What is CBD?

What is CBD?

Cannabidiol (CBD) is the second most prominent cannabinoid found in hemp and cannabis. Cannabinoids are chemical compounds naturally occurring in the cannabis plant (phytocannabinoids) and in the body (endocannabinoids).

As a cannabinoid, CBD interacts with the body’s endocannabinoid system (ECS). Unlike the most prominent cannabinoid Δ9-Tetrahydrocannabinol (THC), CBD is not psychoactive, meaning it does not affect your cognitive function, i.e. ‘make you high’. At the same time, it does not have “abuse potential or cause harm” as coined by the World Health Organisation’s Expert Committee on Drug Abuse in 2017.

In recent support of that, the renowned American Journal of Neurology published a randomized, double-blind, placebo-controlled, crossover study this year - the gold standard for evidence-based investigations of the effects of interventions - showing no signal of abuse. The physiological action of CBD has thus received increasing attention from the medical world. Even though evidence is currently confined to preclinical human trials and preliminary studies carried out in mice, they emphasize a series of health benefits including pain-relieving, anti-inflammatory and anxiolytic qualities among others. Since then, a wide array of CBD products have been developed to harness CBD’s natural qualities for human benefit.

Origins of CBD

How is CBD made?

Endocannabinoid System

What is the endocannabinoid system?

 Although the medical benefits of cannabis have been appreciated for thousands of years it was only in the early 1990s that science started to uncover our endogenous or endocannabinoid system (ECS). As scientists were trying to unravel where in our body cannabis primarily acts, they discovered receptors - the main effector sites in the brain - that bind cannabinoids at a high affinity. Structural comparison between cannabinoids and endogenous compounds revealed a striking similarity between the phytocannabinoids and a group of lipid-based neurotransmitters (compounds that enable communication in the brain). These lipid-based neurotransmitters were thus called endocannabinoids, and the receptors they bind to in order to mediate their effect endocannabinoid receptors. The medical benefits of cannabis are thus, at least in part, ascribed to their ability to naturally complement our own ECS.

The ECS is one of the most important physiological systems involved in maintaining homeostasis. Homeostasis is the concept by which all biological systems within the body are actively regulated and adjusted to maintain “working conditions”  within a narrow range. Examples of bodily maintenance include body temperature, blood sugar levels, ph levels and various hormonal balances - process which the body regulates autonomically. Following a meal for instance, insulin is released from the pancreas to allow rapid uptake of sugar from the bloodstream by every single cell in your body. During fasting, insulin release ceases and less sugar is absorbed. Sugar levels within our bloodstream are thus maintained within a narrow range; if they were not, glycemic ‘sugar’ attacks are prone to occur like in diabetic patients. Thus, and in order for our body to function properly, we need all systems to be in balance - in a state of “zen”.

How does the endocannabinoid system work?

Before we dive into how the endocannabinoid system works, we need to understand how our nervous system communicates.

The structure which enables our nerve cells or neurons to send signals from one to the other is called a synapse. Our brain contains roughly one hundred billion neurons, each making approximately 7000 synapses onto other neurons; their function being the transfer of information. Synapses are made up of a pre- and postsynaptic membrane that form the synaptic cleft. Communication between the cells requires a neurotransmitter, which is released from the presynaptic membrane into the synaptic cleft where it binds to receptors on the postsynaptic membrane. The ‘language’ in which the neurons communicate with each other depends on the specific neurotransmitter and receptor present and combination thereof involved.

There are many different neurotransmitters in the brain and each of them can only activate specific receptors. One way to think about it is as a key and a lock, where the given signalling molecule is a key to opening the specific lock i.e. causing a specific effect by the receptor. When the neurotransmitter has done its job, it will either be recycled or broken down by metabolic enzymes to avoid overstimulation of the receptor.

To summarize briefly, signalling in the nervous system involves three parts: a neurotransmitter (a signalling molecule), a receptor (the effector) and a way of getting rid of the molecule. The endocannabinoid system consists of these three components: the signalling molecules are endocannabinoids, the receptors are known as cannabinoid receptors and the system gets rid of signalling molecules through metabolic enzymes.

Endocannabinoids

The signalling molecules used in the endocannabinoid system are called Endocannabinoids. The two most common endocannabinoids are anandamide and 2-AG. These interact with the cannabinoid receptors and have been suggested to regulate a broad range of functions such as pain, reproduction, psychiatric disease, psychomotor behaviour, memory, wake/sleep cycles, the regulation of stress and emotional state, and learning.

Cannabinoid Receptors

Cannabinoid receptors exist throughout the central nervous system (brain and spinal cord) and peripheral nervous system (spread out through the body), in fact, the body has 10x more cannabinoid receptors than opioid receptors. The two most studied receptor types are CB1 and CB2 receptors. CB1 receptors are primarily found in the central nervous system and CB2 receptors are primarily found in the peripheral tissue and immune cells. As previously mentioned, these cannabinoid receptors are sensitive to some phytocannabinoids due their structural similarity to endogenous endocannabinoids.

Metabolic Enzymes

The metabolic enzymes act within the synaptic cleft to destroy endocannabinoids after they have activated the cannabinoid receptors. The two common metabolic enzymes are FAAH, which breaks down anandamide, and MAGL, which breaks down 2-AG. These enzymes ensure that the endocannabinoids do not overstimulate the receptors. This distinguishes endocannabinoids from many other molecular signals in the body, such as hormones or classical neurotransmitters, which often persist for many seconds or minutes at the receptor, or get recycled and stored for later use.

The three components of the Endocannabinoid System work in synergy and have been shown to regulate several bodily mechanisms including:

One example of how the ECS can bring the body back to a state of “Zen” is in the context of inflammation. Inflammation is a natural protective reaction mediated by the immune system in response to infection or physical damage. The purpose of inflammation is to kill pathogens (germs) and protect damaged tissue during regeneration. Inflammation within a particular area is produced by the accumulation of inflammatory mediators, one of them being histamines, which many may know due to their use in tackling allergic reactions. Among other functions, these inflammatory mediators increase blood flow, as well as increasing the permeability of blood vessels. Combined, this allows for a more efficient delivery of immune cells into the area of inflammation to initiate the healing process.

Inflammation is thus, a very important component in the body’s natural immune system.

Inflammation however, is not always a helpful response. In instances for example, when inflammatory mediators persist even though the healing process has already started, or mistakenly target our own cells, the resultant immune response can be extremely harmful - and painful. Chronic inflammation and autoimmune diseases like rheumatoid arthritis and Crohn’s disease are examples of our immune system getting activated inappropriately. In the context inflammation, the ECS has been shown to limit overactivation of the immune system’s inflammatory signals. Endocannabinoids are in fact, released by immune cells themselves upon activation and appear to regulate the immune response by acting anti-inflammatory. Scientists have thus argued that ECS stimulation by phytocannabinoids may be beneficial for a range of inflammatory diseases. Preliminary data thus far strongly supports the therapeutic potential of cannabinoids for relief of pain-related behaviours and inflammation without evident side-effects.

What can CBD do?

Even though Cannabidiol (CBD) has been used for the treatment of a range of illnesses and ailments throughout the course of history, it is, to this date, not an approved medicinal substance. As such, no medical claims can be made, which is why scepticism regarding the benefits of CBD has remained. However, the recent expansion of clinical and scientific research into CBD has fuelled a paradigm shift: for the first time, evidence for the various benefits of CBD are becoming apparent (1). Pharmacologically, the broad ranging action of CBD can be ascribed to its complex signalling mechanism as it can both activate and silence classical cannabinoid receptors as well as modulate other signalling pathways. Benefits of this complex signalling include analgesic, anti-inflammatory, anxiolytic, antipsychotic and anticonvulsant qualities, which will be discussed in a bit more detail below (2).

Analgesic Properties (Pain Relieving):

Pain relief is a popular and almost anecdotal quality of cannabinoids. As such, it has been the focus of many studies on pharmaceutical cannabinoids, which in recent years found them to be safe, effective and a reasonable option for treating chronic pain (1). However, most scientific studies focus on medicinal cannabis, which contain comparably high concentrations of THC. Only recently has CBD received attention as an isolated pharmacological agent. It was shown to counteract both inflammation-induced (due to outside stimuli) and neuropathic pain (caused by damage to the nervous system) by activating CB2 receptors (3).There is ample evidence that CB2 receptor activation reduces the sensation of pain in a variety of preclinical models. CBD was also proven useful in chronic pain treatment by indirectly blocking neuronal pain signals (4). Particularly with regard to osteoarthritis, a chronic painful joint disease, CBD was found to attenuate the initial inflammatory response by inhibiting the natural breakdown of the endocannabinoid anandamide which suppresses pain initiation (5). Thereby, CBD could even offset the stabbing sensation of pain and numbness in both hands and feet that usually manifest itself at later disease stages (6). Thus, the analgesic effects of CBD are not confined to the duration of treatment, but even prove beneficial following termination of treatment.

Anti-inflammatory Properties:

Inflammation is one of the body’s natural reactions to sources of stress. These can range from a simple paper-cut to an unhealthy diet. The short-term processes of inflammation are highly beneficial, such as the necessary rise in body temperature during fever to eradicate a bacterium or virus. However, as with most things in the body, it is about a balance, and in regard to inflammation, this balance lies in its duration. Low-level chronic inflammation as a result of our modern, unhealthy lifestyles has peaked in recent years, making people more susceptible to diseases including some forms of cancers and rheumatoid arthritis (7).

CBD has been studied extensively for its anti-inflammatory properties. It can reduce the production of natural pro-inflammatory substances and inhibit the natural breakdown of anandamide, an anti-inflammatory endocannabinoid (8). In addition, CBD’s unique function in downregulating overactive immune cells is ascribed to a non-cannabinoid receptor mechanism via the enhancement of adenosine signalling at the A2A receptor (9). Its action here is believed to increase the rate of resolution of chronic inflammation (8) as demonstrated in cases where the use of CBD has improved clinically diagnosed arthritis (10).

Anxiolytic Properties (Anxiety-reducing):

While fear and anxiety are adaptive responses essential to coping with threats to survival, their exacerbation or persistance is often maladaptive, leading to disability. The term ‘Anxiety’ describes a broad range of symptoms found in many neuropsychiatric disorders, including Social Anxiety Disorder (SAD), panic disorder (PD), and post-traumatic stress disorder. The anxiolytic effects of CBD in humans were first demonstrated in the context of reversing the anxiogenic effects of THC. Since then, CBD has been studied in a wide range of animal models of general anxiety and individuals with SAD, which combined found a significant reduction in anxiety as well as an antidepressant effect (11). Furthermore, existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely (12).

Antipsychotic Properties:

Similarly to the anxiolytic properties of CBD mentioned above, numerous psychological studies have highlighted CBD’s ability to counteract psychotic symptoms, including those induced by its closely related compound THC (13). This led to the study of CBD’s general antipsychotic qualities beyond counteracting THC (14). To date, numerous studies and clinical trials that focus on schizophrenia have deemed CBD an effective and extremely safe treatment option (15). Remarkably, a double-blind, randomized clinical trial of CBD vs amisulpride, a potent antipsychotic commonly used to treat schizophrenic individuals, further found CBD to be equally effective, while exhibiting significantly less side effects (16). Even though the exact mechanism of CBD in alleviating  symptoms of psychosis has not been characterized, results suggest the cannabinoid may be an effective option in treating psychosis and particularly schizophrenia (15).

Anticonvulsant (seizure-decreasing):

The use of CBD in epilepsy treatment is one of the more thoroughly studied medical applications of cannabinoids. Traditional anti-epileptic medications lack action in ‘treatment-resistant’ forms of epilepsy, which account for roughly 20% of epilepsy patients, of which most are children (3). Yet, CBD appears to be effective: in 2017 the NYU Langone Medical Center carried out a trial of CBD as add-on medication in drug-resistant seizures in the Dravet Syndrome, a severe form of epilepsy, and showed that on average patients experienced a 54 percent decrease in the number of their seizures (17).

Even though research is showing positive results we at thedrug.strore want to advise you that the dosage of CBD used for these trials is extremely high and products offered through thdrug.store are not the most suitable. Furthermore, we advise you to consult your doctor about medication, especially in severe cases of illness.

CBD and Cancer:

Neither medical cannabis or individual cannabinoids such as CBD can currently be considered a sole cure for cancer. We at thedrug.store want to distance ourselves from such claims.

However, CBD has been used as a palliative agent to complement prescribed medication in the treatment of cancer (3). It was shown to be particularly effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with chemotherapy and radiation therapy, as well as reducing neuropathic pain or nausea (1). Individual studies are also investigating potential qualities of CBD in the domain of disease modulation and cancer treatment (1). A phase II clinical trials is currently evaluating the effect of CBD as a single treatment for solid cancers (18). Nevertheless, we at thedrug.store want to be very clear that even though CBD has been beneficial in a few cases, we want to remind you to consult your doctor about medication, especially in severe cases of illness.

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