In 1993 LP discovered for the first time that, in the basal ganglia (core areas of the end brain, telencephalon, below the cerebral cortex, Cortex cerebri = subcortical basal nuclei, important for functional aspects of motor, cognitive and limbic regulation, such as spontaneity, affect, willpower, initiative, drive, step-by-step planning, anticipatory thinking, expectations, motor selection, further multitasking, etc.) and in the cerebellum a particularly high CB1-receptor density prevails. There, CB1 acts in the area of our sensory and autonomic nervous system, not only regulating our pain perception, but also allowing cardiovascular + gastrointestinal processes to be controlled by the CB1 located there.

 

 

Furthermore, endocannabinoids in hypothalamic zones are involved in controlling different regulatory circuits, e.g., for improving control of our food intake. However, in contrast to the endocannabinoids that primarily target the CB1 receptor in the CNS, activation of CB2 receptors is generally very closely linked to modulation of our cellular and humoral immune response. Thus, CB2 has a considerable effect on inflammatory processes. Meanwhile, endocannabinoids also play a key role when our CNS becomes ill, with a resulting loss of neurons.

 

 

Under such harsh conditions, both CB receptors (1 + 2) are involved. Endocannabinoids exert a direct influence on individual neurons via CB1 receptors, whereas CB2 receptors are found mostly on microglial cells (a type of cell belonging to the immune system, playing a central role in pathological changes in the brain). Endocannabinoids can also thus indirectly influence survival of neurons and therefore the extent of neuronal damage via the CB2 receptor. By inhibiting the excitatory neurotransmission induced by the neurotransmitter glutamate and thus, counteracting excessive activation of glutamate receptors, the endocannabinoids also ultimately slow down the increase in neuronal damage. 

 

 

Finally, it must be noted that, unlike many other chemical signalling substances, endocannabinoids are only produced if and when there is a need for them, and are then released by the respective cell. In addition, they are metabolized into other biologically active substances, since otherwise the degradation of 2-AG produces "arachidonic acid” and the metabolization of AEA via cyclooxygenase produces "prostaglandin E2"* both of which are proinflammatory mediators! *(1. modulates platelet aggregation, 2. activates sensory nerve endings, 3. inhibits the release of neurotransmitters in the autonomic nervous system as well as lipolysis, 4. promotes vasodilatation, etc. see reference in Art. 4, para. 5).

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Art. 4

Risk

The well-known route from medicinal plant to medicine is always via the "drug” and its pharmaceutical development, so in modern phytotherapy this is mostly via the extract concerned, with particular consideration given to material and structural composition. The herbal extract, however, is always to be weighed only in its original, natural and unaltered form, easily digestible for us. The extract is then divided into its ingredient groups, evaluated according to their main/active substances, active and pharmaceutically relevant co-effective ingredients, framework and co-formulants. This diversity of substances in the extract leads to the typical phytopharmacological problem of never being completely identifiable. For this reason, the raw material extract production should focus on reproducibility, which needs to be as standardized as possible, as this already includes many measures leading to reproducible extract market quality and the active substances derived from it. 

 

For example, the active ingredient content in the extract can be standardized, provided that an appropriately standardized extract is available. Such standardization, however, results from adjusting a drug in powder form or an extract to match a fixed standard value, specifying minimum and maximum content, related to a substance or a group of substances, which may be considered as determining the impact. 

 

Information about the ingredients, origin and effect of commercially available CBD preparations is mostly incomplete or even watered down. It is by no means sufficient to know whether such a preparation is available without the psychoactive THC mentioned earlier. As already mentioned, the generally advertised THC in the raw CBD extract is only 1 of ≈ 120 known cannabinoids, whereas not even 10% of all cannabinoids in/from this plant have been examined for their complex mechanisms of action in the human body. And those cannabinoids that have already been subject to more thorough investigation have mostly only been studied in animal experiments. 

 

This short look at the complex, and in many cases complementary interdependent CBD substances in and for the human body is intended to provide an initial, albeit rather superficial insight into the effective complexity of this ICBD product, yet at the same time to point out the responsible approach and care required in marketing it. For example, the CBD plant extract origin and purity must be ensured, above all, along with controlled transport conditions, and of course toxic residues must be checked. 

 

The reason why this test is indispensable can be seen, for example, from the likewise aforementioned fact that the CBD plant extract must be tested for toxicity (Art. 3, last paragraph), specifically "endocannabinoids, contrary to other chemical signaling substances, are only produced when there is a need for them [under normal conditions!] in order to then be released accordingly by the respective cell, since otherwise "arachidonic acid” is produced during breakdown of 2-AG and "prostaglandin E” is produced during metabolization of AEA via cyclooxygenase - both proinflammatory mediators! This indispensable balance of many factors influencing our health alone makes it clear that CBD may only be administered generally if it is ensured that complicating conditions - or mere predispositions that could lead to such when CBD is administered - do not have a proinflammatory effect on CBD intake, which is well tolerated under normal conditions.

 

A brief explanation: Each case of inflammation is almost always accompanied by changes at the molecular level, whereby the trigger stimuli lead to altered gene expression via signal cascades, under which the proinflammatory mediators are expressed. The E2 prostaglandins represented here, for example, are only short-lived, locally effective mediators; they are hormone-like eicosanoids, acting both as autocrine and paracrine, working directly at the site of their synthesis. 

 

In other words: E2 prostaglandins are primarily synthesized in the endoplasmic reticulum and are secreted from the cell. They are, therefore, jointly responsible for many pathological processes. In particular, these include inflammatory reactions, increased sensitivity to pain, bone development, integrity of gastric mucosa, platelet aggregation, renal blood flow, etc. Their synthesis takes place by hydrolysis of membrane phospholipids by phospholipase A. The resulting arachidonic acid is oxidized by COX (cyclooxygenases = enzymes that initiate prostaglandin synthesis from arachidonic acid), producing the unstable intermediate product prostaglandin G2. This PGG2 is then converted to prostaglandin H2 by the peroxidase activity of COX. PGH2 is then the decisive starting molecule for many prostaglandins and *thromboxanes (*prostaglandin-related eicosanoids, which occur primarily in platelets and are thus named after them).