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Hallucinogens and Psychosis

During the 1960s “hippie” counterculture, anti-drugs propaganda emphasized the link between hallucinogens and psychosis, as tabloids featured headlines like “LSD will make you jump out a window.”

There has been a long-standing association between hallucinogens and psychosis, with both characterized by hallucinations and distorted reality. For the most part, psychotic symptoms disappear once the effect of hallucinogens has ended. However, in rare cases, psychosis after hallucinogens has persisted.

Unlike the 1960s anti-drug propaganda, psychedelic research has demonstrated hallucinogenic drugs are relatively safe. So what is the link between hallucinogens and psychosis? We’ve looked at some of the biological mechanisms and evidence linking different hallucinogenics with psychosis to help answer this question.

Hallucinations and Psychosis

What Are Hallucinations and Psychosis?

Hallucinations are sensations (e.g., sights, noises, touch, etc.) created by the mind that seem real, even though they are not. Many things can cause hallucinations, including hallucinogenic drugs (also known as psychedelics) and psychosis.


Psychosis is not a disorder itself but generally presents as a symptom of schizophrenia or other related psychological disorders. Psychosis appears in different ways for different people. For some, it can be ongoing, whereas others may experience psychotic episodes that come and go.

As well as hallucinations, people experiencing psychosis also experience delusions – strong beliefs in false things and events.

Characteristics of Hallucinations in Psychosis vs. Hallucinogenics

Although hallucinations happen in both psychedelic experiences and psychosis, some key differences exist between the types of hallucinations that occur.

Hallucinogenic drugs tend to induce hallucinations that are predominantly visual and often consist of geometrical patterns and pre-existing objects appearing to be moving or pulsating. In comparison, hallucinations in schizophrenia are mainly auditory and often consist of hearing voices.

The Biology of Hallucinations in Psychosis vs. Hallucinogens: 5-HT2A Receptors

Hallucinogens activate 5-HT2A receptors, and it’s thought this action is responsible for generating drug-induced visual hallucinations. To support this theory, scientists investigated the effects of injecting mice with psilocybin – the active ingredient in magic mushrooms – and examined how their brains responded to visual imagery.

The researchers found that under the influence of psilocybin, the mice’s nerve cells had a different response from usual to visual imagery. However, when their 5-HT2A receptors were blocked, nerve cells responded to images the same as usual.

It seems 5-HT2A plays a role in visual hallucinations, but there are likely many other factors contributing to psychosis in schizophrenia.

5-HT2A may also cause hallucinations in psychosis-associated disorders. In Parkinson’s Disorder, where psychosis can often present as a symptom, patients show an increased number of 5-HT2A receptors in particular regions of their brain. Furthermore, drugs used to treat schizophrenia are known to block the function of 5-HT2A, highlighting a role for 5-HT2A in schizophrenic symptoms.

One case study on a schizophrenic patient showed blocking 5-HT2A decreased visual hallucinations, but not auditory hallucinations. This finding highlights how 5-HT2A plays a role in visual hallucinations, but there are likely many other factors contributing to psychosis in schizophrenia.

The Biology of Hallucinations in Psychosis vs. Hallucinogens: Functional Connectivity

Imaging studies have shown that hallucinogenic drugs can alter the brain’s functional connectivity – a term that describes nerve cell interactions between different regions in the brain. Evidence has suggested auditory hallucinations associated with schizophrenia could be caused by changes in functional connectivity between sound-processing areas of the brain.

Temporary changes in functional connectivity could explain why hallucinogens and psychosis have similar effects.

LSD and Psychosis

An early research study compared patients hospitalized with LSD-induced psychosis to a group of patients hospitalized from psychotic episodes related to schizophrenia. The patients were tested for schizophrenic symptoms and cognitive impairment soon after hospitalization and a follow-up three to five years later.

The researchers found that for the majority of measured symptoms, the two groups showed no differences. Moreover, both groups had similar degrees of impaired cognitive ability post-hospitalization, and at the follow-up.

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Findings have shown that LSD psychosis is much more common in people with a family history of schizophrenia. However, while a family history of schizophrenia increases the risk, the likelihood of developing ongoing psychosis from LSD is still minimal. A recent population study showed that people who use LSD are just as likely to develop a psychotic disorder as people who have never used LSD.

Psilocybin and Psychosis

Researchers from Imperial College London have demonstrated how the effects of psilocybin on brain activity may be similar to brain activity in schizophrenia.

Using brain imaging, the researchers showed that psilocybin decreases functional connectivity between a group of brain areas called the default mode network (DMN) and another group of brain areas called the task-positive network (TPN). Whereas the DMN is thought to be involved in internal attention and self-generated thoughts, the TPN is thought to be concerned with externally focused attention and taking in information from the outside world.


Normally when the DMN is active, the TPN is inactive and vice versa. However, psilocybin causes increased functional activity between the two systems.

Brain scans from patients with schizophrenia also show increased functional connectivity between the DMN and TPN. Theories suggest this change in connectivity could be related to schizophrenic symptoms, as having both networks active simultaneously means people with schizophrenia can’t tell the difference between their internal thoughts and the external environment, changing their perception of reality from the normal.

DMT and Psychosis

Researchers investigated whether regular use of ayahuasca, a brew made of DMT-containing plants, increased the likelihood of psychosis. By collecting data from the Uniao do Vegetal (UDV), a Brazillian religion that uses ayahuasca in a ritual setting around twice a month, evidence showed there was an extremely low risk of psychosis from ayahuasca use (<1%).

Mescaline and Psychosis

A study from the early 90s investigated the similarity between mescaline (the psychoactive compound found in various hallucinogenic cacti) and schizophrenia. The study subjects showed an increase in symptoms of psychosis and paranoid depression following drug intake, which stopped once the drug wore off.

Mescaline may have similar psychological effects to psychosis associated with schizophrenia but with neurologically different causes.

Whereas schizophrenia is associated with a decreased activity in a brain region called the pre-frontal cortex, brain imaging showed the volunteers who took mescaline had increased activity in their prefrontal cortex. This finding highlights how mescaline may have similar psychological effects to psychosis associated with schizophrenia but with neurologically different causes.

Summary on Hallucinogens and Psychosis

The effects of hallucinogenic drugs and symptoms of psychotic disorders are both characterized by experiencing hallucinations and having a distorted perception of reality. There may be some similar biological effects between hallucinogens and psychosis, such as the action 5-HT2A receptors and functional connectivity changes. However, there are also likely lots of biological differences.

Although hallucinogens cause psychotic symptoms, they rarely cause psychotic episodes of clinical concern. The chance of hallucinogens triggering psychotic disorders is also very small, but a family history of mental health disorders increases this risk. As such, if you are considering trying hallucinogens, it’s essential to be aware of the risks and investigate any family history of psychosis.

Having a traumatic experience with hallucinogenics also increases the likelihood of drug-induced psychosis and ongoing psychological problems. Traumatic hallucinogenic experiences are more likely when people go into experiences unprepared, therefore it’s critical to pay attention to the set and setting.

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