Auditory Hallucinations

These are the most common, especially in psychosis strongly associated with dopamine, such as that triggered by cannabis, amphetamines, or in some alcohol-related cases.

Classic patterns include:

Hearing voices talking about oneself.
Voices insulting, criticizing, or belittling.
Voices commanding them to do certain things (command hallucinations), e.g.,

“Get out of the house right now.”
“They’re going to kill you, run now.”

The frightening part is that the patient feels the voice comes from outside, not from their own thoughts, and they often respond to the voices as if someone is actually speaking to them.

Visual Hallucinations

Commonly seen with: hallucinogens (LSD, psilocybin), high-dose stimulants, alcohol withdrawal, and ketamine/PCP.

They range from:

Seeing shadowy figures or animals flashing by.
Seeing a stranger who doesn’t exist walking at the foot of the bed.
Distorted images, overly bright colors, bizarre shapes (especially with hallucinogens).

In methamphetamine use, it is often reported that people see “pursuers / shadow people”, which sharply amplifies paranoia.

Tactile Hallucinations

Classic with some stimulant or alcohol cases. For example:

Feeling like insects are crawling under the skin (formication).
Feeling something moving or slithering inside the body.

The sensation can be so realistic that some people use knives or sharp objects to scratch or cut their skin to “get it out” → putting them at high risk of serious injury.

Olfactory / Gustatory Hallucinations

Not as common as auditory/visual, but they do occur. For example:

Constantly smelling smoke or burning, even when nothing is burning.
Tasting strange, unexplainable flavors in the mouth.

Key point:
Hallucinations in SIPD are often intense and raw, especially during periods of high-dose intoxication or withdrawal. The intensity of these experiences can lead to dangerous behaviors, such as running out of the house at night, or climbing off balconies to “escape”.

2.3 Associated symptoms that crush quality of life

Beyond delusions and hallucinations, there are other “accompanying symptoms” that complete the picture of full-blown psychosis:

Disorganized Thinking / Speech

Speech is off-topic, changing subjects rapidly.

Starting one sentence and then drifting into another.

Using odd words or phrases that don’t fit the context.

Listeners feel “I have no idea what they’re trying to say.”

Clinically, this is often viewed through the lens of the formal pattern of speech (formal thought disorder) rather than trying to “read the person’s mind.”

Abnormal Psychomotor Behavior

Agitation: pacing, unable to sit still.

Talking non-stop, with seemingly endless energy (especially with amphetamines / cocaine).

In some cases, the opposite occurs: stupor / staring, minimal responsiveness, which can appear in cases with co-occurring catatonia.

Mood Symptoms

Intense anxiety.

Irrational fear (driven by paranoid delusions).

Depression, hopelessness, and guilt after experiencing a psychotic episode.

Or hyper-euphoria, resembling mania (especially when there is an underlying bipolar diathesis).

Impaired Insight

Patients often “do not realize they are ill.”

They may believe:

They are not hallucinating; other people simply “cannot see the truth.”
They are just “picking up signals” that ordinary people don’t understand.

This makes treatment and motivating them to stop using substances very difficult, because in their view, what they see/hear “is reality.”

2.4 Substance-Specific Flavors — characteristic patterns by substance

1) Cannabis (Cannabis-Induced Psychosis)

Common features:

Paranoia – believing others are watching them, secretly talking about them.
Ideas of Reference – songs / posts / other people’s gestures are “sending messages to me.”
Perceptual distortions – time feels slower or faster, the size/color of objects feels altered.
Auditory/visual hallucinations, ranging from mild (hearing whispers) to fully formed experiences.

Most prominent in:

Users of high-THC strains,
Frequent users,
Those who start young, or
Individuals with genetic vulnerability.

2) Amphetamine / Methamphetamine / Stimulants

Key features:

Very severe paranoid delusions – “Everyone is going to hurt me.”
Tactile hallucinations – feeling insects crawling, sensations of movement under the skin.
Hypervigilance – constantly in “fight-or-flight” mode.
High agitation – insomnia, constant movement, unending racing thoughts.

The dangerous situation occurs when the patient fully believes that “If I don’t act first, I’ll be the one hurt,” which elevates the risk of violent behavior.

3) LSD / Psilocybin / Classical Hallucinogens

Not every “trip” turns into psychosis, but when it breaks bad, it can look like:

Extremely vivid visual hallucinations – seeing wall patterns move, colors blend and morph, objects changing form.

Distortions of self and reality – feeling like one’s self is melting or merging with the environment (ego dissolution).

Experiences ranging from:

Mystical (“I understand the true nature of the universe”), to
Fear-based (“Everything is collapsing / the world is ending”).

If there is pre-existing vulnerability, a single trip can act as the trigger for a prolonged psychotic episode lasting weeks to months.

4) Ketamine / PCP / NMDA-Antagonists

Symptoms typically go in the direction of:

Depersonalization – feeling detached from oneself.
Dissociation – feeling like observing the world through a veil, not truly feeling “This is me, here and now.”
Thought fragmentation – thoughts feel scattered, broken into pieces, not forming coherent sequences.

At high doses, and in the presence of risk factors, these can progress to full-blown psychosis.

2.5 The point at which SIPD becomes “more than just being high”

What differentiates “just intoxicated” from Substance-Induced Psychosis is:

The degree of realism in the delusions/hallucinations.

The persistence of symptoms even as the substance’s acute effects are waning.

The level of functional impairment – inability to work, study, live with others, presence of high-risk behaviors.

The need for psychiatric treatment (e.g., antipsychotics, hospital admission) to prevent harm.

Someone who is just intoxicated may have odd thoughts, feel dreamy, but can still recognize “This is because of the drug, I’m high.”
In SIPD, most patients are fully convinced that “this is reality”, and their behaviors are driven by that belief.

3. Diagnostic Criteria — DSM-5-TR & ICD ways of thinking when encountering Substance-Induced Psychosis

This section is the “formal language” clinicians use to differentiate between:

Substance/Medication-Induced Psychotic Disorder
vs.

Schizophrenia / Schizoaffective / Bipolar with psychotic features

vs.

Simple intoxication / delirium due to substances

3.1 Criterion A — Presence of “true” psychotic symptoms

The first criterion is straightforward but critical:

There must be at least one of the following:

Delusions, or
Hallucinations
(Having both is also possible.)

This means:

Just being confused / groggy / disoriented / talking nonsensically is not enough.
There must be at least:

A false belief strongly deviating from reality (delusion), or
A perception without an actual external stimulus (hallucination).

Tip for writing/communication:
When putting this on a website, you can include a summary graphic like:

“No delusions or hallucinations = not Substance-Induced Psychotic Disorder under DSM-5-TR, even if the person is very intoxicated.”

3.2 Criterion B — Relationship to the substance (the substance as the trigger)

This is the heart of calling it “Substance-Induced.”

There must be evidence that:

The symptoms develop during substance use or within a short period after use.

For example, psychosis begins within minutes–hours after heavy cannabis use.
Or within 1–2 days after an amphetamine binge.
Or emerges during withdrawal (e.g., alcohol withdrawal psychosis).

The substance used has the potential to cause psychosis.

Not just any substance (e.g., vitamin C, saline).
It must be a substance which evidence shows can be followed by psychosis during use or withdrawal, such as:

Cannabis, alcohol, stimulants, hallucinogens, ketamine, some steroids, certain dopaminergic medications, etc.

Sources of information used to confirm Criterion B:

History from the patient – what substances were used, in what amounts, and when was the last use.

Collateral information from family/friends – because patients often omit or cannot recall details.

Physical exam and laboratory testing – urine toxicology, blood tests.

A detailed timeline – mapping:

“Which day and time did they use?” → “When did the hallucinations/delusions begin?” → “When did they resolve?”

3.3 Criterion C — Not a primary psychotic disorder

This is the challenging part, and clinically it translates to the question:

“Is this psychosis caused by drugs, or an underlying psychotic disorder that just happens to occur in someone who uses drugs?”

DSM-5-TR advises that one should lean toward diagnosing a primary psychotic disorder (e.g., schizophrenia) rather than SIPD if any of the following are true:

Psychotic symptoms clearly predate significant substance use.

For example, the patient had hallucinations/delusions starting at age 17.
Cannabis/amphetamine use only started at 19.
Directionality is then “psychosis first” → the substance is not the main cause.

Symptoms persist for longer than expected after substance cessation (e.g., > 1 month).

In pure SIPD, symptoms should gradually subside after stopping the substance and passing the intoxication/withdrawal phase.
If the patient stays abstinent, but after 2–3 months still has clear delusions/hallucinations, you must consider the schizophrenia spectrum or another primary psychotic disorder.

There is a clear history of a prior psychotic episode unrelated to substance use.

For example, they were admitted at age 20 for psychosis without any substance use at that time.
Now, at 25, they start using cannabis and psychosis flares again → the substance may be a trigger, but not the root cause.

There is genetic/biological evidence pointing toward an underlying psychotic disorder.

For instance, multiple family members have schizophrenia.
There were clear premorbid abnormalities (social withdrawal, odd behavior) long before substance use.

In simple terms:
Criterion C is essentially saying:

“We cannot attribute all psychosis solely to substances when evidence suggests an underlying primary psychotic disorder. In those cases, we should diagnose primary psychotic disorder + SUD (Substance Use Disorder) instead.”

3.4 Criterion D — Not just ordinary delirium

Delirium is a state where:

The level of consciousness fluctuates (sometimes alert, sometimes confused/disoriented).
There is a major breakdown in attention, focus, and concentration.
Onset is acute, and mental status fluctuates throughout the day.

In delirium, there may also be:

Hallucinations.
False beliefs.
Odd behavior.

However, DSM-5-TR clearly states that if psychotic symptoms occur “exclusively in the context of delirium”, the appropriate diagnosis is Substance-Induced Delirium, not Substance-Induced Psychotic Disorder.

Why differentiate?

Treatment and prognosis differ.
Delirium usually indicates significant underlying medical/neurobiological issues, such as severe withdrawal, metabolic disturbances, or infection.
SIPD focuses more on the psychosis axis and future risk of chronic psychotic disorders.

3.5 Criterion E — There must be real distress or impairment

DSM-5-TR emphasizes that any psychiatric disorder must:

Produce “distress” or “impairment in social, occupational, or other important areas of functioning.”

In everyday language:

If the symptoms are mild, the person can still live, study, and work without major disruption, then it is not considered a disorder.

For SIPD, this means:

They cannot work / cannot study.
Serious family conflicts occur.
They are fired from jobs.
They are arrested due to behavior driven by delusions/hallucinations.
There is clear risk of harm to self or others.

3.6 ICD-11 perspective — focus on “substance-specific coding” and timeline

ICD-11 also includes a category for “Substance-Induced Psychotic Disorder”, and further classifies it by substance type, such as:

Cannabis-induced psychotic disorder
Alcohol-induced psychotic disorder
Stimulant-induced psychotic disorder
etc.

Key points from ICD-11:

There must be an onset of psychosis closely linked in time to substance use.

Symptoms must be too severe to be explained by ordinary intoxication alone.

It must be differentiated from:

Primary psychotic disorders
Intoxication with mild perceptual disturbances
Delirium

ICD-11 thus allows us to code specifically which substance is associated with the psychosis, which is useful in research and clinical work for mapping patterns across countries and populations.

3.7 Practical Clinical Thinking – How clinicians actually think when they see these cases

When a clinician encounters a patient who:

Has just used cannabis or a strong drug.
Starts speaking oddly and is intensely fearful of being followed.
Reports seeing people in the house when no one is there.

The clinician does not immediately jump to one conclusion, but instead goes through a stepwise mental checklist:

Are there genuinely delusions/hallucinations? (meets Criterion A)

Did they start in clear temporal relation to substance use or withdrawal? (Criterion B)

Is there any history of prior psychosis? Any family history? Do symptoms resolve after substance cessation? (Criterion C)

What is the level of consciousness and attention right now? Do they appear delirious? (Criterion D)

How much is this impacting their life and safety? (Criterion E)

In the end, the diagnosis is not simply a matter of “ticking DSM boxes,” but of looking at the longitudinal picture:

If symptoms resolve fully after stopping the substance → likely pure SIPD + SUD.

If symptoms persist or recur despite abstinence → one must consider Schizophrenia / Bipolar / Schizoaffective + SUD.

4. Subtypes or Specifiers

Although DSM-5-TR uses a broad umbrella term, in practice clinicians often specify the substance type + onset pattern as important “specifiers,” for example (PsychDB+1):

By Substance Class

Alcohol-Induced Psychotic Disorder

Cannabis-Induced Psychotic Disorder

Phencyclidine (PCP)-Induced

Other Hallucinogen-Induced

Inhalant-Induced

Sedative, Hypnotic, or Anxiolytic-Induced

Amphetamine or Other Stimulant-Induced

Cocaine-Induced

Other (or Unknown) Substance-Induced

Onset Type

With onset during intoxication – occurs while the person is intoxicated or shortly after peak effect.

With onset during withdrawal – occurs during stopping or withdrawal from a substance, e.g., alcohol, benzodiazepines.

Course specifiers (used outside DSM but clinically useful):

Acute, resolving – symptoms resolve within a few days after stopping the substance.

Persistent psychosis after substance exposure – symptoms persist for weeks to months; one must consider conversion to schizophrenia/bipolar or a “persistent SIPD.”

Comorbid Substance Use Disorder

Specify, e.g., “with comorbid moderate/severe cannabis use disorder” or others, because this affects both prognosis and treatment planning.

5. Brain & Neurobiology — In-depth brain mechanisms in Substance-Induced Psychosis

This section explains why certain substances can actually cause hallucinations, delusions, fragmented thinking, or severe perceptual distortions to the level of psychosis.

The key point is: this is not just a matter of “the drug is strong so you hallucinate”, but the result of:

Disruption of neurotransmitter systems,
Destabilization of brain networks, and
Pre-existing vulnerabilities in the individual,

all linking together in a single chain.

To make it clearer, let’s look at it layer by layer.

5.1 Dopamine Dysregulation – The core truth that remains central

Even though modern research shows that psychosis is not caused solely by dopamine, dopamine dysfunction in the striatum remains a “neurosignature” of psychosis of all types — both schizophrenia and substance-induced psychosis.

Several key substances, such as amphetamine, methamphetamine, cocaine, and high-THC cannabis, create a state of:

➤ Hyperdopaminergia in the mesolimbic and associative striatum

This underlies one of the best current explanatory models of psychosis:

“Aberrant Salience” — the brain mis-assigns importance to meaningless events.

Ordinary conversation in the background → becomes “They’re talking about me.”
A car parked in front of the house → becomes “They’re watching me.”
Someone’s social media post → becomes “This is a secret message for me.”

This is the root of many delusional themes, especially paranoid and referential delusions.

Why does dopamine surge?

Amphetamine/cocaine → cause massive dopamine release and inhibit reuptake.

High-THC cannabis → disrupts the GABA–glutamate circuits that regulate dopamine firing, leading to unstable dopamine signaling.

When dopamine levels spike at the wrong time and place, the brain “selects what to pay attention to” incorrectly, mislabelling neutral stimuli as highly salient.

This explains why individuals who have used potent stimulants or strong cannabis can “misinterpret the world” so dramatically.

5.2 Cannabis-Induced Psychosis — The specific mechanism of cannabis

The main psychoactive component is Δ9-THC, which is a:

➤ CB1 receptor agonist

CB1 receptors are widely distributed throughout the brain, especially in the:

Prefrontal cortex
Striatum
Hippocampus
Amygdala

When THC enters the system, it overrides the normal endocannabinoid system, which usually fine-tunes synaptic signaling.

Major effects of THC:

(1) Disrupting the GABA → Glutamate → Dopamine chain

Even though THC does not directly spike dopamine like amphetamine, it destabilizes the circuits that control dopamine firing, leading to:

Dopamine surges at inappropriate times,
Paranoia and ideas of reference.

(2) Affecting memory & reality anchoring via the hippocampus

THC interferes with memory encoding.
The person can’t clearly remember what happened in what order.
This can cause incorrect linking of events → making it easier to form delusional explanations.

(3) Chronic use → Receptor downregulation

Heavy, long-term use leads to reduced CB1 receptor density.
This destabilizes brain function in the long run.
It increases vulnerability to psychosis, even after stopping cannabis.

(4) Age of onset matters greatly

Adolescence is a phase of synaptic pruning and myelination.
THC interferes directly with brain development.
This increases the risk of permanent schizophrenia in people with genetic vulnerability.

5.3 Stimulants (Amphetamine / Methamphetamine / Cocaine) — Explosive triggers of psychosis

Stimulants are among the fastest and most powerful inducers of psychosis.

Key mechanisms:

Massive, somewhat chaotic dopamine release.
Increased dopamine and norepinephrine in the prefrontal cortex.
High levels of oxidative stress.
Neurotoxic damage to dopaminergic terminals with chronic use.

Consequences:

Paranoia skyrockets immediately.
Tactile hallucinations such as “insects crawling under the skin.”
Hypervigilance — the person interprets nearly everything as a threat.
Risk of violence increases, due to misinterpretation plus panic.

With chronic use, certain brain regions (e.g., the prefrontal cortex) may suffer lasting damage → leading to impaired decision-making and poor impulse control.

5.4 Hallucinogens (LSD, Psilocybin, NBOMe) — Opening perception beyond the boundaries

The main mechanism is:

➤ 5-HT2A receptor agonism

Effects include:

Abnormal firing patterns of cortical pyramidal neurons.
Disturbed sensory gating.
Reduced activity in the default mode network → ego dissolution.
Excessive activation of the visual cortex → vivid hallucinations.

In otherwise healthy individuals this may just be a “trip,” but in vulnerable individuals, a single trip can trigger psychosis that persists for weeks to months.

5.5 NMDA Antagonists (Ketamine / PCP) — Mechanisms that closely mimic schizophrenia

This group is particularly interesting because these substances:

➤ Block NMDA receptors (glutamate)

This generates a symptom profile that resembles schizophrenia across the full spectrum:

Positive symptoms (hallucinations, delusions)
Negative symptoms (avolition, blunted affect)
Cognitive symptoms (working memory deficits, executive dysfunction)

This is a key piece of evidence that the glutamate system plays a crucial role in psychosis, not just dopamine.

5.6 Network-Level Disruption — Psychosis as a disorder of “circuits,” not just one neurotransmitter

Modern research suggests that psychosis is fundamentally:

A brain network disorder, not simply a single neurotransmitter problem.

Multiple circuits are involved, including:

Salience Network → disruption of the system that decides “what is important.”
Default Mode Network → disturbance at the interface of “self” and “thoughts.”
Frontostriatal loops → abnormalities in behavioral control and reward processing.

Additionally, there is involvement of:

Neuroinflammation
Oxidative stress
Abnormal synaptic pruning

All of this combines so that an initially episodic psychosis can evolve into a chronic psychotic disorder, especially in individuals with genetic risk or underlying trauma.

6. Causes & Risk Factors — What actually drives Substance-Induced Psychosis to occur

This section answers the big questions:
“Who is at risk of developing psychosis from substances? And what factors explain why some people use substances and seem fine, while others crash hard?”

There are six major categories:

6.1 Dose and pattern of use — Dose, Frequency, Potency

This is the most straightforward, direct factor.

Frequent use → increases risk.
Chronic (long-term) use → accumulates neurobiological impact.
High doses → can acutely overload the brain and trigger psychosis.
Using high-THC strains / synthetic cannabinoids → especially risky.
Using stimulants in binge patterns → can trigger a psychotic explosion within hours.

For cannabis specifically, psychosis risk rises sharply when:

Used daily.
Started in adolescence.
THC content > 15–20%.
Used in highly concentrated forms (dabs / wax / shatter).

6.2 Age of Onset — The age at which use begins can be destiny

The adolescent brain is still in the phase of “streamlining and organizing circuits” (synaptic pruning + myelination).

Substance use during this period is equivalent to directly interfering with a developing nervous system.

Findings from several studies:

Heavy cannabis use before age 15 → psychosis risk is many times higher than in those who start at age 20.
Schizophrenia risk increases in individuals with genetic vulnerability.
Stimulant use during adolescence → long-term damage to reward and impulse-control circuits.

This is why CIP and SIPD often begin between ages 15–25.

6.3 Genetics & Family History — Genetics as the silent bomb

Research clearly shows:

If there is a family history of schizophrenia / bipolar disorder / psychosis, the risk of SIPD increases by about 2–5 times.

This is because the brains of these individuals already carry a baseline vulnerability from genetics, and the substance acts as a trigger.

Real-world example:

An average person uses cannabis and feels nothing more than being high.
A person with a family history might reach their 5th–10th use and suddenly experience a severe psychotic episode.

Hence the phrase:
“Genetic load + Substance = Psychosis Switch.”

6.4 Psychosocial Vulnerability — Psychological wounds that render the brain fragile

This factor is often overlooked but extremely important.

Factors that increase psychosis risk when using substances include:

Childhood trauma (abuse, neglect)
Adverse childhood experiences
Being bullied in childhood
Chronic severe stress
Urbanicity (growing up in large cities is associated with higher risk)
Poverty / social exclusion
Pre-existing mental health conditions such as depression, anxiety, PTSD

In such contexts, psychoactive substances become “easy-to-ignite fuel.”

Especially with cannabis:

If the person has trauma + uses high-potency cannabis → psychosis risk is at least 2–3 times higher than in trauma-free users.

6.5 Polysubstance Use — Using multiple substances = a mixed explosive formula

If cannabis is used together with other substances such as:

Alcohol
Benzodiazepines
Stimulants
Ketamine
Opioids

→ The risk of psychosis multiplies.

Why?

Because each substance affects different neurotransmitter systems, and when combined, they produce:

Cross-activation
Disinhibition
Increased neurotoxicity

all of which are more intense than when using each substance on its own.

Furthermore, polysubstance use makes it harder for clinicians to pinpoint which substance is driving the psychosis → increasing the risk of missing an early-stage schizophrenia diagnosis.

6.6 Long-Term Risk — Transition from SIPD to chronic psychotic disorder

Recent meta-analytic data are alarming:

32.2% of Substance-Induced Psychosis cases → progress to schizophrenia or bipolar disorder.
In Cannabis-Induced Psychosis → the rate is as high as 47.4%.

Factors driving the transition from “episodic psychosis” to “chronic psychotic disorder” include:

Continued substance use / repeated use after the first psychotic episode.
Family history of psychotic illness.
Early age of onset for substance use.
Pre-existing personality or psychiatric abnormalities.
Chronic life stress.

This is why, in clinical practice, SIPD warrants long-term follow-up of at least 1–2 years to determine whether symptoms truly resolve or whether the patient is moving onto the trajectory of a chronic psychotic disorder.

7. Treatment & Management

7.1 Acute Management

Assess safety

Is there a risk of self-harm or harm to others?
Who are they living with?
Are there weapons or additional substances present?
If the person is severely agitated / has severe psychosis / is at high risk, consider hospital admission.

Immediate cessation of substances

Stop the trigger substance (cannabis, amphetamine, LSD, etc.).

If there is a withdrawal risk (e.g., alcohol, benzodiazepines), withdrawal must be managed safely. (MSD Manuals+1)

Medications in the acute phase

Antipsychotics (e.g., risperidone, olanzapine, haloperidol, etc.) – to reduce delusions/hallucinations.

Benzodiazepines – used short-term to reduce agitation, anxiety, and muscle tension, with care taken to avoid promoting dependency.

Address co-occurring problems: dehydration, high blood pressure, hyperthermia (in stimulant toxicity), electrolyte imbalances.

7.2 Assessment and treatment of Substance Use Disorder (SUD)

Utilize motivational interviewing, CBT for SUD, contingency management, etc.

May need to refer to:

Rehab programs,
Residential programs, or
Early intervention in psychosis programs that integrate SUD treatment. (nri-inc.org+2, comorbidityguidelines.org.au+2)

7.3 Longitudinal Follow-up

Monitor psychotic symptoms for at least 1–6 months after cessation.

If symptoms resolve with abstinence → more likely pure SIPD.

If symptoms persist or recur even without further substance use → consider primary psychotic disorder / schizophrenia spectrum.

In high-risk cases (e.g., heavy cannabis use + family history of schizophrenia) → provide long-term follow-up and detailed psychoeducation for the family. (PMC+1)

7.4 Psychosocial Interventions

Psychoeducation – provide information to patients and families about:

The risk of psychosis from substances.
The importance of abstinence.
Early warning signs of relapse.

Family intervention – help reduce expressed emotion and improve communication styles.

Social & Vocational rehabilitation – restore functioning in education/work and social skills, etc.

7.5 Harm Reduction (for those who cannot quit immediately)

Reduce amount/frequency of use.
Avoid high-potency THC, synthetic cannabinoids, polysubstance use.
Emphasize safety (no driving, not being alone if they have a history of substance-related psychosis).

8. Notes

8.1 The hardest part = differentiating SIPD from first-episode schizophrenia

Many patients first present to services with psychosis plus recent substance use.

The central question is:

“Is this just drug-related, or is this schizophrenia triggered by the drug?”

In most cases, time and follow-up (longitudinal course) are more informative than a single snapshot. (PMC+1)

8.2 Common misconceptions

“Once you stop using, you’ll get better on your own; no need for treatment.”

This is partly true in mild cases where symptoms resolve within a few days.
However, in many cases, psychosis lingers or recurs even after stopping the substance.

“Cannabis just makes you mellow; it doesn’t make you crazy.”

This is clearly contradicted by research showing that cannabis use (especially high-THC / heavy use / early onset) increases the risk of psychotic disorders and that CIP has the highest conversion rate to schizophrenia among all SIPD types. (PMC+2, adai.uw.edu+2)

8.3 Epidemiological angle worth knowing

Substance-Induced Psychosis accounts for a substantial portion of first-episode psychosis cases in many countries, particularly those with high cannabis/amphetamine use. (Frontiers+1)

This group itself is a “population at risk” for developing chronic psychotic disorders in the future → they should be routed into early intervention services as soon as possible.

8.4 Clinical Pearl – Cannabis-Induced Psychosis

Patterns commonly seen in CIP:

Male adolescents to young adults.

Heavy cannabis use (daily / several times per day) or high-potency THC.

Onset of paranoia, ideas of reference (“Everyone in the room is staring at me”), and auditory hallucinations.

Some may have had mild, vague symptoms before, but with heavier use, the psychosis becomes clearly expressed.

If the person stops cannabis but symptoms persist for months + there is a family history of schizophrenia, clinicians must seriously consider a primary psychotic disorder. (adai.uw.edu+2, adicciones.es+2)

Read Schizophrenia

📚 References

1) Diagnostic Manuals & Authoritative Clinical Sources

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Arlington, VA: APA; 2013.
American Psychiatric Association. DSM-5-TR (Text Revision). 2022.
World Health Organization. ICD-11: International Classification of Diseases 11th Revision. 2019–2024.
National Institute on Drug Abuse (NIDA). Drugs, Brains, and Behavior – The Science of Addiction.
National Institute for Health and Care Excellence (NICE). Psychosis and Schizophrenia in Adults: Prevention and Management.

2) Cannabis-Induced Psychosis / Substance-Induced Psychosis

Arseneault L, Cannon M, Poulton R, et al. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002.
Di Forti M, et al. High-potency cannabis and the risk of psychosis. Lancet Psychiatry. 2015.
Murray RM, Quigley H, Quattrone D, et al. Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis. World Psychiatry. 2016.
Alderson HL, Semple DM, et al. Risk of transition to schizophrenia following first admission with substance-induced psychosis: A population-based retrospective cohort study. Am J Psychiatry. 2017.
Kendler KS, Ohlsson H, Sundquist J, Sundquist K. Prediction of onset of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. Am J Psychiatry. 2019.

3) Dopamine, Glutamate & Neurobiology of Psychosis

Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III—final common pathway. Schizophrenia Bulletin. 2009.
Howes OD, McCutcheon R, et al. Dopamine dysfunction in schizophrenia and psychosis: meta-analysis. Nature Reviews Neuroscience. 2015.
Krystal JH, et al. NMDA receptor antagonist effects, glutamate dysfunction, and schizophrenia. Arch Gen Psychiatry. 1994.
Vollenweider FX, et al. Hallucinogens and MDMA: neurobiological mechanisms and therapeutic possibilities. Nature Reviews Neuroscience. 2010.

4) Stimulant-Induced Psychosis

Curran C, Byrappa N, McBride A. Stimulant psychosis: systematic review. Br J Psychiatry. 2004.
Wearne TA, Cornish JL. Methamphetamine-related psychosis: a model for studying psychotic disorders. Frontiers in Human Neuroscience. 2018.

5) Long-Term Conversion → Schizophrenia / Bipolar Disorder

Starzer MSK, Nordentoft M, Hjorthøj C. Rates and predictors of conversion from substance-induced psychosis to schizophrenia spectrum disorder. Am J Psychiatry. 2018.
Murrie B, et al. Transition from substance-induced psychosis to schizophrenia: systematic review and meta-analysis. Schizophrenia Bulletin. 2020.

6) Trauma, Genetics & Environmental Risk Factors

Van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature. 2010.
Caspi A, et al. Gene × environment interaction in psychosis. Arch Gen Psychiatry.
Read J, et al. Childhood trauma, cannabis use and psychosis: a triple-risk model. Psychiatry Research.

🔑

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Substance-Induced Psychosis (SIPD)