Could taking tiny fractions of the normal prescribed dose of a medication offer a brilliant way to benefit from the drug, without suffering its usual side-effects?
That’s the promise offered by the practice of microdosing – which has become an increasingly popular habit among internet influencers and online medical gurus.
Microdosing – the use of drugs at much lower doses than their conventional strengths – was first popularised in the early 2010s with psychedelics such as psilocybin (found in magic mushrooms) and LSD, used illegally by people in the hope of self-treating psychological conditions such as depression and anxiety but avoiding a psychedelic ‘trip’.
Now, thanks to social media, microdosing has spread into the mainstream use of prescribed medications, most notably with weight-loss injections containing the drug semaglutide (such as Wegovy and Ozempic), and the acne drug isotretinoin (brand name Roaccutane).
One theory is that taking lots of small doses means the drug builds up in your body, so you end up with an effective dose.
But is it safe, as people believe? It seems it depends on the drug itself.
Perhaps one of the most popular of the microdosing drugs is semaglutide, a type of drug known as a GLP-1 receptor agonist – it mimics the hormone GLP-1, which helps the body produce more insulin.
It was developed to control blood sugar levels. But it also suppresses appetite and leads to weight loss, and when the US medicine authority, the Food & Drug Administration, approved the use of GLP-1s for weight loss almost four years ago, demand skyrocketed – leading to spiralling prices and critical shortages of these medicines.
Sarah Blagden is a Professor of Experimental Oncology at the University of Oxford and takes aspirin daily to try to prevent cancer
In response, some users began to ration their own supplies by taking smaller, ‘microdose’ amounts.
But there is another popular reason for microdosing these drugs: on social-media platforms users claim that taking a microdose of semaglutide is a ‘hack’ for lowering blood-sugar levels and losing weight, while sidestepping the unpleasant side-effects of standard doses – such as nausea and constipation.
Weight-loss influencers post their personalised dosing schedules and share claimed results for others.
Some go further: Tyna Moore, a US health influencer with around 300,000 followers on Instagram, claims that around 500 people have enrolled on her online ‘course’ – ‘GLP-1s Done Right University’ – which costs more than £1,500 and includes advice on microdosing.
The influencers’ advice varies hugely, from staying closer to the starting dose of 0.25mg and cutting down to 0.1mg – or simply refraining from injecting every seven days (as is normally recommended). Even some experts are now recommending people try this approach.
Anne Komé, a clinical pharmacist at the University of North Carolina, recently wrote in the journal Diabetes Care: ‘While unconventional, microdosing with semaglutide offers a tailored solution to provide therapeutic benefit, minimise adverse effects and address availability concerns.’
She added: ‘Microdosing can be beneficial for patients who experience significant adverse gastro-intestinal effects, which are common with GLP-1 drugs.’
Furthermore, she said that the lower costs involved with microdosing officially prescribed semaglutide mean that the practice may deter patients from buying cheap – and potentially dangerous – bootleg products online: ‘Continued use of approved products through microdosing may provide a safer and more consistent alternative,’ she said.
Social media users claim that taking a microdose of semaglutide is a ‘hack’ for lowering blood sugar levels and losing weight, while sidestepping the unpleasant side-effects of standard doses
Nevertheless, she acknowledged that microdosing semaglutide ‘is not endorsed by the manufacturer, as no clinical trials have validated its safety or efficacy’ when used in this way.
Indeed, a spokesperson for Novo Nordisk, which markets Ozempic and Wegovy, told Good Health: ‘We do not condone these practices. The approved doses are the only dose strengths that have been studied and are licensed for use.’
But a more promising form of microdosing prescribed medications is with the acne drug isotretinoin, which is also gaining traction.
Isotretinoin is a synthetic derivative of vitamin A, which effectively shuts down the skin’s oil-producing sebaceous glands.
Mail columnist and psychiatrist Dr Max Pemberton revealed recently that he microdoses with Roaccutane to treat his acne.
Usually, Roaccutane is given in a course lasting four to six months, at a daily dose of 0.5 to 1mg per kilogram of bodyweight.
Dr Pemberton first took it 12 years ago on a dose of 80mg per day – the recommended amount for his weight. But after he stopped taking the drug, the acne came back. This is a common problem, affecting more than one in five people prescribed the drug, according to a study published last month in the journal JAMA Dermatology.
Dr Pemberton’s dermatologist suggested he go back on the drug – at a ‘microdose’ level – and stay on it indefinitely to prevent relapses.
He now takes 20mg a week – a fraction of the 560mg a week he took on the full dose – but says it’s ‘just enough to keep his skin clear’ while also reducing the side-effects he had previously suffered, which included dry, flaky skin, itchy eyes, problems seeing at night and sensitivity to the sun. (As Good Health has previously reported, the drug has also been linked to depression and suicidal thoughts.)
A 2016 study in the journal Canadian Family Physician reported that a lowered dose of 140mg a week has similar acne-clearing effects as conventional doses, and may reduce common side-effects by up to a third. It warned, however, that relapse rates may be higher following a reduced-dose regimen.
Penny Ward, a visiting professor in pharmaceutical medicine at King’s College London, says there are important reasons why low-dose isotretinoin can be effective. ‘When this drug was first investigated for acne in the 1980s, there was some beneficial effect on skin at every level, including low doses. In fact, the company never found the “no effect” dose,’ she explains.
‘This caused a challenge when it came to making a dose recommendation that worked for people as a whole. In the end, the maker chose a range that helped clear skin in people with very bad acne and stopped it coming back within six months.’
And ‘significantly smaller doses can be used for people with significantly less severe acne – as dermatologists have found’, she adds.
However, as with all drugs, there may still be side-effects, even at a very low dose. ‘At any dose, for instance, isotretinoin carries a serious risk of causing birth defects – so it must not be taken by women liable to become pregnant, even in microdose,’ warns Professor Ward.
‘Psychiatric risks may also not be negated. It’s now generally accepted that a proportion of people who take isotretinoin will develop severe depressive disorder. So microdosing is not necessarily a get-out-of-jail-free card for side-effects.’
One of the ways that isotretinoin works is by steadily accumulating in the body over weeks and months. And this is how other drugs taken in very low doses may also work, according to Gary Stephens, a professor of pharmacology at the University of Reading.
‘The science suggests perhaps that if you take lots of small doses of a drug then they may accumulate in your body, so that eventually you build up to a dose that might have a therapeutic effect. But the jury is still out on this,’ he says.
‘The crucial thing is that, as we say in pharmacology, “the dose makes the poison”. So if a very low dose of a drug does not have any of the usual side-effects, then it may also not be working at all. There’s practically no such thing as a side-effect-free effective dose.’
The risks involved with regularly ‘microdosing’ a drug have already been demonstrated with the ‘baby aspirin’ pill, which was popularised around 25 years ago as a way of preventing heart disease in people who have not had previous heart problems.
Last year, for example, research by Harvard University, published in JAMA Oncology, concluded that taking low-dose aspirin daily may help lower the risk of colorectal cancer in people with greater lifestyle-related risk factors for the disease, such as smoking, poor diet and lack of exercise – possibly by reducing chronic inflammation.
More recently studies have suggested that low-dose aspirin may be effective at preventing some cancers, particularly colorectal cancers.
Although the low-dose pill contained only 75mg of the drug (as opposed to the usual 300mg), the National Institute for Health and Care Excellence (NICE) now advises against the routine use of low-dose aspirin for preventing heart disease in people who have not already had a heart attack, as the side-effect risk of serious stomach bleeding is too great to warrant it.
This change in guidance came in the wake of a 2010 study in the Journal of the American Medical Association, which found that in healthy older adults, aspirin did not significantly reduce the incidence of heart attack or stroke – but did increase the risk of life-threatening gastric haemorrhages.
(However, the chance that someone who has already had a heart attack or stroke will have another one is generally high enough to justify the risks associated with aspirin. This is called ‘secondary prevention’, and NICE still recommends using aspirin in these cases.)
When it comes to its use as a cancer preventative, as Sarah Blagden, a consultant oncologist and a professor of experimental oncology at the University of Oxford, says: ‘Aspirin prevents some cancers from starting, though we don’t know exactly how.
‘I started taking aspirin at a dose of 75mg a day when I hit 50 (I’m now 55) and will stop taking it when I’m 60, when the risk of side-effects – aspirin can cause stomach ulcers and increase risk of bleeding – will outweigh the benefits.’
Nevertheless, microdosing medications remains controversial. One key question is whether microdosing many drugs is simply working as a placebo. Recent research suggests this may be true with people taking psychedelic drugs, in particular.
For example, a 2021 study in the journal eLife, led by Dr Balazs Szigeti, a neuroscientist at Imperial College London, found that, while people who illegally and informally microdosed themselves with LSD or psilocybin reported that they felt happier and more secure, so did people in the same experiment who microdosed with inactive placebo pills.
‘The benefits are real – but they are not caused by the pharmacological effects of microdosing,’ said Dr Szigeti.
Likewise, with GLP-1 weight-loss drugs, the benefits that some microdosers claim to have seen may be because of the placebo effect – for example, if these people are convinced that they are getting a boost from the medication, they might feel more encouraged to make lifestyle changes that can lead to weight loss, says Professor Stephens.
But we should not dismiss the value of a placebo effect – because in itself it can play a powerful role in healing.
‘We see the benefits of people getting better with placebo pills in situations where they are suffering from pain or psychiatric conditions,’ he says.
‘It even works with fake ops where people go into operating theatres for “sham surgery” for things such as knee and lower back pain,’ he adds. ‘Even though the patients didn’t have an op, we can see recovery-success rates of 60-70 per cent. So we should not dismiss placebo.’
Strangely, therefore, even if microdosing doesn’t work, it could have great benefits for those who believe in it strongly. Sceptics, on the other hand, may prefer to take it all with a pinch of salt – or even a tiny microdose.
