Artemisia annua L. is a common type of wormwood that belongs to the family of the Asteraceae. It is native to temperate Asia but naturalized throughout the world. The active chemical compound (a sesquiterpene lactone) extracted from the leaves and flowers of Artemisia annua.
Artemisinin is the active ingredient of A. Annua extracted from its leaves and flowers. Artemesinin and semi-synthetic derivatives made from artemisinin are used to produce combination therapies for malaria treatment. Animal studies have suggested that artemisinin and related compounds inhibit tumour growth and metastasis.
Efficacy
However, there is currently no evidence from clinical trials that the anticancer effects from animal studies translate into benefits for cancer patients. No clinical trials of A. annua and only two randomised clinical trial of artesunate, a semi-synthetic artemisinin derivate, are available.
Safety
Experiences from malaria treatment indicate a good tolerability of artemisinin-based drugs. In clinical studies, oral artemisinin and artesunate have been shown to be safe with no serious adverse effects. Artemisinin and its derivates influence the activity of cytochrome P450 Cyp3A4, CYP2C9, CYP1A2 and CYP2D6, although the clinical significance is unclear.
Artemisia annua (sweet wormwood, sweet annie, sweet sagewort, Chinese: qīnghāo) is a medicinal plant in the Asteraceae family, native to temperate Asia and now naturalized worldwide. Its bioactive compounds, mainly terpenoids, are produced by glandular trichomes found on the surface of stems, leaves and flowers. (Bhakuni 2001)
Note: Not to be confused with Artemisia absinthium (absinthe, wormwood).
Historically, A. annua was used in traditional Chinese medicine to treat fever. In the 1970s, researchers demonstrated antimalarial activity in animal models, leading to the isolation of artemisinin, now a cornerstone of malaria treatment. (van Agtmael 1999). After the WHO recommended artemisinin-based therapies in 2006, research expanded to explore other potential effects, including anticancer activity. (WHO 2006; Li 2010)
Ingredients
Artemisia annua contains numerous bioactive compounds, including sesquiterpenoids (notably artemisinin), triterpenoids, flavonoids, chromenes, and essential oils. (Bhakuni 2001) The composition of extracts depends on the extraction method. Alcoholic extracts generally contain higher levels of flavonoids and antioxidant activity, whereas aqueous extracts contain higher levels of various quinic acid derivatives and lower amounts of some flavonoids. (Carbonara 2012; Iqbal 2012; Weathers 2012)
Artesunate, dihydroartemisinin, and artemether are semisynthetic artemisinin derivatives which have been studied more extensively than artemisinin itself for potential anticancer effects.
Alleged indications
Artemisinin derivatives e.g., artesunate, artemether, dihydroartemisinin are regulated medicines used for malaria treatment.
Traditionally used for fever, headache, infections, and inflammatory conditions (MSKCC 2021) it has also been promoted as an anticancer treatment based on pre-clinical data, particularly for breast cancer and leukaemia (Singh 2001; Singh 2005).
Application and dosage
Tea or extracts made from Artemisia annua, which contain variable amounts of artemisinin. The Chinese Pharmacopoeia recommends 4.5-9 g of dried herb daily as a tea for fever and malaria. Artemisinin content varies widely (0.02-1.1% of dry weight).
Pharmaceutical artemisinin derivatives (e.g., artesunate, artemether), which contain standardized doses and are approved for malaria treatment. Artemisinin is usually administered orally as capsules, tablets, or herbal preparations. Artesunate is available as oral tablets and intravenous (IV) formulations.
No oral or intravenous artemisinin-derived product is currently approved as an anticancer treatment, and no safe or effective dosing regimen of A. annua or its derivatives has been established for cancer treatment in adults or children.
For malaria treatment, artemisinin derivatives are used in combination therapies at daily doses of approximately 100-200 mg.
In a dose-finding study of intravenous artesunate, the maximum tolerated dose was 18 mg/kg weekly. (Deeken 2018) However, serious adverse effects (CTCAE grade 3), including neutropenic fever and allergic reactions, occurred at doses as low as 12 mg/kg. Other reported adverse effects included diarrhoea, vomiting, hepatitis, and dizziness some severe (CTCAE 4).
Mechanism of anticancer action
Artemisinin and its derivatives (artesunate, dihydroartemisinin, artemether, and arteether) are considered the main compounds responsible for potential anticancer effects. Flavonoids may also contribute. (Firestone 2009; Efferth 2006).
Artemisinin and related compounds show anticancer activity through multiple mechanisms. Cancer cells vary in their sensitivity to these agents, and several genes associated with sensitivity or resistance have been identified, potentially serving as biomarkers for treatment response (Li 2008; Huang 2007). Beyond generating reactive oxygen species (ROS), artemisinin-related endoperoxides interact with specific molecular targets, affect key cell-cycle regulatory proteins, inhibit angiogenesis, and induce apoptosis (Firestone 2009; Efferth 2006; Huang 2007; Li 2007; Chen 2004).
Iron plays an important role in their cytotoxic effects by promoting ROS and carbon-centred radical formation. In many, though not all, cancer cell lines, iron enhances both the potency and AMDT, a sesquiterpene isolated from the hairy roots of A. annua, has demonstrated cytotoxic activity in lung, ovarian, liver, and cervical cancer cell lines, inducing apoptosis via a mitochondrial-dependent pathway (Zhai 2010).
No cross-resistance has been observed between different artemisinin-related compounds, suggesting that resistance to one agent does not necessarily confer resistance to another (Efferth 2011).
In animal models, artemisinin derivatives have inhibited tumour growth and metastasis and prolonged survival across a range of cancers. These effects generally required doses substantially higher than those used for malaria treatment, with intermittent high-dose regimens appearing more effective than continuous daily dosing (Bhakuni 2001; Firestone 2009; NMD 2021; MSKCC 2021).
Alleged indications
Apart from malaria, A. annua is also used in cases of fever, headaches, infections and inflammations). It has been claimed to kill cancer cells and to be especially effective in breast cancer and leukaemia
Legal issues
Artemisia annua is widely available over the counter as teas, capsules, tinctures, and extracts. In contrast, pharmaceutical artemisinin derivatives such as artesunate and artemether are regulated medicines used primarily for malaria and are not approved for cancer treatment.
No clinical trials with A. annua preparations are available. Limited clinical evidence from two trials reports a possible benefit of the semisynthetic derivative artesunate on cancer progression and recurrence, but the studies had significant methodological limitations, preventing firm conclusions about efficacy. (Zhang 2008; Krishna 2014).
In an RCT of 120 Chinese patients with unresectable non-small cell lung cancer receiving vinorelbine/cisplatin chemotherapy with or without artesunate, no significant differences were observed in overall survival, 1-year survival, or quality of life. However, the artesunate group showed a higher disease control rate (88.2% vs. 72.7%) and a longer time to progression (24 vs. 20 weeks). Findings are limited by differences in disease stage at baseline and the lack of blinded outcome assessment, resulting in a high risk of bias (Zhang 2008).
In a small double-blind, placebo-controlled RCT, 20 patients with colorectal cancer received artesunate (200 mg/day) or placebo for 14 days before curative surgery (Krishna 2014). No difference in tumour apoptosis was observed. During a mean follow-up of 42 months, tumour recurrence occurred in six placebo-treated patients compared with one artesunate-treated patient, although the placebo group had slightly more advanced disease at baseline.
Artemisinin derived drugs are available for the treatment of malaria. Except for two case reports, no major side effects have been reported in humans at doses used for the treatment of malaria but it is still unknown whether the higher doses that could be required for the treatment of cancer patients could cause major side effects.
It has been reported that the oral intake of A. annua may cause abdominal pain, bradycardia (abnormally slow heartbeat), diarrhoea, nausea, vomiting, decreased appetite, flu-like symptoms, fever, and decreased reticulocyte count (MSKCC 2021)
In a placebo-controlled study, oral intake of Artemisia extracts up to 300-600mg/day for 12 weeks in 14 patients with osteoarthritis of the hip and knee (Stebbings 2015) did not reveal any serious adverse effects according to CTCAE that were labeled “associated” with the therapy. Moderate adverse effects occurred almost exclusively at high doses (600mg/day) with gastrointestinal discomfort, as well as elevation of transaminases, back pain, and vomiting.
Topical application of A. annua may cause dermatitis (NMD 2021).
Artesunate
Clinical phase 1 and 2 trials have generally reported good tolerability in cancer patients but note that artesunate was administered concomitantly with chemotherapeutic agents, which makes it difficult to assess possible adverse effects specific to artesunate. (Strik 2024)
In a prospective uncontrolled trial of oral artesunate intake up to 200mg daily for 1-37 months in metastatic breast cancer patients, no serious adverse effects were observed according to the authors (von Hagens 2017) The adverse effects that occurred were blood count changes, dizziness and fatigue.
Hearing loss is another known side effect artesunate. A prospective phase 1 clinical trial in 23 breast cancer patients receiving 100-200mg oral artesunate for 4 weeks showed no dose-limiting audiotoxicity. (Koenig 2016)
The authors of a phase 1 trial (Deeken 2018) of intravenous artesunate in 19 patients with advanced solid tumours determined the maximum tolerated dose was 18mg/kg body weight per week. However, higher grade adverse effects such as neutropenic fever or allergic reactions (CTCAE grade 3) were already evident at 12mg/kg in the study. Other adverse reactions at higher doses included diarrhea, vomiting, hepatitis, and dizziness, some of which were also severe (CTCAE grade 4)
Interactions
Preclinical studies had suggested that artemisinin and its derivates could influence the activity of the cytochrome P450 enzymes CYP3A4 and CYP2C19.
One clinical study (Svensson 1998) on 9 healthy volunteers had found no effect of artemisinin on cytochrome p450 3A4 activity, an induction of CYP2C19 activity. Another clinical study (Asimus 2007) with 75 healthy volunteers, divided into 5 groups receiving different derivates of artemisinin, suggested the influence of artemisinin and its derivates on the activity of several cytochrome P450 enzymes, with unclear clinical significance. In this, artemisinin, artemether and dihydroartemisinin (from the prodrug artesunate) induced CYP3A4, artemisinin and arteether induced CYP2C19, artemisinin, dihydroartemisinin and arteether inhibited CYP1A2. There was a two-stage effect on CYP2D6 with an inhibition on day one and an induction on day 5 for the artemisinin and dihydroartemisinin group. The authors conclude, that “the magnitudes of the mean changes were generally low and are not expected to present a problem in the general patient population”
Contraindications
Known serious hypersensitivity (eg, anaphylaxis) (FDA 2020).
The first trimester of pregnancy is a relative contraindication due to potential teratogenic effects, although its safety was shown in clinical studies (Moore 2016).
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Citation
Behzad A, CAM Cancer Collaboration. Artemisia annua [online document], Jun 30, 2022.
Document history
Revised by the CAM Cancer Collaboration in October 2026. Revised in December 2021 by Ali Behzad. Assessed as up to date in June 2019, January 2015 and August 2013 by Barbara Wider. Updated in August 2012 by Klara Rombauts.
Summary first published in March 2011, authored by Klara Rombauts and Arne Heyerick
Next update due: October 2029.
Photos: mp47380087 from Mostphotos.com, licence via UiT The Arctic University of Norway.
