Cannabidiol, a substance derived from cannabis plants, has recently started to appear more frequently in daily life. The cannabinoid known as CBD, which is now permitted in most U.S. states, is available in supermarkets and pharmacies. It is commonly offered in the form of gummies, oils, or creams and is acclaimed for its ability to reduce pain.
Does CBD, however, genuinely lessen the pain? If so, how exactly does it accomplish this? And what would it take to convert CBD's advantageous qualities into a secure and potent pain reliever?
These are some of the issues that Clifford Woolf, an HMS professor of neurology at Boston Children's Hospital, and Bruce Bean, the Robert Winthrop Professor of Neurobiology in the Blavatnik Institute at Harvard Medical School, have teamed together to investigate. Their current research reveals that CBD acts simultaneously on two targets in pain-sensing neurons. This research was done in animal models and cells. Now, they are utilising this knowledge to create medications that, while being equally safe and non-addictive as CBD, are more efficiently absorbed by the body.
Untreated pain is a serious and pervasive health problem that can affect daily activities, result in poor mental health, and generally lower a person's quality of life. According to the American Centers for Disease Control and Prevention, 50 million adults in the United States, or about 20.4% of the population, experience chronic pain, which is defined as pain that lasts longer than three to six months.
According to a previous study, chronic pain costs the US economy between $560 and $635 billion annually. However, some of the currently available and often prescribed painkillers have a high potential for addiction, making those who use them susceptible to dependency.
The need for non-addictive painkillers is significant and remains one of modern medicine's most difficult tasks, according to Bean.
a combination of studies
Better painkiller development is a long-standing common interest of Bean and Woolf. According to Woolf, there are currently just a few effective treatments for pain, and opioid-based medications that are recommended for pain carry a high risk of addiction, which plays a part in the epidemic opioid problem. In reality, the CDC estimates that more than 932,000 individuals have passed away from drug overdoses since 1999. In 2021, opioids were responsible for 75.1% of overdose deaths, taking the lives of 80,816 people.
While most overdose deaths are not directly caused by prescription opioids, they frequently act as a gateway drug to more hazardous synthetic opioids like fentanyl. However, progress in creating novel pain medications has been sluggish, in large part due to the requirement that these medications precisely target specific pain pathways while leaving other sections of the nervous system unaffected.
Pain is undoubtedly one of those disorders, according to Woolf, who added that "both of us are highly interested in conditions for which there is no effective treatment." "By developing fresh classes of very powerful and safe analgesics, we are attempting to discover if we can have a significant influence on patients."
The researchers initially had no plans to collaborate on CBD, though. Bean carries out fundamental investigations into the brain's electrical signalling processes. He focuses on the microscopic channels in neuronal membranes that open and close to regulate the passage of ions, which in turn controls whether or not neurons fire and transmit electrical signals.
The focus of Woolf's research is on developing new medications to combat pain and neurodegenerative illnesses. He specializes in conducting extensive screenings on human neurons to find new therapeutic targets and substances that alter the course of the disease. He concentrates particularly on the membrane receptors and ion channels that control pain and inflammation. Bean's interest in CBD as a painkiller in humans was sparked by investigations showing that it decreases pain-related behaviour in mice and rats as well as anecdotal reports of these findings.
There aren't any effective clinical trials on CBD's ability to treat pain, although many people claim that it does, according to Bean. "To understand what CBD did and how it worked, we started looking at CBD directly on the electrical activity of neurons."
Bean and his team discovered, using mouse models, that CBD blocks two separate types of sodium channels that are present in the membranes of nociceptors, the specialized neurons that perceive and transmit pain. This inhibition keeps the neurons dormant and prevents them from firing and transmitting an electrical signal that would otherwise serve as a "pain" message.
In the meantime, Woolf and his team screened thousands of bioactive substances to see whether any of them interacted with a specific potassium channel that is present in the membranes of nociceptors and is involved in the inhibition of pain signalling; surprisingly, they came across CBD. Woolf and Bean came to the conclusion that CBD opens the potassium channel, allowing potassium ions to enter the nociceptors. This increase in potassium decreases the neurons' firing rate, preventing pain signalling. In actuality, the same process is used by the painkiller flupirtine, whose usage is restricted due to liver damage. Nothing about it was found in the literature, but suddenly, according to Woolf, "out it burst" that CBD also possessed potassium channel-opening action in addition to sodium channel-blocking activity. If we want to influence the excitability of this particular group of neurons, it is precisely what we desire.
The potential of CBD
As a potential foundation for a future painkiller, CBD has various benefits. The fact that it doesn't appear to be addictive and that there aren't many negative effects on people may be the most important factor. In actuality, the FDA has already given its users the green light for youngsters with severe, drug-resistant epilepsy.
We discovered that CBD is extremely intriguing since it interacts with two distinct targets in pain-sensing neurons, according to Bean.
The discovery that CBD has two functions is particularly intriguing, according to Woolf, because there are no medicines that target both sodium channels and potassium channels, which together regulate nociceptors' activity.CBD is still not prepared for widespread use. It is highly varied from batch to batch and may contain additional substances that have adverse effects because it is a herbal product generated from cannabis plants. Because CBD is poorly absorbed by the body in this form, children with epilepsy must drink large amounts of it orally, combined with sesame oil. There are still unanswered questions regarding the safety of CBD, including how it affects different organ systems and how it interacts with other medications.
We must seek to improve CBD because it has certain properties we want but not all of them, according to Woolf.
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