Researchers from Penn State College of Medicine evaluated existing information on five prescription CBD and delta-9-tetrahydrocannabinol (THC) cannabinoid medications: antinausea medications used during cancer treatment (Marinol, Syndros, Cesamet); a medication used primarily for muscle spasms in multiple sclerosis (Sativex, which is not currently available in the US, but available in other countries); and an antiseizure medication (Epidiolex). Overall, the researchers identified 139 medications that may be affected by cannabinoids. This list was further narrowed to 57 medications, for which altered concentration can be dangerous. The list contains a variety of drugs from heart medications to antibiotics, although not all the drugs on the list may be affected by CBD-only products (some are only affected by THC). Potentially serious drug interactions with CBD included
Absolutely. Inhaled CBD gets into the blood the fastest, reaching high concentration within 30 minutes and increasing the risk of acute side effects. Edibles require longer time to absorb and are less likely to produce a high concentration peak, although they may eventually reach high enough levels to cause an issue or interact with other medications. Topical formulations, such as creams and lotions, may not absorb and get into the blood in sufficient amount to interact with other medications, although there is very little information on how much of CBD gets into the blood eventually. All of this is further complicated by the fact that none of these products are regulated or checked for purity, concentration, or safety.
Products containing cannabidiol (CBD) seem to be all the rage these days, promising relief from a wide range of maladies, from insomnia and hot flashes to chronic pain and seizures. Some of these claims have merit to them, while some of them are just hype. But it won’t hurt to try, right? Well, not so fast. CBD is a biologically active compound, and as such, it may also have unintended consequences. These include known side effects of CBD, but also unintended interactions with supplements, herbal products, and over-the-counter (OTC) and prescription medications.
CBD can alter the effects of other drugs
Many drugs are broken down by enzymes in the liver, and CBD may compete for or interfere with these enzymes, leading to too much or not enough of the drug in the body, called altered concentration. The altered concentration, in turn, may lead to the medication not working, or an increased risk of side effects. Such drug interactions are usually hard to predict but can cause unpleasant and sometimes serious problems.
The researchers further warned that while the list may be used as a starting point to identify potential drug interactions with marijuana or CBD oil, plant-derived cannabinoid products may deliver highly variable cannabinoid concentrations (unlike the FDA-regulated prescription cannabinoid medications previously mentioned), and may contain many other compounds that can increase the risk of unintended drug interactions.
Does the form of CBD matter?
CBD has the potential to interact with many other products, including over-the-counter medications, herbal products, and prescription medications. Some medications should never be taken with CBD; the use of other medications may need to be modified or reduced to prevent serious issues. The consequences of drug interactions also depend on many other factors, including the dose of CBD, the dose of another medication, and a person’s underlying health condition. Older adults are more susceptible to drug interactions because they often take multiple medications, and because of age-related physiological changes that affect how our bodies process medications.
While generally considered safe, CBD may cause drowsiness, lightheadedness, nausea, diarrhea, dry mouth, and, in rare instances, damage to the liver. Taking CBD with other medications that have similar side effects may increase the risk of unwanted symptoms or toxicity. In other words, taking CBD at the same time with OTC or prescription medications and substances that cause sleepiness, such as opioids, benzodiazepines (such as Xanax or Ativan), antipsychotics, antidepressants, antihistamines (such as Benadryl), or alcohol may lead to increased sleepiness, fatigue, and possibly accidental falls and accidents when driving. Increased sedation and tiredness may also happen when using certain herbal supplements, such as kava, melatonin, and St. John’s wort. Taking CBD with stimulants (such as Adderall) may lead to decreased appetite, while taking it with the diabetes drug metformin or certain heartburn drugs (such as Prilosec) may increase the risk of diarrhea.
Those combining opioids with cannabis were also more likely to be taking opioids not as prescribed and have symptoms of opioid dependence, in addition to endorsing using other substances. It is possible these individuals may represent a subset of people with chronic pain and greater overall substance use-related problems.
Participants were adults ages of 18 to 64 (74.67% female, average 38.59 years old , standard deviation of 11.09) reporting current opioid use for pain and current chronic pain that persisted for at least 3 months. The sample was predominately White (77.8%), with another 8.7% identifying as Black/African American, 13.1% Hispanic/Latino, 3.3% Native American/Alaska Native, 0.9% Asian/Pacific Islander 2.7% multiracial, and 1.1% other. In terms of education, a little over a fifth (5.8%) did not complete high school, whereas over a quarter of the sample (31.3%) reported attaining a high school diploma, with 22.4% reporting ‘‘some college,’’ and 40.4% having attained an associate ’s degree or higher.
This cross-sectional study surveyed 450 United States adults who endorsed taking opioids to manage chronic pain. Of these 450 people, 176 endorsed also using cannabis for pain management. Participants were asked about their opioid and cann a bis use, as well as any use of other substances , including nicotine. Participants were also assessed for opioid use problems , a s well as anxiety and depression. Questionnaires administered included 1) the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) , an 8-item questionnaire designed to asses risk of substance use involvement , 2) the p atient Health Questionnaire-4 (PHQ-4) , a 4-item self-report measure comprised of the PHQ-2 for depression and the GAD-2 for anxiety , 3) t he Current Opioid Misuse Measure (COMM) that is used to identify individuals who are exhibiting behaviors of problematic opioid use , 4) the Severity of Dependence Scale (SDS) , a measure severity of dependence to opioids , and 5) t he Graded Chronic Pain Scale (GCPS) , a measure that assesses pain intensity and pain disability . The authors statistically controlled for differences among study participants in age, sex, income, and education.
Problematically, those combining opioids with cannabis had greater anxiety and depression than those using opioids alone, although the absolute differences between groups on these measures was not large. Because this is a cross sectional study (i.e., a single survey providing a snapshot in time), it is impossible to know whether cannabis use was leading to greater anxiety and depression, or individuals with greater anxiety and depression were more likely to be using cannabis to cope. If these more vulnerable individuals are, in fact, using cannabis to cope with difficult mental health concerns, it does not seem to be helping subjectively given their poorer functioning, although it could be that they had higher anxiety and depression to begin with, and cannabis use brought this down to the same level.
Figure 1. Graph showing differences between study participants using opioids alone (grey bars), and opioids in conjunction with cannabis (black bars) to manage chronic pain. Measures are reported as estimated marginal means (vertical axis); in other words, the mean response for each measure, adjusted for the other reported measures. The asterisk (*) indicates a highly significant difference at the p< 0.005 level, meaning the differences observed are highly unlikely to be due to chance. It is important to note that the range of possible scores on each measure is different. Participants combining opioids and cannabis reported more anxiety and depression, were more likely to be using opioids not as prescribed and endorse more symptoms associated with opioid dependence, and were more likely to be using tobacco, alcohol, cocaine, and sedatives. PHQ-4 Anx= Anxiety, PHQ-4 Dep= Depression, GCPS Intensity= Pain intensity, GCPS Disability= Pain disability, COMM Total= Current not as prescribed opioid use, SDS Total= Severity of opioid dependence (Source: Rogers et al., 2018).
Also, these individuals were possibly purchasing cannabis from the illicit market in which strains with higher THC contents predominate (the compound in cannabis that causes euphoria/high). This study cannot tease apart whether CBD (a compound in cannabis thought to have some therapeutic benefits but does not cause euphoria/high) in combination with opioids for chronic pain would be associated with different mental health and substance use outcomes.
Many people argue that cannabis is a safe and effective drug for chronic pain management , and have gone as far to say that cannabis can reduce the need for opioid pain medications and the risks that go with this class of drug . At the same time, the co-use of certain substances is generally associated with poorer outcomes than single substance use . In t his article , Rogers and colleagues assesse d whether individuals who were combin ing cannabis with opioid s to manage chronic pain had less self-reported pain than those using opioids alone, and whether individuals combining cannabis and opioids h ad more mood – related problems. The authors also explore d whether these individuals are more or less likely to have problems with opioids and engage in the use of other substances.
HOW WAS THIS STUDY CONDUCTED?
Many promote cannabis as a safe and effective drug for chronic pain management, and have gone as far to argue that cannabis can reduce the need for opioid pain medications. At the same time, it is well appreciated that the co–use of certain substances is generally associated with poorer outcomes than single substance use. In this study, authors found that individuals with chronic pain who combine opioids and cannabis are not functioning as well as those who are only using opioids. Although the exact nature of this relationship is unclear, the results may have implications for medical cannabis in the context of chronic pain management.
C ompared to participants using opioids alone to manage chronic pain, those combining opioids with cannabis endorsed greater anxiety and depression. Notably, participants combining opioids and cannabis were also more likely to be taking opioids not as prescribed and had greater scores on an opioid dependence severity scale , and were more likely to be using tobacco, alcohol, cocaine, and sedatives. This overall pattern of poorer functioning and risky substance use is illustrated in the figure below. At the same time, participants combining opioids and cannabis reported pain levels similar to those using opioids alone .