CBD: The next weapon in the war against opioid addiction?
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CBD, or cannabidiol, is everywhere, with word on the street saying that it can cure everything from a bad mood to cancer. However, most of these claims are not based on scientific evidence. Animal studies suggest that CBD might be beneficial for some health indications, such as pain, inflammation, arthritis and anxiety.
However, until recently, the only medical indication that CBD has been proven to treat in humans is seizures associated with pediatric epilepsy. Now, however, a recent study suggested that CBD curbed cravings in people with opioid dependence. This is one of the first double-blind controlled trials, the gold standard for drug research, to show benefit of using CBD outside epilepsy treatment. Thus, researchers can say with greater confidence that CBD may be helpful in fighting the war against opioid addiction.
While this study is very exciting, as scientists who study drugs and addiction, we want to stress that this study was very narrow and used specific, standardized amounts of CBD. Thus, the results do not suggest that buying a bottle or jar of over-the-counter CBD is going to help with opioid cravings – or any other medical conditions.
Addiction is a brain disease
In order to understand why CBD might be useful to treat opioid addiction, it is helpful to take a closer look at how addiction alters normal behavior. Addiction is broadly defined by the American Psychiatric Association as “a complex condition, a brain disease that is manifested by compulsive substance use despite harmful consequence.” Addiction is classified as a disease because addiction hijacks and alters the way how the brain processes information.
People with opioid addiction issues can often be triggered by seeing drug paraphernalia, which can trigger a relapse. Oleg Mikhaylov/Shutterstock.com
Specifically, areas of the brain critical in controlling the perception of daily and pleasurable activities are susceptible to the influence of addictive drugs. Due to the rewiring of the brain under addiction, the individual often perceives the world in context to their drug of choice. The brain learns to associate drug paraphernalia or the physical location of drug partaking in the context of receiving a drug. These cues become integral reminders and reinforcers of drug use.
These events occur with most known drugs of abuse, such as cocaine, alcohol, nicotine, methamphetamines as well as opioids.
Addiction is often thought of in terms of the pursuit of the “high” associated with the use of a drug. However, most addicts continue to use, or relapse when trying to quit using their respective addictive drug. This difficulty, despite the desire and often pressure by friends, family and co-workers to quit, is often due to the negative effects of drug withdrawal.
Depending on the drug, the symptoms of drug withdrawal can vary and range from mild to severe intensity. In the case of opioid withdrawal, symptoms often include anxiety, nausea, vomiting, diarrhea, abdominal cramps and rapid heartbeat. An individual going through opioid withdrawal experiencing extreme conditions of anxiety is likely to take opioids to alleviate that anxiety. This sort of behavior can be repetitive, leading to a what is called a feed-forward loop of dependence on an abused drug.
A person is often referred to as “dependent” on a drug when the drug must be present for the individual to function normally. Importantly, anxiety and depression are correlated with opioid dependence.
For dependent individuals, ongoing use of a drug is not perceived as a conscious choice, but rather an evil necessity. Medication-assisted treatment with drugs like methadone or buprenorphine, allows for an individual to undergo recovery from an opioid use disorder. The use of medication assisted treatment significantly decreases the likelihood of an individual to relapse and fatally overdose due to withdrawal or dependence symptoms.
CBD and Epidiolex
CBD was tested in several clinical trials and was shown to work and to be safe in treating a rare form of epilepsy. A pharmaceutical grade CBD, Epidiolex, gained FDA approval in June 2018 for this specific usage.
CBD is currently only prescribed as the drug Epidiolex. That is because, up until now, CBD has only been shown to be safe and effective in the treatment of intractable pediatric epilepsy.
Importantly, CBD binds to different receptors than those that lead to opioid addiction.
CBD and opioid addiction
In experiments reported in 2009, rats were trained to press a lever to receive heroin. CBD did not decrease the amount of heroin that the rats self-administered, or the drug seeking behavior displayed by the rat while taking heroin. However, when rats were taken off heroin and given CBD, there was a decrease in drug-seeking behavior when the animals were exposed to a heroin-associated cue.
Initial studies of CBD in humans verified that CBD, when co-administered with fentanyl, is safe and well tolerated in healthy, non-opioid dependent individuals. A 2015 report of a small double-blind study conducted in opioid-dependent individuals found that a single administration of CBD, in comparison to a placebo, decreased cue-induced craving of opioids and feelings of anxiety. A double-blind, placebo-controlled study means that doctors and patients in the study do not know who is getting a real drug and who is getting a placebo. That is to guard against what is known as the placebo effect.
A double-blind placebo-controlled study published on May 21, 2019 adds to these findings by demonstrating that the Food and Drug Administration-approved Epidiolex can reduce cue-induced craving in individuals that had been former heroin users. Furthermore, in these individuals, Epidiolex reduced reports of anxiety, and blood levels of cortisol, a hormone known to increase under conditions of stress and anxiety.
Although further studies are needed, these studies strongly suggest that Epidiolex or CBD may hold promise as a critical weapon in fighting the opioid epidemic.
This could be a big deal.
A bottle of CBD oil may contain unpredictable amounts of CBD, and it also could contain THC. WIRACHAI/Shutterstock.com
Before rushing out to purchase over-the-counter CBD to treat any medical condition, there are several practical considerations that should be considered.
Only Epidiolex is FDA-approved for a medical condition – pediatric seizures. All other forms of CBD aren’t regulated. There have been numerous consumer reports that show that the actual amount of CBD in over-the-counter products is significantly less than what is reported on the label. Also, some of these over-the-counter products contain enough THC to show up on drug tests.
Although Epidiolex was found to be safe in clinical trials, it can interact with other drugs prescribed for migraines and bipolar disorder. This could mean that taking CBD with certain drugs could diminish or enhance the effects of prescriptions, leading to problems controlling particular medical conditions that were once well-managed, or increase side effects of the other medications. For this reason, it is incredibly important to talk to your doctor or pharmacist about potential drug interactions before using CBD.
FDA Warns Companies Illegally Selling CBD Products to Treat Medical Conditions, Opioid Addiction
The U.S. Food and Drug Administration has issued warning letters to two companies for illegally selling unapproved products containing cannabidiol (CBD) in ways that violate the Federal Food, Drug and Cosmetic Act (FD&C Act). This action is a continuation of the FDA’s efforts to pursue companies that illegally market CBD products with claims that they can treat medical conditions, including opioid addiction or as an alternative to opioids.
“The opioid crisis continues to be a serious problem in the United States, and we will continue to crack down on companies that attempt to benefit from selling products with unfounded treatment claims,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D. “CBD has not been shown to treat opioid addiction. Opioid addiction is a real problem in our country, and those who are addicted need to seek out proper treatment from a health care provider. There are many unanswered questions about the science, safety, effectiveness and quality of unapproved products containing CBD, and we will continue to work to protect the health and safety of American consumers from products that are being marketed in violation of the law.”
The two warning letters were issued to:
, LLC of Washington state for marketing and distributing injectable CBD products as well as an injectable curcumin product. These products are marketed for serious diseases and as an alternative to opioids. BIOTA Biosciences markets private label CBD and wholesale CBD extracts, and their products include beverages, bulk CBD extracts, and water soluble CBD, as well as injectable curcumin. of New Hampshire for marketing and distributing CBD products as a treatment to opioid addiction as well as other serious diseases. The firm is an own label distributor for CBD products as well as a retailer for Green Roads CBD products.
Under the FD&C Act, any product intended to treat a disease or otherwise have a therapeutic or medical use, and any product (other than a food) that is intended to affect the structure or function of the body of humans or animals, is a drug. The FDA has not approved any CBD products other than one prescription human drug product to treat rare, severe forms of epilepsy.
Unlike drugs approved by the FDA, there has been no FDA evaluation of whether these unapproved products are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs, or whether they have dangerous side effects or other safety concerns. In addition, the manufacturing process of unapproved CBD drug products has not been subject to FDA review as part of the human or animal drug approval processes. Consumers may also put off getting important medical care, such as proper diagnosis, treatment and supportive care due to unsubstantiated claims associated with CBD products. For that reason, it’s important that consumers talk to a health care professional about the best way to treat diseases or conditions with existing, approved treatment options.
In March, the FDA provided updates on its work related to CBD products with a focus on protecting public health and providing market clarity. The FDA continues to be concerned that some people wrongly think that the myriad of CBD products on the market have been evaluated by the FDA and determined to be safe, or that using CBD “can’t hurt.” The FDA remains focused on educating the public about the number of questions that remain regarding CBD’s safety. There may be risks that need to be considered before using CBD products outside of the monitored setting of a prescription from your health care provider.
The FDA has requested responses from the companies within 15 working days stating how they will correct the violations. Failure to correct the violations promptly may result in legal action, including product seizure and/or injunction.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Cbd oil for opiate addiction
The widespread use of heroin and prescription opioids in the United States during the past decade has resulted in an unprecedented epidemic of opioid addiction, and few treatments for heroin use disorders are currently available. In this study, authors conducted a clinical trial to test whether cannabidiol (CBD), a non-intoxicating cannabinoid that is found in the cannabis plant, could reduce drug craving and anxiety in recently-abstinent individuals with heroin use disorder. The study found that, compared to those who received a placebo, individuals who received a dose of CBD medication showed a reduction in craving for heroin as well as reduced anxiety, which lasted for about a week after taking the CBD medication.
WHAT PROBLEM DOES THIS STUDY ADDRESS?
In the past decade, there has been an unprecedented spike in opioid use disorde r , which has led to more than 300,000 opioid-related deaths in the United States . O pioid use disorder medications such as methadone and buprenorphine (often prescribed in a formulation with naloxone , known by the brand name S uboxone ) help reduce opioid use and reduce risk for opioid-involved overdoses . In some areas, however, t hese medications are often underutilized and therefore can be difficult to access, creating a treatment gap in which those who need medications face barriers to actually receiving them. Further, 20-40% of opioid use disorder patients do not want to take agonist treatments .
One of the hypothesized factors contributing to these barriers is that methadone and Suboxone can be misused or diverted because they can produce euphoria . Consequently, discovering effective alternative medications that can also treat opioid use disorder that circumvent concerns about their psychoactive properties could help more of those affected . To address this problem , the authors investigated whether the cannabinoid , CBD , which is thought to be safe and non-addictive, could be useful in the treatment of opioid use disorder .
HOW WAS THIS STUDY CONDUCTED?
This was a randomized clinical trial with 42 participants who received one of two different CBD medication doses or a placebo once daily for 3 days and were then exposed to drug-related or neutral cues to see whether CBD could reduc e opioid cravings and anxiety – factors strongly associated with relapse to opioid use .
Participants were recruited through advertisements. Most participants indicated preference for intranasal heroin use, most reported currently using more than 10 bags of heroin (one bag = 1 g) daily, and on average, participants had been using heroin for over 10 years. The majority of participants (64.3%) had been abstinent from heroin use for less than 1 month.
The study medication used in this study, EPIDIOLEX, is a n FDA-approved medication that is dispensed through a pharmacy (not to be confused with “medical marijuana , ” which is comprised of a wide variety of non- federally- regulated cannabis projects ) . EPIDIOLEX is a plant-derived CBD liquid formation. P articipants were randomly assigned to receive 400 mg of CBD, 800 mg of CBD, or a placebo medication. CBD or placebo was administered once daily for 3 days . In addition to measuring the effect of the medication on opioid craving, anxiety, the authors also collected measures of positive and negative emotions, vital signs (skin temperature, blood pressure, heart rate, respiratory rate), and salivary cortisol levels , which measure stress response.
At three time points – immediately after the CBD or placebo administration ; 24 hours after the CBD or placebo administration ; and 7 days after the third and final CBD or placebo administration – p articipants were exposed to drug – related and neutral cues . The 3-minute neutral cue condition consisted of a video showing relaxing scenarios, such as scenes in nature. The drug cue condition was a 3-minute video that showed intravenous or intranasal drug use, depending on the participant’s reported preferred route of drug use . Immediately after the presentation of the videos , participants were also exposed to neutral objects or to heroin – related paraphernalia (e.g., syringe, rubber tie, and packets of powder resembling heroin) for 2 minutes. Authors examined whether patients who received CBD, compared to those who received placebo, showed differences in opioid craving, anxiety, positive and negative emotions, or vital signs , after being exposed to the drug or neutral cues.
WHAT DID THIS STUDY FIND?
I ndividuals receiving the non-psychoactive cannabinoid CBD medication reported less craving after being exposed to drug cues compared with i ndividuals receiving placebo . This effect lasted at least a week after the CBD or placebo administration, when i ndividuals receiving the high-dose of CBD (but not the low-dose) still reported less craving compared with those receiving placebo . In addition, CBD reduced measures of stress response after the drug cue – such as heart rate and salivary cortisol increases . I ndividuals receiving CBD reported less anxiety after being exposed to drug cues compared with i ndividuals receiving placebo (though t here w ere no significant difference s in anxiety between participants receiving the low-dose vs . the high-dose of CBD ) . There was no effect of CBD on positive affect or on any cognitive measures.
Figure 1. Figure 2. Figure 3.
WHAT ARE THE IMPLICATIONS OF THE STUDY FINDINGS?
In light of the opioid epidemic, it is important to identify as many strategies as possible to curb opioid addiction. In the past few years, scientists have asked whether or not cannabis use can help individuals recover from opioid use disorder or may serve as a less-risky pain management approach to pharmaceutical opioids . Individuals also report using cannabinoids in an effort to cut back or quit other substances , but currently, data do not support this indication. Some studies have shown no benefit; in fact, studies have shown that cannabis use is related to greater odds of both new-onset opioid use and opioid use disorder 3 years later . The small, experimental study here shows a potential benefit of CBD in reduc ing cue-induced craving and anxiety in heroin-abstinent individuals . This suggest s a potential role for CBD in relapse prevention of heroin use disorder . T his study takes a more rigorous approach that can serve as a model for future studies of cannabinoids and their potential role in OUD treatment and recovery.
- The sample size in this study was very small and , although results are promising, the findings need replication in larger samples. The small sample also did not allow for exploration of sex/gender effects, which could be important given that women typically have higher craving and anxiety than men.
- The study medication used in this study, EPIDIOLEX, is a n FDA-approved medication that you can only get from a pharmacy. Though EPIDIOLEX is derived from cannabis, it is NOT medical marijuana . This medication does not contain THC, which is the compound in the cannabis plant that causes the ‘high’ and euphoria. It is therefore important for patients to realize that although benefits of CBD were found, this study does NOT support the use of “medical marijuana” for opioid use disorder.
- This study only examined opioid craving for 7 days. It is still unknown if CBD would reduce opioid craving past the 7-day window examined in this study o r whether use of CBD actually translates into less use of actual opioids.
- Patients in this study had to be abstinent from opioids, and not taking any agonist therapie s. Therefore, the population in this study r epresent s individuals who are doing well and may respond will to lots of different interventions . However, this population may not be representative of opioid use disorder patients more generally.
- For individuals and families seeking recovery: This study showed that compared to placebo the non-psychoactive cannabinoid , CBD , was associated with substantially de creased cue-induced craving and anxiety for those with heroin use disorder . Many individuals with opioid use disorders are seeking alternative treatments to curb cravings and reduce anxiety, and many are reluctant to try agonist treatments such as methadone or suboxone . While more research is needed to flesh out whether CBD increase s the likelihood of long-term abstinence, this study suggests individuals may benefit from EPIDIOLEX, the FDA-approved CBD medication , but more larger studies are needed to confirm this . It is important to note, however, that individuals are using cannabis in its unregulated forms, and legislatures are passing med ical cannabis laws that identify opioid use disorder as one of the conditions for which cannabis is indicated without evidence to support this indication . Consequently, individuals seeking to use cannabis , in general, for opioid addiction should proceed cautiously .
- Fortreatment professionals and treatment systems: This study showed that compared to placebo, CBD was associated with substantially de creased cue-induced craving and anxiety for those with heroin use disorder . A recent survey found that a considerable percentage (30%) of individuals receiving agonist treatment were worried about encountering negative attitudes related to being prescribed agonists, and only 33% reported their provider discussed this with them prior to attending a meeting . If CBD does pan out as a potential treatment of heroin use disorder, this could appeal to many p atient s, and could be a good complement to recovery support services. It is important for treatment professionals to be aware that the unregulated forms of cannabis, e.g. , those that can be purchased at medical marijuana dispensaries, are still unproven treatments, and may in fact produce more harm than good.
- For scientists: This study showed that compared to placebo, CBD was associated with substantially de creased cue-induced craving and anxiety for those with heroin use disorder . More w ork is needed that more precisely measures whether CBD increases the likelihood of long-term abstinence , as well as for whom, and under what conditions , this medication work best. Greater knowledge in this regard could inform the nature of medication development more broadly . By pursuing investigation into other alternative treatments for opioid use disorder, scientists may be able to help reduce stigma and improve outcomes for patients with OUD .
- For policy makers: This study showed that compared to placebo CBD was associated with substantially de creased cue-induced craving and anxiety for those with heroin use disorder . While more research is needed, CBD may be an alternative to other medications for opioid use disorder, which are limited and not well-accessible to racial/ethnic minorities and those without financial means . Policy makers, however, should be aware that this study does not provide evidence that unregulated forms of cannabis, especially those containing THC, help with OUD. F unding research studies that examine pure forms of CBD, and other alternative treatments for opioid use disorder , could help improve outcomes and reduce the public health burden of the current epidemic of opioid addiction .
Hurd, Y. L., Spriggs, S., Alishayev , J., Winkel, G., Gurgov , K., Kudrich , C., . . . Salsitz , E. (2019). Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial . American Journal of Psy chiatry, ( ePub ahead of print). doi : 10.1176/appi.ajp.2019.18101191