CBD Oil and Prednisone

Does CBD interact with prednisone, and if so, are there risks that should cause concern?

Prednisone is a prescription drug used to provide relief for inflamed areas of the body. It is also indicated to treat conditions, such as inflammation (swelling), severe allergies, arthritis, asthma, eye or vision problems, blood or bone marrow problems, and stomach or bowel problems (1). 

Moreover, doctors prescribe prednisone to help patients with lupus, skin conditions, endocrine problems, kidney problems, ulcerative colitis, adrenal problems, and flare-ups of multiple sclerosis. 

Prednisone is a corticosteroid, or a cortisone-like medicine or steroid. This drug works on the immune system to help relieve swelling, redness, itching, and allergic reactions.

However, this medicine may cause changes in mood or behavior for some patients. Symptoms to watch for include depression, trouble with sleeping, a false or unusual sense of well-being, mood swings, and personality changes while taking this medicine (2).

Can CBD Be Taken With Prednisone?

Taking CBD along with prednisone could either decrease the effects of cannabidiol or increase the amount of prednisone entering the bloodstream.

Whenever one takes CBD or any medicine, it passes through the digestive system to the liver, where an enzymatic pathway, called the cytochrome P450 (CYP450) family of enzymes, metabolizes or breaks down the substance ingested. 

Liver enzymes CYP450 process about 60% of all medications. One of these, CYP3A4, breaks down prednisone to make it available to the body (3).

Studies have demonstrated that CBD strongly inhibits the activity of CYP3A4 liver enzymes (4).

Meanwhile, prednisone is a weak inducer of CYP3A4 (5). Still, prednisone may increase how quickly the liver breaks down CBD when they are taken in combination. 

In particular, the effects of taking CBD along with prednisone could either decrease the effects of cannabidiol or increase the amount of prednisone entering the bloodstream.

The increased prednisone concentration can amplify the drug’s many side effects and raise the risk of severe symptoms, such as dizziness or fainting, blurred vision, irregular or pounding heartbeat, increased thirst or urination, irritability, and unusual tiredness or weakness (6).

Thus, medical experts advise those taking CBD and prednisone to be cautious with this combination (7).

Can CBD Replace Prednisone?

No study explicitly says CBD can be used in place of prednisone. However, studies have shown that CBD possesses many potential therapeutic benefits that may help with some symptoms or conditions for which prednisone is indicated. 

Prednisone is sometimes prescribed for bone marrow problems. Meanwhile, studies have shown that CBD promotes bone health. 

The effect of CBD on bones was demonstrated by a 2015 study that investigated the properties of cannabidiol concerning bone-related conditions. Data showed that that CBD led to an improvement in fracture healing (8).

Like prednisone, CBD can help with skin conditions. A study published in the journal Trends in Pharmacological Sciences has suggested the existence of a functional endocannabinoid system (ECS) in the skin and implicated it in various biological processes (9). 

CBD impacts the TRPV-1 and GPR55 receptors (10). Both receptors are found in the skin and play a role in pain signaling and inflammation.

CBD has also been shown to help with mood swings, depression, dizziness, and sleeping difficulty, symptoms for which prednisone is also prescribed. 

A study published in the Journal of Psychopharmacology found that CBD decreases anxiety levels in individuals with a social anxiety disorder (SAD). 

Results indicated that, relative to placebo, CBD was associated with significantly decreased subjective anxiety (11). 

In another study, results showed that CBD could induce rapid-acting antidepressant-like effects and enhance neurotransmission (12). Neurotransmission is the process of communication between nerve cells.

In a 2019 study published in The Permanente Journal, sleep and anxiety scores were measured in human subjects, and the findings showed that CBD could hold benefits for anxiety-related disorders (13).

Meanwhile, CBD’s antiemetic properties, which prevent nausea and vomiting, are incredibly helpful. 

A 2014 review from the European Journal of Pharmacology established the potential of cannabis to limit or prevent nausea and vomiting from a wide range of causes (14). 

    More importantly, the powerful anti-inflammatory properties of CBD could help with some of the symptoms that prednisone treats. 

CBD’s anti-inflammatory characteristics have been shown in several human and animal studies, like that of a 2014 study published in the Journal of Clinical Investigation and a 2012 research conducted by authors from the Department of Pathology, School of Veterinary Medicine in the University of São Paulo, Brazil (15).

Other studies have demonstrated that the anti-inflammatory and immunosuppressive actions of CBD may be of use in treating rheumatoid arthritis and the associated pain (16).

Meanwhile, research published in the Free Radical Biology & Medicine Journal by George Booz of the University of Mississippi Medical Center showed that CBD, which may interact with the endocannabinoid system, is a promising prototype for anti-inflammatory drug development (17).  

Conclusion

CBD “is generally well tolerated with a good safety profile,” the World Health Organization (WHO) states in a critical review (18).

Still, it is not clear how much to take or how often a person should use it for any particular problem. 

High doses of CBD may also interact with other medications, such as blood thinners, antidepressants, and immune suppressors (19).

Thus, individuals should be cautious when supplementing their existing medications with CBD. 

Do not take other pharmaceuticals unless they have been discussed with a medical professional. 

More importantly, before using CBD as a remedy for specific symptoms or conditions, consult with a doctor experienced in cannabis use for advice.

References

  1. Mayo Clinic. (2020, Feb 1). Prednisone. Retrieved from https://www.mayoclinic.org/drugs-supplements/prednisone-oral-route/side-effects/drg-20075269?p=1.
  2. Mayo Clinic. (2020, Feb 1). Prednisone. Retrieved from https://www.mayoclinic.org/drugs-supplements/prednisone-oral-route/side-effects/drg-20075269?p=1.
  3. PharmGKB. Prednisone. Retrieved from https://www.pharmgkb.org/chemical/PA451100.
  4. Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011;88(15-16):730–736. DOI:10.1016/j.lfs.2011.02.017.
  5. Marcantonio EE, Ballard J, Gibson CR, et al. Prednisone has no effect on the pharmacokinetics of CYP3A4 metabolized drugs - midazolam and odanacatib. J Clin Pharmacol. 2014;54(11):1280–1289. DOI:10.1002/jcph.338.
  6. Mayo Clinic. (2020, Feb 1). Prednisone. Retrieved from https://www.mayoclinic.org/drugs-supplements/prednisone-oral-route/side-effects/drg-20075269?p=1.
  7. MedlinePlus. (2020, Jan 21). Cannabidiol. Retrieved from https://medlineplus.gov/druginfo/natural/1439.html.
  8. Kogan NM, Melamed E, Wasserman E, et al. Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. J Bone Miner Res. 2015;30(10):1905–1913. DOI:10.1002/jbmr.2513.
  9. Bíró T, Tóth BI, Haskó G, Paus R, Pacher P. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009;30(8):411–420. DOI:10.1016/j.tips.2009.05.004.
  10. Sharir H, Abood ME. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther. 2010;126(3):301–313. DOI:10.1016/j.pharmthera.2010.02.004; Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol. 2004;143(2):247–250. DOI:10.1038/sj.bjp.0705920.
  11. Crippa JA et al.Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.J Psychopharmacol. 2011 Jan;25(1):121-30. DOIi: 10.1177/0269881110379283. Epub 2010 Sep 9. DOI: 10.1177/0269881110379283.
  12. Linge R et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology. 2016 Apr;103:16-26. doi: 10.1016/j.neuropharm.2015.12.017. Epub 2015 Dec 19.DOI: 10.1016/j.neuropharm.2015.12.017.
  13. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18–041. DOIi:10.7812/TPP/18-041.
  14. Sharkey KA, Darmani NA, Parker LA. Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Eur J Pharmacol. 2014;722:134–146. DOI:10.1016/j.ejphar.2013.09.068.
  15. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014;124(9):3713–3724. DOI:10.1172/JCI64628; Ribeiro A et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor. Eur J Pharmacol. 2012 Mar 5;678(1-3):78-85. DOI: 10.1016/j.ejphar.2011.12.043. Epub 2012 Jan 12.
  16. Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford) 2006;45:50–52; Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, Feldmann M. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. U. S. A. 2000;97:9561–9566.
  17. Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011;51(5):1054–1061. DOI:10.1016/j.freeradbiomed.2011.01.007.
  18. Expert Committee on Drug Dependence Fortieth Meeting. Cannabidiol (CBD) Critical Review Report. June 2018. Retrieved from https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf.

Harvard Health Publishing. (2019, Oct). Know the facts about CBD products. Retrieved from https://www.health.harvard.edu/staying-healthy/know-the-facts-about-cbd-products.

INTOX Home Page



    HYPERCALCAEMIA



    DEFINITION



    Abnormally high concentration of calcium in the blood (serum calcium

    > 2.58 mmol/L or > 10.3 mg/dL). 



    The ionized calcium is a more accurate reflection of calcium status,

    especially in patients with low serum albumin. The normal ionized

    calcium is 1.12 to 1.23 mmol/L (4.48 to 4.92 mg/dL). 



    TOXIC CAUSES



    Hypercalcaemia is observed most often in chronic intoxications and is

    a consequence of one or more of the following mechanisms:



         Increased bone resorption of calcium

         Increased intestinal resorption of calcium

         Impaired renal excretion of calcium



    Most frequent causes:



         Vitamin D overdose

         Milkalkali syndrome (Burnett syndrome)

         Calcium salts intoxication



    Occasional causes:



         Theophylline 

         Thiazide diuretics



    NON-TOXIC CAUSES



    Hyperparathyroidism

    Some neoplasms and bone metastases



    CLINICAL FEATURES



    Mild hypercalcaemia may be asymptomatic. Moderate to severe toxicity

    may cause constipation, anorexia, abdominal cramps, nausea, vomiting,

    polyuria, polydipsia, dehydration, delirium, stupor, psychotic states,

    asthenia, muscular weakness, shortening of QT interval on the ECG, and

    cardiac arrest.  Acute renal failure may result from calcium

    deposition in the kidney.



    RELEVANT INVESTIGATIONS



    Total serum calcium and ionized serum calcium 

    Other serum electrolyte concentrations including magnesium, phosphate,

      sodium, and potassium 

    Renal function (creatinine, urea)

    Electrocardiograph (QT interval)



    DIFERENTIAL DIAGNOSIS



    Other causes of coma and metabolic encephalopathy

    Polyuria and dehydration from diabetes insipidus or diabetes mellitus



    TREATMENT



    Cease administration of, or exposure to, the causative agent.



    Correct dehydration by administering intravenous fluids.  To promote

    calcium excretion, administer intravenous  normal saline (3 to 4

    L/day in adults).   Furosemide (20 to 80 mg IV in adults) may be

    given following correction of hypovolaemia. Monitor urine output and

    match renal losses with additional intravenous fluids.



     Corticosteroids: Prednisone (1 mg/kg orally) or  hydrocortisone 

    (300 mg intravenously) is recommended for patients with hypercalcaemia

    caused by Vitamin D overdose.



     Calcitonin (5 to 10 units/kg IM every 8 hours) promotes calcium

    uptake in bone, and is mainly used in patients with severe

    hyperparathyroidism.



    Haemodialysis may be indicated if renal failure develops.



    CLINICAL COURSE & MONITORING



    Urine output and fluid and electrolyte balance

    Serum calcium and ionized calcium concentration

    Renal function

    Electrocardiogram (QT interval)



    LONG-TERM COMPLICATIONS



    Hypercalcaemia by itself may cause nephrocalcinosis and/or renal

    insufficiency



    AUTHOR/REVIEWERS



    Author:             Dr V. Danel, Unité de Toxicologie Clinique,

                        Grenoble, France.



    Peer Reviewers:     Cardiff 9/96: V. Afanasiev, M. Burger, T. Della

                        Puppa, L. Fruchtengarten, K. Olsen, J. Szajewski.

    

    HYPOCALCAEMIA

    DEFINITION

    Abnormally low concentration of calcium in the blood (Total calcium
    < 2.20 mmol/L or 8.8 mg/dL).

    The ionized calcium is a more accurate reflection of calcium status,
    especially in patients with low serum albumin. The normal ionized
    calcium is from 1.12 to 1.23 mmol/L ( 2.24 to 2.46 meq/L, 4.48 to 4.92
    mg/dL).

    TOXIC CAUSES

    Ethylene glycol
    Fluorides and fluorosilicates
    Hydrofluoric acid (ingestion or skin contact)
    Oxalic acid and soluble oxalates
    Phosphate enemas
    Valproic acid

    NON-TOXIC CAUSES

    Hypoparathyroidism
    Malabsorption
    Pancreatitis
    Renal failure
    Vitamin D deficiency

    CLINICAL FEATURES

    Severe hypocalcaemia may appear within an hour of acute ingestion of
    hydrofluoric acid, fluorides, fluorosilicates or oxalic acid. 
    Paraesthesias, tetany, and convulsions are often present.  The
    electrocardiograph shows a widened or prolonged QT interval and large
    or peaked T waves.  Dysrhythmias and cardiac arrest may occur.

    DIFFERENTIAL DIAGNOSIS:

    Congenital QT prolongation syndrome
    Type Ia antiarrhythmic agents
    Tetanus
    Hyperventilation
    Strychnine
    Seizures

    RELEVANT INVESTIGATIONS

    Total and ionized serum calcium concentration
    Serum electrolytes: magnesium, phosphate, sodium and potassium
    concentration
    Renal function (urea, creatinine)
    Acidbase status (blood gases, serum bicarbonate)

    Electrocardiograph (QT interval and T wave morphology)
    Consider amylase, valproic acid, ethylene glycol levels in appropriate
    circumstances.

    TREATMENT

    After acute ingestion of hydrofluoric acid, fluorides, fluorosilicates
    or oxalic acid, calcium salts should be given orally or by gastric
    tube as soon as possible (50 mL of 10% calcium gluconate; 1 mL/kg in
    children).  Calcium acts as a chelating agent in the stomach. 
    Magnesium (e.g., magnesium hydroxide found in liquid antacid
    preparations) may also be helpful for fluoride ingestion. 

    Extensive skin contamination by hydrofluoric acid, fluorides,
    fluorosilicates or oxalic acid may lead to systemic toxicity and
    severe hypocalcaemia.

    In all patients with suspected or confirmed hypocalcaemia, perform
    continuous cardiac monitoring, and give intravenous  calcium 
     gluconate (10 to 15 mL over 3 to 5 minutes, 0.01 to 0.02 mL/kg in
    children). Further doses of calcium salts depend on serum calcium
    concentration and ECG.  The required dose of calcium salt may be from
    3 g to 20 g on the first day.  Calcium chloride may also be used, but
    contains approximately 3 times the amount of calcium per mL. 

    CLINICAL COURSE AND MONITORING

    Sudden cardiac arrest can occur - provide continuous
    electrocardiographic monitoring (QT interval, T waves). 
    Serum calcium and ionized calcium concentrations.
    Some of the causes of hypocalcaemia may also lead to severe
    hyperkalaemia - measure serum potassium and electrolytes frequently.

    AUTHOR(S)/REVIEWERS

    Author:        Dr V. Danel, Unité de Toxicologie Clinique, Grenoble,
                   France.

    Peer review:   Cardiff 9/96: V Afanasiev, M Burger, T Della Puppa,
                   L Fruchtengarten, K Olsen, J Szajewski.