CBD – therapeutic power of plants,

For several years in society, the subject of medicinal properties of certain compounds contained in marijuana has not fallen. Marijuana itself has a twofold nature, because it can both harm and help. As it turns out, some of its components carry only pro-health properties. Despite the many controversies and turbulent discussions, access to isolated cannabidiol oils without psychoactive THC eventually becomes trouble-free for every needy person. In the face of the new opportunities that this relationship offers us, let's take a look at its health benefits and analyze who can benefit from it.

1. What is CBD?

In order not to miss anything, at the beginning, let's get some theoretical knowledge. Cannabidiol is a phytocannabinoid contained in cannabis, which was first isolated in 1940. In contrast to the most well-known cannabinoid - delta-9-tetrahydrocannabinol, it does not show any psychoactive effects, does not intoxicate and can not be used for recreation, but nevertheless may have an anti-anxiety and antidepressant effect. We distinguish as many as 30 stereoisomers of cannabidiol.

It is important to choose CBD oils produced from hemp inflorescences, and not only from their seeds, so that we can enjoy the proper therapeutic action. Due to the lack or only traces of THC, these oils are legal and safe. The primary receptors of the cannabinoid system are CB1 and CB2, with cannabidiol being an antagonist of the first and partial agonist of the second one. CB2 receptors are located mainly in immune cells and in glial cells in the brain. It should be noted, however, that cannabidiol is a multitasking compound because its affinity for cannabinoid receptors is not high, and a significant part of the positive effects of this compound is dependent on other mechanisms2.

Interaction is also noted with TRP receptors, especially with the TRPV-1, TRPA-1 and TRPM8 receptor. Other targets are activated PPAR-γ and GPR55 receptors (also members of the cannabinoid system) which are antagonized. The activity of the α-3 and α-1 glycine receptors is also intensified. CBD is also a partial agonist of serotonergic system receptors, particularly the 5-HT-1A subtype. This mechanism results in, among other things, anxiolytic and antipsychotic activity and several other activities listed later in the article.

2. What are differencies  between marijuana and CBD?

In marijuana outside CBD, we can find a few other cannabinoids (modestly, because there are over 80), not all of which have such a beneficial effect on health, and even can cause some disorders when they are abused. Among the other compounds we distinguish, among others, delta-9 and delta-8 tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBND), cannabitriol (CBT), cannabigerol (CBG), cannabichromene (CBC), cannabicklol (CBL) and others. In CBD oil only cannabidiol can be found, thanks to which it is possible to more precisely estimate the action that will affect the body after admission and keep only the therapeutic potential, without any recreational activity.

2. CBD oil benefits

Thanks to its anti-inflammatory properties, CBD can provide relief in chronic pain.

Cannabidiol by interaction with CB1 and PPARγ reduces the expression of proinflammatory factors such as NF-kB and cyclooxygenase-2 (COX-2) [3]. COX-2 inhibition is a mechanism characteristic of popular non-steroidal anti-inflammatory analgesics.

TRP receptors are also involved in the perception of pain. Cannabinoids can activate the TRPA1 and TRPV1 subtypes, which results in less pain transmission. This is another mechanism responsible for the anelgelic properties of CBD and marijuana. The influence of CBD and its metabolites on the TRVV1 vanilloid receptor (or VR1), which is activated by capsaicin, is well known. CBD stimulates these receptors with efficiency similar to capsaicin. Thanks to this, it reduces their sensitivity to painful stimuli[4]. In order to reduce pain, creams and ointments with capsaicin are used to locally reduce the sensitivity of VR1 receptors. CBD ointments are used for similar reasons. Of particular interest is the interaction with TRPM8, which is activated during cold exposure or by cooling agents, such as menthol. It is because of the action of this receptor that we take menthol tablets for a sore throat and treat the aching knee with a cool compress.

Activation of CB2 receptors with fatty acid amido hydroxylase (FAAH)2 inhibition and blocking of re-uptake by (+) - 5'-DMH-CBD and (+) - 7-hydroxy-5'-DMH-CBD4 metabolites results in ejection and increased concentration circulating endocannabinoids - anandamide and 2-arachidonoylglycerol (2-AG), which are known to reduce pain and improve the mood during physical activity, and this effect is also known as the runner's euphoria. The increased release of these compounds also reduces the pain that is not due to training load, and for various other reasons. Lowered levels of endocannabinoids may be one of the causes of pain in diseases such as fibromyalgia, irritable bowel syndrome and migraines[5].

Another mechanism involved in aneloxic action is the enhancement of the action of the glycine α-3 receptors [6], thanks to which efficacy in the treatment of chronic and neuropathic pain is demonstrated.

CBD is an allosteric modulator of delta- and mu-opioid receptors[7]. Activation of these receptors gives a very effective pain neutralizing effect, and this mechanism is used by strong drugs such as tramadol, morphine or fentanyl and its derivatives. A synergy of action between CBD and opioids is demonstrated, so that the therapeutic effect can be enhanced or the opioid doses reduced, which may have a number of really serious side effects.

Hemp oil is known for its effectiveness in the drug-resistant form of epilepsy.

The history of Cannabis use in the treatment of epilepsy dates back to the late nineteenth century, when English neurologists - Reynolds and Gowers began to use this plant for purely therapeutic purposes. In the pathogenesis of epilepsy, excessive activation of the glutamatergic system is important, and thus too strong stimulation of the brain. Cannabidiol has a protective effect against the hyperactivity of the receptors of this system, including the NMDA and AMPA [8] receptors. CBD is effective in reducing the frequency of attacks caused by inhibited or malfunctioning GABA system, but it is not effective in the case of blocking glycine receptors [9].

In one study10 it was shown that 7 out of 8 people with epilepsy who did not respond to other previously known drugs improved their condition as a result of cannabidiol when only one person in the placebo group had an improvement. There are more and more premises indicating the strong anti-epileptic potential of cannabinoids[11,12], which makes neurologists still timid, although more and more often they recommend their patients tests with oils and other hempen products.

Many people should be interested in the impact on well-being, sleep quality and anxiety reduction, especially in the case of social phobia and public appearances.

It is mainly due to the serotonergic system, and as you know, serotonin is a molecule of happiness. CBD is a ligand for the 5-HT-1A receptor of this system and to a much lesser extent 5-HT-2A[13]. The affinity for both receptors is stronger than for THC. In the mouse study, the CBD therapeutic effects are similar to those obtained with the antidepressant drug imipramine[14]. Importantly, CBD gives a quick effect[15], in contrast to popular SSRIs, where even the deterioration of the patient's condition may occur at the beginning of therapy. The effect should persist during the treatment, without impairing the effect.

CBD oils seem to be a great support for people struggling with social phobia and inhibitions. Cannabidiol in experiments in which volunteers were subjected to public performances reduced the accompanying stress[16]. Even after a single dose adopted before the public appearance, CBD can reduce the stress and discomfort that this entails and prevent cognitive disorders, so there are no major problems with forgetting the information that we had to present to the audience[17]. The anxiolytic activity of CBD results from the influence on the activity of the limbic and paralimbal areas of the brain that participate in the processing of emotions [18].

Potentially improved people can be expected to suffer from insomnia, as CBD research has significantly facilitated falling asleep, compared to the placebo [10] group. Certain premises also indicate the effectiveness in improving the quality of sleep in post-traumatic stress disorder (PTSD) [19], although this is just a case study. Either way, the information is interesting and encourages further research.

In addition to the effects on serotonin receptors, also anandamide is important for our mood. It can, among others, favorably affect the feeling of motivation and pleasure, especially that resulting from food intake. Sweet, of course. This relationship occurs, among others, in cocoa, which is why chocolate is so tasty.

Alternative therapies in the treatment of cancer are a hot topic. There are many indications that CBD is a very effective means of supporting treatment and not only in palliative medicine.

It is indicated that the Cannabis extracts are effective in inhibiting the proliferation of cancer cells, and may even lead to their death by reducing their ability to produce energy, and the greatest potential lies in cannabidiol [20]. It may increase the expression of ICAM-1 in lung cancer cells that are lysed by more efficient lymphokine-activated killer (LAK) [21] cells. By affecting CB2 and regulating the expression of Nox4 and p22phox, CBD can also be helpful in leukemia [22]. Another type of cancer being examined is the attacking intestine. The studies have shown that cannabidiol inhibits the proliferation of cancer cells, without showing such action in relation to healthy cells[23]. Anti-cancer properties have also been demonstrated in the case of glioma [24].

A serious factor that destroys the body in cancer is a decrease in appetite, significantly reducing the supply of energy and nutrients, which results in rapid catabolism. This seemingly trivial factor is so important that it is impossible to ignore it when we approach the topic of treatment seriously. Therefore, medicine offers many possibilities, such as rich energy supplements, or nutrition to and parenteral. Once again, we should mention the role of growing anandamide during treatment with CBD oils, which can raise the appetite through a greater feeling of pleasure resulting from the taste of meals. Activation of serotonergic receptors, in turn, translates into a reduction in the feeling of nausea and vomiting [25].

Anandamide (once again) has the ability to inhibit breast cancer cell proliferation by interacting with prolactin receptors, inhibiting its function26.

Interesting is the fact of neuroprotective and support in treatment of neurodegenerative diseases.

Excessive oxidative stress is a serious factor that threatens the health of the nervous system. Cannabinoids appear to be effective antioxidants, thus protecting neurons from degeneration. According to scientific data, the protective potential in this case is stronger than in the case of the most popular antioxidants, i.e. vitamins C and E (alpha-tocopherol) [5]. The studies examined the effect of cannabinoids with the simultaneous administration of cannabinoid receptor antagonists, which did not disturb the neuroprotective effect. This indicates the independence of the protective action from the CB receptor system. For example, activation of 5-HT-1A-R may increase cerebral blood flow, which also acts neuroprotectively [27]. Effects on cerebral circulation also give therapeutic potential in the case of cerebral ischemia [28].

CBD can also be helpful in the fight against Alzheimer. The use of this phytocannabinoid may protect the nervous system from the increase of free oxygen radicals resulting from excess beta-amyloid, lipid peroxidation, increasing the concentration of intracellular calcium ions, DNA fragmentation and the increase in the level of caspase-3 enzyme, which is involved in cell signaling leading to apoptosis [29].

Cannabidiol also has several attractive, less well-known properties that positively influence the condition of the cardiovascular system.

One of them is the inhibition of the 15-lipoxygenase enzyme (15-LOX), which is mainly done by one of the CBD metabolites - cannabidiol-2 ', 6'-dimethyl ether (CBDD) [30]. This enzyme is strongly involved in the formation of inflammatory conditions leading to atherosclerosis, so reducing its activity is a highly desirable phenomenon.

GPR55 antagonism is responsible for the hypotensive properties. In a rat study, CBD has also been shown to inhibit the increase in blood pressure and heart rate in response to stress, and this effect is once again due to the agonism of 5-HT-A1 [31].

Can people struggling with autoimmune diseases also help with CBD oil?

Yes, especially in the case of Th17 arm dominance of the immune system, which can be inhibited in response to cannabidiol [32]. In the experimental model of asthma, CBD has been shown to inhibit the synthesis of proinflammatory cytokines. The decrease in the cytokines of both arms was confirmed - Th1 (TNF-α and IL-6) and Th2 (IL-4, IL-13, IL-10 and IL-5), thus reducing chronic inflammation associated with autoimmunity.

Cannabinoids can even control the risk of developing diabetes. In the mouse study, subjects treated with cannabidiol had a significantly lower rate of developing autoimmune type I [33] diabetes. In the CBD group, only 32% of the group was diagnosed compared to 86% in the placebo group. At the same time, an immunomodulatory effect was found, manifested by an increase in IL-10 and a decrease in IL-12. There is also a suppression of the general cytokines of the Th1 arm that accompany this type of diabetes [34].

In the era of the flood of all diseases from the autoaggression category, the immunomodulatory effect of cannabinoids is a very attractive prospect.

Cannabinoids support bowel health.

And this is supported by scientific data. The endocannabinoid system is involved in the regulation of inflammatory cytokine production in enterocytes, the rate of wound and erosion regeneration, and the inhibition of tumor cell proliferation in IBD and colon cancer [35]. It is suggested that the protective effect against IBD results in part from the ability to activate PPARγ [36] and block the pro-inflammatory properties of lipopolysaccharides [37] and from antioxidant properties [38].

Interesting information is that cannabinoids, including cannabidiol, may have antibacterial activity even against antibiotic-resistant pathogens, as proven by methicillin-resistant Staphylococcus aureus (MRSA) [39].

Can CBD oil be helpful in ... treating addiction to marijuana?

It turns out that yes! And contrary to popular opinion - yes, marijuana can be addictive and so, overused can cause serious damage to health, mainly in the form of memory and sleep disorders, anxiety and psychosis [40,41,42,43]. Chronic exposure to this popular stimulus is reflected in the cannabinoid receptor's density [1]. As with most receptors in the brain, too strong / frequent stimulation of some kind means that something happens that disturbs homeostasis. To return to it, the natural defense mechanism requires reducing the number of receptors to weaken the action of a substance that overactivates a given system. So it is with the CB1 receptor, which is mainly responsible for the psychoactive action of marijuana. Their reduced density means that when we are not under the influence of THC, our endogenous cannabinoids are unable to produce an effect that will be able to keep us in the proper physical and mental condition.

The use of isolated CBD may, firstly, reduce the effect of THC due to blocking CB1 receptors. Thanks to this, the pressure of smoking is reduced, because a less-active stimulant is no longer so attractive. CBD also reduces some of the undesirable effects of taking THC, such as lethargy, poorer reaction time, or problems with the next day's memory [44]. THC may cause anxiety in some patients, whereas the presence of CBD may reduce this effect [43].

On the other hand, blocking the receptors causes their regulation, that is increasing the density, by a mechanism opposite to that described in the previous paragraph - weak receptors must be propagated to reach homeostasis. In this case, the perversity of nature indicates a partial truth coming from the saying that one should be treated with what has been poisoned.

And what about other addictions?

CBD can be helpful here too. An example is cigarette addiction. In one trial, a reduction of as much as 40% of the number of cigarettes smoked during the week with inhalations from cannabidiol was demonstrated, with no significant differences in the placebo group [45].

The heaviest and most debilitating type of addiction is opioid. Fortunately, cannabidiol can potentially help you out even from such an addiction. In experimental trials it was shown that the CBD administration affects the smaller feeling of satisfaction with the intake of morphine and heroin, which translates into more control over the train to these substances [46,47]. However, the unfortunate information is that in cocaine there was no similar relationship. Therefore, better to avoid cocaine.

We have already pointed out a multitude of positives resulting from the use of CBD. What else can this measure surprise us with?

For example, therapeutic potential in prion diseases, among which we distinguish, among others, mad cow disease (BSE), Creutzfeldt-Jakob disease (CJD) or scrapie [48]. The model of scrapie disease has demonstrated the protective effect of CBD against neurotoxicity of prions and the reduction of their accumulation.

Cannabidiol can be used as a potential acne drug, as it regulates the activity of the sebaceous glands and affects the condition of the skin through several mechanisms, and is much safer and does not give as many and strong side effects as the most commonly used drugs with isotretinoin [49].

CBD treatment may also accelerate the reparation of broken bones, as demonstrated in studies in mice [50]. Cannabinoids may also be helpful in psoriasis due to the ability to inhibit keratinocyte proliferation [51]. Immunosuppressive and anti-inflammatory actions, however, may be helpful in rheumatoid arthritis (RA) [52].

4. Are CBD oils safe?

In general, yes, side effects are rarely reported, but the benefits are significant. At oral doses, doses up to 1500mg per day did not cause toxicity. However, it must be borne in mind that CBD is metabolised by certain cytochrome P450 isoenzymes in the liver and may reduce their activity, and this may result in interactions with other drugs, increasing or prolonging their effect. This effect is of course dose dependent, minimal daily amounts CBD does not have to significantly affect these enzymes, however, it is a highly individual issue. Among the CBD-inhibited enzymes, CYP2C19, CYP2C9, CYP2D6 and CYP2A6 can be cited which are blocked by competitive inhibition, however CYP2A6 is also inhibited in a non-competitive manner, like CYP2B6. The CYP3A enzymes, particularly 3A7 and 3A4 are also weakened. It is therefore advisable to seek medical advice when planning to combine CBD oil with any drug. Among the drugs that we know of interacting with CBD, you can mention sildenafil (Viagra), warfarin, clobazam and several other anti-epileptic drugs.

5. Summary

The appearance of readily available products with cannabidiol on the market provides many fresh therapeutic options in ailments where up to now it has been problematic to choose an effective treatment. The multitude of forms that the CBD can provide is also impressive. In the case of local pain we can reach for the ointment with this phytocannabinoid, while for chronic systemic diseases we have available oils of various concentrations (also in the form of nanoparticles and liposomes), capsules, pastes, drinks, or vaporizers for vaporization. Considering the lack of side effects of the treatment, the balance of benefits and losses recorded in most studies seems to be unquestionably positive.

6. References