cbd and immunosuppressants

Cbd and immunosuppressants

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.

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.

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.

Does the form of CBD matter?

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.

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.

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

Doubling up on side effects

People considering or taking CBD products should always mention their use to their doctor, particularly if they are taking other medications or have underlying medical conditions, such as liver disease, kidney disease, epilepsy, heart issues, a weakened immune system, or are on medications that can weaken the immune system (such as cancer medications). A pharmacist is a great resource to help you learn about a potential interaction with a supplement, an herbal product (many of which have their own drug interactions), or an over-the-counter or prescription medication. Don’t assume that just because something is natural, it is safe and trying it won’t hurt. It very well might.

Cbd and immunosuppressants

Mice (B6C3F1, 5 per treatment group) were administered CBD (25, 50 or 100 mg/kg) or THC (50 mg/kg) in corn oil by oral gavage for 3 days. On the second day, mice were sensitized with 5 × 10 8 sRBC per mouse by i.p. injection. Four days after sRBC sensitization, mice were sacrificed and total body, spleen, thymus and kidney weights were recorded. Single cell suspensions of splenocytes were then generated and used to determine the in vivo AFC response as described above.

Pathogen-free female B6C3F1 or C57BL/6 mice, 6 weeks of age, were purchased from Charles River Breeding Laboratories (Portage, MI). On arrival, mice were randomized, transferred to plastic cages containing sawdust bedding (5 animals/cage), and quarantined for 1 week. CB1 -/- /CB2 -/- mice were kindly provided by Dr. Andreas Zimmer (University of Bonn) and were bred at Michigan State University. Mice were given food (Purina Certified Laboratory Chow) and water ad libitum and were not used for experimentation until their body weight was 17-20 g. Animal holding rooms were kept at 21-24°C and 40-60% relative humidity with a 12-hr light/dark cycle. All procedures involving mice were performed in accordance with guidelines set forth by the Institutional Animal Care and Use Committee at Michigan State University.

2.8 Mixed lymphocyte response (MLR)

CBD suppressed cytokine production in PMA/Io-stimulated B6C3F1 splenocytes. A-B.) Splenocytes (8 × 10 5 cells) were treated with CBD (0.1-15 μM) for 30 min, followed by cellular activation with PMA/Io for 24 hr. Supernatants were harvested and the amount of IL-2 (A.) or IFN-γ (B.) was determined by ELISA. The data are expressed as the mean Units/ml ± SE of triplicate cultures. C-D.) Splenocytes (5 × 10 6 cells) were treated with CBD (0.5-10 μM) for 30 min, followed by cellular activation with PMA/Io for 6 hr. Real time PCR was performed for IL-2 and IFN-γ. Fold change was calculated as compared to NA. * or ** denotes values that are significantly different from the vehicle control at p < 0.05 or 0.01. Results are representative of at least two separate experiments. NA, naïve (untreated); VH, vehicle (0.1% ethanol).

In order to determine whether splenic T lymphocytes are direct targets of inhibition by CBD, splenocytes were activated with anti-CD3/anti-CD28, which exclusively stimulates T lymphocytes via the T cell receptor. Although not as marked as the inhibition of cytokines produced in response to PMA/Io, CBD also suppressed IL-2 and IFN-γ produced in response to anti-CD3/anti-CD28 from splenic T lymphocytes ( Figures 4A and B ). Furthermore, PMA/Io-induced IL-2 and IFN-γ production from purified splenic T cells (i.e., >95% purity) was also suppressed by CBD ( Figures 4C and D ). It is noteworthy that purified T cells were particularly sensitive to CBD in the presence of PMA/Io and therefore, lower concentrations of CBD were used for these studies.

2.2 Animals

Previous work from our laboratory demonstrated that CBD was one of the most potent cannabinoids for suppression of PMA/Io-induced IL-2 production in splenocytes [9]. As seen in Figure 1B , CBD also suppressed PMA/Io-induced IFN-γ production, although the potency with which CBD suppressed IFN-γ was not as marked as for IL-2 (shown in Figure 1A as a comparative control). The CBD-induced suppression of both cytokines occurred at the level of mRNA ( Figure 1C and D ). With the demonstration that IL-2 is a sensitive target of suppression by CBD, we next determined the effect of CBD on expression of the IL-2 receptor α chain (CD25). CBD suppressed cell surface expression of CD25 in a concentration-dependent manner in PMA/Io-stimulated splenocytes ( Figure 2 ). Interestingly, there was not a large population of CD25 + cells in the absence of stimulation, suggesting the primary effect of CBD on CD25 occurs during T cell activation as opposed to an effect on the T regulatory cell population. Finally, there was no difference in the ability of CBD to suppress PMA/Io-stimulated IL-2 and IFN-γ from splenocytes derived from either C57BL/6 wild type or CB1 -/- /CB2 -/- mice ( Figure 3 ).