General
In terms of its molecular structure, the cannabinoid cannabidivarin, or CBDV for short, has similarities to its relative, CBD. Both share a lineage and are similar in many ways.
CBDV is also a non-psychoactive phytocannabinoid. It is found in high concentrations in the landrace Cannabis Indica plant from northwest India and Nepal.
Most strikingly, when higher CBDV levels are present, these plants mainly have a low THC content.
CBDV can be derived from CBGVA, i.e. cannabigevarin acid. This cannabinoid reacts to an enzyme from CBDA and eventually converts to cannabidivaric acid (CBDVA). Through the addition of heat, the acid still contained can ultimately dissolve to form the end product of cannabidivarin, i.e. CBDV.
However, this is not the end of the chain. Acidic conditions change the arrangement of atoms and lead to the conversion of molecules. The successive cannabinoid, THCV, then arises from CBDV.
So far, CBDV is one of the lesser known phytocannabinoids from the cannabis plant. However, various research carried out in recent years could change this. CBDV is increasingly associated with procedures for epilepsy and is cited as an alternative anticonvulsant medicine.
Despite this, initial studies have yet provided extensive information on the full medical potential.
However, there is a disadvantage to CBDV. In contrast to many other phytocannabinoids, cannabidivarin only has very low water solubility. This means that it is not easy for the body to ingest the plant cannabinoid and work effectively before being destroyed by various digestive tract enzymes. After oral ingestion, only a small percentage (in the single digit range) makes its way into the bloodstream.
Liposomes could help to solve this with their double-layered membrane shells made of molecules. They enclose the cannabinoid, protect against the destructive effect of enzymes and help the body not to excrete CBDV too early on.
Effects
Most phytocannabinoids can influence cells through binding to receptors in the endocannabinoid system. The endocannabinoid system, ESC for short, was only discovered, isolated and finally detected in 1992, thanks to new knowledge and closer research into cannabis plants.[1] Since then, researchers have been better able to understand the structures of the ECS.
Endocannabinoids are the neurotransmitters produced by our body. They are the body's own substances with methods of action similar to cannabis in the human organism. They are found in the regulation of our brain and spinal cord nerve cells, as well as in cells in other organs like the heart. They also play a role in maintaining homeostasis.
Just like endocannabinoids, phytocannabinoids can also bind to corresponding receptors in the endogenous cannabinoid system. However, CBDV is a great and very special exception.
A very special feature is that the phytocannabinoid takes effect entirely without binding to CB receptors in the endocannabinoid system. It is one of the few cannabinoids from the cannabis plant that does not seem to want to bind to CB1 and CB2 receptors, nor does it cancel out or even block their effects.
Instead, it lays a path through our cellular ion channels, known as TRP channels. These play a major role in various human perceptions, including being able to distinguish different tastes such as sweet, sour, bitter and savoury, feel temperature differences or even pain. Other living creatures also seem to need TRP channels to be able to see.
There is further evidence that the therapeutic effects of CBDV can partially develop through GABA receptors, which are transmembrane proteins in the nerve cells. As a rule, y-aminobutyric acid, also known as GABA, binds to these receptors to distribute an inhibitory action on the nerve cells.
Like CBDV, GABA can also act as an anticonvulsant. This messenger substance can stabilise our blood pressure. It also has analgesic effects, can aid relaxation and promote sleep.
Since many clinical cases that have disturbed neurotransmitter networks display lower than normal GABA levels, scientists have discovered suitable cannabinoids like CBDV. Neurological diseases can include, for example, epilepsy, depression or schizophrenia. The cannabis cannabinoid could also possibly change accompanying feelings of chronic pain in the future.
In the late 1960s, CBDV was found to have antiepileptic and anticonvulsant (antispasmodic) effects. This effect throws CBDV into the mix for possible new drugs for a number of diverse clinical pictures.
CBDV in medicine
CBDV is one of over a hundred cannabinoids already identified and often gets lost in the crowd, which is rather unfair, in spite of the fact that its many important properties particularly interest internal medicine, more precisely, neurology.
As already mentioned, the GABA concentration in people with neurological disorders is often buried deep down. People affected include, for example, epilepsy patients. The consequences of aminobutyric acid deficiency are can differ and include cravings for sweet food and sugary drinks, an increasing tinnitus-like whistling, sweating when at rest or a changed perception and disturbance in the sense of smell, just as much as anxiety attacks, inner restlessness, hyperventilation or even epileptic seizures.
Diabetics can also suffer from a GABA deficiency. The result is an overproduction of glucagon, the chemical part of aminobutyric acid. Scientists have not yet fully clarified whether CBDV can balance this or even control it.
Central anticonvulsant in epilepsy
Through TRP channels, scientists have been able to capture the connection between CBDV and neurological diseases that can lead to epileptic seizures. More specifically, the focus is on TRPV1, one of the largest groups of the TRP channels. TRPV1 sensors are responsible for our visual and auditory perceptions and for converting chemical signals into electrical signals. If the TRPV signal is overstimulated, signal transmission can no longer be controlled, which can lead to epileptic seizures.
Therefore, an endocannabinoid research group from Italy has researched non-psychotropic, vegetable cannabinoids such as CBDV for their desensitising and activating effect on TRPV1 channels.[2]
This study deserves special attention since epilepsy is the most common neurological disease, with around 50 million people worldwide suffering and a change in the structure of TRP channels is linked to neurodegenerative clinical cases.
Like cannabidiol (CBD), CBDV can have antispasmodic effects in humans. Also, in various tests, these cannabinoids indicated a possible increase in calcium within the cells.
CBDV can even activate and desensitise several TRP channels depending on the dose. This includes TRPV1 and some channels that are part of the subfamily V Type 2 (TRPV2) and A Type 1 (TRPA1).
This desensitisation has a calming effect on the channels concerned, thereby rebalancing the natural homeostasis. Therefore, CBDV and CBD have an anti-epileptic effect acting through the TRP channels. In addition, scientists observed a definite desensitisation in the hippocampus tissue.
However, more piolet tests are needed in epilepsy patients to gain more detailed information on the exact effects of CBDV in TRP channels.
Studies carried out by the University of Reading in England have also been able to show that cannabinoids have promising effects for patients with epilepsy.
Scientists found that CBDV has the potential to reduce the frequency of epileptic seizures without causing side effects like uncontrolled tremors in those affected.[3] Another research team confirmed that the herbal cannabinoid is far superior to conventional antiepileptics in this respect.
Appetite suppressants
Cannabis users know full well about the hunger pangs the body feels as a result of consumption. However, not all cannabinoids have this effect. Many cannabinoids behave very differently in this respect, especially in an isolated, pure form. CBDV is one of these.
In 2012, a study was conducted, screening various anti-obesity drugs for an overview of their safety and mode of action.
Once again, medicine can benefit from the considerably lower percentage of unwanted side effects that cannabis brings as a medication. Many of the drugs used to suppress hunger help patients suffering from diabetes or obesity to regulate feelings of satiety. However, some are said to have serious side effects such as depression. The quality of life and general well-being of patients can be quickly and severely affected by various side effects such as high blood pressure, a rapid heartbeat, loss of balance, tension and disrupted sleep patterns.
Nausea
CBDV also has an effect on nausea and vomiting. This is evident in patients suffering from persistent nausea due to chemotherapy.
This impact has long been suspected and was even shown in a study in 2013. Scientists from the Canadian Department of Psychology and Neuroscience Graduate Program at the state university of Guelph carried out tests on rats to see the potential of tetrahydrocannabivarin, THCV for short, and CBDV to act on nausea.[4]
The way in which CBDV works is easy to explain. Certain CB1 receptors in the brain are located in the centres that control feelings of nausea and, ultimately, vomiting. Cannabinoids interact with these CB1 receptors and ultimately produce an anti-emetic effect.
The study came to the same conclusion. When both CBDV and THCV cannabinoids were tested, this provided researchers with evidence that they have a therapeutic potential that could significantly reduce nausea.
Ion channels are also involved. 5-HT receptors in the central and peripheral nervous system are activated by serotonin. The main task of these receptors is to activate the centre responsible for vomiting.
Since the phytocannabinoid CBDV addresses the cellular ion channels (TRP channels) instead of the CB1 and CB2 receptors, it is useful in such cases.
As cannabinoids, THC and CBD have already found their way into chemotherapy procedures. Cannabinoids can help to alleviate and improve some patient complaints associated with chemotherapy. These include pain, anxiety, depression and sleep disorders. Since cannabis has been legally used as a medicine in Germany since March 2017, people can also apply to health insurance companies to pay for this medication.
Even if various cannabinoids have been successful to a greater or lesser extent in dealing with cancer, they are not a panacea and should only be taken with other medicines if the doctor has given such advice.
Epilepsy
A British biopharmaceutical company has been researching CBDV for several years in order to use it for relieving the symptoms of epilepsy. In particular, this herbal cannabinoid could compete with drugs that have many negative and sometimes even serious side effects in patients with neurological disorders. Since CBDV shows great potential to act as an effective alternative method in epilepsy, it was even subject to a patent so the isolated phytocannabinoid could be used alone, as well as in combination with existing anti-epileptic drugs. The clinical studies carried out at the same time are intended to help out patients with epileptic seizures and improve the control of generalised and temporary lobe seizures.
As a neurological disease, epilepsy is extremely complex. Uncontrolled waves of electrical activity and the synchronous discharge of large groups of nerve cells in the brain lead to the involuntary dysfunction, which manifests as epileptic seizures. These are the typical key symptoms suffered by epilepsy patients.
These attacks only last a few seconds to minutes and happen spontaneously. Although many marketed drugs are supposed to provide relief to sufferers, around 30% will have no benefit.[5]There are many reasons for this. Many patients cannot tolerate the strong side effects, which are not uncommon. In some cases, the seizures simply cannot be contained. Another big advantage has been seen in several models where CBDV can actually suppress seizures. This means that cannabidivarin could also be used in combination with existing medication for better results.
Since CBDV from the cannabis plant has no psychoactive effects, so far, potential side effects from this herbal cannabinoid have been manageable.
CBDV and the immune system
Scientists also found that CBGV and CBDV can work together at precisely coordinated and normally low, concentrations to inhibit cytokine expression, i.e. the growth and differentiation proteins of cells.[6]These proteins are responsible for the messages between cells and for sending signals. Our immune cells also use cytokines to act on the brain and hormone glands.
This means that blocking excessive cytokines helps the overburdened immune system to return to a natural level. Inflammatory reactions cease and the associated pain and inflammatory skin swelling can also decrease. Therefore, CBGV could presumably also be used as a drug in immunotherapy and as a natural remedy without serious side effects. It could help to protect the body from deficiencies and against inflammatory messenger substances.
Autism
Autism has no specific clinical picture. The initial symptoms of this complex neurological development disorder appear very early in childhood. There is no certainty that CBDV will be used regularly in the future to deal with autism.
However, initial scientific studies have indicated a positive outlook. When used in combination with CBD, people with autism seem to have increased cognitive abilities. Positive effects can also be seen in social terms.
A study on children suffering from various forms of autism began in June 2017 with the title “Cannabidivarin (CBDV) vs. Placebo in Children with Autism Spectrum Disorder (ASD)”. Researchers have paid particular attention to the safety of the active ingredient while also examining the effect on the irritability of patients participating during their childhood.[7]/span>
Side effects: DNA damage
The more scientists know about CBDV, the more they continue to look at the best areas for its use in medicine. Also, more questions are arising as to the possible side effects of cannabidivarin in patients/consumers.
A particular long-term negative effect appears to be on DNA. When examined, both cannabinoids CBDV and CBD were tested and showed positive results for damage to DNA in human cell lines.
According to scientists' findings, CBDV and CBD induced DNA damage in the liver cell line. This results from gene amplifications and dicentric chromosomes.
Liver enzymes can increase this genotoxic effect.[8]As a result, research has established that even low concentrations of both plant cannabinoids can damage human genetic material in cells. Other studies have also shown that chromosomal damage to the genome is part of the process of the progressive, possibly fatal, course of the disease. Accordingly, the phytocannabinoids might even have carcinogenic properties in humans.
CBDV and endocannabinoids
Another feature of this phytocannabinoid is its ability to participate in producing the body's cannabinoid 2-arachidonylglycerol. This is known as 2-AG for short. The endocannabinoid is found in particularly high concentrations in the central nervous system. It has also been found in dairy and breast milk.
Rat studies have shown that it also appears in organs such as the kidneys, liver, spleen, lungs and brain.
In 1995, a research group led by the Israeli university professor of chemistry and natural products, Raphael Mechoulam, the "father of cannabinoids", first published the 2-AG discovery at the Hebrew University of Jerusalem.
Animal experiments have shown that 2-AG can activate both types of receptors in the endocannabinoid system. The effects are similar to those of THC, the most popular representative of all cannabinoids. A reduced sensation of pain and restrictions in muscle movement have been seen, according to the administered dosage. 2-AG can also reduce rectal temperature and activity. Thanks to CB1 receptors, the endocannabinoid can stimulate bone growth[9] and have a neuroprotective effect after a brain injury.
CBDV interacts with 2-AG by inhibiting the activity of the primary enzyme responsible for the synthesis of 2-AG.
This has no effect on the anticonvulsive, i.e. antiepileptic effect of CBDV.
[1] https://www.pharmazeutische-zeitung.de/inhalt-06-2005/titel-06-2005/
[2] https://www.ncbi.nlm.nih.gov/pubmed/25029033
[3] http://www.reading.ac.uk/psychology/news/pcls-120912.aspx
[4] https://www.ncbi.nlm.nih.gov/pubmed/23902479
[5] https://www.drugbank.ca/drugs/DB14050
[6] https://patentscope.wipo.int/search/en/detail.jsf?docId=US226135163&tab=NATIONALBIBLIO
[7] https://clinicaltrials.gov/ct2/show/NCT03202303
[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342871/
[9] https://www.fasebj.org/doi/10.1096/fj.06-7957com