It’s all fun and games until someone loses their mind. Well, cannabis consumption is about a bit more than fun; the closest thing to a panacea to ever grace humanity. Nonetheless, whether used recreationally or medically, cannabis can have a host of deleterious side effects– the most damning being cannabis-induced psychosis.

That’s right. The same substance known for curbing anxiety, depression, post-traumatic stress disorder (PTSD), and a whole host of other medical conditions can, for some at-risk populations, end up doing more harm than good. That harm is by way of triggering a psychosis– a disturbing mental state hallmarked by hallucinations that can lead to the onset of disorders such as Schizophrenia.

What is psychosis?

The bible for psychologists and psychiatrists alike, the Diagnostic and Statistical Manual of Mental Disorders (DSM), now on its 5th Edition (DSM-5), characterizes psychosis as seeing persistent hallucinations and delusions. When these disruptions to a person’s thoughts and perceptions are so persistent that it becomes difficult for them to recognize what is real and what isn’t, then the person is diagnosed as having a mental disorder like Schizophrenia or Schizoaffective disorder.

cannabis-induced psychosis is hallmarked by hallucinations

Substance-induced psychosis has a slightly different definition, though. While still hallmarked by prominent hallucinations or delusions, the hallucinations don’t count if the person knows they are substance-induced. As such, if you’re looking at the back of your hand swirl as it swirls into a beautiful paisley pattern and you think to yourself “the acid must be kicking in”, you probably aren’t experiencing a psychosis; you’re just tripping.

What is a psychotic event?

In what is known as either brief psychotic episodes or psychotic breaks, a psychotic event typically has a short, impermanent duration of hallucinations and delusions. Typically, such events are onset by stressors (e.g. natural disaster, loss of a loved one)– a brief reactive psychosis. Most people will fully recover from a psychotic event, but others may experience the development of symptoms, with an eventual progression into Schizophrenia or PTSD, depending on the initial trigger.

Experiencing a brief psychotic disorder is rare. They typically happen for the first time when people are in their 20s or 30s and is more common in women than in men.

Substances can also be characterized as stressors– capable of inducing psychotic events by offsetting internal brain chemistry in the same way a trauma could. A psychotic even can last up to a month, but most substance-included psychoses will last between 4 and 72 hours depending on the substance, dosage, environment, and many other factors.

Can cannabis induce psychosis?

The suggestion of cannabis-induced psychosis dates back to a nineteenth-century study from Colonial British India, aptly named “Indian Hemp and Insanity”. The study was recently revisited and was largely confirmatory, foreshadowing the contemporary understanding of cannabis’ impact on psychosis: cannabis-induced psychosis is frequency and dose-dependent and more common in those with a personal or family history of mental illness.

The relationship between cannabis-induced psychosis and mental illness (particularly schizophrenia) is intimate. A 2006 study showed that high scoring schizotypes (i.e. the degree to which you are schizophrenic) were more likely to report both psychosis-like experiences and unpleasant after-effects associated with cannabis use. Indeed, individuals under 18 who use cannabis and also have a family history of psychotic disorders are even more likely to have a psychotic episode after using weed — whether eating or smoking it.

Naturally, individuals who already have psychosis will have their symptoms exacerbated by cannabis use.

cannabis can induce a psychosis

A 2008 study helped to tease apart the differences between acute schizophrenia and cannabis-induced psychosis. Surprisingly, their results showed that males with cannabis-induced psychosis had an expansive mood and ideation, derealization/depersonalization, visual hallucinations, and disturbances of sensorium that were more frequent than those with acute schizophrenia.

The same research team also found that premorbid schizoid personality traits were more frequently associated with acute schizophrenia and antisocial personality traits to cannabis-induced psychosis.

Did you know: If you have a genetic predisposition to schizophrenia or schizotypal disorder, you may never exhibit symptoms except following the consumption of cannabis, according to a number of studies.

Cannabis-induced psychosis is rare, affecting only 1% of the consuming population. However, with over 35M near-daily consumers in the US alone, that means over 350,000 individuals are at risk for experiencing this adverse drug event.

Another risk factor is daily use; individuals who consume cannabis daily almost double their risk of experiencing a cannabis-induced psychosis.

Individuals that experience psychotic-like experiences after using cannabis are more likely to cease consumption compared to those who did not have such negative experiences, according to a 2019 study. Given that an increase occurrence of psychotic episodes can lead to psychosis disorder, such consumers are quite prudent to do so.

How can cannabis induce a psychosis?

The role of dopamine in cannabis-induced psychosis

Given that dopamine (the feel-good chemical responsible for reward-driven behavior and basic muscle movement) levels have been a classic biomarker of schizophrenia and other psychotic disorders, early research into cannabis-induced psychosis attempted to find a dopaminergic mechanism of action.

A 2014 study found that regular cannabis consumers, specifically those who meet the qualification of abuse/dependence, have reduced dopamine synthesis capacity in the striatum. They found that dopamine synthesis capacity was negatively associated with higher levels of cannabis use (i.e. more cannabis use, less dopamine) and positively associated with the age of onset of cannabis use (i.e. the younger you started, the less dopamine).

That means that the production of dopamine is less if you consume cannabis. However, the researchers found that reduced dopamine synthesis was not associated with cannabis-induced psychotic-like symptoms.

These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.

Bloomfield et al. (2014)

∆9-THC has consistently been shown to stimulate the neuronal firing of mesolimbic dopamine neurons and elevate striatal dopamine levels in animal models, so the relationship between cannabis consumption and dopamine should come as no surprise.

Dopamine, the feel-good neurotransmitter, seems to be related to both cannabis consumption and psychoses, but may only play a downstream role in cannabis-induced psychosis.

However, it appears that while dopamine levels are indeed affected by cannabis consumption, the relationship between consumption and altered glutamate levels is more likely to be the driving force behind cannabis-induced psychoses. Δ9-THC does not affect dopamine release directly but via CB1-dependent modulation of glutamate signaling.

Δ9-THC administration induces a dose-dependent increase in the brain’s glutamate levels through the activation of CB1 receptors at glutamatergic presynapses in cortical and subcortical brain regions, reflecting a reduction in synaptic glutamate levels and receptor functioning.

The role of glutamate in cannabis-induced psychosis

Researchers published a 2019 study showing that an increase in striatal glutamate (a specific type of chemical messenger known as a neurotransmitter) levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic (psychotic-like) effects and may have important public health implications.

Essentially, the study found that individuals that experience a cannabis-induced psychosis have lower baseline levels of glutamate and an almost 200% increase in glutamate after ingesting THC compared to those who did not have a cannabis-induced psychosis.

These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.

Colizzi et al. (2019)

Since glutamine in the striatum is responsible for responding to different stimuli, such as rewarding and stressful information, a disruption to this system with cannabis could trigger stress and reward in the absence of actual outside stimuli. Aberrant glutamate function has been previously suggested as a determining factor in developing psychosis and related disorders. The finding was region-specific; selective to glutamate in the striatum, but not other control regions like the hippocampus or anterior cingulate.

CBD and Psychosis

One cannabinoid found in the cannabis plant, cannabidiol (CBD), chemically isolated and administered by a doctor in a controlled setting, has actually been used to treat psychosis, according to a robust body of cutting-edge research.

CBD is referred to as non-psychoactive or non-psychotropic because it doesn’t have an effect on your mental state. However, that’s not exactly accurate. Given its marked ability to help reduce anxiety, CBD can certainly affect your mental state. However, CBD doesn’t get you mentally “high” the same way THC does.

cannabis-induced psychosis can be mitigated with CBD
CBD can theoretically be used to help mitigate the negative side effects of high-THC cannabis consumption, including cannabis-induced psychosis.

In fact, consuming CBD when under the influence of THC can actually help to lessen the high. This works because both THC and CBD interact with your endocannabinoid system (ECS). While they both act preferentially on different components of the ECS, they both act like keys that “compete” for the same locks. If all the locks are occupied by CBD keys, THC can’t get you as high.

Genetic predispositions for developing cannabis-induced psychosis

A 2015 study revealed genetic factors that explain the differences in individual sensitivity to the psychosis-inducing effects of cannabis.

Researchers identified the following genes to have an association with cannabis-induced psychosis: DRD2 and AKT1. When individuals have specific variants at both of these genes, they showed an increased odds of having a psychotic disorder.

GeneSNP
DRD2rs1076560
AKT1rs2494732

The genes affect the D2-AKT1 signaling pathway, which is responsible for the effects of dopamine and is particularly compromised in individuals with Schizophrenia. This finding brings back the potential role of dopamine in cannabis-induced psychosis. While the previous study found that dopamine synthesis wasn’t related to cannabis-induced psychosis, it could be the case that this genetic finding, which is associated with dopamine receptor density (i.e. how many dopamine locks there are), brings dopamine back into the picture– a perspective that would fit well with current neuropsychiatric models of psychosis.

In line with previous findings, the psychosis risk in cannabis users depends on the frequency of use, with the highest probability of psychotic disorder among daily users carrying both the risk variants.

Colizzi et al. (2015)

This research followed up on a landmark 2012 study which showed that variations at the AKT1 gene were associated with cannabis-induced psychosis, but not psychosis disorders or cannabis use in general.

How to tell if you are at risk for cannabis-induced psychosis

At-home genetic tests have the capacity to test whether or not you have a genetic variation at specific locations on your genome that increase your likelihood of experiencing a cannabis-induced psychosis. However, the genetic test must be run in such a way that it looks for variations at the AKT1 and DRD2 genes mentioned in the previous section.

A cannabis DNA test, like the one provided by Strain Genie exists, is specifically designed to identify genetic biomarkers than affect your body’s response to cannabis. Strain Genie’s test will let you know if your genetic profile places you at a normal, slightly increased, or significantly increased risk of developing cannabis-induced psychosis.

A Cannabis DNA test can tell you about your risk for cannabis-induced psychosis

Cannabis-induced psychosis only affects 1% of the population, so even if you are at risk, it is by no means a guarantee that you will develop the disorder. Nonetheless, those with an elevated risk should proceed with caution when using high-THC products and try to focus on products containing more CBD than THC for the “key” vs. “locks” rationale outlined above.

If you’re bummed about finding out you are at risk for cannabis-induced psychosis, it may be wise to mentally treat your avoidance the same way you would a gluten allergy, peanut allergy, or shellfish allergy.