What Is Cannabidiol
Our CBD (Cannabidiol) extract is made from American hemp, unlike medical & recreational cannabis products, which are usually made from plants with high concentrations of psychoactive tetrahydrocannabinol (THC). Our cannabidiol (CBD) extract is derived from CBD rich American hemp flowers – not stalks or seeds – ensuring higher quality and concentration. Because our products contain zero THC, these CBD extract based products are non-psychoactive and aid in relieving a variety of everyday discomforts.
How Does CBD Work?
CBD or cannabidiol is the main active compound in hemp and unlike THC, it is not psychoactive, so it doesn’t make you high. As you may know, inside the human body there’s the endocannabinoid system, with receptors spread throughout the brain and body. THC activates the CB1 and CB2 receptors, while CBD does not directly stimulate these receptors.
What Are CB1 & CB2 Cannabinoid Receptors?
Cannabinoid receptors are involved in a series of processes inside the human body, including the regulation of mood, pain sensation, appetite and memory.These receptors can be activated by endocannabinoids (produced by the human body) as well as by plant cannabinoids (like those found in hemp or cannabis), and they’re grouped into two main categories: CB1 and CB2. CB1 receptors are found mostly in the central nervous system, and in smaller numbers in the liver, kidneys and lungs, while CB2 receptors are part of the immune system and found in the hematopoietic blood cells as well.
CBD’s Effects on the Body
CBD does not stimulate these two receptors; instead, it activates other receptors, like the vanilloid, adenosine and serotonin receptors. By activating the TRPV-1 receptor for example, cannabidiol plays a role in the mediation of body temperature, pain perception and inflammation. Then, CBD inhibits the FAAH enzyme, a compound that activates the CB1 receptor. By doing so, CBD minimizes the activation of CB1 by THC, reducing its psychoactive effects.
The activation of adenosine receptors by CBD gives the anti-anxiety and anti-inflammatory effects of cannabidiol. Adenosine receptors are also involved in the release of dopamine and glutamate, two neurotransmitters that play major roles inside the body. Dopamine is involved in cognition, motor control, motivation and reward mechanisms, while glutamate is one of the major mediators of excitatory signals, being involved in memory, learning and cognition.
High concentrations of CBD have been shown to activate the 5-HT1A serotonin receptor, exerting anti-depressant effects. The same receptor is involved in a series of processes from pain perception, appetite, nausea and anxiety to sleep and addiction mechanisms.Finally, CBD blocks CPR55 signaling, decreasing bone re-absorption and cell proliferation. GPR55 is widely present inside the brain, being linked with the modulation of bone density and blood pressure, as well as with cell proliferation.
As previously said, CBD blocks the psychoactive action of THC, this being one of the reasons it’s generally considered advantageous to combine CBD and THC when for treatment purposes. However, the positive effects of cannabidiol are not dependent on the presence of THC, so you can still take advantage of the health benefits of CBD by purchasing products that contain only non-psychoactive CBD.
Curious about current scientific information about CBD? Read below from the most recent U.S. Senate hearing on CBD and its therapeautic effects:
The following information is taken from a presentation given to the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH). During the hearing, what is known about the biology and the potential therapeutic effects of cannabidiol (CBD) is reviewed.
To date, 23 states and the District of Columbia have passed laws allowing marijuana to be used for a variety of medical conditions. Fifteen additional states have enacted laws intended to allow access to CBD oil and/or high-CBD strains of marijuana. Interest in the potential therapeutic effects of CBD has been growing rapidly, partially in response to media attention surrounding the use of CBD oil in young children with intractable seizure disorders including Dravet syndrome and Lennox-Gastaut syndrome. While there are promising preliminary data, the scientific literature is currently insufficient to either prove or disprove the efficacy and safety of CBD in patients with epilepsy.i and further clinical evaluation is warranted. In addition to epilepsy, the therapeutic potential of CBD is currently being explored for a number of indications including anxiety disorders, substance use disorders, schizophrenia, pain, inflammatory diseases and others. My testimony will provide an overview of what the science tells us about the therapeutic potential of CBD and of the ongoing research supported by NIH in this area.
CBD Biology and Therapeutic Rationale
CBD is one of more than 80 active cannabinoid chemicals in the marijuana plant.ii Unlike the main psychoactive cannabinoid in marijuana, tetrahydrocannabinol (THC), CBD does not produce euphoria or intoxication.iii,iv,v Cannabinoids have their effect mainly by interacting with specific receptors on cells in the brain and body: the CB1 receptor, found on neurons and glial cells in various parts of the brain, and the CB2 receptor, found mainly in the body’s immune system. The euphoric effects of THC are caused by its activation of CB1 receptors. CBD has a very low affinity for these receptors (100 fold less than THC) and when it binds it produces little to no effect. There is also growing evidence that CBD acts on other brain signaling systems, and that these actions may be important contributors to its therapeutic effects.ii
According to a 2013 review published in the British Journal of Clinical Pharmacology, studies have found CBD to possess the following medical properties:
|Medicinal Properties of CBD||Effects|
|Antiemetic||Reduces nausea and vomiting|
|Anticonvulsant||Suppresses seizure activity|
|Antipsychotic||Combats psychosis disorders|
|Anti-inflammatory||Combats inflammatory disorders|
|Anti-oxidant||Combats neurodegenerative disorders|
|Analgesic||Relieves sensation of pain|
|Anxiolytic/Anti-depressant||Combats anxiety and depression disorders|
Preclinical and Clinical Evidence
Rigorous clinical studies are still needed to evaluate the clinical potential of CBD for specific conditions.i However, pre-clinical research (including both cell culture and animal models) has shown CBD to have a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties.
A number of studies over the last two decades or more have reported that CBD has anti-seizure activity, reducing the severity of seizures in animal models.vi,vii In addition, there have been a number of case studies and anecdotal reports suggesting that CBD may be effective in treating children with drug-resistant epilepsy.viii,ix,x However, there have only been a few small randomized clinical trials examining the efficacy of CBD as a treatment for epilepsy; the total number of subjects enrolled in these studies was 48. Three of the four studies reported positive results, including decreased frequency of seizures. However, the studies suffered from significant design flaws, including failure to fully quantify baseline seizure frequency, inadequate statistical analysis, and a lack of sufficient detail to adequately evaluate and interpret the findings.viii Therefore, the currently available information is insufficient to draw firm conclusions regarding the efficacy of CBD as a treatment for epilepsy; a recent Cochrane review concluded, there is a need for “a series of properly designed, high quality, and adequately powered trials.”xi
NIDA is currently collaborating with the National Institute on Neurological Disorders and Stroke to evaluate CBD in animal models of epilepsy in order to understand the underlying mechanisms and optimize the conditions under which CBD may treat seizure disorders, and determine whether it works synergistically with other anti-seizure medications. In addition, clinical trials are currently underway by GW Pharmaceuticals, testing the efficacy of Epidiolex, a purified CBD extract, for treatment of pediatric epilepsy.
Neuroprotective and Anti-Inflammatory Effects
CBD has also been shown to have neuroprotective properties in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s,xii,xiii,xiv stroke,xv glutamate toxicity,xvi multiple sclerosis (MS),xvii Parkinson’s disease,xviii and neurodegeneration caused by alcohol abuse.xix Nabiximols (trade name Sativex), which contains THC and CBD in roughly equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity associated with MS. It has not been approved in the United States, but clinical trials are ongoing, and two recent studies reported that nabiximols reduced the severity of spasticity in MS patients.xx,xxi There have been limited clinical trials to assess the potential efficacy of CBD for the other indications highlighted; however, a recent small double-blind trial in patients with Parkinson’s disease found the CBD improved quality-of-life scores.xxii
There have been multiple clinical trials demonstrating the efficacy of nabiximols on central and peripheral neuropathic pain, and rheumatoid arthritis.xxiii In addition, nabiximols is currently approved in Canada for the treatment of central neuropathic pain in MS and bodily pain unresponsive to opioid therapy. However, the current evidence suggests that the analgesia is mediated by THC and it is unclear whether CBD contributes to the therapeutic effects.xxiv THC alone has been shown to reduce pain;xxv,xxvi we are unaware of clinical studies that have explored the efficacy of CBD alone on pain. However, the anti-inflammatory properties of CBD (discussed above) could be predicted to play a role in the analgesic effects of nabiximols. Recent research has also suggested that cannabinoids and opioids have different mechanisms for reducing pain and that their effects may be additive, which suggests that combination therapies may be developed that may have reduced risks compared to current opioid therapies. However, this work is very preliminary.xxvii
Marijuana can produce acute psychotic episodes at high doses, and several studies have linked marijuana use to increased risk for chronic psychosis in individuals with specific genetic risk factors. Research suggests that these effects are mediated by THC, and it has been suggested that CBD may mitigate these effects.xxxi There have been a few small-scale clinical trials in which patients with psychotic symptoms were treated with CBD, including case reports of patients with schizophrenia that reported conflicting results; a small case study in patients with Parkinson’s disease with psychosis, which reported positive results; and one small randomized clinical trial reporting clinical improvement in patients with schizophrenia treated with CBD.xxxii Large randomized clinical trials would be needed to fully evaluate the therapeutic potential of CBD for patients with schizophrenia and other forms of psychosis.
CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological (e.g., heart rate) measures of stress and anxiety.xxxiii,xxxiv In addition, CBD has shown efficacy in small human laboratory and clinical trials. CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task.xxxv In a laboratory protocol designed to model post-traumatic stress disorders, CBD improved “consolidation of extinction learning”, in other words, forgetting of traumatic memories.xxxvi The anxiety-reducing effects of CBD appear to be mediated by alterations in serotonin receptor 1a signaling, although the precise mechanism remains to be elucidated and more research is needed.xxxvii
Efficacy for Treating Substance Use Disorders
Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphinexxxviii and reduced cue-induced heroin seekingxxxix in animal models. A few small clinical trials have examined CBD and/or nabiximols (THC/CBD) for the treatment of substance use disorders; however, the available data are not sufficient to draw conclusions. NIDA is supporting multiple ongoing clinical trials in this area.
Safety of CBD
For reasons discussed previously, despite its molecular similarity to THC, CBD only interacts with cannabinoid receptors weakly at very high doses (100 times that of THC),xl and the alterations in thinking and perception caused by THC are not observed with CBD.iii.iv,v The different pharmacological properties of CBD give it a different safety profile from THC.
A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages, including acute and chronic dose regimens, using various modes of administration.xli CBD is present in nabiximols which, as noted earlier, is approved throughout most of Europe and in other countries. Because of this, there is extensive information available with regard to its metabolism, toxicology, and safety. However, additional safety testing among specific patient populations may be warranted should an application be made to the Food and Drug Administration.
More studies will be needed to conclusively determine the entire spectrum of Cannabidiols medicinal applications.
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