Herbs contain an abundance of constituents that interact to produce an effect. Drugs are singular compounds targeted to specific receptors. How do they differ?
Pharmaceuticals vs herbs: What is the difference?
Besides their difference in origin (synthetic vs natural), the main difference between pharmaceuticals and herbal medicines is their chemical complexity and composition.
Pharmaceuticals are mostly single compounds, whereas herbal medicines are chemically complex with hundreds or thousands of molecules in each extract. It is precisely this chemical abundance and diversity that offers many of the medicinal virtues of herbs, but more on this later.
Wider differences in the philosophies and treatment protocols within the different doctrines of allopathic medicine and herbalism also exist and account for disparity between practices. Our series on herbal formulations shares some insights on different herbal medical systems.
Reductionist science
Reductionist science is a way of explaining and studying complex systems by breaking things down into small parts and investigating the separate parts. This helps us understand how things work, and can be fantastically helpful, but like any tool, it has its limits.
The approach of reductionist science, for example, in the study of heart anatomy and pathology, would be to focus investigations into the intricate component parts. From the level of the cardiovascular system, to the organ, tissue, and cells, e.g. cardiomyocytes, fibroblasts or pericytes. Then, the mechanisms within those cells at the level of the proteins, such as enzymes and receptors, would be further researched to understand how they work.
Pharmaceutical companies then find singular compounds to stimulate/block these receptors and processes, which have an effect on the body and can be used for medicine. Typically, this molecule is then patented and sold for profit. The drive for drug discovery continues, and oftentimes pharmaceutical companies explore traditional medicine resources to find new compounds to isolate and purify in a process called bioprospecting.
Humans have been using medicines from nature for thousands of years, but in the 1800s this began to change due to rapid advances in chemistry (1). The sourcing of medicine shifted from whole plant extracts to single isolated compounds. This led to significant developments, like morphine from poppy (Papaver somniferum) in the early 1800s and salicin from willow bark, which was used to synthesise acetylsalicylic acid — aspirin (2). Since then, the pharmaceutically-motivated medical system has been centred around finding “silver bullets” to cure diseases, which has come with both its benefits and limitations.
What are the benefits and limitations of isolating compounds?
There are some benefits to using isolated compounds, for example, pharmaceutical drugs can have a faster onset of action and greater potency (a smaller quantity has a greater effect). The use of isolated compounds also allows for greater precision with dosing, where the exact measure of the bioactive compound is known and administered. In plants, the concentration of active constituents in an extract can vary owing to a multitude of factors — environmental conditions, soil health, time of harvest, biodiversity etc.
However, the use of isolated compounds as medicine is often associated with a higher incidence of side effects. The integrative use of herbs in conjunction with pharmaceutical agents can help to mitigate these effects (3).
Research that has isolated compounds has also facilitated understanding of which plant constituents are active and contribute to a plant’s medicinal effects. From this work, marker compounds have been identified which allow for the standardisation of whole plant extracts, which mitigates the aforementioned variability and is a means to uphold quality and safety of products in the herbal industry by meeting pharmacopoeial standards.
Scientific research has increasingly recognised the limitations of using single compounds for treatment. Whilst this approach is very popular in modern drug discovery, many complex diseases (such as cancer, degenerative disorders and inflammatory conditions) have limited success with treatment with single compounds, as the mechanisms underpinning the pathophysiology of the disease are so multifaceted (4). In this understanding, increasingly scientists are investigating multi-targeted molecules in the search for more effective medicine (5).
Chemical complexity in medicines
Traditional herbal medicines are extracted using a range of natural solvents (such as water, alcohol, vinegar, and an array of other things). As whole plant and fungi parts are used, these preparations are chemically complex owing to the vast variety of these compounds extracted from them. My phytochemistry teacher, Dr Jose Prieto, used to joke, “if anybody tells you herbs don’t work just explain to them a plant is like a bag of chemicals!”. Plants and fungi are living organisms with complex metabolic processes and so have a vast array of chemicals within them, much like us. On a pharmacological level this means that no one compound is in the body working alone. Phytochemist Chris McGurdy describes pharmaceuticals in comparison to plant extracts as “having an instrument or having an orchestra”.
There are an array of benefits to this, due to the multiple constituents together producing additive, antagonistic or synergistic effects. Most prominently is the phenomena known as synergy (6) — also referred to as the entourage effect. Synergy is the combined effect of substances that creates an outcome that is greater than the sum of its parts (the effect of each substance in isolation). This may occur via the modulation of the bioavailability or metabolism of one compound by another. Antagonism is where one substance will have an opposite effect to another — it is this interaction between plant constituents that can account for the lower incidence of side effects and better safety profile of herbal medicines. Together, synergistic and antagonistic effects can reduce toxicity and improve therapeutic potential.
The other benefit of this chemical complexity (or chemodiversity) is that instead of having a single receptor target, the molecules in the extracts are able to interact with an array of receptors, tissues and systems in the body. This is why their effects are often so multifaceted and widespread, and why sometimes herbalism is referred to as “systems medicine” as entire systems in the body are affected.
This means that herbal medicines are suitable for treating multifactorial conditions and can be a useful adjunct to conventional treatment too, making the therapeutic approach more comprehensive (7). Most conditions (mood disorders, chronic conditions and many others) are multifaceted in their pathophysiology and so herbal medicines are helpful in many situations. They are also often safer because we share many of the same metabolic processes as plants and so our body takes what it needs from the extracts to recalibrate, and in herbalism we are simply supporting the body’s natural healing capabilities by resourcing our bodies with the molecules it needs.
Challenges of chemically complex extracts
With improved safety profiles and a multifaceted approach, these medicines are incredibly valuable, but this also comes with its own challenges. For example, often there is a compound (or several) with the most pharmacological activity, but we cannot always be sure which one unless extensive lab testing is done. This makes it hard to know which compounds to monitor and ensure growing conditions are optimal to produce and makes it harder to discern what a quality extract is (that is if active compound levels are the main quality marker). There are ways to discern quality extracts from poor ones (8), but the more we know about a plant and its activity then the better.
Secondly, the chemical complexity also makes it difficult to standardise the medicines and get precise doses of different compound groups. We can manipulate growing conditions to help this, but ultimately it is much more difficult to control than isolated compounds where dosage can be quantified to the milligram.
Herbal examples
Cannabis (Cannabis sativa)
Cannabis is a traditional remedy in many countries as far back as the copper age 3500–2300 BCE in China and after across Europe. You can read more about its fascinating history in our article, Cannabis: A folk remedy in Europe. In the last decade medical research and use of the plant has surged in popularity, in part due to the discovery of the endocannabinoid system and in part owing to cannabis’ ability to treat very difficult conditions with limited treatment options (9).
It was the cannabis industry that popularised terms such as ‘synergy’ and ‘entourage effect’ (10), after a multitude of studies showed there were significant differences in the effect of isolated CBD or THC (the active compounds in cannabis) both in medical efficacy and side effects (11,12).
For example, a study showed the full spectrum (most chemically complex) extract is more potent than cannabidiol (one of the heralded active compounds) alone. The research team stated “in stark contrast to purified CBD, the whole-plant extract provided a clear correlation between the anti-inflammatory and antinociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses” (12). Another study showed that just 0.2% of tetrahydrocannabinol markedly increased the bioavailability of cannabidiol, demonstrating that they work together (11). Tetrahydrocannabinol isolated can have horrible side effects such as paranoia, impaired memory, anxiety and in extreme cases psychosis, but is much safer in a balanced extract.
Medical cannabis is now legal in many countries including the UK, and it is a potent and famous example of how single compounds vary in toxicity and efficacy versus whole compound extracts. The attention is in part due to how strong the plant can be but also because of the vast resources dedicated to its research.
Turmeric (Curcuma longa)
A fantastic article “Turmeric, rather a lot more than curcumin” highlights the case of the compounds in the highly medicinal turmeric, often regarded as a panacea within herbalism (14). Curcumin is a compound found in turmeric that has incited vast interest with claims that it is responsible for turmerics medicinal properties, that can help with an array of conditions from mood disorders to arthritis and cancer. Consequently, curcumin is the subject of extensive research and is now widely available as an isolated extract. This isolation of a compound from a plant and dismissal of the whole plant in research exemplifies the increased reductionist approach to natural medicines.
In traditional Chinese medicine, turmeric is prepared using a water extract (decoction), which is interesting as curcumin is not water soluble. This suggests the biological activity and medicinal value in the rest of turmeric’s compounds. Phytochemical analysis has shown that beyondoutside of curcumin turmeric contains compounds with antibiotic, antitumour, anti-inflammaotry and antioxidant properties, showing there is far more to it than curcumin (15,16).
Curcumin alone has over 6000 citations, but there are far less on turmeric. Turmeric has over 300 compounds including tumerone, zingiberone, sugars, proteins, resins, volatile oils and an array of curcuminoids (13). It is believed that turmeric’s effectiveness for inflammatory conditions may at least in part be attributed to its immunomodulatory properties and the ability to affect multiple signalling pathways that conduct the inflammatory response. Turmeric affects multiple pathways including Nrf2, COX-2, NF-KB, LOX-5 (14). This diverse array of targets would not be possible to target with a single compound and it is chemical complexity that allows a process as complex as inflammation to be effectively mediated.
Conclusion
To summarise, it is clear there are many benefits to using full-spectrum extracts for medicine. Illness is complex and multifaceted and so it makes sense that medicines and treatment protocols reflect this. Though there is much research needed to understand the nuances of how things work together, medicinal plants offer both safe and effective medicine, and hold great promise for integration with conventional healthcare to maximise therapeutic potential of both treatment modalities and improve patient outcomes.
References
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- Pole S. Give herbs a chance | Evidence | Herbal Reality. Herbal Reality. https://www.herbalreality.com/herbalism/safety/give-herbs-a-chance/. Published October 23, 2024.
- Thompson E. Integrative medicine and how we can work together | Herbal projects | Herbal Reality. Herbal Reality. https://www.herbalreality.com/herbalism/herbal-projects/integrative-medicine-and-how-we-can-work-together/. Published May 21, 2024.
- Thomford NE, Senthebane DA, Rowe A, et al. Natural Products for Drug discovery in the 21st century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences. 2018;19(6):1578. https://doi.org/10.3390/ijms19061578
- Suckling CJ. The allure of targets for novel drugs. RSC Medicinal Chemistry. 2023;15(2):472-484. https://doi.org/10.1039/d3md00621b
- Efferth T, Koch E. Complex Interactions between Phytochemicals. The Multi-Target Therapeutic Concept of Phytotherapy. Current Drug Targets. 2010;12(1):122-132. https://doi.org/10.2174/138945011793591626
- Aracil A. The integration of biomedicine and herbal medicine: A comparison of cost and application | Western herbal. Herbal Reality. https://www.herbalreality.com/herbalism/western-herbal-medicine/the-integration-of-biomedicine-and-herbal-medicine-a-comparison-of-cost-and-application/. Published September 24, 2024.
- Lazarou R. Herbal quality and safety: What to know before you buy | Safety | Herbal Reality. Herbal Reality. https://www.herbalreality.com/herbalism/safety/herbal-quality-safety-what-know-before-you-buy/. Published August 28, 2024.
- Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nature Reviews Neurology. 2019;16(1):9-29. https://doi.org/10.1038/s41582-019-0284-z
- Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British Journal of Pharmacology. https://doi.org/10.1111/j.1476-5381.2011.01238.x
- Berthold EC, Kamble SH, Kanumuri SRR, et al. Comparative pharmacokinetics of commercially available cannabidiol isolate, Broad-Spectrum, and Full-Spectrum products. European Journal of Drug Metabolism and Pharmacokinetics. 2023;48(4):427-435. https://doi.org/10.1007/s13318-023-00839-3
- Gallily R, Yekhtin Z, Hanuš LO. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using & Cannabis & Extract Enriched in Cannabidiol. Pharmacology &Amp Pharmacy. 2015;06(02):75-85. https://doi.org/10.4236/pp.2015.62010
- Iweala EJ, Uche ME, Dike ED, et al. Curcuma longa (Turmeric): Ethnomedicinal uses, phytochemistry, pharmacological activities and toxicity profiles—A review. Pharmacological Research – Modern Chinese Medicine. 2023;6:100222. https://doi.org/10.1016/j.prmcm.2023.100222
- Peak. Turmeric: An old world, modern-day panacea or state-of-the-art sports medicine? | Western herbal medicine |. Herbal Reality. https://www.herbalreality.com/herbalism/western-herbal-medicine/turmeric-an-old-world-modern-day-panacea-or-state-of-the-art-sports-medicine/ Published August 4, 2024.
- Dehzad MJ, Ghalandari H, Nouri M, Askarpour M. Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials. Cytokine. 2023;164:156144. https://doi.org/10.1016/j.cyto.2023.156144
- Zhang HA, Kitts DD. Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases. Molecular and Cellular Biochemistry. 2021;476(10):3785-3814. https://doi.org/10.1007/s11010-021-04201-6