Microdosing is an exciting new prospect for the psychedelic community; what better way to incorporate the healing and mind-expanding benefits of psychedelics into our everyday lives? But with any change in lifestyle comes risk and psychedelics are relatively poorly understood in terms of what they do to our bodies. Although it appears that relatively infrequent, even large doses of psychedelics dont do much harm to healthy individuals, we dont have any evidence that regular microdosing is safe. There are reports of people microdosing for many months in succession, with no ill effects aside from tiredness but there is always the chance that with longer term microdosing regimens, unwanted physiological side effects could start building up.

One thing thats of some concern is the risk of heart disease. MDMA has been the centre of attention in this respect various studies have shown that there is alink between regular, high-dose MDMA use and heart defects. Although the conclusion of this research is that the occasional dose of MDMA will not harm you, it has potential implications for long-term psychedelic use, including microdosing.

MDMAs harmful effects on the heart are due to itsactivation of the 5-HT2B receptor. This receptor is present all over the heart, andconvincing evidence suggeststhat the long-term activation of this receptor leads to the formation of valvular strands, which can lead to Valvular Heart Disease (VHD) in extreme cases.

Again cases of VHD are only found in people who use MDMA very frequently (several times a week) and at high doses. The question we want to answer is: do the classic psychedelics (LSD and psilocybin) that we microdose with also activate the 5-HT2B receptor on our hearts, and is there a risk of VHD with long-term microdosing?

LSD and psilocybin work by mimicking the effect of our natural neurotransmitter, serotonin. Therefore both these psychedelics activate a wide range of serotonin receptors, including the 5-HT2B receptor. The real question is, are these psychedelics activating the 5-HT2B receptor enough to cause damage to the heart?

Unfortunately, we dont have an answer to that question. We know that LSD and psilocybinbind strongly to the 5-HT2B receptor, but we dont know how comparable this is to the way that MDMA (and other cardiotoxic molecules) binds to 5-HT2B. So right now, there is no way of knowing for sure if there is any risk.

We can, however, make some educated speculation.

We can look at a previous study of a compound that definitely causes heart damage through the 5-HT2B receptor: fenfluramine. This was a weight-loss drug that was withdrawn in the 90s after a small percentage of people developed heart disease after using it.

Studies found that fenfluramine roughly doubled the risk of developing VHD after a 90-day treatment course, at a dose of around 30mg/day (Sachdev et al, 2002). Fenfluramine has an affinity (Ki) for the 5-HT2B receptor of around 30nM (Rothman & Baumann, 2009).

LSD has a similar affinity for the 5-HT2B receptor as fenfluramine, a Ki of around 30nM (Passie et al, 2008). A typical microdosing regimen involves taking much less LSD than 30mg/day (actually the equivalent of3ug/day, several thousand times less than fenfluramine).

The comparison to fenfluramine isnt great its quitepossible that a daily dose of fenfluramine (rather than a dose every three days when microdosing) affects the 5-HT2B receptor differently. Additionally,we dont know to what extent LSD is activatingthe 5-HT2B receptors of the heart in comparison to fenfluramine. However, it seems reasonable to assume that microdosing has nowhere near the heart risk associated with fenfluramine.

Although there have been no long-term studies of the risk of microdosing in humans,one studygave 10ug/kg of psilocin to ratsevery otherday for several weeks.The findings of this study are unconvincing, to put it mildly, and it doesnt really tell us anything about the heart risks of microdosing.

Overall, we dont yet know anything for sure. Microdosing needs tobe studied in more detail and looking at the scarce evidence we have, its hard to draw any conclusions about the relative safety of microdosing.

While we believe that short-term microdosing is relatively safe, what remains to be seen is whether long-term microdosing regimens (i.e. for many months or even years) have a potential to damage the heart. This is why we advise to microdose for no longer than 90 days, and spread out your microdosing regimens throughout the year. If you have a pre-existing heart condition, it is especially important to avoid extended periods of microdosing.

We think that the potential heart risk of psychedelics actually highlights the need for their legalization. Without legalization, people will probably continue taking psychedelics without considering the risks, and as the popularity of microdosing increases, we might see more negative side effects.

But if psychedelics are legalized, we couldsee companies vying to produce psychedelic analogues that have beneficial psychological effects, without being damaging to our bodies in long-term use. Imaginea psychedelic designed specifically for microdosing; one that boosts our creativity and awareness, but doesnt damage our heart or other tissues.

The answer could be a psychedelic that only becomes active when it crosses into the brain; or a psychedelic that does not activate the 5-HT2B receptor in the heart. Perhaps we could even co-administer psychedelics with drugs that totally block the 5-HT2B receptor. To develop these ideal drugs, we first need legalisation, and for policymakers to accept that psychedelics will never leave our culture.

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Do Psychedelics Carry A Heart Risk? - The Third Wave