There are various drugs in the world, and they have a tremendous effect on the brain and body. From cocaine to heroin to nicotine to cannabis, each drug triggers different feelings that can affect your health.
One particular drug that has gained notoriety is cannabis. Cannabis is usually a smoked drug (similar to nicotine in cigarettes), but it can also be eaten. Cannabis has been linked to the development of schizophrenia (due to the harmful effects of cannabis). We will evaluate the research on this topic while acknowledging the effects of cannabis on schizophrenia.
- We are going to explore the role of cannabis in schizophrenia. First, we will highlight the meaning of cannabis.
- Then, we will discuss brain neurochemistry and the adverse effects of cannabis.
- We will briefly touch upon the benefits of cannabis.
- We will also provide a list of all known cannabinoids.
- Finally, we will delve into the other roles cannabis has in schizophrenia.
Fig. 1 - Cannabis plays a role in schizophrenia.
What is the Meaning of Cannabis?
To understand the role of cannabis in schizophrenia, we must first establish the meaning of cannabis. What is cannabis?
Cannabis is a drug derived from a flowering plant. The cannabis plant contains compounds known as cannabinoids. Cannabis can be smoked, eaten and even vaped and has many different names such as marijuana, dope and weed. When smoked, it usually begins to take effect after two minutes; when eaten, after about an hour. How long it lasts varies.
Cannabinoids are drugs/substances that bind to cannabinoid receptors in the brain and body.
The two main active cannabinoids are known as delta-9-tetrahydrocannabinol (d-9-THC) and cannabidiol (CBD).
Brain Neurochemistry and the Effects of Cannabis
Cannabis works by binding d-9-THC to specific sites in the brain and body, acting as a partial agonist (i.e., it has a lesser effect than a full agonist because it has a lesser potency than a full agonist. This can sometimes be advantageous because it can work in tandem with naturally occurring neurotransmitters near your receptors).
Agonist
A chemical that binds to and activates a receptor.
When cannabis is used, d-9-THC binds to receptors in the brain (known as CB1R) that mediate the inhibitory effects of certain excitatory and inhibitory neurotransmitters (e.g., dopaminergic, GABA, and serotoninergic neurotransmitters).
For example, dopamine is strongly involved in the brain's reward system.
d-9-THC is thought to inhibit the release of neurotransmitters such as GABA.
GABA normally inhibits the release of neurotransmitters such as dopamine and suppresses dopamine neurons. This then consequently leads to an increased release of dopamine and acetylcholine.
d-9-THC binds to the CB1R and less selectively inhibits the release of certain neurotransmitters (a partial agonist).
Cannabis causes the following feelings/effects:
List of all Known Cannabinoids
For those who want to know a little more about cannabis and cannabinoids, here is a list of all known major cannabinoids:
- CBD - Cannabidiol.
- THC - Tetrahydrocannabinol.
- CBN - Cannabinol.
- CBG - Cannabigerol.
There are also other minor cannabinoids:
- CBC - Cannabichromene.
- CBF - Cannabifuran.
- CBR - Cannabiripsol.
Fig. 2 - Cannabis is a partial agonist.
What is the Role of Cannabis in Schizophrenia?
Considering one of the main effects of cannabis is hallucinations and general psychosis experiences (which can quickly become adverse effects of cannabis, as these experiences can lead to psychotic symptoms in some), we must acknowledge the potential role of cannabis in schizophrenia, as these two effects are positive symptoms in schizophrenia and often one of the first signs of the disorder.
First, we need to determine whether cannabis increases the risk of developing schizophrenia and why this might be the case.Let us first look at genetic predisposition.
Cannabis and Genetic Risks in Schizophrenia: Adverse Effects of Cannabis
Studies suggest that people who use cannabis have a higher risk of developing schizophrenia if they are genetically predisposed to it than non-cannabis users. Why is this the case?Originally, schizophrenia was thought to be due to a single 'schizogene’. Meehl (1962) proposed this thesis, assuming that schizophrenia was due to an internal vulnerability (a diathesis) and an environmental trigger (stressor) - the diathesis-stress model.Today, we know schizophrenia is a polygenetic disorder and we consider the environment an important factor.
Gottesman (1991) studied the rate of development of schizophrenia in twins. In the case of monozygotic (MZ; identical) and dizygotic (DZ; not identical) twins, MZ twins had a concordance rate of 48%, whereas DZ had a concordance rate of only 17%.
Since identical twins have 100% of their DNA in common, the results suggest that, whilst there is a genetic factor, the environment also has an influence on the development of schizophrenia (otherwise there would be a 100% concordance rate in MZ twins).
So we know that schizophrenia has genetic factors. How does cannabis affect that?Wainberg et al. (2021), in a cross-sectional study of 109,308 participants, examined how schizophrenic polygenic risk modulates the association between self-reported cannabis use and self-reported psychotic experiences, specifically:
They found that the psychotic experiences of cannabis users had an earlier onset and were more distressing for the participants. They found a strong dose-dependent relationship between cannabis use and the above psychotic experiences.A stronger relationship between cannabis use and psychotic experiences was found in individuals with high polygenic risk scores for schizophrenia. The finding suggests cannabis is an overall predictive risk factor for psychotic experiences. Those who are genetically susceptible to schizophrenia are at higher risk for psychotic experiences when using cannabis.
Similarly, Vaissiere et al. (2020) found positive phenotypic correlations in 11 of 12 pairs of cannabis users and schizotypic phenotypes when assessing the genetic overlap between cannabis use and subclinical psychosis (schizotypy).They stated there was a robust association between elevated symptoms of schizotypy and cannabis use.Thus, if an individual has a genetic susceptibility to the development of schizophrenia, it is believed cannabis use contributes to the development of schizophrenia. This is evidenced by the fact that it causes psychosis-like symptoms in those who use cannabis. Genetic susceptibility exacerbates these experiences and can lead to the onset of schizophrenia.
Fig. 3 - Those with genetic vulnerabilities are more likely to develop schizophrenia if they smoke cannabis.
The AKT1 Gene: the Role of Cannabis in Schizophrenia
We mentioned above the d-9-THC compound, which activates AKT1.The AKT1 gene encodes proteins important for the striatal dopamine receptor signalling cascade (Morgan et al., 2016). This process helps mediate motivational and cognitive control.
Studies have found people who carry polymorphisms of the AKT1 gene (particularly those with two copies of the C allele) have a higher risk of developing psychotic disorders when they use cannabis. However, these were retrospective reports - they did not examine the acute effects of current cannabis use and AKT1 associations at the time of cannabis smoking. There was also a family history of psychotic disorders in the patients, so we cannot say conclusively that this is not the determining factor.
Morgan et al. (2016) tried to solve these problems. In their study of active cannabis users without a family history of schizophrenia, they found that variations in the AKT1 gene predicted psychotic responses to cannabis (in addition to dependence on the drug). They suggested the AKT1 pathway may be a potential treatment focus area for those who use cannabis and are at risk of developing schizophrenia.
Adverse Effects of Cannabis and Benefits of Cannabis
Cannabis doesn't have exclusively harmful effects on a person, but benefits as well. The benefits of cannabis in medical use include helping those suffering from various disorders, such as patients with pain and those with mental disorders such as anxiety and depression (within reason, as excessive use has also been linked to increased anxiety and depression symptoms).
Adverse effects include how cannabis may also impact the development of schizophrenia when we consider other factors such as age.
While the brain is still developing, external factors that affect brain cognition, especially those that trigger psychosis experiences, can irrevocably alter the brain, and studies have noted the impact this has on brain development into adulthood and schizophrenia.
Cannabis can also be used to self-medicate people with schizophrenic symptoms. So when people with schizophrenic symptoms use cannabis to self-medicate, we can not say conclusively whether their symptoms are caused or exacerbated by cannabis.
Cannabis may also be therapeutic, as some studies have shown that people who use CBD have been successful in alleviating their psychosis symptoms. THC can trigger the symptoms, but other substances can help them.
Henquet et al. (2005) studied the effects of cannabis and the development of psychotic symptoms in 2437 adolescents and young adults. They found a dose-response relationship between those who self-reported their cannabis use at baseline and the likelihood of developing psychotic symptoms.
Those who reported it were more likely to develop psychotic symptoms at a 4-year follow-up. They concluded the risks associated with cannabis use and psychotic symptoms are increased in younger people but are significantly more problematic for those with a predisposition for psychosis
Role of Cannabis - Key takeaways
- Cannabis is a drug derived from a flowering plant that contains various compounds known as cannabinoids. It can be smoked, eaten and even vaped, and has many different names such as marijuana, dope and weed.
- The main active cannabinoid is known as delta-9-tetrahydrocannabinol (d-9-THC).
- Cannabis works by binding d-9-THC to specific sites in the brain and body and acting as a partial agonist (i.e., it has a lesser effect than a full agonist). It is said to increase the release of neurotransmitters such as dopamine (involved in the reward pathway).
- One of the main effects of cannabis is hallucinations and general psychotic experiences. Other effects include drowsiness, giddiness, anxiety, and paranoia.
- Genetic susceptibility to schizophrenia has been shown to increase with cannabis use, and the AKT1 gene is one example. Those who smoke cannabis with genetic vulnerabilities are more likely to have symptoms of psychosis and issues with schizophrenia.
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