How Cannabis Genetic Testing Works

_________________

Cannabis causes psychosis, is addictive and makes you stupid. That is the common opinion that you hear when you bring up the subject of cannabis. In fact, there are always rare individual cases in which there appears to be a causal connection between the consumption of cannabis and psychotic illnesses such as schizophrenia.

It is important to understand at this point that this illness is not caused by cannabis. The illness would have broken out sooner or later on its own or with the aid of other factors. While in the past external factors were almost exclusively blamed for the development of illnesses, in recent decades it has become increasingly clear that a large proportion of them are genetic. In most cases, whether someone is susceptible to a certain illness is actually genetically pre-programmed. Other influences such as stress, serious life events, or excessive consumption of cannabis or other drugs can cause a latent psychosis to break out acutely. With today's testing methods, it is possible to carry out a genetic test that provides information on whether someone has a genetically increased susceptibility to the negative effects of cannabis.

How DNA Sequencing Works

But how does such a genetic test work? How can you determine whether someone is susceptible to certain diseases? To understand this, you have to delve a little deeper into the subject of DNA sequencing. Put very simply, you can imagine the human genome as a computer program, with the only difference being that it is not described using the values 0 and 1, but rather the genome encodes its information through the arrangement of four different nucleic bases.

A gene consists of the four nucleic bases adenine, thymine, guanine and cytosine. These are connected to one another by means of a phosphate and a sugar residue and form the familiar shape of a double helix. Every characteristic of the body, whether eye color or susceptibility to a disease, is assigned to a gene. If you change the order of the four bases in a gene at just one point, this has a strong effect on the respective characteristic. If you want to determine which DNA coding leads to an increased susceptibility to psychosis, you have to sequence the DNA of a statistically sufficiently large number of affected patients and healthy people. Sequencing means creating a linear sequence of the four bases from all genes.

This can best be illustrated with a computer program. A computer program is a sequence of the characters 0 and 1 on a hardware level. If you sequence human DNA, you get an innumerable long sequence of the letters A, T, G and C, which are abbreviated to the four bases. There are several methods available to carry out this sequencing. The oldest and one of the most common methods is Sanger DNA sequencing. Frederick Sanger was a British chemist who received the Nobel Prize in 1980 for his revolutionary invention.

First, a DNA sample is taken, for example in the form of saliva. The sample is then heated, which causes the double helix to open. You can imagine this as an opened zipper. The DNA is now present as a long, open chain consisting of a sequence of four different bases. The trick now is to break this chain down, base by base, and to create small color reactions with the individual bases on a specially prepared plate, so that in the end you get a kind of barcode that depicts the DNA.

The long chain-like molecules are broken down using a specially synthesized nucleotide, which is also called a termination nucleotide. The difficulty is that the nucleotide splits the DNA chain at a random point. For this reason, the amount of termination nucleotides added and the amount of DNA to be tested must be precisely determined so that the DNA chain is split once at each point. These fragments broken off from the DNA chain then migrate almost identically, as is known from chromatography, through a plate made of a specific gel. Short-chain fragments can continue to migrate through the plate as long chains. The last base of a molecular chain triggers the color reaction at the point on the plate where it comes to a stop. If you let the process run long enough, you get a barcode with four colors that depicts human DNA.

A software then checks this code to see whether there is a specific subsequence in the patient group's sequence that is found in all affected patients but does not occur in the healthy group. In this way, it is possible to determine which coding must be present in which gene in order to be more susceptible to a certain disease.

A genetic test is carried out in exactly the opposite order. First, the DNA from a sample is sequenced to obtain the code and then this code is checked using software to see whether it contains a certain sequence that is known to make the person more susceptible to the disease being sought. This is exactly what has been done in connection with cannabis and some genes or codes on these genes have been discovered that are associated with an increased likelihood of side effects.

Relevant genes associated with cannabis use

There are now several providers of genetic tests that sequence DNA based on a saliva sample and look for gene sequences that are associated with an increased risk of side effects typical of cannabis. The most important gene in this context is probably called AKT1. A certain sequence in this gene makes people more susceptible to the typical psychological side effects. People with this genetic trait have an increased risk of paranoia and psychosis. In this case, people can be susceptible to both short-term psychotic episodes and long-term consequences in the form of schizophrenia.

The importance of this gene was confirmed in 2016 in a study of 442 cannabis users using a standardized questionnaire for psychotic symptoms. Users with a specific sequence in the AKT1 gene showed significantly more psychotic side effects. This was in line with expectations, as a specific sequence in the AKT1 gene was associated with precisely these symptoms. The gene called COMT is also very relevant. A specific DNA sequence in this gene increases the likelihood of memory disorders. It is assumed that if there is a specific change in this gene, short-term memory can be reduced by up to 40% through cannabis. This gene primarily controls the breakdown of dopamine. The neurotransmitter dopamine plays an important role in memory formation, among other things. If a specific change in this gene causes dopamine to be broken down more quickly, short-term memory is significantly impaired under the influence of cannabis.

It is assumed that around 30% of all people are affected by this genetic change. The way in which THC is metabolized in the body is also largely determined by the genes. The coding of the CYP2C9 gene determines how quickly THC can be broken down by liver enzymes. 15-20% of people carry a change in this gene, which means that the metabolism of THC takes 2 to 3 times as long. The significantly slower breakdown means there is a higher risk of overdosing, especially when THC is taken orally. With oral consumption, the greatly delayed onset of effects makes it easier to take another dose.

For someone who metabolizes THC much more slowly, this can be an unexpectedly strong and overwhelming experience. The metabolism of CBD is also influenced by a gene. The CYP2C19 gene determines how quickly CBD is broken down by liver enzymes. Around 25% of all people carry a variant of the gene that causes CBD to be metabolized more slowly than normal. In another 25%, CBD is metabolized more quickly than usual. Knowing how quickly CBD is metabolized can be an aid in determining the individual dosage in order to achieve optimal treatment success.