Herb-Drug Interactions
Given that about 66% of all U.S. adults take prescription drugs, and that among those who take prescription medications, the average number of medications taken is four, herb-drug interactions are a primary safety consideration. It is our responsibility as herbalists to consider safety when sharing about, educating, and ingesting herbs yourself or for others.
The research is ongoing here, and much of the established research is theoretical as it is primarily based upon petridish (in vitro) trials that may not translate to human physiology. This research gives us an idea of where and with what herbs we may need to proceed cautiously in their use.
The two primary herb-drug interactions that can occur are:
- Pharmacokinetic Interactions - when an herb alters or interferes with the absorption, distribution, metabolism, or excretion of a drug.
- Herb can inhibit metabolism of a drug (slow down enzyme path)
- Although some drugs need to be metabolized first in order to release the actives
- Induction of enzyme pathway (speed up enzyme path)
- Clears the drug out of the body faster, thus encouraging therapeutic failure
- For example: Saint John's Wort induces CYP3A4 pathway which encourages therapeutic failure of the drug (see info on the CYP 450 Enzyme system below)
- Herb can inhibit metabolism of a drug (slow down enzyme path)
- Pharmacodynamic Interactions - when an herb alters sensitivity and responsiveness of tissues or receptor sites to drugs.
Cytochrome P450 enzymes are essential for the metabolism of many medicines and endogenous compounds. The CYP3A family is the most abundant subfamily of the CYP isoforms in the liver. There are at least four isoforms: 3A4, 3A5, 3A7 and 3A43 of which 3A4 is the most important.
CYP3A4 contributes to bile acid detoxification, the termination of action of steroid hormones, and elimination of phytochemicals in food and the majority of medicines.
This huge family of enzymes (over 50,000) help transform xenobiotics into stuff we can use – both herbs & pharmaceuticals affect this enzyme system.
Most Common Subfamilies:
• CYP3A4 pathway: St. John's Wort
• CYP2D6 pathway: Black Cohosh, Echinacea
• CYP4E8 pathway
These two routes of interaction can lead to synergistic effects (the combination potentially increases the effect of the herb and/or drug), counteracting effects (the combination potentially decreases the effect of the herb and/or drug), an increase in the risk of side effects, and an alteration of drug clearance (may increase or decrease the amount of time a drug circulates in the body). For this last effect, St. John’s Wort is the most popular example, and one to be aware of, as St. John’s Wort is said to affect liver metabolism and as a result can either increase or decrease a drug’s effects.
The primary resource we have as herbalists is the American Herbal Products Association's Botanical Safety Handbook 2nd Edition by Zoë Gardner and Michael McGuffin. This book comes at a steep price so if you ever have a question about a particular herb, explore the resources you have available and reach out to me for information from this book.
Some additional things to keep in mind:
Herb-drug interactions tend to occur at the small intestine, not the liver.
- Staggering doses by three hours is often a safe bet unless client is on list of narrow therapeutic index drugs or drugs with a longer half life.
If client has an auto-immune condition, or is on pharmaceuticals... always consider the possibility of herb-drug interactions.
- Especially Narrow Therapeutic Index Drugs
- aminoglycosides
- ciclosporin
- carbamazepine
- digoxin
- digitoxin
- flecainide
- lithium
- phenytoin
- phenobarbital
- rifampicin
- theophylline
- warfarin
Terms related to herb-drug interactions you might encounter:
- Pharmacokinetics – A branch of pharmacology dedicated to describing how the body affects a specific substance after administration.
- how an herb is going to influence, interact, distribute, and eliminate from the body
- Pharmacodynamics – The study of the biochemical and physiologic effects or actions of drugs.
- Ligand – any molecule that binds to a receptor site
- Binding Affinity – the tenacity at which one molecule binds to another
- Agonist – binds and activates a receptor
- Antagonist – binds to receptors without activating them (effectively jamming the lock)
- Competitive Antagonism – There is a belief that some herbs are strong enough to competitively block receptor sites that pharmaceuticals need to bind to. This is a theory that encourages some doctors to discourage the use of herbs.
- According to many of my teachers, there isn't much evidence for this and something we need not worry about as much as other factors.
- Substrate – a drug or molecule that is believed to be affected by an herb
- Metabolite – a by-product of metabolism
- Xenobiotic – a substance that is foreign to the body; non-nutrient plant constituents
- Bioavailability – if and how much a xenobiotic makes it into the bloodstream
- Coadministration – Taking an herb and drug at the same time
- this is where most herb-drug interactions occur
- If you need to take a pharmaceutical on an empty stomach do not take this pharmaceutical with herbs.
- Therapeutic Index – aka, the 'therapeutic window' – the range between the minimum effective level of a drug and its toxicity level
- Area under the curve – how much of a drug reaches a person's bloodstream given a period of time after the drug is given
- Drug Half Life – the time it takes for the amount of a drug's active substance in your body to reduce by half.
- This depends on how the body processes and gets rid of the drug. It can vary from a few hours to a few days, or sometimes weeks.
Related: Herb Safety & Dosage
Herb-Drug Interaction Resources
More Conservative Resources:
- Integrative Medicine: Search About Herbs | Memorial Sloan Kettering Cancer Center
- Herbal Contraindications and Drug Interactions by Francis Brinker (4th ed)
Less Conservative Resources:
- The Essential Guide to Herbal Safety by Mills & Bone
- American Herbal Products Association Botanical Safety Handbook by Zoë Gardner and Michael McGuffin
Other Resources:
- A-Z Guide to Drug-Herb-Nutrient Interactions by Alan Gaby (2nd ed; old but some good basic info)
Websites
- Mytavin is a useful place to look up drug-induced nutrient depletions
- Drugs.com provides solid info on most medications, although their herb-drug interactions are not nuanced
- The Efficasafe database seems like a solid source, although I haven’t used it extensively. You can get several free searches to test it out.
- If you have access to a Natural Medicines Database subscription, they have an interaction checker (some schools/university libraries have it)
- Integrative Therapeutics has a drug-nutrient interaction checker that does include herbs. You do have to give them your email address to access it.
- MediHerb's Potential HDI chart for Commonly-Used Herbs
- Eric Yarnell's resources on Herb-Drug Interactions via CYP 450 enzymes
- The Massachusetts College of Pharmacy has a Center for Drug Information and Natural Products where healthcare providers & consumers can get free information about HDI, safety issues, etc from sixth-year pharmacy students. This center is run by Lana Camiel, a pharmacist and professional member of the AHG.
Trainings
- Continuing Education program (free) via NCCIH: Clinically Relevant Herb-Drug Interactions: Past, Present, and Future with Dr. Bill Gurley (CME available)
- Here are a series of past conference recordings relating to HDI from botanicalmedicine.com
Resources Section adapted from Camille Freeman’s HDI Resources
Member discussion