Panacea or Placebo? A Critical Overview of CBD
After decades of prohibition, the legal cannabis industry is beginning to take shape in numerous countries throughout the world. While there are recreational, agricultural, ancillary and biotech sectors of this industry, the key driver of its emergence is the growing legalisation of cannabis for medicinal purposes in various jurisdictions. The efficacy of these medicinal cannabis formulations is allowing them to gain traction within the scientific community and general population, as they are used to treat a range of conditions such as pain, anxiety and epilepsy.
The term medical cannabis is used to describe any plant-based medicine derived from the cannabis plant that is typically prescribed by a physician. The key constituents of these medications are pharmacologically active compounds called cannabinoids, which are associated with cannabis’ potential therapeutic effects. Of these compounds, CBD is the one that has received the most interest and can be found in the large majority of medical cannabis products.
These CBD formulations can either be pharmaceutical or nutraceutical products. The pharmaceutical CBD products are medicines that have been designed to treat specific conditions, while nutraceutical CBD products are dietary supplements that are taken for their health benefits and can contribute to an improvement in wellness. CBD has garnered plenty of hype thanks to its profile of wide-ranging potential benefits and can be found in all sorts of compositions in places where it is legal.
CBD has plenty of advocates, with scientists and celebrities alike singing the cannabinoid’s praises. Manufacturers are attempting to profit greatly from all this hype and positive attention by including CBD in just about anything, despite the FDA only approving one specific CBD medication. So what exactly is all the hype about, and is it justified? Read on to find out.
What is CBD?
With all the hype surrounding CBD, you may be confused about what it actually is and what it can do for you. If that’s the situation you find yourself in, then don’t worry, we’ve got you covered.
CBD is an abbreviation of cannabidiol, which belongs to a group of molecules called cannabinoids. CBD is just one of close to 120 (possibly more) cannabinoids that can be found within hemp and cannabis plants. These molecules are referred to as phytocannabinoids (i.e. the phyto- prefix meaning derived from plants).
Interestingly enough, our body can also produce naturally-occurring cannabinoids which are called endocannabinoids. Both types of cannabinoids interact with the endocannabinoid system (ECS), which maintains homeostasis within the body. This system mediates a wide range of physiological functions including appetite, sleep cycles, emotion, memory, body temperature, nociception (pain processing), nerve signalling and immune responses, amongst others.
The endocannabinoid system is comprised of CB1 and CB2 receptors. CB1 receptors can be located in abundance throughout the central nervous system (the brain and spinal cord), while CB2 receptors are located outside the CNS, mainly on cells in the immune system. Unlike the cannabinoid THC (tetrahydrocannabinol), which exerts its effects after binding to the CB1 receptors, CBD does not directly stimulate either the CB1 or CB2 receptors at all.
Instead, CBD interacts with the ECS in two different ways. It stimulates the body’s natural production of endocannabinoids by the ECS and it also down-regulates the activity of some cannabinoid receptors, rather than activating them. This down-regulation may explain why CBD is able to counteract the psychoactive and anxiety-inducing effects of THC consumption.
In regards to psychoactivity, THC is the molecule responsible for the intoxicating effects of the cannabis plant, known as the “high”. Some of the effects associated with this high include euphoria, relaxation and cognitive impairments such as deficits in memory, judgement and coordination. In contrast, CBD is only mildly psychoactive and does not contribute in any way towards this high. This lack of psychoactivity is one of CBD’s major marketing points, as it means that consumers are able to enjoy a lot of the potential therapeutic benefits of cannabis without any of the cognitive impairments.
This leads to another major marketing point for CBD - that it has a wide range of potential therapeutic benefits rather than one specific one. As CBD interacts with the ECS, which is involved in a range of neurological, inflammatory, gastrointestinal and metabolic processes, it has displayed a diverse array of physiological effects, some of which are beneficial.
Because of this, consumers have been known to take CBD often and incorporate it into their daily lives in the hope of treating various conditions. Some of the conditions consumers often utilise CBD for include pain (acute or chronic), inflammation, anxiety, insomnia, nausea, migraines, acne and different types of epilepsy. While this may sound like CBD is a wonder drug with a myriad of uses, there are still reasons to be cautious when it comes to the advertised claims of CBD products.
Scientific claims behind CBD
When it comes to medicinal products, such as those that contain CBD, it is important to distinguish anecdotal evidence from clinical evidence and health claims made by manufacturers from claims with scientific proof.
Currently, the only CBD-containing medication that has received FDA approval is Epidiolex. This medication is a CBD tincture that is administered orally and is used for the treatment of Lennox-Gastaut syndrome and Dravet syndrome. These conditions are two rare forms of epilepsy that predominantly affect children and had proven difficult to treat prior to the approval of Epidiolex. The exact mechanism of action remains unclear, but numerous studies have shown that CBD has the ability to reduce the frequency and duration of seizures in epileptic patients.
Even though scientific evidence supports CBD’s effectiveness in managing epilepsy, there are still many conditions that CBD has not yet been proven to treat. This has become an issue in the past, as many of the claims about CBD’s health benefits from product manufacturers and advocates have been unfounded or heavily based on anecdotal evidence. A lot of these grandiose claims have drawn the ire of the FDA, who have found themselves sending warning letters to numerous companies which they have deemed as breaching federal law with the claims they have made.
While CBD has not yet been approved for any other conditions, there is still promising research that highlights its wide range of potential beneficial effects. Currently, there is a vast number of studies available on PubMed regarding the endocannabinoid system (ECS) and cannabidiol (CBD), with well over 20,000 citations.
Outside of epilepsy, the major reason most consumers choose to utilise CBD is to relieve both acute and chronic pain. The latter is made up of either neuropathic pain, inflammatory pain or a combination of both. Neuropathic pain is a result of damaged neurons in the nervous system, whereas inflammatory pain is a result of tissue damage and the subsequent inflammation.
Studies have found that CBD has potential in managing both types of pain by inhibiting the release of glutamate and other inflammatory agents. This also has a neuroprotective effect which dulls the prickling and burning sensations that neuropathic pain is characterised by. These anti-inflammatory, neuroprotective and analgesic effects mean that CBD can be helpful in managing a range of pain-related conditions.
CBD’s effectiveness in treating pain has been highlighted in other studies for conditions such as arthritis, fibromyalgia, migraines and cancer pain. In addition to helping reduce cancer-related pain, The National Cancer Institute (NCI) in the US has deemed that CBD may have the potential to reduce some other side-effects of chemotherapy, including nausea and lack of appetite.
CBD is also viewed by some as a potential alternative to anxiolytic medication. Clinical research on CBD as a treatment for anxiety disorders has proliferated in recent times due to anecdotal and scientific evidence attesting to its therapeutic potential. For generalised anxiety disorder (GAD), CBD has been shown to reduce stress in animals such as mice and rats. These test subjects have displayed lower behavioural signs of anxiety and a reduction in anxiety symptoms such as an increased heart rate after being administered with CBD.
Studies have also found that CBD could have potential in managing other forms of anxiety, such as social anxiety disorder (SAD) and post-traumatic stress disorder (PTSD). While the research into anxiety seems promising, a 2017 review on CBD and psychiatric disorders concluded that there wasn’t enough evidence to suggest that CBD was an effective potential treatment for conditions such as depression.
Some consumers have found that CBD can also help with their insomnia by acting as a sleep aid. While many studies also attest to CBD’s ability to improve sleep and the symptoms of REM sleep behaviour disorder (RBD), the exact mechanism by which it does so remains unclear. Most scientists believe that CBD is effective in managing insomnia due to its ability to treat comorbid conditions such as pain and anxiety.
Outside of these potential benefits, scientists are also researching a range of novel CBD applications. Tumour inhibition and apoptosis, acne management, reduction of psychotic symptoms, lowering of blood pressure and the prevention of diabetes are just some of the effects that have been investigated in these studies.
Does that mean CBD has proven to be effective in consistently producing these effects and therefore should be used in the treatment of cancer, acne, schizophrenia, hypertension and diabetes? Not exactly, but at least there are credible CBD studies being conducted on these conditions with promising evidence for future clinical trials.
However, it is important to note that a lot of this research has been conducted on cell cultures and various animal models, but not much has been conducted on humans. Despite promising scientific evidence, Epidiolex remains the only FDA-approved CBD medication, and further research and clinical trials are required before any other CBD medications are approved for other conditions. As it stands, many consumers are currently utilising CBD for conditions it has not yet received approval for.
CBD & COVID-19
Earlier in the year, the FDA even had to send out warning letters to several companies for what seemed like a ridiculous claim - that CBD could cure COVID-19. Were these claims unfounded, with very little scientific basis behind them? Most definitely. But while CBD can’t cure or prevent the onset of the novel coronavirus, there is some interesting research to suggest that it could be effective in managing its symptoms.
After being infected with COVID-19, the immune system of an affected individual comes under serious distress. When the immune system comes under attack, “communication molecules” called cytokines are released, which mediate the inflammatory response. Cytokine proteins are released to help repair the tissue in the lungs that have been damaged due to respiratory distress. However, if too many cytokines accumulate they can cause even further damage - a process known as a “cytokine storm”.
This cytokine storm can worsen the immune system’s response to COVID-19 and lead to other complications, such as a fever, cough, muscle pain and extreme lung inflammation.
The inflammation of the lungs results in serious damage, and the onset of acute respiratory distress syndrome (ARDS). The combination of ARDS and the cytokine storm disables lung function and creates an environment for the virus to manifest. All of these symptoms make breathing laborious, and the most severe cases of ARDS requires patients to utilise a ventilator for their survival.
As the endocannabinoid system plays a role in mediating inflammatory and immune responses, it is thought that CBD might be able to aid patients infected with COVID-19. Earlier in the year, researchers from the Texas Biomedical Research Institute and the University of Nebraska published a review that detailed the potential use of CBD in reducing the lung inflammation caused by COVID-19 and ARDS.
The review highlighted previous research that displayed CBD’s beneficial anti-inflammatory effects in pre-clinical models of various chronic inflammatory diseases.
They deemed that CBD had a high margin of safety and was a feasible treatment to reduce SARS-CoV2-induced lung inflammation and disease severity.
In a 2019 animal study conducted by researchers from the University of Santa Catarina and the University of Rio de Janeiro, CBD was found to successfully reduce the production of pro-inflammatory cytokines. The study also found that CBD has the ability to reduce pulmonary fibrosis, which damages and scars lung tissue. Pulmonary fibrosis is another side-effect of a severe reaction to COVID-19.
Another animal study published in in the Cannabis and Cannabinoid Research Journal found that pure CBD can assist in preventing lung damage caused by COVID-19. The study monitored the lung function of rodent models that were injected with a replicated copy of the COVID-19 virus. As COVID-19 is highly contagious, there are only a limited number of facilities throughout the world that are permitted to perform tests with it.
Lung function, oxygen levels and inflammation levels improved in all rodent models after being administered with CBD. The findings also supported previous research, as CBD was found to inhibit the excessive release of proteins and reduce the cytokine storm. In doing so, CBD can serve as a protectant against inflammation, pulmonary complications, and long-term damage to lung tissue. It can also help to improve oxygen levels which enables structural lung recovery.
Ultimately while these findings are promising, further research and clinical trials are necessary in order to fully understand the benefits of CBD in regards to the inflammatory and immune responses within the airways. As it stands, CBD has shown promise for use as an adjunct to other therapies rather than for use as a monotherapy. Some companies are even beginning to include CBD in their potential COVID-19 medications, which are being investigated in clinical trials.
The effectiveness of the recently announced vaccine from Pfizer will determine whether these clinical trials and subsequent research into CBD as a treatment for COVID-19 will continue. While this may be unlikely, the research indicates that CBD may yet have a role to play in treating a range of respiratory diseases in the future.
A critical view of CBD
One of the major criticisms of CBD is that the hype surrounding the compound and some of the advertised health claims have led people to believe that it’s too good to be true. CBD’s reputation as a panacea for a range of different symptoms and diseases can sometimes do more harm than good. Because of this, CBD is sometimes viewed as a miracle cure-all, similar to “snake oil”. But CBD is neither, and there is some evidence to suggest that in some cases, its potential risks may outweigh the benefits.
Even with promising scientific evidence highlighting CBD’s potential benefits, there is still a need for further research to be conducted on humans in addition to clinical trials for new medications. This is to ensure that the data and findings from cell cultures and animal studies translate to how CBD interacts with the human ECS so that the reported health claims can be substantiated. Consumers should also be wary of CBD product manufacturers that make false claims, are selective with the information they provide and suppress negative information regarding their products.
Many consumers hold the belief that CBD can only be beneficial, with minimal to no risks or adverse effects. However, this is not entirely accurate. Some of the acute adverse symptoms that can present after CBD consumption are nausea, diarrhoea, fatigue and irritability. These symptoms typically only present when higher doses of CBD are consumed.
The biggest concern in regards to adverse effects is how CBD interacts with other prescription medications. CBD is both a substrate and inhibitor of CYP450 enzymes, which means it can interfere with the metabolism of other drugs. CYP3A4 is the main enzyme responsible for metabolising CBD as well as various other prescription medications. CBD can inhibit this enzyme, which will increase the concentration of these drugs in the bloodstream and prolong their effects. This can result in toxicity and the onset of adverse effects.
CBD acts in a similar manner to grapefruit in this regard, which can also inhibit CYP3A4. You can assume that any medication with a warning about the consumption of grapefruit will interact with CBD in the same way. Some of these medications include blood (e.g. warfarin), anti-convulsants, anti-depressants, cholesterol-lowering drugs (e.g. statins), hypertensive drugs and some anti-cancer agents, amongst others. Consulting with a medical practitioner is highly recommended for consumers wanting to try CBD while on other medications.
Lastly, the way in which our body metabolises CBD can have a large impact on the onset of effects or whether they kick in at all. Other reasons why CBD might not take effect are that the consumer has not taken a high enough dose or waited for enough time. But sometimes when people don’t feel the effects of CBD, it leads them to another conclusion - that CBD is a placebo.
The placebo effect & why CBD affects people differently
A placebo is a substance or other kind of treatment that looks just like a regular medicine but is not. Placebos are designed to seem like the real thing, they just don’t contain any active medicinal components (e.g. sugar pills). They are often used in research studies or clinical trials alongside the actual treatment. This allows the research to remain as unbiased as possible and helps to verify whether or not the treatment is actually effective.
The placebo effect describes the phenomenon in which some test subjects or individuals experience a therapeutic benefit after being administered a placebo. This effect can be quite profound and has been observed throughout numerous medical studies. There are even studies where patients knew that they were receiving a placebo, and it was more effective compared to the control group.
Research would suggest that CBD is not a placebo. As discussed earlier, there is a large number of studies that detail the potential therapeutic effects of CBD. The presence of the endocannabinoid system is another reason why CBD is most likely not a placebo. This system regulates a wide range of physiological functions, and it simply wouldn’t exist if it wasn’t important to our maintenance and survival. The fact that CBD interacts with this system and can modulate how it functions would suggest that CBD can stimulate some kinds of physiological effects, even if they are not immediately apparent.
However, there are still many people in the scientific community and general public that believe that the wide-ranging effects and applications of CBD are merely due to the placebo effect. The main reason behind this might be that CBD doesn’t work the same for everyone. The amount of time it takes for CBD to take effect, or whether it does at all, depends on the individual. In fact, there are several different factors which can influence how CBD interacts with our bodies.
Biological factors such as gender, age, weight, metabolism and blood circulation can all impact the bioavailability of CBD. Bioavailable CBD is the amount of CBD that is available to the ECS in order to exert its effects. Bodyweight has a major impact on metabolism and blood circulation as people that weigh more tend to have more fat cells, which is where CBD is deposited after circulating through the blood cells. Individuals that have a high body fat content can absorb and store more CBD, which can prolong its effects.
Dosage is another factor that can affect CBD absorption and the expected effects, with higher doses achieving an increase in bioavailable CBD. Increasing your dose of CBD should be approached with caution though. Some consumers find that their CBD is taking longer than they expected to work, or they conclude it isn’t working at all. In these instances, they may be tempted to re-dose and end up consuming too much. This can increase the likelihood of adverse effects, such as diarrhoea or fatigue.
The concentration and quality of CBD products also play a role in the bioavailability of CBD. Similar to increasing the dose, increasing the concentration of CBD in a particular product makes them more potent, meaning that consuming lower doses of this product is recommended. In regards to product quality, some CBD products can contain impurities and additives, which can affect how CBD is absorbed, processed and metabolised within the body. Consumers should aim to find third-party tested brands from licensed and reputable labs and CBD products that contain whole-plant extracts, as these offer the best safety profile and medical benefits.
Of all the factors that can affect the absorption and effects profile of CBD, the method of consumption seems to have the largest impact on CBD’s effectiveness. Knowing what to expect from different delivery modes aids consumers in determining how their CBD will affect them and how long they should wait before re-dosing.
Oral consumption of CBD is the most popular method, and it involves swallowing and ingesting a wide-range of CBD-containing products. Orally administered CBD has a low bioavailability as it has to travel through the digestive system and is processed in the gut and liver before reaching the bloodstream. The process by which CBD is metabolised by enzymes in the gut and liver is known as “first-pass metabolism”. As oral consumption is the most popular delivery mode, it is not surprising that some consumers might not feel the effects of CBD, as first-pass metabolism can greatly impact its effectiveness.
Sublingual consumption involves applying CBD preparations such as tinctures or sprays directly under the tongue. This is another popular method of consumption as CBD’s effects are felt quickly, and re-dosing is easy. CBD consumed sublingually takes effect much faster than oral CBD due to the vast network of capillaries that are located underneath the tongue. These capillaries can absorb compounds quickly and deliver them into the bloodstream. This allows CBD to bypass first-pass metabolism as it doesn’t enter the digestive system or go through the liver.
Consumption through inhalation involves either smoking or vaporising CBD and absorbing it into the bloodstream via the lungs. This is the fastest method of consumption as the inhalation of CBD has rapid absorption rates. Inhaled CBD enters the systemic circulation in mere seconds after consumption as the lungs transfer the CBD directly into the bloodstream, again avoiding first-pass metabolism.
Lastly, topical application involves applying CBD directly to the skin or a localised area. When CBD topicals are applied to the skin, the CBD diffuses across the skin surface and targets inflammatory cells, spasmic muscles, and painful nerve centres. Almost none of this CBD enters the bloodstream due to the skin acting as a barrier and the amount of time it takes for these topicals to produce their effects depends on the CBD content of a particular product.
If consumers feel like they aren’t getting any of the therapeutic benefits from their chosen CBD product even after re-dosing, then trying a different type of CBD product is encouraged. This is especially true in cases where the initial product is being consumed orally. Everyone reacts differently to CBD, so experimenting with different products allows consumers to figure out what works best for them. If there is still no change in effects after trying different products, then consulting with a medical professional may help in understanding if any of the aforementioned or additional factors are rendering the CBD ineffective.
Available forms of CBD
The hype surrounding CBD and the great deal of interest in its potential health benefits has led to a wide variety of CBD products currently on the market. This diversity in products greatly benefits consumers, as it enables them to find the most effective product or the one that’s just right for their needs.
These products are typically either CBD isolate or full-spectrum and broad-spectrum CBD extracts. CBD isolate is pure cannabidiol with no additives, and it comes in either powder or crystal form. These compositions are extremely versatile and can be consumed either orally by direct ingestion, as a food additive or sublingually. CBD isolate is hydrophobic and does not dissolve properly in water but can be mixed with carrier oils, infused into edibles or added to other CBD products to increase their concentration.
Full-spectrum extracts contain CBD in conjunction with other compounds collected from cannabis and hemp plants during the extraction process. Some of these molecules, such as terpenes, flavonoids and additional cannabinoids, can provide therapeutic effects of their own and it is believed that full-spectrum extracts provide a wider range of health benefits than CBD isolate alone. Broad-spectrum extracts contain all of the same components as full-spectrum extracts with the exception of THC.
Of these products, CBD oil is the most popular among consumers. These oils are full-spectrum extracts that can also contain additives such as carrier oils, flavourings or additional terpenes. They are typically contained within a small bottle that has a dropper built into the lid to ensure easy and accurate dosing. CBD oil is consumed either orally or sublingually.
Another popular product due to their ease of consumption are CBD capsules. The most common types are softgel capsules that contain an oil-based CBD extract or two-piece capsules that contain CBD isolate. CBD capsules are also consumed orally and have no flavour, which makes them a more palatable option for consumers who don’t particularly enjoy the taste of CBD oil.
CBD edibles are another type of CBD product that can be consumed orally. They are created by infusing CBD extracts or isolate into food products, with the most popular choices being gummies, lollies, chocolates, brownies and cookies. CBD edibles are easy to consume and can mask the taste of CBD, but they also have a low bioavailability due to oral consumption and variable dosing.
For consumers who prefer to have their CBD kick in faster than oral consumption can allow, there is also a whole range of CBD vape products available on the market. Some of these products include disposable vape pens, vape cartridges and vape oil (aka vape juice). While inhalation of CBD has the quickest onset of any method of consumption, some risks include the potential development of respiratory issues.
Due to the presence of skin-based cannabinoid receptors, CBD can also be applied topically. The CBD is then absorbed through the skin to provide localised relief from pain and inflammation. As CBD cannot enter the bloodstream through the skin, these topicals must be applied to the exact location where pain or inflammation is felt. Some examples of the available CBD topicals include balms, salves, gels, creams, lotions and massage oils.
All of these options are the mainstream types of CBD products that are popular amongst consumers, but there is also a whole range of niche products that currently exist on the market. CBD itself is hydrophobic and is therefore not soluble in most liquids but “water-soluble CBD” is currently under development. This has opened the door to a new market of CBD-containing beverages including CBD water, energy shots and powdered drink mixes.
While not the most glamorous method of consumption, CBD suppositories are also available for purchase. Suppositories might seem invasive and unpleasant, but there is a good reason for their existence, as they are incredibly effective and have a rapid onset. They may not be for everyone, but consumers who utilise suppositories can experience some serious benefits in doing so.
If CBD suppositories didn’t seem strange enough, there is also a range of CBD products that are suitable for pets! As it turns out, cats, dogs and certain other animals such as mice also have their own endocannabinoid systems which CBD can interact with. These pet-specific CBD products aim to improve your pet’s quality of life by managing conditions such as pain, inflammation, anxiety and epilepsy. These products are designed for use by pets only, and some examples include CBD treats, tinctures, capsules and sprays.
The bottom line on CBD
Despite the seemingly unlimited potential of CBD from a medical and wellness sense, it is understandable why there is still scepticism surrounding the effects and benefits of CBD products. Although this isn’t unique in the world of medicine, CBD does not work the same for everyone. This can lead some people to believe that all the reports, claims and evidence of CBD’s therapeutic benefits are exaggerated or caused by a potential placebo effect.
While CBD is by no means a panacea or cure-all drug, there is a growing body of scientific research and evidence from clinical trials that show CBD has real effects and that many of them could be beneficial. Just like with every other medication, consumers are advised to do their due diligence when purchasing CBD products, use them correctly and allow enough time for them to take effect.
The medical potential of CBD as a therapeutic compound should never be confused with issues surrounding the CBD industry, such as unregulated quality standards and unproven health claims. It is also important to remember that while some of CBD’s therapeutic benefits are backed up by scientific evidence, they are still under investigation. Only Epidiolex is an FDA-approved CBD medication. When purchasing CBD products, only purchase them from reputable brands and sources, unless you have conducted your own thorough research.