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CBD Science: Surpassing the Snake Oil Stereotype

Health is wealth, and there is certainly no shortage of ‘snake oil’ on the market looking to exploit this. Whether its poor extraction techniques leading to low quality products, deceptively low concentrations, an uncomplimentary blend of ingredients, poor delivery or regulation, there’s often a molecular component behind the inefficiency of both natural and synthetic supplements alike.

As CBD is an emerging industry, regulation is currently lagging behind. This means that like many other products in the natural supplements space, fraudulent marketing and PR claims may prevail unchecked. Brands need to practice robust self-regulation, which will not only serve their customers, but also benefit themselves in the long term by ensuring longevity and integrity.

When looking at natural supplements like CBD oil, vape oil, shatter or edibles you want to consider factors such as – whether it is a whole extract or an isolate, the concentration, filler ingredients, whether it is extracted from an organic source, combined with synergistic ingredients such as a carrier fat like MCT oil, and consider whether it's synthetic or natural.

The future of healthcare will be personalised medicine, whereby a patient’s very makeup can be analysed via genomic analysis, and the interactions of specific compounds predicted and measured accordingly. On route to that path, we increasingly rely on self-experimentation and most importantly, consumer education, especially in the CBD oil health and wellness space.

One of the biggest hindrances to the industry is that of scientific research, which is not where it should be thanks to the prohibition era. One of the leaders in the space is Israel, and other countries are beginning to fall in line. Some of the most promising areas of research include studies on how an individual’s DNA is expressed and how they, as a unique being, interact with compounds such as those found in Hemp as a result.

Then there are the new technologies designed to increase bioavailability and absorption, including nanotechnology and Liposomal delivery, the safety and efficacy of which is currently being investigated further. All of this is vital to being able to maximally harness and absorb the natural benefits of this historically medicinal plant. 

As a whole, the research tends to show that natural products, when properly extracted, formulated and delivered, are critical to maximising health, alongside holistic lifestyle intervention. We are at a pivotal point in history, in terms of working out how these compounds should be created and used, as well as innovated going forwards.

One of the main barriers to research is the fact that CBD remains a schedule 1 in the United States. There is a regulatory disconnect, in which the public can self-medicate using a product that scientists are struggling to access to perform high quality clinical trials, creating a novel and odd situation at best. It is extremely expensive to attain enough pharmaceutical CBD for a gold-standard clinical trial. 

This is mainly because the process of extracting CBD from the cannabis plant is complex and arduous. Clean extraction methods such as CO2 distillation are even more expensive than less environmentally friendly fossil fuel or solvent based methods.

As a result, several companies have turned to manufacturing synthetic forms of CBD. This eliminates the concerns around purity, but it still falls under the Schedule 1 classification in the US. It could also potentially have very different effects from its naturally-derived cousin, despite being the same molecular structure.

Even in countries where Cannabis has been legalised, such as in Canada, there is a complex application process for clinical trials, with more than a 6 month waiting list for government authorisation to conduct CBD studies in people or animals. If studies such as these are not done, and not done soon, we will be left with a poorly monitored and informed market place for a long time. 

Nevertheless, it is not a field with entirely non-existent data and there are papers out there that indicate where the promising potential of CBD lies, alongside its centuries old historical use. A good example is a review published in June, evaluating a massive amount of data with the intention to synthesise and strengthen overarching conclusions.

The resultant findings summarised that CBD is mostly safe to use, provided people take into consideration possible contraindications when using prescription medicine. There is a major need for more research, as well as more varied research, as the majority of studies performed were for the treatment of either epilepsy or psychotic disorders.

The most common side effects reported seem to be tiredness, diarrhoea, and changes in appetite or weight, although it has comparatively fewer side effects than most prescription medication (for the same conditions in question), which could help increase patient-adherence. CBD is predominantly a complimentary or supplemental therapy.

 

CBD Research Paper Findings

Refractory Epilepsy

In terms of the results for refractory epilepsy, around 50 million people worldwide suffer from the illness, which is more than Parkinson’s and Cerebral Palsy combined. It is the fourth most common neurological disorder in the US. In one small scale study using CBD, the frequency of seizures decreased in 40% of patients and disappeared completely in 27%.

60% of patients were able to control around half their seizures and in terms of the neurocognitive changes, many patients experienced improvements in behaviour, language, sleep and eating habits. Almost all patients reported that their mood had improved since using Cannabidiol.

Dravet Syndrome

This study focused on children with a form of epilepsy known as Dravet Syndrome. This is a rare, genetic neurological disorder that develops in the first year of the child’s life. It can cause developmental disabilities and means a lifetime of adherence to a mixed bag of prescription medication.

The trial was a double blind, placebo-controlled cohort of 120 young children and adults with treatment-resistant seizures and Dravet syndrome. Over 14 weeks they were randomly assigned either placebo or a CBD oral solution, with dose based on body weight, as an adjunct to their conventional medication.

While the rate of non-convulsive seizures did not change, the CBD-treated convulsive seizures decreased by almost half. In addition, 5% of the patients given CBD became seizure-free, compared with none in the placebo group. An incredible 62% of the CBD group reported a significant improvement in their overall condition, compared to only 34% in the placebo group. The drawback was the side effects, some of which were possibly due to interactions with the prescription medication, including vomiting and fever.

CBD and Fear 

An animal study focused on how CBD can be used to weaken the fear response. This is relevant to conditions caused by fear associated with adverse memories, such as in PTSD.

277 rats were given a dose of CBD immediately after receiving a small electric shock. When reintroduced to the context for the fear-inducing event, the CBD-administered rats were found to spend less time frozen than their placebo oil counterparts. This suggests that CBD disrupted consolidation (memory strengthening) of their specific and long-term fear memory.

CBD was also found to disrupt the consolidation of general fear memories, when administered immediately after the event. The timing of the administration seemed to be vital, as results suggested that delayed administration did not have the same effectiveness.

CBD and Public Speaking 

Fear of public speaking is known as Glossophobia. A double blind study involving 60 males and females between the ages of 18 to 35 divided subjects into groups who either received placebo, 100mg CBD, 300mg, 900mg, or Clonazepam (a pharmaceutical medication for panic disorder).

Each participant gave a speech in front of their peers, after which they filled out an anxiety questionnaire and had their blood pressure and heart rate measured. Clonazepam was the front runner, consistently reducing anxiety in a more sedative way than either the placebo or CBD administration.

However CBD at a dose of 300mg was shown to significantly reduce subjective anxiety in the post-speech phase. The same was not true for the 100mg or 900mg doses.

This suggested that CBD produces an inverted U shaped dose response curve, stressing the importance of careful choice of dose range and therapeutic window when investigating the effects of CBD. At smaller doses, the dose may be too low to have an effect, whilst at higher doses, the effect may be negated by side effects.

CBD and panic disorders

A review published in 2017 defines panic disorder as a disabling psychiatric condition that affects approximately 5% of the worldwide population (around 355 million people). The authors analysed existing data to look into the therapeutic effects offered by Cannabinoids, and in particular, CBD. Prior studies ranged from electrical stimulation in animals to public speaking in small scale human trials.

The most compelling conclusion was that as well as offering promise as a therapeutic agent for such conditions, CBD was not habit forming, and did not decrease tolerance. This is a big benefit compared to the conventional benzodiazepines and antidepressant drugs, which can be addictive.  

CBD and high Blood Pressure

Another study from 2017 explored the relationship between CBD and decreases in blood pressure. The randomised, placebo-controlled double-blind cross-over study using 9 healthy male volunteers was the first of its kind. Participants were given either 600mg CBD or a Placebo. They were then monitored for changes in their cardiovascular system. 

Using stress tests such as maths without a calculator, cardiovascular outputs were monitored. The study found that CBD reduced resting systolic blood pressure and stroke volume, as well as ‘blunting the blood pressure response to stress’.

High blood pressure has a multitude of beneficial lifestyle treatments, including making healthy and consistent changes to both diet and exercise. This study essentially adds CBD to the list of beneficial adjustments.

CBD and Psychoactive effects

THC is the molecule from the cannabis plant that causes the psychoactive high, whereas CBD does not. This is due to the different molecular structure of the compounds and their binding sites. However, as cannabis is predominantly known for, and associated with the high caused by THC, this tends to be what defers most people from trialling CBD as a therapeutic adjunct.

Previously, studies have infamously misinterpreted results to suggest that CBD is processed by the body and converted to THC, which is incorrect. The first misinterpreted study analysed the changes in CBD in a petri dish when mixed with acid, in order to artificially simulate acid digestion in the human GI tract. The second study analysed whether CBD was converted to THC orally.

In the first study, CBD did convert to THC in certain artificially simulated conditions, such as in the petri dish, however this was not suggested to be the case in humans or other living organisms. Culture-dish results give us an indication of what may happen, however living organisms present a more complex environment where the results will be slightly different.

In the second study using human volunteers, the results were taken out of context. Traces of THC were not only extremely minimal in the volunteers themselves, but there was also no THC to be found in their urine samples.

It is a reminder than in vitro results are suggestions not proofs of processes in real life. The glaring difference between CBD and THC is also the inability of CBD to bind to a persons cannabinoid brain receptors (more scientifically referred to as CB1). This means that it lacks the stereotypical intoxicating effects of cannabis.

The researchers note that while conversion to THC may occur under artificial conditions, over 40 years of research does not suggest that this takes place in vivo after oral administration. The more unexpected a result, the more authors should be cautious when interpreting and extrapolating, as highlighted by author Gerhard Nahler.

CBD and the Munchies

In a study where volunteers were given chocolate milk to drink, scientists compared the different effects of THC and CBD on appetite and taste, given cannabis’ association with ‘the munchies’ and appetite increase.

Over the course of 3 sessions, the study found that while THC did increase desire to eat, as expected, CBD and placebo did not have any significant effect on consumption.

CBD and Schizophrenia

Schizophrenia is listed as a psychiatric illness requiring heavy anti-psyhotic drugs and sedatives in order to manage a normal daily life. However this systematic review mentions that such drugs provide ‘limited cognitive benefits’, and have many debilitating side effects. The review also discusses the possible use of CBD in such conditions.

CBD has both anti-inflammatory and antipsychotic characteristics. The review aimed to evaluate preclinical and clinical literature on the effects of CBD in relation to the symptoms of schizophrenia. The authors looked through 27 articles from the last 26 years.

The overarching theme demonstrated that ‘CBD improves cognition in multiple preclinical models of cognitive impairment’ including schizophrenia, alzheimers disease, neuro inflammatory conditions (like fibromyalgia) and neurological disorders such as epilepsy. However, due to the lack of clinical trials and therefore evidence, an effective dose has not been determined.

Therefore the papers suggest that this is certainly an area worth exploring further with proper funding and large scale trials in place. 

CBD and irritable bowel disease

There is currently no known cure for Irritable bowel disease, which is believed to be brought on by a host of possible factors including stress. As noted in this review medication does exist that allows people to manage their symptoms reasonably well. However, they have often been found to have limited molecular benefit and tend to lose their efficacy over time.

As the Endocannabinoid System (ECS) is believed to play a role in colitis, it would make sense to look at possible treatments targeting the ECS, of which there are currently few on the market. The ECS has 3 main components: cannabinoid receptors, Endocannabinoids and the metabolic enzymes that breakdown and recycle the Endocannabinoids after they have been used.

Results indicated that the CB1 and CB2 Endocannabinoid receptors, along with cannabinoids produced by the body (endocannabinoids), are “up-regulated in inflammation, and their presence and stimulation attenuate murine colitis”. In plain English, as a response to inflammation in the body, the ECS produces more endocannabinoids and cannabinoid receptors, in an attempt to bring down the inflammation and its resulting symptoms. From this we can deduce that targeting the ECS could offer an effective means of providing substantial relief from the effects of colitis. 

Possibly as part of the chronic stress epidemic, the review notes that cases of IDB are on the rise. This reinforces the urgent need for more research into such a promising area, and its potential therapies. At present, IDB is estimated to cost the US an excess of $6.3 billion.

Liver injury and CBD

As with many other compounds, CBD is metabolised by the liver, this is the reason why those on medication that interacts with liver enzymes need to consult their doctor before adding it to their health regimen.

One study looked at how subjects with liver injury from chronic alcohol consumption were affected by CBD, by feeding it to mice and human blood samples that had been fed alcohol. Chronic alcohol consumption causes an increases in liver enzymes, and liver triglycerides (fatty liver deposits) – the analysis found that CBD was able to reduce both of these. 

This indicates that CBD holds the potential to be investigated as a therapeutic treatment for ‘alcoholic liver diseases’ associated with inflammation, oxidative stress and steatosis, given its ability to possibly reduce liver metabolic impairment and abnormal retention of lipids. 

CBD and recovery after stroke

When blood flow to the brain is blocked due to the narrowing of arteries (from fatty deposits) or a clot, it can cause what is known as Arterial Ischemic Stroke (AIS). This can even happen in neonates (new borns), and very little is known about what causes or treats NAIS, but it can cause lifelong disability from brain injury.

A study in 2016 showed that CBD has the potential to reduce the damage caused to the brain and improve recovery in the new born rat subjects it was administered to. The effects on the brain were analysed using MRI, behavioural tests and other system studies. Researchers found that giving CBD to the rats after induced artery blockage led to ‘long term functional recovery’.

In this study, CBD reduced the loss of neuronal structure and function, the abnormal increase of astrocytes (brain cells), cell death and damage, and inflammation of the nervous tissue. With more human studies, this treatment could hold promising new potential. 

Pain and CBD

Pain in a complex multi-dimensional issue. It is defined as ‘an experience that that has somatosensory, affective, motivational and cognitive characteristics.’ The relationship between pain and perception is known as ‘affective motivational dimension’. It affects several regions of the brain, which makes the relationship difficult to analyse and measure.

However this study attempted to measure whether CBD affects pain perception and experience in a number of different ways. It found that systemic CBD application did indeed reduce mechanical allodynia (other pain) in injured subjects. Systemic means whole body or system wide e.g. via an oral solution, whereas localised would mean the administration of CBD solely to the affected area e.g. via a cream.

The researchers also concluded that there is evidence that ‘CBD influences different dimensions of the response of rats to a surgical incision’. This was one of the first studies to show that CBD can have a positive effect on pain perception, which yet again paves the way for promising future research in the area.

In Summary

As mentioned in the intro, there are still many barriers that exist to conducting good quality, large scale research within the realms of cannabis medicine, despite its promising potential as a plant-based remedy to a hugely diverse array of conditions.

Although some of them are smaller scale than ideally desired and of a broad range, they are not the first of their kind. Many of the reviews build on earlier findings, theories and research efforts.

The result of such studies is a call to action, reflecting the crucial need to dig deeper into a field yielding potential benefits in the use of CBD as both an alternative and complimentary therapeutic option. There needs to be more research into dosage, efficacy, long term effects, and the extensive and individual nature of the complex endocannabinoid system, in order to explore possible new paradigms in healthcare.