CBD - Cannabidiol: Hope and Hype
by Sharon Reynolds
Medical marijuana is in the spotlight. When people think of marijuana, they likely picture the whole plant with its distinctive leaves. But any one species of plant may contain hundreds of compounds that can affect the human body in different ways. Marijuana is no different.
In marijuana, the most notorious compound is one called THC (short for tetrahydrocannabinol). THC causes the high associated with marijuana, and its effects can range from relaxation to hallucinations. But another compound found in marijuana has been hogging the press lately. This is cannabidiol, more often called by its abbreviation, CBD.
Unlike THC, CBD produces no high, and is not addictive. But early research suggests that it has other effects on the brain and body. Some of these effects may have the potential to be harnessed for medical uses. However, hope and hype about CBD has gotten far ahead of what scientists actually know about the compound.
Early Days in CBD Research
“We don’t have a ton of sound data from studies in people” about the uses of CBD, says Staci Gruber, Ph.D., an associate professor of psychiatry at Harvard Medical School and Director of the Marijuana Investigations for Neuroscientific Discovery Program (MIND) at McLean Hospital in Belmont, Massachusetts, where she is running the first randomized clinical trial testing of a whole plant derived CBD product for the treatment of anxiety.
Because it can be isolated from the marijuana plant, CBD currently exists in a grey area of legality. It is classified by the U.S. Drug Enforcement Agency as a Schedule I drug, even though it does not produce a high and is not addictive. Schedule I drugs are labeled as having no currently accepted medical use
To study whole plant marijuana or any of the individual constituents, like CBD in clinical trials with human subjects explains Dr. Gruber, researchers must obtain a special license from the government and use only products supplied by the National Institutes on Drug Abuse (NIDA) . Her own trial took several years from initial approval to enrolling its first patient given the myriad of requirements.
Because permission is hard to come by, few clinical studies of CBD have been run to date. Those that have received permission to test the compound have been small and often used non-plant derived forms of CBD. However, some have shown interesting early results.
A small study testing CBD in people with schizophrenia showed that, over a 4 week period, CBD was as good as a prescription drug called amisulpride at alleviating symptoms.
CBD also lacked some of the unwanted side effects of amisulpride, including weight gain. Marijuana has a reputation for making the symptoms of schizophrenia worse, but researchers now think this is due to THC, not CBD, and that CBD may actually have the opposite effect.
But “the number one indication that falls under the mental or behavioral health umbrella that people are interested in exploring cannabis for in our studies is anxiety,” says Dr. Gruber.
Early studies have suggested that CBD can reduce acute feelings of anxiety. This effect corresponds to changes in blood flow and brain activity that can be seen on brain imaging scans, explains Dr. Gruber. Some participants in her trial will undergo brain imaging during treatment, to gather more information on how CBD changes the way the brain processes information.
Ongoing trials in other countries—and a few slated for the U.S.—are testing CBD for the treatment of bipolar disorder, depression, drug and alcohol addiction, and inflammatory bowel disease, among other conditions.
Scientists are even starting to test whether CBD and other compounds from the marijuana plant have anti-cancer effects. However, such studies to date have only been in the laboratory, not in people. Any claims from CBD manufacturers that their products can be used to treat cancer are false.
Changing the Rules?
A recent event may change the research landscape for CBD. On June 25th, 3018, the U.S. Food and Drug Administration (FDA) approved a CBD-based drug called Epidiolex for the treatment of some types of epilepsy in children. Epidiolex is the first drug made directly from the marijuana plant to receive FDA approval for any indication.
A few other drugs made from so-called synthetic cannabinoids have received approvals. These drugs contain compounds that are identical to those found in marijuana, but are produced in the laboratory, not extracted from the plant. Examples of this type of drug include Marinol, which is used to treat nausea caused by some other medications, and Sativex, which is used to treat symptoms of multiple sclerosis.
But even though it received FDA approval, Epidiolex cannot be sold in the U.S. unless CBD is removed from the list of Schedule I drugs, a process called reclassification. If, how, and when this will be done are still uncertain.
If CBD gets reclassified, “I think it will be much easier to do research,” says Dr. Brenda Porter, a neurologist at Stanford Medical School. “It’s very complicated to get a Schedule I license, which has delayed research not only into CBD but in THC and all the other compounds that are found in marijuana,” she adds.
Unknown Risks and Differences
Reclassification would also make it easier for researchers to study the potential risks of CBD. Currently, these risks are relatively unknown, explains Dr. Porter.
One thing that CBD does appear to do is slow down the rate at which the body processes other drugs, Dr. Porter adds. If this happens to some prescription drugs, they could build up in the bloodstream to potentially dangerous levels.
People may find it hard to talk to their doctor about using CBD, particularly if they’re concerned about its legality. But these conversations are important, especially if they’re taking prescription drugs, says Dr. Porter. A lot of people who want to talk about CBD may feel like their doctor doesn’t want to discuss it. But it’s more likely that their doctor doesn’t feel like they can comment on a subject that not a lot is known about, she adds.
“But I try to keep an open dialog with my patients, because I don’t want them doing it and not telling me. It’s worth talking to your doctor, just saying “I’m going to try this, I know you can’t give me advice, but I want you to know in case something goes wrong,” continues Dr. Porter.
Another thing that could come from more research, explains Dr. Gruber, is a better understanding of the difference between CBD and other cannabinoids made synthetically—in the lab—versus extracts made directly from the plant.
“There have never been any studies assessing the differences between plant-derived and non-plant derived CBD. I would hazard a guess that they may exert different effects,” says Dr. Gruber. CBD seems to work differently when accompanied by other compounds found naturally in marijuana, she adds, and researchers are only beginning to understand what and why.
Buyer Take Care
Despite all the unknowns, products containing CBD or advertised as such are widely available for purchase on the Internet today. Most of these are made from industrial hemp. Hemp is the same type of plant as marijuana, but has been bred to contain very little THC. Many of these products are marketed as dietary supplements or foods, even though the FDA has stated that this is not legal.
The current CBD industry, outside of products being tested in clinical trials, is unregulated and unsupervised. People aren’t often aware of that fact, Dr. Porter says. They often think that if a product is for sale, someone has verified that it is what it says it is. But there’s no guarantee of how much—if any—CBD is in any one product, or if that stays consistent over time.
“Just because something is for sale doesn’t mean it’s been vetted,” adds Dr. Gruber. Some CBD manufacturers have been in business for a long time and perform outside testing of their products, but many do not, she explains. She recommends that people do their research on manufacturers and the testing they do before trying any product containing CBD.
Some states, such as Massachusetts, even allow individuals to send products they’ve purchased online or from dispensaries to laboratories for testing, to verify what’s actually in them, says Dr. Gruber. Such testing is not inexpensive, “but I think it’s always best to be cautious,” she concludes.
 Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry. 2012 Mar 20;2:e94. doi: 10.1038/tp.2012.15.
 Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014 Jun;55(6):791-802. doi: 10.1111/epi.12631. Epub 2014 May 22.
 Crippa JA, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology. 2011 Jan;25(1):121-30. doi: 10.1177/0269881110379283. Epub 2010 Sep 9.