systematic review
Needle-based acupuncture is used in some detoxification settings. However, its efficacy for illicit drug use disorders remains uncertain because prior reviews often mixed comparator types, co-interventions, or non-needle modalities. This review aimed to evaluate needle-based acupuncture monotherapy using comparator-stratified meta-analysis.
The authors searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM/SinoMed, trial registries, and supplementary sources from inception to September 12, 2025. The quantitative synthesis was restricted to randomized trials of manual acupuncture, electroacupuncture, or needle-insertion auricular acupuncture delivered without concomitant pharmacotherapy or psychotherapy. Although the registered protocol allowed non-randomized comparative studies, none were pooled because of insufficient comparability and a higher risk of confounding. Sensitivity analyses excluded trials with moxibustion co-treatment.
Thirteen randomized trials (n = 1,027) were included in the meta-analysis. For the prespecified primary outcome of withdrawal severity at the end of treatment, acupuncture favored blank/no-acupuncture controls [g = −2.089, 95% confidence interval (CI): −2.869 to −1.309; τ² = 0.712; I² = 82.9%], but the prediction interval (PI) crossed the null (PI: −4.306 to 0.128). Against active non-acupuncture comparators, the pooled effect was imprecise (g = −1.70, 95% CI: −5.43 to 2.02; PI: −23.49 to 20.09). Against sham acupuncture, two comparisons yielded an imprecise estimate (g = −1.45, 95% CI −9.41 to 6.51), and no PI was estimated. Among secondary outcomes, anxiety favored acupuncture over blank/no-acupuncture controls (g = −1.537, 95% CI: −2.047 to −1.026; PI: −2.939 to −0.134), whereas evidence from sham-controlled studies was less certain (g = −0.998, 95% CI: −1.744 to −0.252; PI: −2.828 to 0.832). For depression outcomes, PIs crossed the null in both blank- and sham-controlled analyses. The certainty of the evidence was low to very low.
The authors concluded that acupuncture exhibited favorable average effects on withdrawal severity, but null-crossing PIs limited confidence in the reproducibility of these effects across different settings and treatment protocols. Anxiety was interpreted as a secondary finding. No serious acupuncture-related adverse events were explicitly reported, although surveillance was often passive or insufficiently described.
The review treats acupuncture as “effective” for illicit drug disorders by highlighting short-term improvements in craving or anxiety, while the outcomes that matter for addiction – abstinence, relapse, use frequency, and retention – show no reliable benefit.
This, I think, is a classic case of presenting a negative result as a positive finding!
The review explicitly found no consistent difference between acupuncture and comparators for substance use endpoints, and the apparent positive outcomes were limited by low-quality evidence and publication bias. By foregrounding surrogate outcomes and obscuring the lack of clinically decisive effects, the paper misleads readers into perceiving acupuncture as a viable monotherapy for drug use disorders. Yet the evidence does clearly not support that conclusion.
The effect of calcium, vitamin D, or combined supplementation on fractures and falls in adults were assessed in this systematic review and meta-analysis. Randomised clinical trials were eligible, if they compared calcium, vitamin D, or combined supplementation with placebo or no treatment in adults (≥18 years) not receiving drug treatment for osteoporosis. The primary outcome was the risk of any fracture. Secondary outcomes included the risk of hip fracture, non-vertebral fracture, vertebral fracture, and falling, as well as the total number of falls. Pairs of reviewers independently screened trials, extracted data, and assessed risk of bias using the second version of Cochrane’s risk of bias tool. Findings were synthesised using random effects meta-analyses and appraised using Grading of Recommendations Assessment, Development and Evaluation, with application of thresholds for absolute effects considered important.
The review included 69 trials involving 153 902 participants. Participants in most of the trials were community dwelling (87%) and not at high risk of fractures or falls (73%). For the primary outcome of any fracture, little to no effect was found from use of calcium supplements (11 trials, 9067 participants; risk ratio 0.91, 95% confidence interval 0.81 to 1.01; moderate certainty), vitamin D supplements (36 trials, 92 045 participants; 1.00, 0.95 to 1.06; high certainty), or combined supplementation (15 trials, 51 126 participants; 0.91, 0.84 to 0.99; high certainty). Calcium, vitamin D, or combined supplementation appeared to have little to no effect on other fracture and fall outcomes, based largely on moderate to high certainty of evidence. The findings remained robust after an extensive exploration of heterogeneity across multiple subgroup analyses. Evidence for high risk patients or those requiring residential care was limited for many outcomes for calcium monotherapy and for combined supplementation.
The authors concluded that, based on absolute risk reductions and thresholds considered clinically meaningful, this review found little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls.
An accompanying BMJ editorial points out that observational studies have associated low dietary calcium and low serum levels of vitamin D with low bone density and falls. Consequently, calcium, vitamin D, or combined supplementation has been widely promoted for preventive musculoskeletal health in older adults…
Th editorial concludes that other interventions, such as balance and resistance exercise, and several multicomponent interventions (eg, combining exercise, hazard assessment, or education with other interventions tailored to risk assessment) have been shown to offer meaningful prevention of falls and falls related injuries.
This new systematic review is a prime example for the slaying of a beautiful hypothesis with an ugly fact. But all is not negative – think of the money that can now be saved and put to better use!
Insomnia is a prevalent disorder that is associated with substantial impairment. Homeopathy has been proposed as a complementary treatment for insomnia, but its clinical effects remain uncertain.
This systematic review assessed the efficacy, effectiveness, and safety of homeopathic treatments for insomnia. Prospective comparative studies evaluating any homeopathic preparation for insomnia were included. Searches in MEDLINE, EMBASE, seven additional databases, and three trial registries were conducted through August 2025. Risk of bias, intervention complexity, model validity, and pragmatism were assessed using respectively RoB 2, ROBINS-I, iCAT, MVHT, and RITES. Data were synthesized using random-effects meta-analyses, and certainty of evidence was evaluated using GRADE.
Eight randomized controlled trials (RCTs; n = 364 participants) and four non-randomized studies (NRSIs; n = 517) met the inclusion criteria. In adults, sleep quality (MD = −2.6 points; 95% CI −5.5 to 2.6; low certainty) and insomnia severity (MD = −3.2; 95% CI −5.68 to −0.72, moderate certainty) were reported in one RCT each. For total sleep time, the pooled MD of three RCTs was 0.65 hours (95% CI −0.9 to 2.2; low certainty). In children, one open-label RCT suggested a difference in insomnia severity, but certainty of evidence was very low. Adverse events were rarely reported, resulting in low certainty evidence.
The authors concluded that the current evidence is mainly limited by imprecision and risk of bias. The available evidence does not allow firm conclusions regarding the effects of homeopathy for insomnia. High-quality, replicated trials with systematic adverse event monitoring are needed.
15 years ago, I published a similar review entitled “Homeopathy for insomnia and sleep-related disorders: a systematic review of randomised controlled trials” (Focus on Alternative and Complementary Therapies Volume 16(3) September 2011 195–199)). Here is its abstract:
The aim of this review was the critical evaluation of evidence for the effectiveness of homeopathy for insomnia and sleep-related disorders. A search of MEDLINE, AMED, CINAHL, EMBASE and Cochrane Central Register was conducted to find RCTs using any form of homeopathy for the treatment of insomnia or sleep-related disorders. Data were extracted according to predefined criteria; risk of bias was assessed using Cochrane criteria. Six randomised, placebo-controlled trials met the inclusion criteria. Two studies used individualised homeopathy, and four used standardised homeopathic treatment. All studies had significant flaws; small sample size was the most prevalent limitation. The results of one study suggested that homeopathic remedies were superior to placebo; however, five trials found no significant differences between homeopathy and placebo for any of the main outcomes. Evidence from RCTs does not show homeopathy to be an effective treatment for insomnia and sleep-related disorders.
The findings of the two reviews are remarkably similar. For the following reasons, I find this notable:
- One would have hoped that 15 years are a long enough time for clarifying the issue, particularly as insomnia is not an unimportant condition for homeopathy.
- The new review is authored by well-known proponents. It seems unexpected that they (almost) go as far as admitting that the evidence for homeopathy as a treatment for insomnia is not positive.
- We have here, I think, a textbook example of how proponents of homeopathy prettify results that do not confirm their belief.
SO FAR, SO GOOD.
But now consider this: There are two further reviews of the same subject!
The first is entitled “Homoeopathy for insomnia: A meta-analysis of clinical evidence – Journal of Integrated Standardized Homoeopathy“. Here is its abstract:
Objectives: Insomnia is a prevalent sleep disorder characterised by challenges in initiating, maintaining or achieving restorative sleep, resulting in compromised daytime functionality. Traditional therapeutic modalities frequently encompass pharmacological treatments, which may have adverse effects and potential for dependency. Numerous patients pursue alternative methodologies, such as homoeopathy, which is attributed to its personalised, holistic and non-invasive treatment framework. This thorough examination assesses the effectiveness of homoeopathy in promoting better sleep quality and overall wellness in people with insomnia by analysing randomised controlled trials (RCTs).
Material and Methods: This meta-analysis sought to ascertain whether homoeopathy induces a statistically significant enhancement in the management of insomnia, concentrating on aspects of sleep quality, duration and general well-being. All RCTs addressing insomnia treated with homoeopathic interventions were included in this review. All studies were meticulously documented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three evaluators independently reviewed and compiled the literature, extracting comprehensive details regarding participants, study designs, therapeutic interventions and follow-up pertaining to homoeopathic treatment. The primary outcome of the investigation was disease assessment based on sleep diary scores, with an additional outcome being the enhancement of quality of life.
Results: The analysis revealed that homoeopathic remedies exhibited statistically significant improvement over placebo in the management of insomnia. The overall pooled effect size, standardised mean difference (random), was −0.60, standard error (random) was 0.42 and confidence interval (random) at 95% ranged from −0.93 to −0.26. The risk of bias was assessed for all studies.
Conclusion: This meta-analysis shows that homoeopathic remedies are effective in treating insomnia, but more studies are required for accuracy.
The last review is entitled “Effectiveness of Homeopathic Interventions for Insomnia and Sleep Disorders: A Systematic Review and Meta-Analysis“. Here is its abstract:
Insomnia is a common sleep disorder, and many individuals seek alternative treatments like homeopathy. However, evidence for its effectiveness remains controversial. This systematic review and meta-analysis evaluated the effectiveness of homeopathic interventions for insomnia and sleep-wake disorders. A comprehensive search of PubMed, MEDLINE, CINAHL, and the Cochrane Library was conducted for studies published between 2010 and 2025. We included randomized controlled trials (RCTs) and non-randomized studies involving adults (≥18 years) with primary insomnia receiving any homeopathic intervention compared to placebo, no treatment, or active care. Primary outcomes included validated sleep quality measures (e.g., Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI). Four reviewers independently performed study selection, data extraction, and risk of bias assessment using RoB 2.0 and ROBINS-I. A random-effects meta-analysis was conducted for controlled trials, and a narrative synthesis for non-randomized studies. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). The search yielded 1304 records; 12 studies (nine RCTs and three non-randomized) met inclusion criteria. Meta-analysis showed a large, statistically significant positive effect of homeopathy on sleep outcomes (SMD = 0.81, 95% CI [0.24, 1.38], p = 0.0055), with substantial heterogeneity (I² = 86.04%) and publication bias (Egger’s test, p = 0.0079). Most studies had high or critical risk of bias, and overall certainty was low. Homeopathic interventions showed a large positive effect on sleep outcomes, but due to high bias, heterogeneity, and publication bias, evidence remains low-certainty and insufficient to support effectiveness. High-quality RCTs are needed.
What should we make of this?
We now have two reviews concluding that there is no good evidence and two implying that homeopathy is effective for insomnia! This clearly demonstrates how easy it is to mislead the public with seemingly rigorous reviews.
I must say, I pity all the interested lay people who are trying to make sense of this mess.
How can they arrive at the best available, most reliable evidence?
We have here, I think, another textbook example; one of how important it is to run reality checks. But surely, we cannot possible ask of a lay person to understand why the last two reviews are badly misleading. What we need is an accessible tool for differentiating the science from the pseudoscience, the reliable from the unreliable.
Unfortunately, such a tool does not exist. But there are a few indicators:
- Is the journal that published the review reputable?
- Are the authors affiliated to reputable institutions?
- Do the authors have a history of critical analysis or one of uncritical promotion?
- Do they explain clearly and provide the essential details of their work?
These are issues that lay people might be able to check relatively easily. The above 4 reviews demonstrate that using them does not always provided an entirely clear cut-off. However, it might give some valuable pointers into the right direction.
Spinal manipulative therapies, including chiropractic and osteopathic maneuvers, are widely practiced for musculoskeletal complaints. However, serious complications such as cerebrospinal fluid (CSF) leak with subsequent intracranial hypotension (IH) have been described. The pathophysiological mechanism is presumed to involve mechanical stress on the spinal dura during high-velocity movements, leading to dural tears, particularly in the cervicothoracic region.
A team of Italian neuroscientists conducted a scoping review in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines, through a comprehensive search of PubMed and Scopus. They complemented the review with an illustrative case from their own institution.
The researchers identified 21 eligible papers, including 21 patients with IH following spinal manipulation. Most patients were women (81%), aged 29-54 years, and the majority underwent cervical maneuvers.
SMT techniques vary, most often involving high-velocity cervical maneuvers. The most frequent were axial tension with rotation in seven cases (33.3%), unspecified cervical manipulation in four cases (19%), and thoracic spinal manipulation in two cases (9.5%). Less common single-case techniques included rotation with hyperextension, combined cervical and thoracic mobilization, axial tension with lateral flexion, and occipital/shoulder tension technique (n = 1 case each).
Symptom onset was typically within the first week, and all presented with orthostatic headache, often accompanied by nausea, neck pain, tinnitus, or visual disturbances. Neuroimaging consistently revealed features of IH, with pachymeningeal enhancement and subdural collections as the most frequent findings; spinal imaging frequently demonstrated extradural CSF collections. Management was conservative in about one-third of cases, but most required epidural blood patching, which was effective in the majority. Surgical repair was necessary in rare, refractory cases, particularly in the presence of structural spinal abnormalities. Overall prognosis was favorable, with 95% of patients achieving full recovery.
The authors’ illustrative case highlights the potential for severe complications such as subdural hematomas and recurrence if the underlying leak is not addressed:
A 65-year-old patient without a previous history of headache presented with a progressively worsening headache, with orthostatic features, poorly responsive to medical therapy, that has lasted for the past 20 days. The patient denied any recent trauma. He reported having undergone cervical osteopathic manipulations within the past 3 months for recurrent cervicalgia. A brain MRI without contrast was performed, showing a large bilateral subdural hematoma with significant mass effect on the cortical gyri. The patient was admitted to the emergency department and underwent neurosurgical evacuation of a bilateral chronic subdural hematoma via burr holes. Subsequently, endovascular embolization of the middle meningeal arteries was performed as an adjunctive treatment to reduce the risk of recurrence. The surgical procedure was performed without complications. A cranial CT scan showed a reduction in the volume of the hematoma. Therefore, the patient was discharged. However, after a transient improvement in the symptoms, the patient continued to present a fluctuating headache without positional features, with four to five episodes per month. He was readmitted to our clinic and, upon arrival at the ER, a head CT scan showed an increase in pneumocephalus and a recurrence of the hematoma. The following day, an MRI of the neuraxis with contrast was performed, which revealed radiological findings suggestive of IH: pachimeningeal enhancement, subdural fluid collection, dural venous engorgement, cervical spinal longitudinal extradural collection, and effacement of the suprasellar cistern. The Bern score was 7. Given these findings, a surgical revision of the previous burr holes was performed without periprocedural complications. After the first day, a non-targeted epidural blood patch (EBP) was performed under local anesthesia by injecting 16 mL of autologous blood into the L3–L4 epidural space. The procedure was uneventful. A cranial CT scan showed satisfactory surgical outcomes, highlighting a reduction in the volume of the hematoma and of the pneumoencephalus. The patient was subsequently discharged with complete resolution of the headache.
The authors concluded that clinicians should recognize the possibility of CSF leaks after spinal manipulation, especially in patients with new-onset orthostatic headache.
I feel compelled to point out that, considering the multiple risks of upper spinal manipulations and the almost total lack of evidence of benefit from such treatments, the risk/benefit balance of spinal manipulation is clearly not positive. It follows, I think, that it would be wise for patients not to allow such therapies being carried out, and for healthcare professionals to discourage them.
When a top journal like PNAS (Procedings of the Nationsl Academy of Science) publishes an article entitled “What’s the science behind acupuncture?“, I must take notice. Here is my take on the (sadly disappointing) effort:
My very short summary of the paper (I do encourange my readers to read it in full)
The article starts from the premise that acupuncture is proven to work, an assumption that – as we will see in a minute – is not based on sound evidence. It describes the evolution of acupuncture from a traditional practice rooted in ancient concepts like “qi” and “meridians” to a modern medical treatment increasingly validated by science. It argues that practitioners like Min Chen are today able to provide evidence-based explanations for their work. While early clinical trials were plagued by the “sham” acupuncture paradox, the text argues that more recent, rigorous studies and technological projects are bridging the gap between Eastern philosophy and evidence-based medicine, suggesting that acupuncture’s effects are physiological realities rather than mere placebo.
My concerns of the paper
The article attempts to bridge the gap between Traditional Chinese Medicine (TCM) and conventional medicine suggesting that several anatomical discoveries “correspond” to ancient meridians. This, however, is a post hoc ergo propter hoc fallacy. Finding a morphological structure (e.g. fascia) and claiming it represents the meridian system ignores that meridians were conceptualized as functional energetic conduits, not anatomical vessels. Citing an 80% overlap between acupoints and connective tissue planes lacks specificity. Given the ubiquity of connective tissue in the human frame, any randomized point on the body would likely “overlap” with a tissue plane, rendering the “meridian” map a possible exercise in pattern-seeking rather than anatomical discovery.
The paper acknowledges the “most puzzling” finding that sham acupuncture often produces results comparable to “true” acupuncture. This, it would seem to me, invalidates the foundational TCM theory of specific “acupoints” and “meridians” is invalidated. Yet, the article suggests that sham acupuncture is “not a true placebo” because it also triggers biological pathways. If needling anywhere produces an effect, acupuncture is merely a generalized, non-specific neuro-modulatory stimulus.
The article quotes Chen on “harmonizing organ functions” and “regulating qi” as well as researchers referring to “fibroblast activation” and “vagus nerve stimulation”. The author seems to consider both to be true; yet they seem mutually exclusive. Translating metaphysical concepts into physical phenomena does not “validate” the original theory but merely replaces it.
The article employs the opioid crisis to justify the rise of acupuncture. Yes, the need for non-pharmacological pain management is urgent, but clinical necessity does not equate to scientific validity. The text quotes the “lasting benefits” observed in some meta-analyses without discussing the often fatal flaws in these papers. Furthermore, it fails to cite the substantial body of evidence suggesting that acupuncture is not effective. Moreover, it hardly mentions the small effect sizes and hence limited clinical usefulness found in the positive studies.
The final section of the paper essentially rebrands acupuncture as “bioelectronic medicine”. If its mechanism of action is purely the electrical stimulation of the vagus nerve or the release of endogenous opioids, then the TCM concepts are all but superfluous. If a cheap and wearable TENS unit is more or less equivalent, the “meridian” and “qi” myths are obsolete.
In summary, the paper reads, I fear, only marginally better than a Chinese government promotional text – most disappointing for an article published in a journal of high standing. It attempts to preserve the cultural prestige of TCM while stripping it of its internal logic in order to make it compatible with science. For acupuncture to gain a true “scientific footing”, research must, in my view, move beyond finding “tantalizing” correlations. It should address fundamental problems, e.g.:
- As long as we have no convincing proof that acupuncture works beyond placebo, discussions about its mechanisms are futile.
- If qi, acupoints and meridians are illusions and irrelevant for the clinical outcome, then the science is not validating acupuncture but merely re-discovering a well-known non-specific form of peripheral nerve stimulation.
The Spanish Agency for Medicines and Medical Products (AEMPS) has just published a comprehensive technical report entitled “Homeopathy and Homeopathic Products: Evaluation of Evidence on Their Efficacy and Safety”, which categorically concludes that there is no scientific evidence supporting the efficacy of homeopathy as a therapeutic tool. After a systematic review of scientific literature and evaluations by state agencies internationally, the report states that the observed effects are comparable to placebo.
The report, which analyzed 64 systematic reviews published since 2009, highlights that most studies suggesting benefits from homeopathy have low methodological quality, often invalidated by small samples, short follow-up periods, or biases in randomization. Furthermore, it notes that as the quality and rigor of clinical trials increase, the supposed effect of homeopathy diminishes until it disappears entirely.
From a scientific standpoint, the principles of homeopathy clash with the laws of physics and current pharmacology. In typical dilutions like 12 CH—where one part of the original substance is mixed with 100 parts of solvent twelve times consecutively—it is mathematically impossible for a single molecule of the original ingredient to remain in the preparation, breaking any cause-and-effect relationship between the product and the therapeutic effect.
To illustrate this disproportion, the report points out that a dilution of just 6 CH (far less extreme than 12 CH) equates to dissolving a packet of sugar in the entire Mediterranean Sea. For this reason, the AEMPS classifies theories like “water memory”—the belief that the liquid retains the properties of a substance even without its molecules—as empirically baseless postulates that challenge scientific and rational thinking.
In compliance with European and national regulations, the AEMPS has completed a regularization process that has resulted in the market withdrawal of numerous products. As of the report’s publication date, no homeopathic product with authorized therapeutic indications exists in Spain. The 976 that remain registered did so via a simplified procedure, based on extreme dilutions ensuring the preparation’s innocuousness, which does not require proof of therapeutic effect and legally prohibits any therapeutic claims on labeling.
Spain aligns with a global trend of health institutions adopting critical stances:
- United Kingdom: The Science and Technology Committee recommended halting public funding and requiring labeling warnings about lack of efficacy.
- Australia: The National Health and Medical Research Council concluded that homeopathy should not be used for chronic or serious diseases.
- France: The Haute Autorité de Santé eliminated public reimbursement for these products in 2021 due to lack of demonstrated efficacy.
- Germany: Approval is expected in 2026 for the definitive removal of homeopathy coverage from statutory health insurance.
- United States: The Food and Drug Administration (FDA) considers these products “unapproved new drugs,” and the Federal Trade Commission requires warnings that there is no scientific evidence of their functioning.
Although there is a popular belief that these preparations are innocuous because they are “natural,” serious adverse reactions have been reported, including poisonings from poor dosing and infant deaths linked to teething products in other countries.
However, the AEMPS warns that the main associated risk is the abandonment or delay of proven effective medical treatments. Citizens opting for homeopathy to treat serious or chronic conditions may endanger their health by replacing evidence-based therapies with products lacking such evidence.
The AEMPS report reaffirms the Ministry’s commitment to public health protection and evidence-based medicine. In line with other international agencies, it emphasizes the need for transparent information so citizens can make safe health decisions. The conclusion of the report is firm:
Given the lack of evidence of efficacy, homeopathy cannot be considered a valid therapeutic alternative, and its use must not lead to delaying or abandoning treatments proven to be effective.
We all know, I think, what homeopaths say about homeopathy. We also know what everyone else says about it. And the two set of opinions could not be more different. In this context, it might be interesting to learn what writers have to say about the subject. Here is a list of quotes from the non-medical, non-scientific literature (I am sure there are many more; if you know some, please let me know):
Boyd, W. (Restless, 2006)
“She had a small leather case of homeopathy remedies, Nux Vomica, Pulsatilla, Arnica, that she treated like a traveling reliquary.”
Coetzee, J.M. (Elizabeth Costello, 2003)
“He is a believer in homeopathy, in the healing power of water, in the memory of water. He is a man of the eighteenth century, really.”
Cunningham, M. (The Hours, 1998)
“She has tried everything: homeopathy, psychotherapy, prayer. She is a woman who lives in the hope of a miraculous adjustment.”
Enright, A. (The Gathering, 2007)
“My mother had a great belief in homeopathy, which is just a way of saying she had a great belief in nothing at all, provided it came in a very small bottle.”
Franzen, J. (The Corrections, 2001)
“Enid was deep into a phase of homeopathy, convinced that a decillionth of a gram of honeybee sting would cure her husband’s tremors.”
Márquez G.G. (“Serenade: How My Father Won My Mother”, 2001)
“…devoted his talent as an autodidact to a science on the decline: homeopathy.”
Hustvedt, S. (The Blazing World, 2014)
“He was the kind of man who treated his neuroses with homeopathy and his physical ailments with intense, silent resentment.”
McEwan, I. (Solar, 2010)
“He had no time for homeopathy, which he considered a form of witchcraft for people who were too polite to carry crystal wands.”
O’Farrell, M. (Instructions for a Heatwave, 2013)
“She kept a kit of homeopathy in her bag, tiny glass vials of white pills that looked like the breath of ghosts.”
Self, W. (How the Dead Live, 2000)
“Lily’s faith in homeopathy was such that she believed if she diluted her own death enough, she might eventually become immortal.”
St. Aubyn, E. (At Last, 2011)
“He had reached that stage of desperation where even homeopathy seemed like a robust and evidence-based option.”
H.G. Wells (Tono-Bungay, 1909)
“By the time my uncle had taken to homeopathy, I realized that his faith in science was of a very elastic kind.”
George Bernard Shaw (Preface to The Doctor’s Dilemma, 1906)
“I have a faith in homeopathy that would make a Harley Street physician shudder, though I suspect it rests less on evidence than on temperament.”
Thomas Mann (The Magic Mountain, 1924)
“He spoke of homeopathy with a curious mixture of irony and conviction, as though the less there was of it, the more there must be.”
Aldous Huxley (Eyeless in Gaza, 1936)
“She placed her trust in homeopathy, preferring infinitesimal certainties to the gross invasions of modern medicine.”
Doris Lessing (The Golden Notebook, 1962)
“She was experimenting with diets and homeopathy, as if the body might be coaxed into sanity by gentler means.”
Margaret Atwood (Cat’s Eye, 1988)
“My mother believed in homeopathy, in small doses and invisible forces, which seemed to me another way of saying she believed in hope.”
Zadie Smith (White Teeth, 2000)
“He dabbled in homeopathy, convinced that the less substance there was, the more profound the cure.”
David Lodge (Therapy, 1995)
“I tried homeopathy for a while, but it seemed to require a belief in something so small it might not exist at all.”
Hilary Mantel (Giving Up the Ghost, 2003)
“Homeopathy offered the promise of healing without intrusion, a whisper of cure rather than a command.”
Martin Amis (The Information, 1995)
“He regarded homeopathy as a joke that had somehow outlived the punchline.”
______________________
It seems to me that, when it comes to homeopathy, the writers tend to agree with the scientists.
Some papers on so-called alternative medicine (SCAM) are such that I am almost lost for words. Here is the abstract of such an article:
Background: Autism Spectrum Disorder is a complex neurodevelopmental condition with characteristic
challenges like persistent deficits in social communication, restricted and repetitive behaviors, sensory
processing anomalies. Defined by DSM-5criteria, it affects about 1in 100 children globally and 1in 36 in
united states and poses a significant burden for families and healthcare systems. Research on homoeopathy
and Bach flower Remedies as adjunctive or primary therapies has often explored by families and clinical
interest in complementary and alternative medicine for additional support.
Materials and Methods: A comprehensive study of related review articles, related different components
of Autism spectrum disorder treated with homeopathy treatment, Bach Flower Remedies and
complementary medicine in children were search out. Databases search is PubMed, Google Scholar,
ResearchGate and Web of Science, Scopus and Homoeopathic journal.
Result: Reviewed evidence indicates that no systematic studies have been done to manage autism
spectrum disorder with Bach flower Remedies as an adjuvant or primary treatment along with
homoeopathy. Although individualized homoeopathic treatment has promising results in reducing core
and associated symptoms in children including improvement in social interaction, hyperactivity,
communication and behavioral regulation. Although there is less data available thorough trails, Bach
Flower Remedies especially Rescue remedy that have help in treating the emotional dysregulations and
anxiety that are frequently connected with autism spectrum condition.
Conclusion: The available clinical data on autism spectrum with homoeopathy and Bach flower remedies
is not enough to provide new and sufficient evidence. To overcome this more well-designed study of RCT
and larger sample with standardized procedures will be able to help to this rising burden of autism
spectrum disorder.
In the article itself, the authors state the following: “This review article indicates that both homoeopathy and Bach Flower Remedies are promising adjunct intervention in treatment of Autism spectrum disorder in children especially marked improvement in social interaction, communication, behavioural rigidity, emotional dysregulation and sensory processing. Based on the reviewed data from case series, controlled clinical trials and systematic reviews it can be state that individualized homeopathic treatment leads to clinically relevant improvement in core and associated symptoms of autism spectrum disorder.
Studies on Bach flower remedies specifically in autism spectrum disorder are very less but it suggests that Bach flower remedies offer practically accessible intervention for emotional and behavioural dimension mostly in anxiety, emotional dysregulation, sensory hyperactivity and resistance to change. Evidence from controlled trials and clinical studies shows a statistical and significant in symptom.
Homoeopathy and Bach flower remedies should not replace evidence-based behavioural and development intervention for autism spectrum disorder, but rather be investigation as complementary modalities within an integrative care framework. Despite of growing clinical observations, the field of homoeopathy and Batch Flower remedies in autism spectrum disorder is characterised by substantial and identifiable research gaps that limit the formulation of evidence-based clinical guidelines and urgent research priorities include the multicentric, double-blind RCTs with standardised diagnostic criteria and validated core outcome sets; longitudinal follow-up.”
Bearing in mind that this comes from the “Head of the Department, Department of Practice of Medicine, Bharati Vidyapeeth (Deemed to beUniversity), Homoeopathic Medical College”, this is remarkably embarrassing!
Why?
The review is badly written and poorly done. More importantly, according to the data provided by the authors, there is only one rigorous RCT. Here is its abstract:
Objective: To evaluate the effectiveness of Bach flower remedies in the treatment of children with attention deficit hyperactivity disorder (ADHD), in a double blind prospective controlled study.
Methods: Fourty Children with ADHD, aged 7-11 years, diagnosed according to the DSM criteria, were randomised to Bach flower remedies or placebo treatments for a period of 3 months. Children’s performance was evaluated by the teacher before commencement of treatment and subsequently each month during the study period.
Results: Bach flower remedies have no statistically significant effect when compared to placebo in the treatment of children with ADHD. There was a significant correlation between treatment duration’s and improvement of performance, with no difference between the treatment group compared to the placebo.
Conclusions: There is no statistically significant difference between the effects of Bach flower remedies compared with placebo in the treatment of children with ADHD.
If a head of department nonetheless concludes that “both homoeopathy and Bach Flower Remedies are promising adjunct intervention in treatment of Autism spectrum disorder in children especially marked improvement in social interaction, communication, behavioural rigidity, emotional dysregulation and sensory processing”, it is, I fear, high time to replace him.
Today, there is a strong scientific and medical consensus that homeopathy lacks reliable evidence of efficacy. Many of the strongest rejections come, after independent evaluations of the evidence, from national and international scientific bodies of undoubted repute. Here is my list:
- Advertising Standards Authority (UK) The ASA requires that efficacy claims for homeopathic products be supported by robust clinical evidence and has ruled that unsupported claims are misleading.
- American Academy of Pediatrics (USA) Warns that unproven alternative treatments, including homeopathy, should not delay or replace effective medical care, particularly in children.
- American College of Medical Toxicology & American Academy of Clinical Toxicology (USA) Jointly stated “no evidence exists” homeopathy is effective, noting it can be harmful by delaying evidence-based care; they recommended “against using homeopathic treatment for disease or prevention.”
- American Medical Association (USA) Issed statements that there is “no good-quality evidence” homeopathy is effective for any condition and opposed its integration into mainstream practice.
- Argentine Medical Association (AMA, Argentina) The AMA has criticized homeopathy’s inclusion in medical practice, stating it lacks scientific evidence and warning against its promotion as a valid treatment.
- Belgian Health Authority The Belgian Federal Public Service Health halted reimbursement for homeopathy in 2020, following advice from the College of Physicians that it lacks scientific evidence.
- Canadian Health Authorities Health Canada mandates warning labels on unlicensed claims: “This product is neither approved nor authorized for any indication,” aligning with evidence that homeopathy lacks reliable clinical support.
- Canadian Medical Association (CMA) Via editorials in its journal (CMAJ), the CMA has condemned the licensing of homeopathy as a “loophole” that implies efficacy without scientific proof, stating it “makes a joke of the regulatory process.”
- Chief Medical Officer for England (Dame Sally Davies) Publicly called homeopathic preparations “rubbish” that function only as placebos with no therapeutic benefit beyond psychological effects.
- European Academies’ Science Advisory Council (EASAC) Issued a 2017 statement finding “no evidence that homeopathic products are effective” and reiterated that explanations for homeopathy’s efficacy are “scientifically implausible.”
- Federal Trade Commission (USA) Requires that homeopathic products must not claim effectiveness without evidence; otherwise, they must clearly state a lack of scientific support.
- Federation of American Societies for Experimental Biology (FASEB) Asserted “no convincing evidence” for homeopathy’s clinical efficacy, as its mechanisms contradict established chemistry and physics.
- Food and Drug Administration (USA) States “No homeopathic product is FDA-approved”; products are not reviewed for safety or effectiveness. The FDA also warns they may pose risks.
- French Academy of Medicine Rejected homeopathy as scientifically invalid, stating its theoretical basis and clinical evidence are inadequate or absent.
- German Medical Association (Germany) In 2020, removed homeopathy from the model further education curriculum for doctors, declaring it “is not a medical procedure based on scientific findings.”
- House of Commons Science and Technology Committee (UK) In its 2010 report, concluded “the systematic reviews and meta-analyses conclusively demonstrate that homeopathic products perform no better than placebos.”
- Medicines and Healthcare products Regulatory Agency (UK) Followed committee advice by restricting licensing; homeopathic products should not make medical claims without evidence and are no longer endorsed as medicines.
- National Cancer Institute (USA) States homeopathy has “not been shown to be effective” for cancer treatment or symptom relief, with no rigorous studies supporting benefit beyond placebo.
- National Health and Medical Research Council (NHMRC, Australia) After reviewing over 1,800 studies, it concluded “there are no health conditions for which there is reliable evidence that homeopathy is effective.”
- National Health Service (NHS, England) Formally stated “no NHS funding will be spent on homeopathic medicines,” with guidance that homeopathy performs “no better than placebos.”
- National Institute for Health and Care Excellence (UK) NICE does not recommend homeopathy in any clinical guideline and bases its recommendations on the best available evidence.
- Royal Society (UK) Numerous Fellows have publicly criticized homeopathy, and the Society has supported evidence-based medicine principles incompatible with homeopathy’s claims.
- Russian Academy of Sciences Described homeopathy as “pseudoscience” with principles that “contradict known laws of chemistry, physics, and biology.”
- Spanish Medical Associations (Collegiate Medical Organization of Spain) In 2018, rescinded recognition of homeopathy as a “medical procedure,” declaring it “not scientifically sound.”
- Swedish Medical Association The Swedish Medical Association and National Board of Health declared homeopathy scientifically unfounded in 2010, advising against its use in healthcare.
- Swiss Academy of Medical Sciences Concluded homeopathy lacks scientific evidence and should not be reimbursed by health insurance.
- Swiss Federal Office of Public Health After a 2005-2011 review, it rejected renewed inclusion in basic health insurance (though it was later reintroduced in 2017 under specific political conditions).
- World Health Organization (WHO) Explicitly stated homeopathy “should not be used” for serious diseases like HIV, tuberculosis, or malaria, warning reliance “can be dangerous.”
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And what about institutions supporting homeopathy? I am aware of just one:
- Ministry of AYUSH (India) “Homoeopathy is a cost-effective system of medicine and is widely practiced for both acute and chronic conditions.”
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Across decades of systematic reviews and independent evaluations by scientific and medical authorities worldwide, no credible evidence has emerged to support the efficacy of homeopathy. Its principles conflict with well-established scientific laws, and its effects are indistinguishable from those of placebo in rigorous studies. The broad convergence of expert opinion is therefore this: homeopathy has no effects beyond placebo. Its continued use represents a divergence from evidence-based medicine, and reliance on it, particularly as an alternative to effective care, poses a clear risk to public health.
In recent decades, acupuncture has attracted extensive research spanning an astonishingly wide array of medical conditions, from chronic pain and neurological disorders to infectious diseases and psychiatric ailments. However, the proposed mechanisms of action—ranging from peripheral sensory stimulation to central nervous system modulation—fail to provide a coherent, biologically plausible explanation for efficacy across this disparate spectrum (Zhao et al., 2022; WHO, 2003).
The aim of this post is to examine the breadth of published acupuncture trials, delineate the leading scientific hypotheses for its mode of action, and outline the profound implausibility of these mechanisms universally applying to such varied pathologies, ultimately framing acupuncture as non-specific rather than a specific therapeutic modality (Meissner et al., 2019; Ernst, 2018).
Acupuncture has been subjected to thousands of randomized clinical trials (RCTs) and systematic reviews across virtually every medical specialty. A comprehensive 2022 evidence map published in BMJ Open synthesized 120 systematic reviews, encompassing 1,402 individual RCTs and addressing 77 distinct conditions within 12 broad therapeutic categories (Zhao et al., 2022). These categories include neurological disorders, musculoskeletal conditions, cardiovascular diseases, and beyond, reflecting a research enthusiasm that transcends conventional biomedical boundaries.
Neurological applications dominate, with trials targeting stroke sequelae such as hemiplegia and aphasia, vascular dementia symptoms, migraines, tension headaches, and facial nerve palsies like Bell’s palsy (Li et al., 2022; Zhao et al., 2022; WHO, 2003). Musculoskeletal trials are equally prolific, examining low back pain, knee osteoarthritis, fibromyalgia, tennis elbow (lateral epicondylitis), sciatica, shoulder periarthritis, rheumatoid arthritis, and even gouty arthritis (Li et al., 2022; Zhao et al., 2022; Choi et al., 2019; Lam et al., 2020; WHO, 2003). Cardiovascular research has probed essential hypertension, primary hypotension, and pain from thromboangiitis obliterans (Shanghai Medical Clinic, 2025; WHO, 2003). Gynecological and obstetric domains feature prominently, including dysmenorrhea, labor induction, breech presentation correction, pregnancy-related nausea and vomiting, and fertility enhancement (e.g., improved clinical pregnancy rates in IVF protocols) (Zhao et al., 2022; Shanghai Medical Clinic, 2025; Smith et al., 2021; Carr, 2022; WHO, 2003).
Acupuncture trials also extend to psychiatric conditions like generalized anxiety disorder (especially in perimenopause), depression, and other mental disturbances (Zhao et al., 2022; Zhang et al., 2025; WHO, 2003); respiratory issues such as allergic rhinitis and hay fever (Li et al., 2022; Shanghai Medical Clinic, 2025; WHO, 2003); gastrointestinal disorders including acute and chronic gastritis, biliary colic, and postoperative nausea/vomiting (Zhao et al., 2022; Shanghai Medical Clinic, 2025; WHO, 2003); urogenital and nephrological problems like renal colic and radiation-induced leucopenia (often in renal contexts) (Shanghai Medical Clinic, 2025; WHO, 2003); infectious diseases such as acute bacillary dysentery, pertussis (whooping cough), and epidemic hemorrhagic fever (WHO, 2003); pediatric applications, albeit more limited, for post-extubation pain relief and whooping cough (ClinicalTrials.gov, 2013; WHO, 2003); and oncology support for cancer-related fatigue and chemotherapy/radiation side effects (Zhao et al., 2022; Shanghai Medical Clinic, 2025). Additional niches include ear-nose-throat conditions (e.g., rhinitis), eye disorders, connective tissue diseases, metabolic/nutritional imbalances, and skin pathologies (Zhao et al., 2022; WHO, 2003).
This extraordinarily wide spectrum, drawn from seminal analyses like the World Health Organization’s (WHO) 2003 review of controlled clinical trials (WHO, 2003) and Cochrane overviews on pain (Choi et al., 2019; Lee et al., 2011), clearly demonstrates that acupuncture is considered by its proponents to be a ‘cure all’. This begs the question whether such an assumption can be reasonable. The effect sizes are typically modest, and true acupuncture is often no different from sham interventions (e.g., superficial needling at non-acupoints), suggesting limited specific efficacy (Lee et al., 2011).
The scientific literature proposes a constellation of mechanisms to explain how acupuncture might work, integrating peripheral, spinal, supraspinal, and systemic processes. These are often conceptualized through the “Neural Acupuncture Unit” (NAU) model, which posits low-threshold mechanosensitive afferents (Aδ and C fibers) at acupoints converging with brain networks to elicit bidirectional signaling (Zhang et al., 2012).
- Peripheral and Local Mechanisms. Needle manipulation is claimed to induce immediate tissue responses: adenosine triphosphate (ATP) breakdown to adenosine activates A1 receptors, dampening nociceptor firing (Kelly & Suckley, 2016); axonal reflexes release neuropeptides like substance P and calcitonin gene-related peptide (CGRP), modulating local inflammation; and stromal cells exhibit cytoskeleton remodeling, with collagen fibers “wrapping” around needles to propagate mechanical signals (Kelly & Suckley, 2016; Zhang et al., 2012; Li et al., 2025). The characteristic deqi sensation (aching, soreness) correlates with these events, potentially amplifying sensory input (Staud & Price, 2014).
- Spinal Cord Level. Ascending afferents are said to activate the gate control system, presynaptic inhibition, and diffuse noxious inhibitory controls (DNIC), releasing endogenous opioids (β-endorphin, enkephalins, dynorphins), serotonin, norepinephrine, and acetylcholine to suppress nociceptive transmission in the dorsal horn (Kelly & Suckley, 2016; Zhang et al., 2012; Staud & Price, 2014). This underpins analgesia and autonomic regulation, such as reduced sympathetic outflow (Kelly & Suckley, 2016).
- Central Nervous System Modulation. Functional neuroimaging (fMRI, PET) reveals deactivated limbic hyperactivity (amygdala, anterior cingulate), normalized hypothalamic-pituitary-adrenal (HPA) axis activity, and enhanced prefrontal connectivity, particularly in pain, stress, and mood disorders (Kelly & Suckley, 2016; Zhang et al., 2012; Wang et al., 2025). Top-down expectancy modulates descending inhibitory pathways, integrating with reward and mirror neuron systems (Zhang et al., 2012).
- Systemic and Humoral Effects. Acupuncture is also thought to influence immune homeostasis by shifting cytokine profiles (e.g., ↑IL-10, ↓TNF-α, ↓IL-6), autonomic balance (vagal enhancement), and endocrine axes, providing a basis for visceral, metabolic, and inflammatory conditions (Kelly & Suckley, 2016; Li et al., 2025). Recent integrative studies emphasize network pharmacology, where multi-point stimulation perturbs interconnected pathways (Li et al., 2025).
These potential mechanisms have been empirically observed in animal models and/or human imaging studies. They might offer a partial rationale, primarily for analgesia and stress-related syndromes (Kelly & Suckley, 2016; Zhang et al., 2012). The question, however, is whethr they can provide a full explanation for acupuncture’s efficacy in all the above-named conditions.
No synthesis of these mechanisms plausibly accounts for acupuncture’s claimed benefits across unrelated conditions, exposing a core scientific paradox. Musculoskeletal pain might align with local adenosine/opioid effects and spinal gating (Kelly & Suckley, 2016), but how do these explain microbial clearance in bacillary dysentery, hypertensive vascular remodeling, or synaptic imbalances in major depression? (Meissner et al., 2019; Ernst, 2018). Gynecological infertility involves ovarian endocrinology, distant from needle-evoked sensory cues; infectious pertussis implicates Bordetella immunity, not HPA modulation (WHO, 2003; Meissner et al., 2019). This biological implausibility echoes homeopathy critiques: a single intervention cannot verifiably target such heterogeneous pathophysiologies without invoking non-specific forces (Fabrizio et al., 2010).
Trial data reinforce these doubts: meta-analyses consistently show that verum acupuncture is hardly different from sham acupuncture, and sham elicit up to 80% of verum’s effects (Kelly & Suckley, 2016; Meissner et al., 2019; Fabrizio et al., 2010; Kaptchuk et al., 2013). Such considerations implicate patient and therapist expectations, therapeutic ritual, and patient-practitioner alliance as the true mechanism behing the observed outcomes (Meissner et al., 2019; Kaptchuk et al., 2013). Neuroimaging effects often mirror expectancy manipulations in non-needling studies, suggesting top-down confounds (Fabrizio et al., 2010). Lab phenomena (e.g., adenosine release) occur but yield trivial clinical effects, dwarfed by psychosocial amplification (Fabrizio et al., 2010).
Acupuncture’s elaborate ritual maximizes contextual healing, outperforming inert pills but lacking disease-modifying specificity (Meissner et al., 2019; Ernst, 2018). Paradoxes abound—positive preclinical signals evaporate in blinded RCTs; cultural bias inflates Asian trial positives; poor sham penetration and blinding failures perpetuate illusions (Fabrizio et al., 2010; Ernst, 2018). For non-pain conditions, evidence thins further, with publication bias and flexible outcome reporting inflating apparent successes (Fabrizio et al., 2010).
Acupuncture carries risks including minor issues like bleeding, needle site pain, vegetative reactions (e.g., dizziness or nausea), and symptom aggravation, alongside rarer serious events such as pneumothorax, infections, or organ injury. Overall, at least one adverse event in 9.31% of patients undergoing a treatment series or 7.57% of treatments, with half of these being mild local reactions. Serious adverse events seem to be uncommon. Reliable prevalence figures do not exist because there is no adequate surveillance system in place (Ernst 2006).
Acupuncture’s trial proliferation signals cultural and patient-driven demand rather than mechanistic or evidential triumph. Its broad therapeutic claims by far overreach evidence (Staud & Price, 2014). Rigorous advancement would require objective biomarkers (e.g., cytokine assays, EEG), dose-response optimization, adaptive sham designs, and large pragmatic trials stratifying contextual from specific effects (Zhang et al., 2012; Fabrizio et al., 2010). Until compelling evidence exists, acupuncture remains a testament to human suggestibility’s power, but not a biomedical panacea.
References
- Carr, D. (2022). Acupuncture as Treatment for Female Infertility. Medical Acupuncture, 34(1), 12-21.
- Choi, D., et al. (2019). Cochrane reviews on acupuncture therapy for pain: a snapshot of the current evidence. Systematic Reviews, 8, 231.
- ClinicalTrials.gov. (2013). Pediatric Laser Acupuncture and Renal Biopsy (NCT01879826).
- Ernst, E. (2006). Acupuncture–a critical analysis. J Intern Med, 259(2):125-37.
- Ernst, E. (2018). Acupuncture Research: The Problem. Pain Medicine, 19(6), 1287-1288.
- Fabrizio, P., et al. (2010). Paradoxes in Acupuncture Research: Strategies for Moving Forward. Explore (NY), 6(4), 231-239.
- Kaptchuk, T. J., et al. (2013). Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, or Placebo Needle in Irritable Bowel Syndrome. PLoS ONE, 8(7), e67485.
- Kelly, R., & Suckley, S. (2016). Mechanisms of acupuncture. European Journal of Integrative Medicine, 20, 1-11.
- Lam, M., et al. (2020). Acupuncture and Chronic Musculoskeletal Pain. Medical Acupuncture, 32(6), 357-366.
- Lee, M. S., et al. (2011). Acupuncture for pain: an overview of Cochrane reviews. Chinese Journal of Integrative Medicine, 17(3), 187-189.
- Li, T., et al. (2022). Evidence on acupuncture therapies is underused in clinical practice. Frontiers in Medicine.
- Li, Y., et al. (2025). Integrative research on the mechanisms of acupuncture. Neural Regeneration Research.
- Meissner, K., et al. (2019). Acupuncture for the Treatment of Pain – A Mega-Placebo? Frontiers in Neuroscience, 13, 1119.
- Shanghai Medical Clinic. (2025). WHO Approved Acupuncture List of Conditions.
- Smith, C. A., et al. (2021). An Overview of Systematic Reviews of Acupuncture for Respiratory Diseases. Frontiers in Public Health.
- Staud, R., & Price, D. D. (2014). Acupuncture therapy: mechanism of action, efficacy, and safety. International Review of Neurobiology, 111, 171-189.
- Wang, L., et al. (2025). Possible antidepressant mechanism of acupuncture. Frontiers in Neuroscience, 19, 1512073.
- WHO. (2003). Acupuncture: Review and Analysis of Reports on Controlled Clinical Trials.
- Zhang, R., et al. (2012). Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture. Evidence-Based Complementary and Alternative Medicine, 2012, 429412.
- Zhang, Y., et al. (2025). Patient-reported outcome tools of acupuncture clinical trials. Journal of Pain Research.
- Zhao, C., et al. (2022). Evidence mapping and overview of systematic reviews of the effects of acupuncture therapies. BMJ Open, 12(6), e056803.
