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 don’t do much harm to healthy individuals, we don’t 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.

 

MDMA AND HEART RISK

One thing that’s 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 a link 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.

MDMA’s harmful effects on the heart are due to its activation of the 5-HT2B receptor. This receptor is present all over the heart, and convincing evidence suggests that 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?

 

DOES MICRODOSING LSD/PSILOCYBIN ACTIVATE THE 5-HT2B RECEPTOR?

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 don’t have an answer to that question. We know that LSD and psilocybin bind strongly to the 5-HT2B receptor, but we don’t 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 of 3ug/day, several thousand times less than fenfluramine).

The comparison to fenfluramine isn’t great – it’s quite possible that a daily dose of fenfluramine (rather than a dose every three days when microdosing) affects the 5-HT2B receptor differently. Additionally, we don’t know to what extent LSD is activating the 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 study gave 10ug/kg of psilocin to rats every other day for several weeks. The findings of this study are unconvincing, to put it mildly, and it doesn’t really tell us anything about the heart risks of microdosing.

Overall, we don’t yet know anything for sure. Microdosing needs to be studied in more detail – and looking at the scarce evidence we have, it’s hard to draw any conclusions about the relative safety of microdosing.

 

CONCLUSIONS

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.

 

LEGALIZATION = SAFER DRUGS

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 could see companies vying to produce psychedelic analogues that have beneficial psychological effects, without being damaging to our bodies in long-term use. Imagine a psychedelic designed specifically for microdosing; one that boosts our creativity and awareness, but doesn’t 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.

Important Note: This is a constantly-evolving document. If you believe we’re missing something important, please let us know via the contact page.

By Patrick Smith on

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Comments

  1. Nora Noslavde says

    I once microdosed ~12.5ug of LSD every day for two weeks. I experienced no cardiac concerns at the time, but over 7 months later have been having abnormalities in my digestive tract that have developed into causing some frightening effects on my heart. I cannot say there is a correlation, but we know that the majority of serotonin activity is in the gut. So this mention of serotonin receptors in the heart makes me wonder if LSD’s strong binding affinity to the 5HT receptors can cause some long term effects. I cannot use MDMA anymore because of its effects on my heart- palpitations and arrhythmia. I also wonder if using them together greatly increases the risk.
    This is why we need them to be studied extensively. We need to know, not wonder.

    • Mike says

      I am reading about microdosing LSD because I suffer from anxiety. I am 55 years old. When I was much younger say 18 years old I had taken massive amounts of LSD for maybe a year. I could take 10 to 15 tabs a day. It was awesome. The reason I say this.is because I feel it had no negative effect on my health. I Iike to work out and ride my bike 40 km every morning. I have had many tests done on my heart because of my anxiety and they have found no problems. When I say I took lots of LSD I am not exaggerating when I say thousands of tabs. I dont think it has negative side effects.

      • Bruce says

        Mike, you are missing just one important thing in your post :
        “For you”.

        What is good/unharmful for you, might be bad/lethal to others. Some people might develop heart issues with just a small dose. other might drown in the compound before having an issue.

      • John says

        I have been taking acid weekly for about 3 years now, usually 1/2 to 1 tab on the weekend. I drink beer and smoke weed as well.

        I have mild high blood pressure, and take Losartin Potassium 100 mg and Hydrochlorothiazide 12,5 mg daily, which seems to control it.

        I haven’t noticed any symptoms of heart issues, and my blood pressure is fine taking the medication, so I think you are probably safe.

        I didn’t realize there was any evidence of a connection until tonight.

  2. michal says

    I wonder if microdosing with san pedro for 2 month might cause some heart condition as well?
    This question is actualy very argent…

    • Patrick Smith says

      It’s unlikely to cause a heart issue, as microdosing is such small quantities. However since mescaline is similar in structure to MDMA, we would advise against frequent high doses, and it’s best to avoid microdosing for longer than a few months.

      • Ben says

        There is people taking San Pedro daily since decades, i’d believe that there would be at least anecdotal evidence if anything similar to MDMA would occur.

  3. Coyote Fred says

    Could you please post a full copy of the 2006 rat study on cardiotoxicity? Several of us would like to be able to see/read it. Thank you!

  4. Gordon Gould says

    Any information about the cardiac risks of moderate to high dose but infrequent (1-2x every 30-60 days) use of iboga or dmt or 5-meo dmt?

  5. benjmalcolm says

    The receptor affinities quoted for LSD from the Passie article are receptors from rats. I found this article that has a comparative table of receptor affinities in humans https://www.ncbi.nlm.nih.gov/pubmed/28447622. It does seem LSD can activate the 5HT2B receptor still, although psilocin does not seem to have a very high affinity. I’ve also read a few places that psilocybin is fairly selective for the 5HT2A receptor. Just my opinion but I’d be personally less worried about psilocybin/psilocin cardiotoxicity compared to LSD or MDMA.

  6. carol randall says

    Hi…Im 72 years old and have taken psychedelics since I was 18 years old…large doses…micro’s of all types …Shrooms…mescaline…L S D …dmt…you name it …never took a brake…continual use…over 50 years…My heart is fine …I am very active…creative…actually my heart is better than fine…its taught me a lot …what a gift…what
    a sacred substance…its a sacrament…just had to respond…Carol Randall of The Brotherhood of Eternal Love…look up our Orange Sunshine Documentary…good work…
    Fabulous web sight…really keep up the good work…Love carol.

    • Jaybird says

      One has to wonder if the repeated exposure to psychedelics is what caused Pravasi to suffer repeated heart attacks in his 70s. In the end its what took him from us two years ago. RIP Brother.

      • Phil says

        For what its worth, my friend with a heart murmur used to get down on beans and molly. Sadly he passed away due to heart peoblems at 24 years old 🙁 RIP James R.

  7. ceres1369willyson says

    i have an abnormal heart murmur but i love psychedelics i have done LSD and mushrooms but i have not yet took MDMA and I have a plug for it i just don’t know if it is safe for me to take so uhh heart surgeons that lik tripping give me the info

    • Anonymous user says

      From a personal perspective, I would advise against much if any MDMA use or experimentation. Although there are many other contributing factors for myself, I have no doubt that extended use at least contributed to current heart related issues. Because there is no regulation on production, there ard many other ingredients that WILL have ill effects upon multiple parts of the body, the heart. Although I wouldn’t have changed my educated decisions of taking said chemical, it does alter many aspects of long term health and experiences. My advice for anyone with any heart condition is to stay away unless you have access to lab produced MDMA and even then just be aware there are always risks.

  8. TheDude says

    I consumed 200ug lsd every 2 – 4 days for 6 months. Followed by another 4 years of taking 200uq up to 1mg hits every weekend.
    This was 20 years ago. I now suffer from severe anxiety. I was merely 16 years old and continued my high LSD use up to the age of 21

    While you are still developing i would stay away from psychedelics.
    I firmly believe my anxiety issues today is a direct result of taking large amounts of lsd.

    Today i find that going through a high dose of psilocybin once every 4 months curbs my anxiety for 4 months at a time.

    • Michael Hart says

      This is helpful info. I think my anxiety is related to my lsd use in teens and early 20s and don’t know what to do. I thought about going to a retreat help to provide insight on my situation and my life. I would like to grow my own shrooms and have read the articles and this gives me one more reason to do

  9. Aaron casas says

    Hello i am Aaron and i am a user of psychedelics and both times have took very high doses i thought i was gonna die but in reality i was fine actually both my experiences were life changing my first great trip was 500mu of lsd my second trip was 3 grams of mushrooms and after i did the mushrooms i realized i had diabetes it was truly a life changing thing for me but actually good because before that i never knew i had any illness and the day after my life was changed for forever so i respect the psychedelics and everything they bring even though i believe i have HPPD life is still great and would never ever change the experience i had on them all thanks to this girl i call my girlfriend but actually she is the devil quoted from juice wrld girls bring nothin but problems, fights, many other bad things because a womens touch can make a man do anything shoutout to adam and eve

  10. Chifaun smiley says

    I took 4 grams of shrooms my first and last time. I really can’t explain the experience but I went into a bad trip shortly after I had an asthma attack. Anyways is the day after and I’m still having some chest pain should I be concerned? Ig it’s not my brightest idea since I have a heart and lung problem…..but ig I didn’t think it would be major

  11. Mike says

    I am reading about microdosing LSD because I suffer from anxiety. I am 55 years old. When I was much younger say 18 years old I had taken massive amounts of LSD for maybe a year. I could take 10 to 15 tabs a day. It was awesome. The reason I say this.is because I feel it had no negative effect on my health. I Iike to work out and ride my bike 40 km every morning. I have had many tests done on my heart because of my anxiety and they have found no problems. When I say I took lots of LSD I am not exaggerating when I say thousands of tabs. I dont think it has negative side effects.

  12. T says

    Man, I’m glad that I waited to try psychedelics until I was in my early-mid 20’s..cuz I’ve always had severe depression & anxiety, ever since I was 12 or 13, which just continued to get worse into my later teen years and into adulthood. I still have both, but they’re def. managed much better nowadays (I’m 31 now). I do have to say though, when I first began raving in my early 20’s, I used to roll just about every weekend for a few months straight and I DEF noticed it negatively impacting my moods and overall mental health days to weeks after I had taken it..and I’d only ever take 1, occasionally 2 pills per roll. That being said, I do still wish that there was more access to lab-created MDMA, because then there’d be FAR less of a chance of any adulterants being thrown into the mix vs pressed pills/questionable molly.

  13. Ghost-141 says

    Hey guys,

    Just wondering is there any risk in consuming psychedelics occasionally ( just shrooms and Ayahuasca) if you have a minor case of pericarditis? Thanks in advance

    • Britt at The Third Wave says

      Hi Ghost-141,

      Unfortunately, there is not enough research available on this subject to give you an informed answer. It would be advised for you to consult a medical professional before taking psychedelics with any health condition.

  14. Davie says

    I just ran across this page and thought I would make a few interesting points.

    The fenfluramine mentioned that was withdrawn from use due to heart defects was originally dosed at 60-120mg per day. It was withdrawn due to heart damage. More recently low dose fenfluramine (up to 20mg per day) has been shown to be a powerful anti-epileptic and appears safe at those low doses. It’s phase 3 trial data showed better results than GW’s CBD Epidiolex.

    I was also just looking at a page that touted the dangers of MDMA on the heart. It is typical of the anti-drug hysteria that I have seen over the years regarding the dangers of cannabis.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882794/

    You’ll notice that the poor rats involved in this research were given MDMA doses of 5 or 10mg/kg of body weight every 2 hours for a total of 4 injections. They were then decapitated and examined.

    This is the equivalent of me injesting 4-8 strong ecstasy tablets every two hours. Which I think would probably kill me.

    The only point of this sort of nonsense is to provide the anti-drugs brigade with scary headlines, expecting people not to delve to deeply.

    • Britt at The Third Wave says

      Thanks for contributing, M! You’re right – there’s just not as much research being done as we would like with regards to psychedelics and microdosing. We believe that we’ll see that change, however.

      With my light and love,

      – Britt at The Third Wave

  15. Clayton Tharp says

    Massive heart attack 18 months ago (1-2-18). Any insight into taking enough mushrooms to get high–not microdosing, but like 1 or 2 good sized caps and stems? I’m in great health.

    • Ziva says

      I am now off Adderall and microdosing because the long term effects of Addrerall was getting scary at my age.

  16. Daniel Shields says

    Thank you for sharing and spreading awareness! Mushrooms are really indeed a magical fungus. As studies progress, it unfolds a lot of possible uses and applications in science and medicine. I hope this could be the future treatment of a lot of diseases. It has endless capabilities!

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