Introducing CBD and Conolidine: A Natural Approach to Pain Management – Alphagreen Academy

– CBD and conolidine are both natural plant compounds. CBD (cannabidiol) is a non-psychoactive cannabinoid extracted from cannabis plants. Conolidine is extracted from the bark of the Tabernaemontana divaricata plant (crepe jasmine).

– There are five common types of pain: Acute pain, Chronic pain, Functional pain, Neuropathic pain, Nociceptive pain, and Radicular pain. Pain can be very complicated and can fit into more than one category.

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– CBD and conolidine have great potential to be included as part of a holistic approach to pain management. Both have little or no known adverse side effects. The scientific research into both are still in their infancy, and they have been considered safe to use and have had many reputed benefits.

– Before buying any CBD or conolidine product, make sure you have done your research. CBD products, for example, should only be purchased if they have been lab-tested by a third party and have a valid certificate of analysis. This will help ensure the product is safe for use, contains the CBD amount advertised, and is legal to use.

An increasing number of us are turning to nature to help support pain management. The various holistic options out there have given us more freedom in how we chose to cope with pain and its effects on our daily lives. Many of the natural ingredients advertised to modern consumers have been around and used for hundreds of years as part of pain management. In this article, we are going to look into the potentials of two well-known compounds known as cannabidiol (CBD) and conolidine.

CBD is a natural compound found in cannabis plants. It is non-psychoactive and shows many positive signs of being an excellent addition for those who want to take a natural approach to pain management. CBD is made by extracting it from CBD-rich plant material, being refined, and then formulated into a variety of consumable products. From CBD oils, CBD tinctures to CBD topicals and CBD edibles.

Conolidine is another natural compound and is found in the bark of the Tabernaemontana divaricata plant (otherwise known as crepe jasmine). This plant is native to Asia and has long been used in traditional Chinese, Thai, and Ayurvedic methods for easing pain. Like CBD, conolidine can be turned into many different products, providing consumers with an array of options on how they prefer to use the compound.

CBD and conolidine have both captured the scientific community’s attention due to their potential benefits to pain management. Research is in progress, but the initial results are looking promising for those wanting to follow a natural holistic method to soothing aches and pains.

Pain is something many people have to live with on a daily basis. It is the body’s way of signalling an injury or illness, which makes it an essential alarm to make us aware that something is not right. The sensation of pain is meant to make you feel uncomfortable, so you are aware you need to do something or stop doing whatever you are doing.

When you do something that is causing damage to your body, your brain activates the pain response. For example, if you come into contact with something hot, the painful sensation is your body’s way of informing you that you should stop touching it and do something to cool your skin. If you are eating ice cream and it triggers shooting tooth pain, it is also your body telling you to stop. Pain is not something to be disregarded, and we should act when it sets in.

The perception of pain differs from person to person. One person could break a bone and not even notice the injury, while another would find it excruciating. This is owing to the fact that nerve fibres mediate pain in the body. The nerve fibres are responsible for sending pain signals to the brain, which tends to happen rapidly. Once the brain has received the signal, it acts to make you aware of the pain. Because everyone’s bodies are different, their nerve fibres and brain signals react differently to the same stimuli. This helps to clarify why pain perception and pain tolerance can vary so much from one person to another.

Although we can experience pain in many different ways, there are five common types of pain. Some pain can fit into more than one classification, which is why pain can be hard to manage. The five most common forms of pain are:

• Acute pain
• Chronic pain
• Functional pain
• Neuropathic pain
• Nociceptive pain
• Radicular pain

Some of the terms are better known than others. Here is a short summary of each to help you get a better idea of what each pain type entails:

• Acute Pain – Relatively speaking, acute pain tends not to last very long. The duration can last from minutes to about three months (sometimes up to half a year). Acute pain also has a tendency to be associated with a soft-tissue injury or a temporary illness. This means it more often than not diminishes after the injury heals or the illness subsides. Acute pain from an injury can develop into chronic pain if the injury does not heal correctly or if the pain signals fail.
• Chronic Pain – Chronic pain lasts longer in duration than acute pain. For some, they can experience intermittent pain, but for others, it is constant. An example of intermittent chronic pain is a headache. They can be considered chronic pain when the headache continues over several months or years, even if the pain is not always present. Chronic pain can sometimes be caused by a health condition, such as arthritis, fibromyalgia, or a spinal injury.

• Functional Pain – This is pain that is caused by no apparent injury or discomfort to the body. Functional pain has a tendency to be chronic, though acute functional pain may also develop. BJA Education reported that an estimated 15% of the global population has functional pain syndrome. Some of the well-known examples of functional pain syndromes include:

Fibromyalgia (widespread pain throughout the body)

Irritable bowel syndrome (abdominal pain)

Temporomandibular dysfunction (jaw pain)

Chronic cardiac chest pain (chest pain)

• Neuropathic Pain – Neuropathic pain occurs when there is damage to the nerves or other parts of the nervous system. People often described it as shooting, stabbing, or burning pain. Some find it feels more like pins and needles, which can be just as uncomfortable. Neuropathic pain can also change the way you experience sensitivity to touch and even cause difficulty in feeling hot or cold sensations. Neuropathic pain is classed as chronic pain, although it may be intermittent but severe. Even with the pain coming and going, the severity can make some everyday tasks very difficult to carry out. As neuropathic pain can interfere with normal movement   (meaning it comes and goes), and it can be so brutal that it makes performing everyday tasks difficult. It can also lead to mobility issues as the pain can interfere with normal movement.  

• Nociceptive Pain – This type of pain is caused by body tissue damage. Some describe it as a sharp, achy, or throbbing pain that is often caused by an external injury. For example, you may experience nociceptive pain if you stub your toe, twist your ankle, fall on your knees, or hit your elbow. This form of pain is often felt in the joints, muscles, skin, tendons, and bones. Nociceptive pain can be both chronic and acute.
• Radicular Pain – Unlike the other four types of pain, radicular pain is a particular type that occurs when the spinal nerve gets compressed or inflamed. This form of pain has a tendency to radiate from the back and hip into the leg(s) along the spine and spinal nerve root. Those who have radicular pain may experience discomforts such as tingling, numbness, and muscle weakness. The pain that emanates from the back and into the leg is known as radiculopathy. It is more commonly known as sciatica, as the sciatic nerve triggers the pain. This form of pain is often constant and can be felt deep in the legs. Everyday activities from walking to sitting can make sciatica worse. Sciatica is one of the most common forms of radicular pain.

These forms of pain may require different approaches to help relieve discomfort. However, natural holistic methods can be applied to any of the above. With CBD and conolidine being available in so many different product forms, there is something out there to suit all types of pain and lifestyles.

Cannabidiol and Pain Management

Many people are aware of medical cannabis being embraced as part of pain management. However, the non-psychoactive compound CBD is now also being included as part of a natural approach. CBD can be applied for a range of purposes, and unlike medical cannabis, the user does not need to experience any adverse side effects.The compound responsible for the mind-altering effects found in cannabis plants is known as tetrahydrocannabinol (THC).

CBD is a relatively recent discovery and was isolated for the first time in the 1940s by the American chemist Roger Adams.  CBD accounts for around 40% of the compounds extracted from cannabis plants. However, due to the illegal classification of THC, there has been limited research conducted into the potential benefits of CBD. Nevertheless, researchers have anticipated substantial evidence suggesting that CBD could be beneficial in supporting overall wellness and may be included as part of pain management.

The way CBD may be a great addition to a healthy lifestyle and support a holistic approach to pain management is due to how it reacts with the endocannabinoid system (ECS). During scientific research into THC in the 1990s, the ECS was discovered. It is a complex cell-signalling system, and experts are still attempting to understand how it functions fully. We do know that it has a significant role in regulating many of our body’s functions and processes, such as:

• Pain
• Inflammation
• Skin and nerve function
• Mood
• Sleep
• Memory
• Appetite

The endocannabinoid system is present and naturally exists in the body, whether you use cannabis-derived products or not. The ECS contains three fundamental components: endocannabinoids, endocannabinoid receptors, and enzymes. Unless you are an ECS expert, you may not be familiar with these components, so here is a breakdown of each:

• Endocannabinoids – These are also sometimes referred to as endogenous cannabinoids and are tiny molecules that are naturally produced by your body. The scientific community has detected two main endocannabinoids so far, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The two endocannabinoids support our internal functions and help them to keep running smoothly. It is challenging to determine the typical levels for each endocannabinoid as our bodies are thought to produce them as and when needed.
• Endocannabinoid Receptors – The endocannabinoid receptors are thought to be located right through our bodies. Endocannabinoids bind to them to signify that the ESC needs to take action. There are two forms of endocannabinoid receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). It is understood that endocannabinoids can bind to either receptor. However, the effects will depend on where the receptor is located and which endocannabinoid attaches itself.
• Enzymes – The enzymes are responsible for breaking down the endocannabinoids once they have fulfilled their purpose. There are two enzymes principally responsible for this function. The first is fatty acid amide hydrolase (FAAH), which breaks down anandamide (AEA). The second is monoacylglycerol acid lipase, which breaks down the 2-arachidonoylglycerol (2-AG) endocannabinoid.

It is not yet fully known precisely how the properties of CBD and the biological pathways support pain relief. Nonetheless, there have been some research advancements into the potential CBD interactions with receptors within the endocannabinoid system (ECS) and immune system. The ECS controls immune-system responses (linked in inflammation) and pain, leading to the theory of interaction between CBD and the ECS being the most likely reason for CBD potentially supporting pain management.

One of the primary receptors within the ECS is the cannabinoid 1 receptor (CB1). It has been found that both CBD and THC bind to CB1. However, rather than activating the receptor (as THC does), CBD decreases the signalling effects of this receptor. This is also one of the justifications why CBD does not have the same psychoactive properties as THC. CBD has also been found not to stimulate dopamine release, indicating that it may be beneficial to aid the relief of pain.

Some researchers also predict that CBD functions to inhibit or activate compounds within the ECS rather than directly influencing its receptors. For example, CBD may inhibit tissues within the body from absorbing anandamide, a compound known to regulate pain. Consequently, increased CBD levels in the blood may act to decrease pain.

Many studies have been carried out to determine whether CBD could be used as part of a holistic approach to chronic illnesses. One study in 2016 explored the potentials for CBD to support the care of arthritis. Using a rat model of arthritis, the scientists ascertained that those injected with CBD had decreased inflammation and diminished overall pain in the affected joints, with no visible side effects. Although studies are still in their early stages, CBD is looking like a promising candidate for supporting those with painful conditions such as arthritis.

The majority of studies regarding CBD use to support different types of pain indicate positive results. This positively signifies the potential positive effects of CBD. Moreover, numerous findings have shown that CBD is well tolerated. So as more studies are being carried out and the full benefits being understood, it is safe to use as part of our everyday lives.

Conolidine As A Natural Pain Relief

Conolidine is located in the bark of the Tabernaemontana divaricata shrub, more commonly known as crepe jasmine or the pinwheel flower. It is indigenous to Southeast Asia and has been widely used in traditional Chinese medicine to support pain relief and various other ailments. The Tabernaemontana divaricata plant contains a vast range of compounds, so some of them are detrimental as they have the same side effects linked with opioid painkillers. Conolidine is not an opioid and has been found to provide pain relief without causing any adverse complications related to its fellow Tabernaemontana divaricata compounds.

Conolidine was first extracted in 2004, but it was not until Glenn Micalizio led a rigorous research group into the synthesis of the extract. Within this seven-year laboratory study, they unearthed conolidine’s potential therapeutic benefits. It took the team such a long time to study the compound as the Tabernaemontana divaricata shrub only comprising trace amounts (0.00014%) of conolidine. Therefore, to explore its therapeutic properties, a synthetic version had to be created in a complicated nine-step process. There were also unwanted by-products generated during each step of this process, resulting in an overall conolidine yield being only 18%.

Using the synthetic conolidine, the research group began their first experiments to assess its analgesic effects. By injecting conolidine into mice, the group concluded that conolidine was effective in reducing both inflammatory and visceral pain. Crucially, they discovered conolidine is potentially effective at suppressing the two phases of the pain:

• Phase One – The initial rapid response to pain (known as tonic pain)
• Phase Two – The ongoing discomfort (know as persistent pain)

Conolidine may also be able to suppress the acetic acid writhing response. This is a universally used marker to test the pain-relieving effects of a potential new therapy, as it induces prolonged severe pain. This property has also been detected in opioid painkillers, successfully demonstrating the parallels in pain relief attributes that conolidine shares with opioid analgesics, minus the severe side effects. Moreover, it has been found that conolidine can stay within the plasma and our brain for up to four hours post-injection, indicating it has long-lasting effects.

Despite the many similarities between conolidine and opioids, conolidine has been found to function via a different biological pathway. Unlike opioids, conolidine is unable to provide relief for pain caused by a thermal stimulus. Conolidine does not target μ-opioid receptors (morphine’s primary target receptors) or any other subtypes of opioid receptors known to induce psychoactive responses. In addition to this, unlike opioids, despite their ability to enter the brain simultaneously, conolidine does not stimulate brain locomotor activity. Increasing locomotor activity is a typical CNS response to opioids (particularly morphine). These findings suggest that conolidine may have fewer adverse side effects than opioids and is unlikely to be addictive.

In a recent study, they used a new method to try and understand how conolidine works in the body. By equating the profile of conolidine against a selection of well-studied compounds, the researchers were able to establish a similarity between conolidine and a molecule known as CVIE (a potent calcium channel blocker). Calcium channels have an essential role within the central nervous system, where they are able to modulate pain perception and signalling. The research group’s experimental findings were able to verify that conolidine acts in a way to block these calcium channels. This indicates a potential method by which conolidine is able to prompt a form of pain relief. Nevertheless, the researchers concluded that there are still a number of unidentified biological targets that give conolidine its potential analgesic properties.

In 2019, Pharm Origins became the first pharmaceutical company to offer a sublingual conolidine formula. They claimed their product is able to alleviate daily aches and pains within 15 minutes of use. Many users have advocated that this product has helped with their pain management, and it is probable that conolidine will eventually become a more common and readily available natural ingredient for pain management. There is, however, still a noticeable lack of scientific research surrounding the recommended dose and the best method of administration.

Many people may have concerns over the possible side effects of natural ingredients. This unease is mainly due to the lack of understanding or scientific backing, even if it has reputed results dating over hundreds of years. To help minimise some of the concerns, let’s explore the possible side effects of CBD and conolidine.

There has been a lot of research conducted into the safety and effects of CBD on the body. CBD is generally extracted from hemp plants rather than marijuana, as hemp tends to have a higher CBD content. Cannabis, hemp, and marijuana often get muddled and jumbled together as if they are interchangeable. These are, in fact, all terms for plants in the Cannabaceae family, and there are some significant differences between them.

• Cannabis – The word cannabis is a taxonomic term used to describe a genus of flowering plants that are all members of the Cannabeceae family. There are about 170 of these plant species which divided into three groups:

1. Cannabis Sativa
2. Cannabis Ruderalis
3. Cannabis Indica

The entire history of the cannabis genus has not been fully identified, as there is a lack of the required fossil evidence. This has made it very challenging for botanists to spot the cannabis genus evolutionary divergence from other organisms. They have applied a molecular clock and computer algorithms to approximate the cannabis genus age to try and get around this. Researchers have been able to determine that cannabis probably diverged from a common ancestor, Humulus, around 27.8 million years ago. Humulus is considered cannabis’ most closely related genus.

Irrespective of the plant’s origins, the key element to takeaway is that “cannabis” is a broad classification containing both marijuana plants and hemp plants. So regardless of their differences, hemp and marijuana are both cannabis.

• Hemp – The hemp plant is a specific type of cannabis, more formally referred to as Cannabis Sativa L. Although hemp and marijuana from the same family, the hemp plant has a very different chemical makeup and effects on the body. Hemp plants have a trace level of the intoxicating THC compound. THC is the compound marijuana is famous for containing and producing a ‘high’. Hemp, on the other hand, has high concentrations of the non-intoxicating CBD compound.

Hemp is considered by many as one of the most outstanding versatile plants on the planet. For example, the stalks can be made into textiles for garments or even utilised for the advancement of biofuels. Hemp seeds are a popular food and are also turned into hemp seed oil which has multiple uses. The buds can be used to make CBD extract which is added to an array of products, from topicals to edibles.

• Marijuana – This is hemp’s intoxicating cousin. Marijuana is mainly composed of Cannabis Sativa plants. So while marijuana and hemp share a species, they are chemically and legally very different.

Due to marijuana containing high concentrations of THC, it can cause those who consume it to experience intoxicating effects. Due to the effects, marijuana is only lawful in a few countries. The compound THC, however, has been legalised in many jurisdictions but with strict thresholds in place. For example, the European Union at this time allows products containing 0.2% THC content or less to be sold and used in member states.

Marijuana is now sold in various ways, but the most common method is still the traditional dried and cured flower form. There is, however, a rise in demand for extraction methods to be used to create concentrated THC oils. Consumers would like the option to use THC oils on their own or added as an ingredient to other products such as edibles.

Historically, the word “marijuana” was used to differentiate between cannabis that is hemp and cannabis that is not, based on the THC levels. This may seem an illogical way to make a distinction. However, the industry has also implemented this methodology when new strains of cannabis plants are bred, keeping the THC threshold in mind. It may also appear even more illogical than cannabis plants (which contain countless cannabinoids alongside many more chemical compounds) are divided by THC content. This is, however, the standard for the legal cannabis and CBD industries.

When it comes to the physical side effects of CBD, it has been found that in rare cases, it can cause tiredness, diarrhoea, and changes in appetite and weight. With regards to conolidine, there are no recorded side effects. With both natural products, it is essential to only use high-quality extracts from reputable providers.

Finding Trustworthy Suppliers of Natural Products

With the natural product market growing at such a fast pace and the number of CBD products increasingly becoming legal in the UK, it is essential more than ever to ensure consumers are aware of the risks of buying products from unreliable suppliers.

As a general rule, consumers should conduct thorough research before buying CBD or conolidine products. CBD, for example, can be extracted in many different ways, and it can have a huge impact on the purity and quality of the final product. Some extraction methods can leave unwanted or even harmful residues, which can compromise the outcome. There are currently four main CBD extraction methods:

• Carbon Dioxide (CO2) Extraction – This is currently the most widely used method and is fast becoming the gold standard within the CBD industry. The favourability of CO2 extraction is due to it being the most efficient technique, with its final product having the highest purity. In addition to the quality levels, CO2 is also a safe solvent to use and can be reused, making it economical for large-scale production.

Carbon dioxide extraction can be divided into three types: supercritical, sub-critical and mid-critical. Supercritical is the most general approach, whereby the process begins with CO2 being converted into a liquid solvent by applying a precise temperature and pressure. It is then passed through the plant, where the CO2 extracts CBD out for further filtration. The resulting solution goes through a separator to deliver a refined CBD extract.

• Alcohol Extraction – Another popular method of CBD production is via alcohol extraction. It works similarly to other solvent methods, but it uses ethanol which is safe for consumption and does not create harmful contaminants. The process begins with the plant being decarboxylated (meaning the plant is heated to a specific temperature for a precise period of time to activate the chemicals within). It is then packed into a tight container, and ethanol is dripped through the container, taking the cannabinoids with it as it drops into a collection reservoir below.
• Carrier Oil Extraction – Unlike the alcohol extraction method, which uses ethanol, carrier oil extraction uses an oil product such as olive oil. The hemp plant is first decarboxylated, with its materials then being added to the carrier oil and heated over a number of hours. The main idea is to pull the cannabinoids out of the plant and into the carrier oil. This method is considered by some as more affordable and does not possess a high risk of contamination. Nevertheless, it is still not the most effective method for commercial use. The oil can perish very quickly in the absence of additives which means only small amounts of CBD can be produced using carrier oil extraction. It can also result in the CBD oil extracted being lower in potency and ultimately any pain-relieving properties.
• Solvent extraction –  This method involves the use of alcohol, ethanol, butane, propane, or isopropyl to extract the CBD. It is one of the least costly options and is also fast and easy to do. However, with the smaller price point comes the risk. It is one of the most dangerous ways to extract CBD due to the highly flammable contents of the liquids used as part of the process. This method also dissolves the plant waxes, which themselves hold quite a few nutrients. It extracts not only the cannabinoids but also the chlorophyll, which gives some products a nasty bitter flavour.

The process begins by putting the hemp flowers and plant trimmings into a container. The solvent is then soaked or run through the material, stripping it of the cannabinoids. Finally, the evaporation process takes place, leaving the concentrated cannabinoids in an oil form.

Besides being a hazardous process, the danger is that the solvent residue can be toxic if they are not entirely removed during the evaporation step. Some studies have found traces of naphtha hydrocarbons or petroleum residue in CBD products that have been extracted using solvents which is not something you want to ingest or put on your body.

Marketplaces, such as Alphagreen, make a conscious effort to educate their customers. This allows consumers to make their own conclusion as to what product suits their needs best. All the products sold on the platform have been third-party lab tested and the certificate of analysis alongside all products.

The Takeaway

Remember that pain is a sign that something is wrong with your body. Although it should not be ignored, there are steps you can take to help alleviate some of the discomforts so you can go about your daily life.

In general, the most effective way to manage pain is to tackle the underlying cause (if it can be identified). In some cases, the illness or injury causing the pain may heal or resolve on its own. In other cases, you may need some extra help to relieve the discomfort.

It is evident that both CBD and conolidine have pain-relieving properties and appear to have very few or no adverse side effects. Although more research is still necessary to identify how these natural compounds actually work on the body, we continue to see a growing demand for these types of products for a natural approach to pain management.

Whatever method you choose as part of your holistic approach to health, complete in-depth research before deciding what natural product suits you best. Investing in your wellbeing may help reduce pain and allow you to live your life to the fullest.

Anastasiia Myronenko

Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.