Cannabis, Psychosis, and Dopamine: What’s the Connection?

Summary: Researchers identified elevated dopamine-related activity in brain areas associated with schizophrenia among patients with cannabis use disorder and symptoms of psychosis.

Key Points:

• Cannabis impacts dopamine-related activity in brain areas associated with psychosis
• Cannabis impact dopamine-related activity in brain areas associated with schizophrenia
• Compared to patients without cannabis use disorder, patients with cannabis use disorder reported higher rates of first-episode psychosis (FEP)

About Drug-Induced Psychosis

The phenomenon of drug-induced psychosis is well-known to mental health experts, and most mental health providers and experts are aware of the most common type, cannabis-induced psychosis. However, cannabis is not the only substance associated with psychosis.

A study published in 2020 shows the substances most often linked with psychosis:

• Cannabinoids such as marijuana, hashish, and THC derivatives delivered by vape devices
• Stimulants such as amphetamine, methamphetamine, and cocaine
• Hallucinogens such as LSD and PCP

Another study, this one published in 2017, examined the relationship between drug-induced psychosis and subsequent diagnosis with mental health disorders such as schizophrenia and bipolar disorder, with the following results:

• 32.2% of patients with drug-induced psychosis subsequently received a diagnosis or schizophrenia or bipolar disorder.
• 47.7% of patients with cannabis-induced psychosis subsequently received a diagnosis or schizophrenia or bipolar disorder.

In this article, we’ll focus on the association between cannabis-induced psychosis (CID) and schizophrenia. Previous research shows the following associations between CID and schizophrenia, in addition to the study above:

• Patients with psychosis or psychotic disorders who use cannabis report earlier onset psychosis, compared to patients who don’t use cannabis
• Ingestion of Δ9-tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis, triggers dopamine release in striatal and cortical brain areas
• Ingestion of THC induces positive symptoms of psychosis that mirror the positive symptoms of schizophrenia, including suspiciousness, delusions, and hallucinations
• The dominant hypothesis for the neurobiological basis of positive symptoms of schizophrenia proposes that striatal hyperdopaminergia – e. excess dopamine in the striatal area of the brain – plays a primary role in the delusions and hallucinations associated with schizophrenia

However, the connection between cannabis, psychosis, and the dopamine system has not been fully explored by researchers. In this article, we’ll review the results of a new study that addresses this gap in knowledge.

Cannabis, Psychosis, and the Dopamine System: Imaging Brain Structure and Function

To examine the connection between psychosis and the dopamine system – and the impact of THC on brain structure and function, the authors of the paper “Convergence of Cannabis and Psychosis on the Dopamine System” posed the following research question:

“Is cannabis associated with the same midbrain dopamine pathway involved in psychosis?”

Researchers recruited 25 patients with excess cannabis use (diagnosed with CUD) and 36 patients without excess cannabis use (no CUD diagnosis). Each patient:

• Received an MRI scan of areas of the brain associated with cannabis and the positive symptoms of psychosis at baseline
• Received an MRI scan of the same areas of the brain after one year (12 months post-initiation)
• Completed screening for schizophrenia at baseline
• Completed screening for first-episode schizophrenia after one year (12 months post-initiation)

At baseline, differences between the CUD group and the non-CUD included:

• Lower IQ in CUD group
• Lower language fluency in CUD group
• Higher nicotine use in CUD group
• Higher salivary THC in CUD group

After one year – 12-months post-initiation of study – the results showed the following:

• Patients in CUD group showed higher dopaminergic (dopamine-related) signaling in brain areas associated with the positive symptoms of schizophrenia, compared to the non-CUD group.
• Patients in CUD group showed higher dopaminergic signaling in subregions of the brain associated with the severity of psychotic symptoms, compared with the non-CUD group
• The CUD group showed more patients with first-episode psychosis (FES) than the non-CUD group:
  • CUD: 17 instances of FES
  • Non-CUD: 13 instances of FES

Overall, the experimental results confirmed what the researchers hypothesized: a convergence between brain activity associated with cannabis and brain activity associated with schizophrenia/psychosis in dopaminergic neurons in brain areas associated with the positive symptoms of schizophrenia, such as delusions and hallucinations.

We’ll elaborate below.

Cannabis, Psychosis, Dopamine, and Mental Health Symptoms

We admit it. That last sentence was a real mouthful. There’s a simpler way of describing the results of this study. Let’s look back to the question at the core of the study:

“Is cannabis associated with the same midbrain dopamine pathway involved in psychosis?”

The experimental results say:

“Yes.”

But why is this important?

There are several reasons these results matter. First, the trend towards cannabis legalization around the country – medical cannabis is now legal in 38 states and recreational cannabis is legal in 24 states – means its more available, which means average levels of use will likely increase nationwide. Second, this likely increase in use may also likely lead to increases in substance-induced psychosis. Third, this research enables scientists to understand the similarities and differences – on a neurobiological level – between psychosis associated with mental health disorders and psychosis with another origin and cause, such as cannabis.

Scientists are aware of several differences between cannabis-induced psychosis and psychosis associated with schizophrenia:

• People with schizophrenia typically experience four distinct types of psychotic symptoms, including hallucinations/delusions, disorganized speech/thought, negative symptoms (flat affect, asociality), and cognitive disorganization.
• People with cannabis-induced psychosis typically experience two types of psychotic symptoms: hallucination and delusions.
• To meet clinical criteria for schizophrenia, symptoms of psychosis must last/recur for at least six months
• Psychotic episodes caused by cannabis or other substances typically last several hours, and in extreme cases, several weeks, far short of the threshold for schizophrenia-related psychosis

Now, with this research, they understand – on a neurobiological level – the underlying mechanisms common to both cannabis-induced psychosis and psychosis associated with schizophrenia.

New Evidence, New Knowledge, New Understanding

This new understanding leads to the following conclusion, as elucidated by the study authors:

“Increased dopamine functioning in the SN/VTA may be associated with the risk of psychosis in people with cannabis use disorder.”

While the wording of that conclusion is relatively reserved, these results can help us help our patients in at least two ways. First, we can affirmatively advise patients with schizophrenia to avoid cannabis, which we already do, but now we can offer this empirical data to support the advice, and second, we can screen potential schizophrenia patients for cannabis use, which can help clarify the diagnostic process, and give us valuable insight into the presence – or absence – of schizophrenia in patients seeking professional mental health support.