The cannabis compound known as CBD is being touted as a treatment for a variety of conditions. But the substance’s uncertain legal status is stalling serious investigation. CBD oil is used for almost 100 different ailments or diseases. But, what does the science say? Is CBD as versatile as we belive? Learn what research says.
The reality behind cannabidiol’s medical hype
The cannabis compound known as CBD is being touted as a treatment for a variety of conditions. But the substance’s uncertain legal status is stalling serious investigation.
- Michael Eisenstein0
- Deep investigation into CBD took off in 2006 when a young girl, Charlotte Figi’s, seizures almost disappeared after being treated with CBD oil.
- Cannabidiol is used as a wellness supplement and medicine for conditions that have limited scientific research.
- CBD oil is used as part of the treatment regime for epilepsy, chronic pain, nausea and vomiting, MS and sleep disorders.
Michael Eisenstein is a freelance writer in Philadelphia, Pennsylvania.
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Cannabidiol oil has purported health benefits, including helping to relieve chronic pain. Credit: Don Bartletti/Los Angeles Times/Getty
Cannabidiol (CBD) is an illegal drug with no redeeming value. It is also a useful prescription medicine for epilepsy, with considerable potential for treating numerous other conditions. And it is a natural dietary supplement or ‘nutraceutical’ with countless evangelists in the health and wellness community. Although contradictory, all three statements are true from different perspectives, and clinical researchers are frustrated.
“In New York City, you can go to a latte shop and get a CBD product, but if I want to do a clinical trial, I’ve got to get a 2,000-pound safe and go through six months of paperwork and licensing,” says Orrin Devinsky, director of the NYU Langone Comprehensive Epilepsy Center in New York City. Like the cannabis plant from which it is derived, CBD, a type of cannabinoid, is classified by the US Drug Enforcement Administration in the same way as are heroin and lysergic acid diethylamide (LSD) — schedule 1 substances with “high potential for abuse” and “no currently accepted medical use”.
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This flies in the face of current evidence. Numerous studies have shown that CBD is a safe and non-habit-forming substance that does not produce the ‘high’ associated with tetrahydrocannabinol (THC), the main psychoactive component of cannabis 1 . In 2018, the US Food and Drug Administration (FDA) determined that Epidiolex — a purified CBD product developed by GW Pharmaceuticals in Histon, UK — effectively reduces the frequency of seizures in certain rare forms of paediatric epilepsy. This approval has heartened the cannabinoid research community, which has long recognized the medicinal potential of CBD but come up against scepticism and regulatory constraints on the road to the clinic.
But at the same time, the many manufacturers that promote CBD-laden oils, lotions and foods as a panacea for various health issues, often with minimal regard for local laws or medical evidence, are putting CBD’s medical advocates in an uncomfortable position. “I get calls and e-mails all the time — not just from families, but from physicians who have no clue how to address the requests they get from patients,” says Yasmin Hurd, director of the Addiction Institute of Mount Sinai in New York City. “It’s a real problem.”
Stuck in the weeds
The breakthrough approval of Epidiolex was driven by strong investment from GW Pharmaceuticals, as well as vigorous advocacy from families of children with epilepsy who had heard tantalizing anecdotes about CBD’s effects from jurisdictions in which medical cannabis is legal. “About eight years ago, a patient’s father said he was hearing stories about families in Colorado and California who use high-CBD strains for their kids’ epilepsy,” says Devinsky. “He asked me to do a trial.” As a medical student, he had been taught the history of medicinal cannabis, including well-documented uses of the plant by nineteenth-century physicians to treat seizures. Indeed, cannabis has been part of the clinical armamentarium for epilepsy for more than 4,000 years.
Research on CBD in the 1970s and 1980s focused on its interplay with other cannabinoids, and particularly THC. “Whereas THC can induce psychotic symptoms, impair cognition and make people anxious, CBD appears to do the opposite,” says Philip McGuire, a psychiatrist at King’s College London.
The first clues that CBD might suppress epileptic episodes came from a small clinical trial 2 in 1980. It was led by Raphael Mechoulam, a chemist at the Hebrew University of Jerusalem, whose work on the synthesis and biochemical characterization of cannabinoids in the 1970s had led researchers to begin to explore the medicinal properties of CBD. A number of other trials that explored the compound’s pharmaceutical properties followed, although scientists conducting early forays into CBD clinical research faced an uphill battle. F. Markus Leweke, a psychiatrist who specializes in mental illness at Sydney Medical School, Australia, recalls struggling for seven years to publish findings from a randomized controlled trial that demonstrated that CBD might offer an effective treatment for psychotic symptoms in schizophrenia 3 . “We got about 15 rejection letters,” says Leweke. “And this is a paper that has since been cited almost 500 times.”
Claims about the health benefits of cannabis are often overstated and lack supporting evidence. Credit: Rodger Bosch/AFP/Getty
Forty years on from Mechoulam’s initial work, extensive randomized controlled trials have decisively shown that this purified cannabinoid can profoundly benefit children with certain epileptic disorders. “Over those trials, we saw about a 26–28% reduction in frequency over placebo in all convulsive seizures for Dravet syndrome and drop seizures for Lennox–Gastaut syndrome,” says Devinsky, who has led several such studies 4 , 5 . “Some of the patients became, and remain, seizure-free.”
Preclinical data from rodent and cell-culture studies have hinted at the possible benefits of using CBD to help treat disorders that range from Parkinson’s disease to chronic pain. The range of conditions in which CBD is being tested might seem diverse, but it is a compound with far-reaching, if poorly understood, physiological effects. Antonio Zuardi, a psychiatrist at the University of São Paulo in Brazil, notes that something on the order of 20 possible mechanisms of action have been described to date for CBD. “These multiple pharmacological effects may justify the wide range of possible therapeutic activities.”
The mechanism of CBD’s action on cannabinoid receptors, at least, is well understood. CBD can bind to the cannabinoid receptor CB1, which is the same receptor that THC seeks out in the brain. Unlike THC, however, CBD restrains rather than activates CB1 signalling, and therefore doesn’t induce the psychoactive effects of its cannabinoid cousin.
But CBD wears many hats. It seems to mediate its antiepileptic effects by binding to a protein called GPR55, which can otherwise trigger the onset of seizures by promoting the hyperactivation of neurons 6 . In addition, CBD acts on receptors that mediate pain signalling and inflammation, as well as at least one receptor for the neurotransmitter serotonin, 5-HT1A 7 . Gabriella Gobbi, a psychiatrist and neuroscientist at McGill University in Montreal, Canada, has found that CBD’s physiological effect on the brain resembles that of selective serotonin reuptake inhibitor (SSRI) drugs 8 , which are used to treat clinical depression. “After a few days, you get this desensitization of 5-HT1A, like you would with an SSRI, and increased serotonin signalling,” she says. Further experiments in rats failed to capture an antidepressant effect, but her team found that CBD-mediated modulation of 5-HT1A could relieve neuropathic pain in the animals.
Beyond epilepsy, clinical data to support the medicinal benefits of CBD are more limited, mainly due to the small scale and inconsistent design of trials. “We have very few double-blind, randomized placebo-controlled trials,” says Gobbi. But exciting progress is being made towards treating several conditions.
Psychosis — particularly in the context of schizophrenia — is one such area of promise. In 1995, Zuardi and Mechoulam reported the case of a person with schizophrenia who experienced meaningful relief from their symptoms when treated with high doses of CBD 9 . Several subsequent small-scale clinical studies detected similar hints of efficacy. In their groundbreaking trial 3 , Leweke and his colleagues put the compound through a particularly rigorous test by comparing its effects with those of amisulpride, a potent medication for schizophrenia. “We saw a significant decrease in symptoms over time for both compounds, and CBD beat amisulpride in terms of side effects, by far,” Leweke says. The team also found a clue to the mechanism by which CBD might exert its antipsychotic effects: treatment with CBD was associated with elevated levels of anandamide, a cannabinoid produced by the body that seems to offer protection from psychosis.
McGuire and his colleagues conducted a randomized controlled trial that showed that CBD can have an additive effect when used with conventional antipsychotic drugs 10 . Together, they were better able to control symptoms such as hallucinations and delusions than could conventional medication alone. His team has received funding for a large, international trial to test whether CBD can be developed as a licensed medicine for treating psychosis.
Anxiety disorders are another mental-health condition that CBD has been shown to help alleviate. Zuardi and his colleagues used a test that simulates speaking in public to show that pretreatment with a single dose of CBD can reduce the associated discomfort in people with social anxiety disorder 11 . A similar effect has been observed in healthy people in anxiety-inducing situations 12 , and several researchers are exploring CBD as a means of soothing social stress in people with autism spectrum disorder. Devinsky notes that many of his patients with epilepsy have also been diagnosed with autism spectrum disorder, and he is involved in two clinical trials that aim to test whether CBD can meaningfully reduce the irritability and anxiety of those with autism. “Many parents wanted to keep their children on it even if the seizures didn’t improve, because they’re calmer and sleeping better,” he says.
And although cannabis been demonized as a gateway to more dangerous substances, Hurd has found that it might actually contain an effective antidote for potentially deadly addictions. After observing that rats with a heroin addiction were less likely to seek out the opioid when treated with CBD, she began to investigate whether CBD might have the same effect on people with an opioid dependency. On the basis of an encouraging pilot study, Hurd and her team conducted a randomized controlled trial in 42 abstinent heroin users, who had avoided taking the drug for up to three months after years of routine or heavy use 13 . The researchers then exposed the participants to drug paraphernalia and videos that showed heroin use — cues that normally provoke strong cravings in people with a dependency — and then measured participant-reported responses and physiological indicators of stress and anxiety. “Cue-induced craving is associated with increased cortisol levels and increased heart-rate, and CBD reduced those,” she says. Participants receiving CBD also reported lower levels of drug craving and anxiety relative to placebo group, and Hurd notes that the beneficial effects persisted for a week after the final administration of CBD.
A difficult delivery
Despite its promise, CBD’s impact as a drug has been mixed. Importantly, it is relatively safe. The side effects most commonly associated with a high dose of Epidiolex include digestive problems, rash and drowsiness, as well as the potential for liver damage in patients taking certain other medications. For example, Devinsky notes that patients who are receiving valproic acid to treat seizures or migraines might be at an elevated risk. But in many of the CBD trials conducted so far — particularly in the realm of antipsychotic drugs, which are known for their strong side effects — CBD has proved more tolerable than existing alternatives. “The side effects weren’t significantly worse than with placebo,” says McGuire of his 2018 study of CBD in people with schizophrenia 10 .
This is important because people typically require large doses of the drug to experience a clinical benefit — in many studies, the doses used are as high as 1 gram or more. This is because CBD is poorly absorbed by the body, with most of every dose being excreted before it can take effect. “If you take it orally, the bioavailability is in the range of 4–6%, which is terrible,” says Devinsky. “If you take it after a fatty meal, you can get that up to 16–20%.” Zuardi notes that his group routinely observes a bell-shaped dose–response curve for CBD. For example, whereas 300 milligrams of CBD might reduce a person’s anxiety, the same person might not get any relief from a dose of either 100 milligrams or 900 milligrams. To complicate matters further, this sweet spot for CBD dosing can differ not only between symptoms, but also between patients.
Campaigners show support for legalizing cannabis for medical use in Atlanta, Georgia. Credit: Erik S. Lesser/EPA/Shutterstock
This is one of several reasons why researchers caution against self-medication with CBD products targeted at consumers. CBD is available in shops worldwide, but the legality of such sales varies widely. In Canada, selling cannabis and its derivatives is legal, whereas the European Union authorizes the sale of CBD derived from hemp (low-THC varieties of cannabis) but not from marijuana (high-THC cannabis). In the United States, the latest Farm Bill, which was enacted in 2018, potentially legalizes the production of CBD from hemp under certain conditions — although the sale of CBD products generally remains ostensibly illegal. Regardless of the legal situation at the federal level, CBD commercialization remains something of a free-for-all in the United States — individual states are making their own laws, and the FDA has taken only limited action to enforce federal laws on CBD. “They’ve sent some notices to companies that have made medical claims, but that’s about it,” says Marcel Bonn-Miller, a psychologist at the University of Pennsylvania, Philadelphia, and global scientific director at Canopy Growth Corporation, a cannabis company in Smiths Falls, Canada. (An FDA spokesperson responded that the agency “is working quickly to continue to clarify our regulatory authority over products containing cannabis and cannabis-derived compounds like CBD”.)
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Many such claims lie beyond the bounds of medical evidence — including that regarding CBD preparations that purport to prevent cancer or to treat Alzheimer’s disease. However, even products that make more modest claims could be problematic. In 2017, Bonn-Miller and his colleagues performed chemical analyses on 84 products purchased online from 31 companies, and found that only 31% were accurately labelled with regard to CBD content 14 . What’s more, many commercially available preparations have been found to be contaminated with intoxicating doses of THC, heavy metals and pesticides, as well as toxic solvents from the CBD extraction process. In a case reported by the US Centers for Disease Control and Prevention, up to 52 people in Utah became seriously ill or were hospitalized after using a CBD oil that contained an intoxicating synthetic cannabinoid drug. The possibility of such contamination is concerning to all potential users, and especially to people who are seeking relief from the effects of a health condition. “It’s one thing if you’ve got too much THC in gummy bears you’re using with friends, but something entirely different if it’s a kid you’re giving CBD for medical reasons,” says Bonn-Miller. “I don’t trust any CBD product until I’ve done the tests.”
Between two worlds
The regulatory disconnect that surrounds CBD creates an odd situation in which the public can self-medicate using a potentially questionable product, while scientists face a struggle to perform high-quality clinical trials. “The fact that CBD remains schedule 1 in the United States is unconscionable,” says Devinsky. That restrictive classification, he says, “is impairing research”.
Obtaining sufficient quantities of pharmaceutical-grade CBD to conduct a well-powered clinical trial is already difficult. “It’s extremely expensive,” says Leweke. “You need about one gram a day, and the list price is about 60 euros [US$67] per gram.” This is because the process of extracting CBD from the cannabis plant is complex and arduous — and when the goal is to obtain CBD for use in people, the substance must meet the high bar set for clinical-grade preparations, under which only minimal quantities of THC or other contaminants are permissible. Several companies have developed strategies for manufacturing fully synthetic CBD, an approach that essentially eliminates concerns about purity. But synthetic CBD still falls under the schedule 1 classification in the United States, which creates extra economic and bureaucratic hurdles for clinical trials. Even in Canada, where recreational cannabis has been legalized, Gobbi describes a complex application process and a more than six-month wait to obtain government authorization to conduct a CBD study in people or animals.
Unfortunately, if studies such as these are not done — or not done properly — then consumers will be left to fend for themselves in a poorly monitored marketplace. In that scenario, the signal of true clinical benefit would almost certainly be drowned out by the noise from personal anecdotes and the placebo effect, which could jeopardize the future of a potentially valuable medicine. “Humans are notoriously bad when they think they see patterns,” says Devinsky. “When everyone is convinced that they’re right with no data, I call that religion — and CBD is currently religion for the average person.”
Nature 572, S2-S4 (2019)
This article is part of Nature Outlook: Cannabis, an editorially independent supplement produced with the financial support of third parties. About this content.
Updates & Corrections
Correction 23 July 2020: An earlier version of this Outlook article misquoted Gabriella Gobbi. She said that 5-HT1A is desensitized in response to cannabidiol, not sensitized.
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CBD Oil Uses & Scientific Evidence
In this article you’ll learn about the scientific research behind CBD oil. While there is limited research on CBD oil as a medicine, CBD oil is used to treat numerous diseases and ailments. See what the research and the TGA say about CBD oil.
What is CBD oil used for?
In Australia, cannabidiol (CBD) is only used for medicinal purposes. It is prescribed by a physician and is used to treat a range of chronic medical conditions. As of February 1, 2021, however, low dose CBD is legal over the counter in pharmacies. While legal, we won’t see it in pharmacies for at least another 18 months. Low dose CBD will be used for short term treatment of minor conditions which are still to be determined.
CBD is only clinically proven to help with a reduction of seizures in epilepsy.
In the last article of our guide to CBD, you learned some general CBD terminology that is often misunderstood, the three main types of CBD oil and the difference between an oil and a tincture. Now that you know about the types of CBD concentrates, you’ll learn the science behind CBD oil and its uses.
The focus of this article will explain the outcomes of research on CBD and medical conditions. In the next article in our guide, we’ll cover some of the benefits and side effects of CBD oil. While people know about CBD oil’s benefits for epilepsy and chronic pain, there’s limited understanding of other issues and ailments CBD oil can help. In this article you’ll read:
Throughout the article, we’ll direct you to the research behind CBD and give you insight into what the Therapeutic Goods Administration (TGA) recommends regarding cannabinoid treatment of each medical condition.
CBD Oil Uses: The Modern Beginning
The CBD craze we are currently witnessing all began with a little girl named Charlotte in 2006. Charlotte was three months old when her seizures started. Before she was one year old, Charlotte was having grand mal seizures regularly and doctors couldn’t figure out why. By the time she was three years old, she had been diagnosed with Dravet Syndrome and was having up to 300 seizures a week, unable to walk, talk or eat.
When Charlotte was five years old, the doctors were at the point where they couldn’t do anything else. Charlotte’s parents decided it was time to test cannabis. They bought a high CBD strain and started making oil themselves. Charlotte’s seizures reduced immediately.
This case illuminated the potential benefits of cannabis as a medicine, particularly for epilepsy both amongst the general public, and the medical community. While scientific research on cannabis has been conducted for quite some time, it’s recent research that has proven the numerous medicinal benefits of cannabis.
CBD Oil: What Science Says
Globally, millions of people use CBD and other forms of cannabis for medicine and wellness purposes. CBD oil specifically, has been touted as a miracle drug. In the USA where CBD oil is available over the counter and can be found in pretty much every store, the Food and Drug Administration (FDA) has begun to crack down on false advertising of CBD.
What we do know is that CBD can help with certain medical conditions. Animal trials are showing promise regarding CBD and multiple medical conditions. There are also numerous Australian clinical trials for CBD and cannabis more broadly.
The TGA, via the National Drug and Alcohol Research Centre (NDARC), has created guidance documents for medical cannabis treatment relating to certain medical conditions. To do this, the NDARC did their own reviews and created recommendations based on their findings. Here’s what the current research says about CBD as well as the TGA guidance (if any):
Epilepsy & Seizures
Research shows that seizure reduction is a key medicinal benefit of CBD. A 2017 study specific to Lennox-Gastaut Syndrome showed that the addition of CBD oil to an existing treatment plan reduced the frequency of seizures.
Across the globe, adults and children with epilepsy are turning to cannabis, CBD specifically, for relief from seizures that otherwise were considered untreatable. Trials on CBD and seizures continue to advance what we know about CBD’s impact on epilepsy and seizures.
The TGA (Therapeutic Goods Administration) approves CBD oil for treatment of seizures. Their recommendations however are:
- Epilepsy treatment using medical cannabis or cannabinoids is only recommended as an adjunctive treatment.
- It is also recommended that when CBD be used in children or young people aged up to 25 year, the primary aim is to decrease seizure frequency and improve the overall quality of life of the patient.
- Patients should be re-evaluated after 12 weeks.
The research behind cannabis, CBD and pain reduction is interesting because numerous studies contradict each other.
In 2017, the National Academies of Science, Engineering & Medicine published a report on the health effects of cannabis and cannabinoids. This report stated that there is conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults.
A 2017 review by the US Dept of Veterans Affairs found that there is low-level evidence that a CBD and THC treatment may help with neuropathic pain but no evidence that it can help with other types of pain.
As a counter-example, a review from Cochrane stated that there is, “a lack of good evidence that any cannabis-derived product works for any chronic neuropathic pain” in adults.
While two of these papers contradict one another, it’s widely held that cannabis and certain products containing CBD can help individuals with pain.
The TGA review looked at numerous studies relating to chronic non-cancer pain (CNCP). The recommendation for CNCP is that while there is evidence of limited efficacy of cannabis in treating neuropathic pain with traditional analgesics, the current evidence is not enough to cement a place for cannabis in the treatment of CNCP. That being said, the TGA has approved cannabis for the treatment of pain.
Nausea and Vomiting
The research behind cannabis and nausea and vomiting is specific to these symptoms as a result of chemotherapy. A 2017 report from the National Academies said that there was conclusive or substantial evidence that cannabis is effective in the treatment of Nausea and Vomiting during Chemotherapy.
A systematic review of 30 clinical trials showed that oral cannabinoids (in this case synthetic) are more effective at treating chemo-induced nausea than traditional drugs. It also concluded that while patients preferred cannabis to other treatments, there are some serious adverse effects. Some of the adverse effects, such as feeling euphoria or sedation, could be seen to be beneficial to a patient in pain. Other effects, depression and paranoia, are reasons to avoid using cannabis as a treatment.
Based on their nausea and vomiting guidance, the TGA sees medical cannabis as a last-resort treatment for this condition.
Note: The main cannabinoid used to help with vomiting and nausea is THC.
Multiple Sclerosis (MS)
Multiple Sclerosis comes along with numerous symptoms. The symptoms include ataxia and tremors, bladder function, disability progression, pain, quality of life, sleep, spasticity.
There have been numerous studies and reviews of studies on spasticity in both MS patients and spinal cord injuries. One of the major reviews from the National Academies said that there is substantial evidence that oral cannabinoids improve symptoms as reported by patients. This, however, does not mean that it’s effective when measured from a clinician standpoint. So, there aren’t any clinically proven results for cannabinoids and multiple sclerosis.
The TGA does approve cannabis for symptoms of MS. The TGA cites that there is, “Good scientific evidence,” for Dronabinol and THC extract when treating pain related to MS. There is also, “Good scientific evidence,” for using Nabiximols to help improve patient quality of life. Generally, cannabis is recommended to supplement other medications and is not a first-line intervention.
NOTE: these are not CBD products, they are THC products.
The same 2017 review that looked at studies on chronic pain and epilepsy also reviewed the used of cannabis to help with improving sleep. They found that there is moderate evidence that cannabinoids are an effective treatment to improve short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.
There was also a 2007 study where researchers showed that 40-50% of patients given a 1:1 ratio of CBD to THC reported good or very good sleep quality. There is also a study, involving only eight people, that while cannabis helps induce sleep, it also decreases your REM sleep which may be good or bad depending on your condition.
While there is no conclusive research as to whether cannabis improves sleep outcomes, there are indications that a CBD product may help with sleep. The TGA doesn’t have any information or recommendations regarding cannabinoids and sleep.
There are more medical conditions and ailments that people use CBD for than listed in this article. The conditions mentioned, however, have the most scientific backing. Whether or not there is clinical evidence that CBD treats many of the conditions people use it for, there is value in patient perception and quality of life. Currently, research shows a limited number of short side effects from using CBD.
In conclusion, there needs to be much more research conducted on CBD and cannabinoid medicine in general. While there are many therapeutic indications, CBD has only been proven to help treat epilepsy by reducing seizures. With CBD legal as an over the counter product in many countries, people are using it as a nutritional supplement and a substitute for other medications.
In Australia, CBD is only legal with a prescription and therefore only used as a medicine. In the next article in our guide to CBD, you’ll learn about the scientific and perceived benefits and side effects of CBD oil more broadly.