Research Study on CBD and Patients with Dravet Syndrome

CBD is a compound which is extracted from the plant Cannabis sativa. This plant belongs to the family Cannabaceae.

Cannabis sativa is the one species that is accepted and confirmed, from 13 different species of Cannabis.

This plant has many uses, due to which it is being used in research. Unlike its psycho-active counterpart, (marijuana), CBD is non-psychoactive.

What is Dravet Syndrome?

This condition is a rare but very severe form of epilepsy (fits). It first manifests itself in an infant (18 months) as febrile (fever- triggered) seizures.

It doesn’t respond well to treatment, and can even worsen due to some antiepileptic drugs.

A baby suffering from the Dravet Syndrome experiences motor difficulty, speech retardation, and stunted intellectual development from around 2 years of age.

This disease occurs due to a mutation in the gene required for the development of brain cells.

What Happened in the Study

As explained prior, Dravet Syndrome causes severe epileptic fits in infants and children. Its was shown in this study that CBD reduces the seizures in childhood epilepsy syndromes, including DS (Dravet Syndrome).

A compound made from CBD has obtained the ‘Orphan Drug’ designation for these kinds of syndromes. Research using this compounds for these syndromes are going on.

A drug is granted the orphan status when it is used for the treatment/ prevention of rare diseases (like DS).

The reason and the process of how CBD affects the system is not known. It is speculated that it could be due to certain CBD – sensitive receptors in the body, seen in the treatment of other neurological disorders.

Hence, this study deals with understanding if these same receptors are activated in this treatment if the body’s endocannabinoid system is dysregulated (not functioning properly).

The body’s endocannabinoid system is a physiological system in the human body that helps in maintaining human health. Receptors for endocannabinoids are found throughout the body, in various organs.

It plays a role in the immune system, nervous system, most of the organs in the body, hence its an indispensable system of the body.

To understand this process, the patient’s lymphocytes were used, to analyze the gene expression of transmitter receptors and transporters, of ion channels, the genes that code for the endocannabinoids and the enzymes that are associated with effects of CBD.

Lymphocytes are a type of white blood cells (WBC). Ion channels are nothing but a pathway for charged ions in the body, so that they can pass through the semi-permeable cell membrane of the cell in the body.

Plasma endocannabinoid levels were analyzed, which means that the number of endocannabinoids in the plasma of the blood was scrutinized.

There was no difference observed between the DS patients and the controls in most of the CBD receptors analyzed.

But, there was an increase in the voltage-dependent calcium channel alpha-1h subunit.
The voltage-dependent calcium channel alpha-1h subunit is nothing but a protein that is controlled by a type of gene called CACNA1H.

It was also seen that cannabinoid type 2 receptor gene expression was increased in the patients suffering from DS.

Cannabinoid type 2 receptor (CNR2), controlled by the CNR2 gene, is a peripheral cannabinoid receptor. It gets activated when any cannabinoid substance enters the body.

So, the study implies that the action of the CNR2 gene was heightened in DS patients.
There were no changes in other endocannabinoid-related receptors and enzymes, as well as in the blood plasma levels of endocannabinoids.

Along with this elevation, there was an increase in CD70 gene, which marks the activation of lymphocytes. There were fluctuations in the levels of proteins related to inflammation,(e.g., peroxisome proliferator-activated receptor, gamma receptors, cytokines).

Peroxisome proliferator-activated receptors are nothing but nuclear proteins, which on activation cause processes like fat metabolism, glucose metabolism, etc.

Metabolism means breaking down a particular molecule into smaller molecules in the body.

Cytokines are proteins secreted by cells that have a particular effect on cell-cell interactions.

What did the Study Conclude?

This study concluded with the findings that along with the changes in the voltage-dependent calcium channel alpha-1h subunit, there was an increase in the action of CB2 (CNR2) receptors.

This was associated with an activation of the lymphocytes and changes in the inflammation related genes.

Similar changes were also reported in inflammation-related disorders. This maybe the proof to the occurrence of a potential dysregulation of the endocannabinoid system in the brain.

What does this mean?

Even though Dravet Syndrome is a rare condition, it does affect a small fraction of infants. This study showed that CBD may succeed in places where antiepileptic drugs didn’t, in giving some relief to the patients.

Read the research paper here-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804326/

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