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In our previous article, CBD 101, we gave the brief conclusion that trying CBD is still an experimental undertaking, but also mentioned that it’s generally safe. The key word here is generally. CBD has a complex range of actions in the body – around 20 mechanisms described to date (1) – which makes it really difficult to assess all the potential risks.
While research shows CBD’s side effects are generally mild (2), specific cases of drug interactions have been reported (3,4,5), and there is evidence that others are possible (6). We don’t know much in detail about these potential interactions yet, and we know even less when it comes to things like CBD and pregnancy/breastfeeding or long-term use.
This article is meant to highlight notable areas of concern and give a basic idea of both what the associated risks are (or might be) and how well we understand them so far – not to scare anyone, but to help those interested in CBD make safe and informed decisions. And of course, this article isn’t meant to be a substitute for professional medical advice – we’ll talk more about that as well. But first, here’s a quick reference table (there’ll be more below for dedicated readers):
|Area of Concern||Understanding of Risks||Level of Risk||Comments|
|Side Effects||Good||Currently low, excluding side effects from drug interactions||In available clinical trial data, serious side effects have only been seen in studies involving rare forms of epilepsy, with most patients taking other medications (2,7,8). Excluding these, diarrhea was the only side effect associated with CBD – sedation occurred often as well, but placebo as a cause couldn’t be ruled out confidently (2).|
|Drug Interactions||Limited||Varies depending on drug; risks mostly unknown; potentially high||CBD has a kind of “grapefruit effect”, where it can interfere with the body’s ability to break down or transport certain drugs throughout the body (6). Talk to a doctor before trying CBD if you’re taking medication.|
|Reproductive Health||Very Limited||Possible risk for men; unknown for women||In vitro and animal studies suggest CBD has negative effects on male reproductive functions at very high doses (mainly 30+ mg/kg, some at 15); however no effects have been seen in oral doses up to 10 mg/kg (equivalent to ~600 mg for a 130-pound human) (9).|
|Very Limited||Potentially high||Animal studies suggest using cannabinoids during pregnancy/breastfeeding (including CBD) could increase the chances of birth defects and negatively impact child development (9,10,11).|
|Long-term use||None||Unknown||While some clinical trials and follow-up studies indicate a good safety profile for use up to ~2 years (12,13,14), there is no data indicating how CBD affects health on longer time scales.|
|Child development||None||Unknown||No long-term data available.|
As a quick point of clarification, keep in mind that there may be long-term risks to reproductive health and pregnancy/breastfeeding in addition to any other long-term risks. Also, we’ve listed the side effect risk as “currently low”, as further clinical studies and analysis may show otherwise. The most current analysis (excluding epilepsy studies) includes 233 patients from 7 studies (2), so the evidence is looking good so far.
When do the Risks Outweigh the Benefits?
That’s a good question, and a tough one. Indeed, the whole point of investigating the medical worth of a substance is to weigh the potential benefits against the potential risks. Often times, potential benefits depend on quality of life: in the case of children with severe treatment-resistant epilepsy, things like mild side effects and unknown long-term risks associated with CBD pale in comparison to the benefit of having 25-100% less seizures. As Master Po once said: “Sometimes one must cut off a finger to save a hand.” Pregnant women with severe illnesses may feel the same way.
But a medical professional is best equipped to help navigate a situation like this. A good example is a 2018 case study where a man who, among other complications, had treatment-resistant epilepsy and was also taking warfarin, a blood-thinning medication. He had entered a CBD research program for his epilepsy, but after starting the researchers noted that his INR – a number measuring how long blood takes to clot (15) – had increased, indicating there was more warfarin in his blood than usual, and in turn a drug interaction between CBD and warfarin. Throughout the program, his warfarin dose was lowered by about 30%, bringing his INR back to normal.
To reiterate, this is why it’s best to talk to a doctor, especially if you’re taking medication. But CBD is a relatively new sensation, and the market is moving much faster than the science. How much does the average doctor know about CBD?
Seeking Professional Advice
Unfortunately this one can also be tough. Two years ago a relative of mine asked her specialist about using CBD for pain while she was on heart medication. The specialist just shrugged at her. While this experience is now two years out of date, I’m not sure how much better it’s gotten – Michael Eisenstein’s 2019 article in Nature outlines some rough circumstances in New York City, where the director of the Addiction Institute of Mount Sinai talks about “physicians who have no clue how to address the requests they get from patients” constantly calling and emailing.
If you ask your doctor and they don’t know enough to help, consider trying to get them to work with you: perhaps you’re on medication but have other complications and think CBD might help more than hurt – ask if they can monitor you through follow-up appointments. Maybe they can help adjust doses of other medications in response to how CBD affects you. Again, I’m not sure how knowledgeable doctors are about CBD in 2020, but I’d love to hear comments about others’ experiences with asking their doctors about CBD.
- CBD has a lot of potential benefits with minimal side effects, but it’s not totally risk-free – especially for those who are pregnant/breastfeeding and/or taking medication.
- It’s all about weighing the potential benefits against the potential risks.
- Talk to your doctor about the risks. If they don’t know, try and get them to work with you!
Thanks for tuning in everybody – hopefully this puts you on a path towards safer choices with CBD, or helping others do the same! Stay tuned for next time, where we’ll be talking about some of the commonly-encountered jargon in the world of CBD.
See you next time,
- Eisenstein M. The reality behind cannabidiol’s medical hype. Nature. https://www.nature.com/articles/d41586-019-02524-5. Updated July 23, 2020. Accessed September 3, 2020.
- Chesney E, Oliver D, Green A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020;45(11):1799-1806. doi:10.1038/s41386-020-0667-2 – PubMed
- Gaston, T.E., Bebin, E.M., Cutter, G.R., Liu, Y., Szaflarski, J.P. and (2017), Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia, 58(9):1586-1592. doi:10.1111/epi.13852
- Grayson L, Vines B, Nichol K, Szaflarski JP; UAB CBD Program. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10-11. Published 2017 Oct 12. doi:10.1016/j.ebcr.2017.10.001 – PMC
- Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. doi:10.1111/ajt.15398 – PubMed
- Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989. Published 2019 Jul 8. doi:10.3390/jcm8070989 – PMC
- Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ, O’Sullivan SE. A systematic review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019;85(9):1888-1900. doi:10.1111/bcp.14038 – PMC
- Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects [published correction appears in CNS Drugs. 2019 Apr;33(4):397]. CNS Drugs. 2018;32(11):1053-1067. doi:10.1007/s40263-018-0578-5 – PMC
- Carvalho RK, Andersen ML, Mazaro‐Costa R. The effects of cannabidiol on male reproductive system: a literature review. J Appl Toxicol. 2020; 40(1):132-150. https://doi.org/10.1002/jat.3831
- Fish EW, Murdaugh LB, Zhang C, et al.Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction. Sci Rep.2019;9(16057). https://doi.org/10.1038/s41598-019-52336-w
- Carty DR, Thornton C, Gledhill JH, Willett KL. Developmental Effects of Cannabidiol and Δ9-Tetrahydrocannabinol in Zebrafish. Toxicol. Sci. 2018;162(1):137-145. https://doi.org/10.1093/toxsci/kfx232
- Szaflarski JP, Bebin EM, Comi AM, et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. 2018;59(8):1540-1548. doi:10.1111/epi.14477 – PMC
- Devinsky O, Nabbout R, Miller I, et al. Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Epilepsia. 2019;60(2):294-302. doi:10.1111/epi.14628 – PMC
- Laux LC, Bebin EM, Checketts D, et al. Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results. Epilepsy Res. 2019;154:13-20. doi:10.1016/j.eplepsyres.2019.03.015
- International Normalized Ratio. University of Rochester Medical Center. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=international_normalized_ratio. Accessed September 15, 2020.
These articles are not intended to serve as medical advice, and in the case of referenced sources, do not necessarily reflect the authors’ or collaborators’ opinions. Our aim is to help present reliable information in a way that’s accessible to the average reader, and we try, to the best of our ability, to preserve the context of our sources in this endeavour.