By now you’ve probably heard about cannabidiol, more commonly known as CBD, one of many active compounds found in the cannabis plant. Over the past few years CBD has turned into a global health phenomenon, and you’re likely to find dozens of different CBD products lining the shelves of your local CVS.
Despite all the publicity, however, there is a lot of confusion over what CBD oil actually is, where it comes from, how it works, and whether it is legal or not.
Sweeping claims have been made about CBD oil as a miracle cure for anything from cancer to insomnia. Yet it is still considered a Schedule I drug, meaning it officially has no medical use (and is addictive). So what is the truth about CBD? As with most things, the truth lies somewhere in the middle. As we will see, cannabis has been used for medicinal purposes for thousands of years, and there is no doubt that the plant offers a long list of health benefits. Modern scientific research is scant, but as CBD’s popularity explodes, interest is increasing, and more and more funding is going toward research to help us understand how CBD affects our bodies and our minds.
The Long History of Cannabis
Although CBD seems to have become a craze only in the last few years, using cannabis medicinally actually has a very long history. The very first documented case dates back to 2737 BC, when Emperor of China Sheng Nung used cannabis tea to help him improve his memory as well as to attenuate the symptoms of rheumatism and malaria.
The cannabis plant also has a long history in India, where it is central to traditional medicine and is thought of as a sacred plant. The hemp variety of the cannabis plant was widely used in Egypt to make rope and other items, but an ancient manuscript proves that it was already known as a medicinal plant. The Ebers Papyrus, which was written around 1550 BC, is one of the oldest medical textbooks in existence and mentions hemp in several of its formulations as an ingredient to alleviate pain and inflammation.
The Romans, too, used cannabis for healing. Around A.D. 77, a scholar called Pliny the Elder wrote that cannabis could be used to relieve different kinds of discomfort.
By the 16th century, hemp was widely cultivated in Europe, and it soon became an important crop in the Americas too. The plant was not widely used as medicine but was mostly employed in the making of rope, fabric, and even ship sails.
The medicinal properties of cannabis were almost buried until, in 1839, Irish physicians and medical researcher William B. O’Shaughnessy looked into its therapeutic properties and medical applications. His findings turned out to be quite controversial, but he opened the door to further research and changed the way we use cannabis to this day.
Cannabis became a common ingredient in medications to help with sleep, coughs, menstrual pains, and more, but by the 20th century, opioids started taking their place. Soon enough, the war on cannabis began, and both growing and using the plant became highly illegal. The Controlled Substances Act of 1970 deemed cannabis a Schedule I substance, meaning it didn’t it doesn’t have any accepted medical use and is highly addictive. This designation includes hemp and marijuana varieties of the plant.
Although cannabis is still illegal, things are slowly changing. CBD’s huge surge in popularity has seen an increase in research into its myriad uses as well as a push to change its legal status.
But with so much information out there, it’s hard to know what you can trust. Not to talk about the seemingly infinite list of products that seem to find their way onto more and more shelves every day. So what exactly is CBD? How does it work, and how can it help us? What kinds of products should we try, and what should we look out for? Keep reading to find out.
What is CBD Oil?
CBD is a naturally occurring component of the Cannabis sativa hemp plant and was only discovered by Dr. Roger Adams and his team at the University of Illinois in 1940. It’s one of many components of the plant, and makes about 40% of it. The rest is made up of phytocannabinoid compounds as well as terpenoids, flavonoids, vitamins, enzymes, and more. Tetrahydrocannabinol (THC), another compound found in the Cannabis sativa plant, is better known and more controversial, as it is what makes users feel high. It is found in higher concentrations in marijuana and much less in hemp. CBD won’t get you high, and it has a whole range of benefits.
But if CBD comes from the cannabis plant, how come it doesn’t get you high? This is a really common question and a source of confusion, so it’s worth spending some time examining the differences between CBD, THC, and the plants they come from: hemp and marijuana.
Hemp Versus Marijuana
Hemp and marijuana are two different strains of the cannabis plant. Most CBD products come from hemp, a variety which contains little to no THC, and has been used throughout history to make fabric, rope, paper, and food. Because hemp naturally contains so little THC you can be sure that your CBD products will not get you high. In fact, by law they must contain less than 0.3% THC.
Marijuana is a variety of Cannabis sativa that contains more than 0.3% of THC (typically between 2% and 30% by dry weight). It contains very small amounts of CBD, so isn’t usually used to make CBD products but is, of course, grown (legally and illegally) for weed and its derived products, which definitely will get you high.
Types of CBD Oil
If you’ve spent any time browsing CBD websites or the CBD shelves at your local health shop, you will have noticed that there are a lot of different types of CBD on offer, and sometimes it’s not easy to know what is what.
Full spectrum CBD isn’t “pure” CBD: It contains all the other chemical compounds present in the cannabis plant, such as terpenes, flavonoids, other phytocannabinoids, along with small traces of THC. Full spectrum is a preferred choice by many because of the health benefits that all these other compounds have, especially when taken all together. A 2015 study, in fact, found that different compounds interact with each other and boost each other, in a process named “the entourage effect.”
Broad spectrum CBD also offers the benefits of the entourage effect, as it contains many of the same compounds that full spectrum does. However, in this type of solution, all traces of THC have been removed, so this is a good choice if you are afraid of traces of THC showing up in blood and urine tests.
CBD Isolate is a very pure form of CBD, containing about 99.9% CBD and no other compounds. People choose isolate because it offers the most CBD and is easier to dose, as it often comes in crystal or powder form and can be added to other products. You won’t be reaping the benefits of the entourage effect, but if it’s strictly CBD you’re interested in, this could be the type for you.
As we’ve seen, CBD is naturally present in the cannabis plant, but how does it get from existing in the flower and buds of a hemp plant to becoming an oil, a crystal, or a gummy bear? There are three different ways of extracting CBD:
CO2 Extraction is one of the most natural and advanced ways of extracting CBD from the plant. This method uses supercritical carbon dioxide (a fluid state of carbon dioxide where it is held at or above its critical temperature and critical pressure) to separate the CBD oil from the hemp plant. No heat or drying is applied to the plant material during the CO2 extraction processes, so the resulting CBD is what you call “Raw CBD,” and all its chemical compounds, vitamins, and minerals are left intact and not modified by the heating process. And no chemicals are used, meaning that the resulting CBD is clean and pure.
Lipid Extraction uses fats to extract the plant’s compounds. The process starts with the raw materials being decarboxylated (which simply means heated) until they reach a certain temperature. Olive oil is then added, everything is heated again, and then the CBD is extracted. Although the resulting CBD product isn’t very concentrated (so you need to take this into account when dosing) it is a natural and cheap option. Also note that olive oil (or other types of oil, such as organic coconut) is quite perishable, so you need to be careful and store this in a cool and dark place.
Solvent Extraction is a cheap way of extracting CBD that uses ethanol, isopropanol, or alkanes. The process starts by running solvents through cannabis flowers and buds, and then making them evaporate so that only the concentrated cannabinoids are left behind in oil form. Although it is cost-efficient, solvent extraction is not the most loved by CBD users because there are lots of chemicals involved, and if not done properly, the process can leave behind harmful traces in the product.
The Health Benefits of CBD
As we’ve mentioned, humans have been using the cannabis plant for thousands of years to reap its multitude of health benefits. Although there are also healthy vitamins and minerals in the plant, the main health benefits come from cannabinoids. Out of the close to 500 chemical compounds naturally present in the plant, around 66 are cannabinoids, of which CBD and THC are the best known. Cannabinoids have an effect on our bodies and minds by interacting with specific cannabinoid receptors present on the surface of cells, which are part of the complex endocannabinoid system.
The Endocannabinoid System
Although it was only discovered in the 1990s, the endocannabinoid system (ECS) is considered the “most important physiologic system involved in establishing and maintaining human health”, according to Neuroscientist Bradley E. Alger.
There is still a lot to discover and understand about the ECS, an incredibly complex network of cannabinoid receptors in different cells throughout the body, but it is known to regulate a broad range of functions, including mood, pain, sleep, appetite, reproduction and fertility, and the immune system. The functions and effects of the ECS are so pervasive that it affects both body and mind, linking the two in many different ways.
The ECS works naturally and doesn’t require the use of cannabis, as our bodies naturally produce their own cannabinoids, known as endocannabinoids. The two main ones known by scientists are anandamide and 2-arachidonoylglycerol (2-AG), and they bind with different receptors throughout the body, such as CB1 receptors, which are mostly found in the central nervous system (the brain and nerves of the spinal cord), and CB2 receptors, which are found mostly in the peripheral nervous system, the digestive system, and cells in the immune system.
Anandamide interacts with CB1 receptors in the spinal cord, for example, to relieve pain, while 2-AG activates CB2 receptors, for example, in the immune system to signal that there is an infection to fight.
So what does cannabis have to do with the ECS?
Research shows that the cannabinoid THC binds to both CB1 and CB2 receptors, activating them much like our natural endocannabinoids do.
CBD, on the other hand, does not bind with receptors in the same way, but it stops anandamide from breaking down, resulting in a buildup of the endocannabinoid in the brain and giving it a stronger, long-lasting effect on the body and mind.
So far, studies have shown that, through its interaction with the ECS, CBD may help manage acute and chronic pain and inflammatory skin diseases such as psoriasis, and even reduce inflammation. Let’s take a look at some of the main ways CBD can impact our health.
CBD for Pain
People looking for a natural, safe pain reliever are increasingly turning to CBD as an alternative to commonly used opioid painkillers such as Oxycontin, Percocet and Vicodin, which have lots of side effects and carry with them the risk of dependency. On the other hand, CBD has no side effects (more on this later) and is not addictive.
Studies on the effect of CBD on pain have shown that the cannabinoid may be effective at treating different kinds of pain, such as neuropathic and inflammatory.
Neuropathic pain feels like a shooting or burning pain, and can be fleeting or chronic. It is often the result of nerve damage and doesn’t always respond to traditional painkillers. Neuropathic pain is associated with diseases such as multiple sclerosis (MS), which also causes debilitating muscle spasms, weakness, numbness, tingling, and fatigue. Unfortunately, there is no treatment for MS, but some studies show that CBD may help manage some symptoms: this article in the Frontiers in Neurology journal, for example, concluded that “CBD supplementation may be advisable for [people with] MS to reduce fatigue, pain, spasticity, and ultimately improve mobility.” And in the UK a drug called Sativex that contains both CBD and THC is legal and used to treat the symptoms of MS.
A study by Italian scientists also found that CBD is an effective therapeutic treatment in neuropathic pain, while other research shows that CBD may help manage the symptoms of fibromyalgia, another illness which causes chronic neuropathic pain.
The process by which the body protects itself from infection from bacteria and viruses can cause inflammatory pain. In some cases however the body’s immune system triggers an inflammatory response when there is no infection and ends up attacking itself. These instances are called autoimmune diseases and include the likes of arthritis, inflammatory bowel disease, and multiple sclerosis.
There are several studies that show CBD’s effectiveness in reducing the symptoms of arthritis and other inflammatory ailments. A study conducted on mice, for example, found that CBD has a powerful anti-arthritic effect, while a 2011 study found that CBD helped reduce inflammatory pain in rats. While CBD oil taken orally works well for arthritis pain, a 2016 study found that applied topically (via cream on the skin), it can also work well to relieve localized pain.
CBD has also been hailed as a pain reliever for people who suffer from migraines, even though the connection hasn’t been deeply studied. An Italian study looked at a THC-CBD combination to see whether it worked to reduce symptoms for chronic migraine and cluster headache sufferers. It found that the combination reduced the intensity of pain for 43.5% of patients.
CBD for Cancer
Much has been made of CBD’s ability to prevent and fight cancer, and it is very important to be sceptical of such fantastical claims. CBD cannot prevent cancer or cure it, and although some studies have looked at CBD’s anticancer properties, they couldn’t find enough evidence to support these claims.
However, although CBD may not be a miracle cure, there is a lot of research that shows that it may help alleviate the symptoms of cancer as well as the horrible side effects of chemotherapy, which can include vomiting and nausea, weakness, fatigue, and pain. A study that looked at the effects of CBD on chemotherapy-induced peripheral neuropathy found that CBD is potent and effective in preventing it, at least in mice, especially if used together with THC. An article in the Current Oncology journal also found that “[c]annabis is useful in combating anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression,” while other research found that CBD is a good antiemetic, so it may reduce the nausea during chemotherapy.
CBD and Epilepsy
There is a lot of evidence that cannabinoids, including CBD, can vastly improve the quality of life for people who suffer from epilepsy in several different ways. In fact, epilepsy is the only disorder for which there is an FDA-approved CBD drug, Epidiolex. CBD and derived drugs are especially helpful in drug-resistant types of epilepsy: One study found that there was a 39% drop in frequency of seizures in patients with a rare form of epilepsy, Dravet syndrome, as well as a noticeable change in the frequency of seizures in people suffering from Lennox-Gastaut Syndrome, another very difficult-to-control epilepsy syndrome.
CBD for Sleep
It’s not clear to scientists why CBD helps with sleep, but there is a lot of research to support the anecdotal evidence that it does indeed help. Unless your insomnia is caused by external factors such as too much caffeine, noisy or hot rooms, or too much phone and laptop use just before bed, taking a small dose of CBD can help you get to sleep and stay asleep. Research published as recently as 2019 looked at how CBD could improve sleep: 66.7% of participants reported better sleep after only one month of taking 25 mg of CBD each day.
One study published in the Journal of Clinical Pharmacology found that people who took 160 mg of CBD reported sleeping more and waking up feeling more refreshed than those taking a placebo.
CBD also helps with other issues that often cause insomnia, such as pain, as we mention above, and anxiety, which is one of the most common factors making it difficult for people to sleep.
CBD oil for Anxiety
Anxiety is one of the main reasons people consider taking CBD. Although there is still little research on the effect of CBD on anxiety in humans, some studies do suggest that it can help (and, of course, the thousands of people who take it for this reason swear by it!). A study conducted by the National Institute on Drug Abuse (NIDA) showed that CBD may help reduce the symptoms of generalized anxiety disorder (GAD): Rats exhibiting physiological signs of anxiety were given a small dose of CBD. The study showed that their heart rates went back to normal, and they calmed down.
There is also evidence to suggest that CBD may help people who suffer from social anxiety disorder (SAD): One study that followed a group of people who were given 400 mg of CBD. It that their anxiety decreased, and they had far better results than people who were just given a placebo. According to some studies, CBD may also help with post-traumatic stress disorder (PTSD)
CBD for Depression
Some research suggests that CBD may help with depression. First of all, CBD is known to reduce pain and help with sleep issues and anxiety—which all exacerbate depression. But some studies have shown that CBD’s effect on the brain can directly have an impact on mood disorders such as depression.
Clinical depression is caused in part by a lack of serotonin on the brain, and while CBD cannot increase levels of serotonin in your brain, it modifies the way receptors interact with it. A study carried out on rats, for example, found that the changes brought on by CBD use can result in antidepressant effects.
Also, long-term depression causes part of the brain, the hippocampus — which is responsible for learning, emotion, and memory — to shrink. Thankfully, because of a process called “neuroplasticity,” the hippocampus can regenerate and go back to “normal.” Research related to epilepsy in rats showed that CBD can reduce atrophy in the hippocampus, while a study on humans showed that although chronic use of THC can also cause the hippocampus to shrink, just like depression, CBD can actually help prevent shrinkage.
When it comes to CBD and health, it’s important to remember that research is still in its infancy, and has mostly been conducted on animals. While there are a lot of exaggerated claims out there, and CBD is definitely not a miracle cure, there is a growing body of research that shows that CBD does have some significant positive effects on our health. But are there any risks?
Safety and Side Effects of CBD
The National Institute on Drug Abuse claims that “CBD appears to be a safe drug with no addictive effects,” and scientists agree. A 2017 study on the safety and side effects of CBD found that CBD is safe for humans, even in high doses and for prolonged periods (in very rare cases, CBD can cause tiredness, diarrhea, changes in appetite, changes in weight).
Although CBD itself is safe, that doesn’t mean you shouldn’t pay attention to the products you are buying. Because this is such a new market, it is currently suffering from a lack of regulation, so there are products out there that might not be quite what they seem. In the best cases, products are mislabeled and might contain different amounts than what it says on the label (we have a section farther down in this article dedicated to learning how to read product labels), so, for example, they may have more than the 0.3% of THC allowed by law. In other, rarer cases, products may contain dangerous chemicals, either remnants of insecticides from the farm or traces of solvents leftover from the extraction process.
That’s why it is very important to know what you’re buying. Do your research beforehand, get to know the brands and the terminology, and know what questions to ask. Until the market develops further, it’s on you to make sure you’re buying good quality stuff (although we are here to help).
Although CBD is known to be safe, The U.S. Food and Drug Administration (FDA) has not yet approved CBD health products, as research on humans is still scant. Thanks to the increasing public interest, the FDA is increasingly interested in CBD and recently put out a bulletin titled “What you need to know (and what we are working to find out) about products containing cannabis or cannabis-derived products including CBD,” in which it states that “It is currently illegal to market CBD by adding it to a food or labeling it as a dietary supplement.”
On a different note, you should definitely avoid taking CBD if you are pregnant or breastfeeding. Although there is very limited research about this, it’s better to err on the side of caution. Firstly, there are studies that show that THC can reach the fetus through your bloodstream, so any traces of THC would be harmful. Secondly, some limited studies have shown that high doses of CBD in animals can cause problems in the development of the fetus.
If you are taking different types of medication, you should talk to your doctor about possible negative interactions. Although in some cases CBD can actually enhance the effect of some medications, it can also change the way your body interacts with them: CBD inhibits cytochrome P450, a type of liver enzyme that breaks down toxins, so some drugs are then absorbed differently, with potentially negative effects.
Since CBD products have only recently become so popular, other medications do not explicitly carry CBD warnings on their labels. Luckily for us, however, it is known that CBD interacts with the body much like grapefruit and grapefruit juice, which also inhibits cytochrome P450. So if the drugs you are taking have a grapefruit warning, you know you shouldn’t take CBD with them either.
Is CBD legal?
This is a straightforward question with a not very straightforward answer, and to make things even more complicated, CBD’s legal status is changing day by day (but mostly, thankfully, for the best).
In September 2018, the United States Drug Enforcement Administration (DEA) released an official statement explaining that “FDA-approved drugs that contain CBD derived from cannabis and no more than 0.1 percent tetrahydrocannabinols [THC]” had been removed from the list of Schedule 1 drugs (defined as having no currently accepted medical use and the highest potential for abuse), which is confusing, as there is currently only one FDA-approved drug that uses CBD. Cannabis remains a Schedule 1 drug. But if CBD products are illegal, how come they are ubiquitous online and in your local stores?
Here is where the difference between federal and state law comes in: Many states have taken legalization into their own hands and have either decriminalized or relaxed their rules on the sale and use of CBD oil and other products.
The 2018 Farm Bill, also known as the Agriculture Improvement Act of 2018, played a big part in this, as it legalized CBD that is derived from hemp and contains no more than 0.3% THC by dry weight. However, CBD that comes from marijuana remains illegal.
Because the changes are so recent, many states have not yet updated their laws, and each state has slightly different rules regarding the sale and possession of CBD. To find out what the situation is in your state, you can look up the state’s criminal code, or an easier option is to look through websites such as National Conference of State Legislatures, or Marijuana Policy Project.
As we mentioned above, according to the FDA, it is illegal to sell CBD in food or drink, or as a health supplement. So far, however, the FDA has only targeted manufacturers, and never users, by sending warning letters.
Although the situation is currently confusing, as research progresses and regulators catch up with the market, CBD is bound to become legal and accepted as a health product.
How Do I Take CBD?
Although we have been speaking mostly about CBD oil, CBD actually comes in many different forms and can be taken in lots of different ways. Depending on what you like and what you’re taking it for, you can choose to take it by inhaling it, putting a drop under your tongue, eating a gummy bear, applying a cream, and more. But what are the main differences? Let’s take a look.
One of the most popular methods of taking CBD is to take it orally, but there are a few different ways to do so.
Edibles are common and well-loved by thousands of CBD fans because they are easy to take, a bit subtler than other products, and tasty. Edible products on offer include gummies, brownies, mints, protein bars, dried fruit bars, and even drinks such as CBD water, coffee, and sodas. When you take CBD this way, it is first metabolized by your liver before entering the bloodstream, meaning that it takes longer but also that less of it actually makes it there. In fact, the bioavailability — which indicates the proportion that enters into circulation and actually has an effect — of CBD taken orally is only 6%.
Sublingual application, on the other hand, ensures that CBD is absorbed very quickly and directly into your bloodstream and with a higher bioavailability. For it to work, apply a dose of CBD oil or tincture under your tongue and hold it there for about 60 seconds. You should feel the effects within 15 or 20 minutes.
CBD vaping is another very popular method of taking CBD, but is considered one of the most harmful. One of the main risks comes not from the CBD itself but from bad-quality equipment, which is unfortunately available and can cause lung damage. However, as long as you’re buying lab-tested products from reputable legal stores, there is very little risk.
Another thing to look out for is propylene glycol, a solvent sometimes used in the concentrated oils used in vape pens. When this chemical is heated, it can degrade into formaldehyde, which irritates the eyes and skin, and can cause cancer. Choose pens that have “solvent-free oils” to be safe.
In general, vaping guarantees a quick absorption and high bioavailability, so you will feel the effects pretty quickly.
There is a growing body of evidence that shows that applied on the skin, CBD can help reduce symptoms of skin conditions such as psoriasis and eczema, and can also help with localized pain caused by inflammation and other conditions. A study found that 10% CBD gel can alleviate pain and inflammation in rats with arthritis.
So CBD creams, oils, balms, serums, and lotions are great for skin conditions and localized pain but shouldn’t be used to target other issues such as anxiety, depression, or insomnia, as not enough CBD enters the bloodstream to actually have an effect.
How Much CBD Should I Take?
You’d have to take an impossibly large quantity of CBD for it to be really bad for you, and it’s basically impossible to overdose. However, it’s still a good idea to start slow, taking small amounts when you start and building up from there. So how do you know how much to take? The first thing to determine this is how you’re taking it. As we’ve seen, different ways of taking CBD determine how your body absorbs it. Also, you’ll take more if you’re taking it to manage chronic pain than if you just want to feel a bit more relaxed.
Dosage will also depend on your body weight and metabolism. Since risks are so low, you shouldn’t worry too much when you start taking CBD the first time, but you should still start with a low dose and monitor your response before increasing it.
Also, remember that the way you take CBD determines how long it will take for you to feel the effects. Intravenous (via an injection or IV) is the fastest but by far the least convenient or pleasant! Vaping and tinctures are also pretty fast, as the CBD enters your blood within minutes. Edibles are slower to take effect, but also stay in your bloodstream longer.
Generally, CBD stays in your body around three to four days and should be completely out of your bloodstream a week after you take it. But don’t worry about CBD turning up in drug testing, as current drug tests only test for THC, and not CBD. However, if this is a concern for you, do pay attention to the products you are using and make sure they are correctly labeled and do not contain more than the legal limit of THC.
How to Find Good CBD Oil
According to Brightfield Group, a research company that specializes in cannabis products, the CBD market is set to reach $2.15 billion by 2021 (it was only $292 million in 2018). New products, brands, and retailers are popping up all over the place with very little oversight, and not all of them are high quality. So, how can you tell the bad from the good?
One of the main risks when it comes to CBD oil is that the products are mislabeled and contain less CBD or more THC (for example) than it claims. Similarly, some products are sold as CBD but actually come from hemp seed, and thus contain no CBD. Make sure the products mention cannabidiol, and avoid those that only list hemp seed or hemp seed oil.
Another risk is that there might be traces of pesticides and other contaminants in the product, since cannabis plants easily absorb harmful chemicals and heavy metals. To protect yourself, choose reputable organic brands that are able to provide you with a certificate of analysis (COA).
A COA means that a third-party has tested the product, so results are real and objective. You can sometimes access a digital COA by scanning the product’s QR code or by looking on the company’s website. The COA will contain info about the product’s cannabinoid profile, which also tells you about its potency, terpene profile, as well as heavy metal, microbiology, and mycotoxin, pesticide, and solvent screenings.
The Bottom Line
CBD oil is quickly becoming very popular, and it’s not rare for people to puff on a vape or chomp down on some gummies. A growing body of research shows that CBD may have a role in improving the symptoms of many common health issues, from nausea to depression, anxiety, various types of pain, inflammatory skin issues, epilepsy, and even cancer. Although it is true that CBD boasts this long list of health benefits, as the market grows and our knowledge struggles to keep up, it’s important to be skeptical of sweeping claims about CBD and its ability to cure cancer and other serious diseases.
Although there is still a lot for us to discover about CBD’s different “powers” and applications, for now it is reasonable to say that CBD provides a safe and natural help for many health issues, and there is no harm in trying it as an alternative, or in conjunction with, other medication.