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OfflineHamHead
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Why Chronic Microdosing Might Break Your Heart
    #26402925 - 12/27/19 11:32 AM (4 years, 1 month ago)

https://chacruna.net/why-chronic-microdosing-might-break-your-heart/

There is no shortage of media hype surrounding microdosing psychedelics at the moment, but buyer beware because chronic use could literally end up breaking your heart. While there has been very promising evidence of safety and effectiveness for psychedelics after a few acute macrodoses in clinical trials, the risks and benefits of chronic microdosing still remain largely unknown. As a board-certified psychiatric pharmacist, one of my primary responsibilities is to educate clients about psychotropic medications so they can evaluate the risks and benefits to make informed treatment decisions. After spending some time researching this topic in detail, I became concerned about the potential risk of valvular heart disease (VHD) due to chronic psychedelic-induced changes of heart valve cells via serotonin 2B receptor (5HT2B) activation. I will outline my reasons for these concerns based on the limited evidence currently available.

There have been several FDA-approved medications with 5HT2B receptor activation withdrawn from the US market due to the risk of VHD with heart valve thickening and murmurs: Fen-Phen (fenfluramine/phentermine) and Redux (dexfenfluramine) in 1997 and Permax (pergolide) in 2007. Roughly 25% of patients taking these medications daily developed new onset VHD according to incidence statistics from the medical literature (Hutcheson, Setola, Roth & Merryman, 2011). This is a troubling statistic, since the psychedelics LSD and psilocin (psilocybin’s active metabolite) most frequently used for chronic microdosing also bind to the 5HT2B receptor, in addition to their better-known acute “psychedelic” 5HT2A receptor effects (PDSP certified data, n.d.; Knight et al., 2004).

Isn’t the dose too low to cause an adverse reaction?
If there is any perceptible benefit from microdosing, then this would imply some receptor activation, and therefore both desirable and undesirable receptor effects are possible. The most common way to experimentally measure how tightly a drug binds to a receptor is called binding affinity (Ki), with lower values indicating a stronger receptor affinity. The binding affinities for 5HT2A and 5HT2B receptors are both equally strong for LSD, while psilocin actually has a relatively stronger affinity for 5HT2B than 5HT2A (see below) (PDSP certified data, n.d.; Knight et al., 2004). These strong binding affinities for both 5-HT receptor subtypes suggest that both drugs would have effects even at very low doses.

Why do people with books or websites about microdosing think it is safe?
A recent microdosing critique and commentary article by Kuypers et al. (2019) raised this VHD safety issue and cited a landmark publication by Connolly et al. (1997), which instigated the Fen-Phen FDA warning and subsequent market withdrawal since 5 out of 24 cases of fenfluramine/phentermine-induced VHD required heart surgery (Kuypers et al., 2019; Connolly et al., 1997). This Kuypers et al. (2019) article also had corresponding commentaries with counterarguments by Dr. Passie, a psychiatrist who wrote a book on microdosing, along with Drs. Fadiman & Korb, clinical psychologists who published a website about microdosing (Kuypers et al., 2019). I will present their counterarguments along with an explanation of why I did not find them particularly reassuring.

Dr. Passie mentioned “the studies of Bender and Sankar (1968) in the 1960s involved doses of 100 µg LSD for up to 35 months on a daily basis without any observable damage. However, their methods of investigation might not have been sensitive enough to detect damage” (Kuypers et al., 2019, p. 18). This study cited actually investigated chromosomal breakage and found no significant chromosomal damage in 7 children (aged 7-11) with schizophrenia taking 100-150 µg LSD daily for 5.5 to 35 months, but authors did not report measuring any heart safety monitoring parameters (Bender, Sankar, Irwin, & Egozcue, 1968). Dr. Passie also suggested that “if a valvulopathy is detected in a patient, in all cases it disappears within a short time after stopping the medication” (Kuypers et al., 2019, p. 18). However, in the Graham (1967) article he cited on methysergide-induced VHD, there were actually 12 patients with systolic murmurs and only 5 improved, while the other 7 remained the same after stopping the medication (Graham, 1967). This article also described 2 cases of methysergide-induced valve lesions that required open heart surgery and one of these patients actually died the day after valve replacement surgery (Graham, 1967).

Drs. Fadiman & Korb cited another fenfluramine-related statistic from Hutcheson et al. (2011) stating “norfenfluramine was found to be two orders of magnitude more potent at 5HT2B and 5HT2C receptors compared with 5HT2A receptors,” (p. 16) which was based on measuring half maximal effective concentration (EC50) values for phosphoinositide hydrolysis; just one of several possible lab experiments used to measure receptor activity (Hutcheson, Setola, Roth & Merryman, 2011; Kuypers et al., 2019). However, in a more recent FDA regulatory forum review article, a drug’s 5HT2B Ki was considered a better predictor of VHD risk than EC50 values; particularly a drug’s 5HT2B Ki relative to serotonin’s 5HT2B Ki (Papoian et al., 2017). In one of the most comprehensive receptor binding studies to date, which tested D-LSD, D-norfenfluramine, and serotonin for both 5HT2A and 5HT2B affinity, the Ki values (calculated from pKi and expressed in nM below) were as follows (Knight et al., 2004):

Therefore, this Ki value data showed that D-LSD and psilocin had an even stronger 5HT2B affinity than serotonin at the same receptor, which suggests that chronic LSD or psilocybin dosing may potentially have an even greater risk of VHD than norfenfluramine.

Drs. Fadiman & Korb also stated, “Doses of Fen-Phen used in the 1980s and 1990s far exceed the doses used in microdosing, seemingly resulting in several orders of magnitude more activity at the receptors,” (p. 16) but provide no citation of LSD or psilocin EC50 values for comparison with norfenfluramine to support this statement regarding more activity (Kuypers et al., 2019). Relative drug dose is not necessarily the most predictive factor for the intensity of drug effects and may depend on many other pharmacologic variables such as plasma concentration, binding affinity, binding kinetics, and downstream second messenger system functional activity.

How many people have actually been observed microdosing chronically for extended durations?
Drs. Fadiman & Korb stated, “Of the thousands of people who microdosed, no one has reported any heart valve trouble during their period of microdosing, and many people have been microdosing for over a year. All the people we have surveyed with heart problems had them before they started microdosing” (Kuypers et al., 2019, p. 16). This raises questions about the exact frequency and duration meant by “for over a year”; was this microdosing every 3 days consistently over 365 consecutive days or was it intermittent microdosing for a month here and there over the course of a year?

Interestingly, Dr. Passie cited a statement contradicting the above Fadiman & Korb commentary in his own commentary section from the same article, “as Fadiman’s coworker on his more or less systematic Internet surveys, Sophia Korb has mentioned in a lecture (conference ‘Beyond Psychedelics,’ Prague 2018) that they know of just three persons who have dosed regularly (according to the Fadiman protocol) for more than 3 weeks. These three subjects were terminal cancer patients and felt quite normal up to day 50. Between days 50 and 60, they all became much more psychologically labile, i.e., having larger mood changes…” (Kuypers et al., 2019, p. 18).

So how would someone know if they had VHD and are there ways to limit the risk?

The primary symptoms for VHD are chest pain, shortness of breath, and lightheadedness; but there are also cases with no recognizable physical symptoms (American Heart Association, n.d.). The absence of a heart murmur during a thorough physical exam usually rules out VHD, but the gold standard for detecting any valve damage would be echocardiography (a.k.a. “echo”), which is how VHD was confirmed in the studies for FDA drugs withdrawn from the market and studies of chronic recreational MDMA use (5HT2B Ki = 700) (Hutcheson, Setola, Roth & Merryman, 2011; PDSP certified data, n.d.; Droogmans, et al., 2007). In a study of 29 MDMA users seeking mental health services, 28% had VHD confirmed by echocardiography versus none in the gender- and age-matched controls, where these MDMA users averaged 3.6 tablets per week for 6.1 years (Droogmans et al., 2007). The studies of drugs withdrawn from the market included patients taking daily medication for a year or more, and data also suggested that higher cumulative exposure increased risk (Hutcheson, Setola, Roth & Merryman, 2011). Based on this limited evidence, a shorter duration of microdosing (weeks to months) with longer breaks would likely be lower risk than a longer duration of dosing without any breaks for years.


It’s important to recognize that there are many FDA-approved medications on the US market with a variety of serious adverse drug reactions, including VHD, so, as a pharmacist, I always recommend weighing the benefits against the risks. If and when evidence of microdosing effectiveness is demonstrated, then these benefits should be carefully weighed against the potential risk of VHD. Current microdosing research projects should also begin to collect data that systematically evaluates the risk of VHD. I am an advocate for harm reduction and patient autonomy, which motivates me to provide clients with the most accurate medical evidence I can find, so I hope my summary of this topic has clearly explained why I am worried about the potential for chronic microdosing to break your heart.

Then some references.


--------------------
The Italian researchers’ findings, published by the INT’s scientific magazine Tumori Journal, show 11.6% of 959 healthy volunteers enrolled in a lung cancer screening trial between September 2019 and March 2020 had developed coronavirus antibodies well before February.

https://www.reuters.com/article/us-health-coronavirus-italy-timing-idUSKBN27V0KF

This online first version has been peer-reviewed, accepted and edited,  but not formatted and finalized with corrections from authors and proofreaders

https://www.icandecide.org/


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OfflineMorel Guy
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Re: Why Chronic Microdosing Might Break Your Heart [Re: HamHead]
    #26402948 - 12/27/19 12:00 PM (4 years, 1 month ago)

Take a whopper from time to time.  Go knows that gets through.


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"in sterquiliniis invenitur in stercore invenitur"

In filth it will be found in dung it will be found


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OfflineBabylonRuleDem
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Re: Why Chronic Microdosing Might Break Your Heart [Re: HamHead] * 3
    #26402954 - 12/27/19 12:06 PM (4 years, 1 month ago)

My bullshit detectors are going crazy here:eek:
What was the total number of participants in the 1967 study that had 12 people affected? 100-150ug is not a microdose...and they were giving these doses to 7 year olds?:lolsy:
Taking any drug daily for 35 months is not a good idea, even so this article provides nothing more than anecdotes.

“Of the thousands of people who microdosed, no one has reported any heart valve trouble during their period of microdosing, and many people have been microdosing for over a year. All the people we have surveyed with heart problems had them before they started microdosing”
So why write this article?

correlation does not imply causation, this article is  :shitty:


--------------------
When we all get strange, and we know it, but we're cool with it

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Edited by BabylonRuleDem (12/27/19 12:10 PM)


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OfflineStoic
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Morel Guy]
    #26402973 - 12/27/19 12:26 PM (4 years, 1 month ago)

We all die sometime and according to our "health professionals" everything will kill us, except the drugs, treatments and chemicals they prescribe, but if I am not mistaken prescription drugs have killed more people than the Nazis and will soon overtake religion as the all time mass murder champion of the world. The health care industry is about making profit, which it does by ongoing treatment not curing of diseases, because you only get paid once for a cure. Patients health and well being has taken a back seat to money, hypocritical oath lol. Doctors before the 1970s where middle class just like their patients, now they are millionaires and everyone suffers and dies to fill the coffers that support a life of ultra luxury. When any politician, corporation, or self interested entity tells me that this is good or bad for me, I automatically think that they meant it is good or bad for them, meaning they gain or lose money or power based on the propaganda they are currently spewing forth like a living geyser of feces (old faithless, perhaps). Like any decision in life, a free life, the person making the decision should make it for themselves with knowledge and rationality, which means they need to know about possible negatives of said decision like they hear from health professionals and government, but also need the truth and the other side- positive benefits, which they will not hear from previously stated self interested entities. Advice for everyone is to get information from many different places and use rational thought to sift through and find truth, whole truth, and then make an educated rational choice for themselves.


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OfflineKorean Jesus
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Stoic]
    #26402993 - 12/27/19 12:47 PM (4 years, 1 month ago)

Idk how I feel about these studies, psychedelics are so personal that it’s hard to generalize. A few macrodoses permanently messed up my vision (not to the extent that it impedes anything in my life, just very brief afterimages and other barely noticeable phenomena) and changed the way my brain works (in a good way, I think), contrary to what the studies say.


--------------------
:rastamon::getstoned::rastamon:


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OfflineSabnock
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Korean Jesus]
    #26403077 - 12/27/19 02:03 PM (4 years, 1 month ago)

I took oral DMT daily/near daily for 4 years, in full dosages for the most part, no heart problems and it's been said DMT shows some binding to the 2B receptor as well but as far as i know no study has looked at if it's a good agonist at that receptor. Plus the fact that Psychedelics, at least the natural ones, have been used by people all over the world throughout Human history, no physical issues that we know of. But imo, it does deserve more study to make sure of potential risks, i know they say you're not supposed to consume Psychedelic if you have a heart condition but i think that has more to do with the intensity of the experiences rather than something to do with the 2B receptor or dramatic heart rate increase, my most intense oral DMT/Aya experience i checked my blood pressure and heart rate, and it was only very slightly increased but for the most part normal even though it felt like i was having a panic attack and it was very intense. but that's me.


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OfflineBabylonRuleDem
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Sabnock] * 1
    #26403099 - 12/27/19 02:33 PM (4 years, 1 month ago)

Quote:

Sabnock said:
But imo, it does deserve more study to make sure of potential risks, i know they say you're not supposed to consume Psychedelic if you have a heart condition...



I agree, but the article is still shit with loose allegations and goes as far as to lump MDMA in with psilocybin.

MDMA is an amphetamine, of course its going to affect the heart with chronic use:huxleyfacepalm:


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When we all get strange, and we know it, but we're cool with it

Trade List(WIP)


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OfflineKorean Jesus
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Re: Why Chronic Microdosing Might Break Your Heart [Re: BabylonRuleDem]
    #26403153 - 12/27/19 03:27 PM (4 years, 1 month ago)

FWIW my heartrate definitely goes up on shrooms


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:rastamon::getstoned::rastamon:


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OfflinePrimalSoup
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Korean Jesus]
    #26403210 - 12/27/19 04:15 PM (4 years, 1 month ago)

I've never been able to tell 'cause I can't figure out how clocks work when I'm :trippnballs:

But I've tripped on shrooms well over a thousand times and never had any concern about heart problems.  OF COURSE that's just anecdotal. :cookiemonster:


--------------------

if you stand too close to the machine it'll start to eat you
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OfflineCosmic Eye
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Re: Why Chronic Microdosing Might Break Your Heart [Re: PrimalSoup]
    #26403408 - 12/27/19 06:08 PM (4 years, 1 month ago)

Hmm interesting read. I think any drug over time will have an adverse effect of some sort. Its not meant to be for chronic/daily use and that goes for just about anything. Commercialized pharmaceuticals tho, I agree 100% and Ill leave it at that.

I have self diagnosed AFib because its obvious to me that my heart has episodes of defibrillation. Would this be discovered clinically after a microdose study? Is Afib and conditions like it really that common? But there must be some sort of truth to it if the receptors are known to be effected. Over time any consequence is possible and who know whats truely happening long term, but this is a reasonable argument to consider. Its a bit extreme and maybe a more modern day study is needed. Who will be the volunteer?


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OfflineKorean Jesus
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Re: Why Chronic Microdosing Might Break Your Heart [Re: PrimalSoup]
    #26403470 - 12/27/19 06:41 PM (4 years, 1 month ago)

Quote:

PrimalSoup said:
I've never been able to tell 'cause I can't figure out how clocks work when I'm :trippnballs:

But I've tripped on shrooms well over a thousand times and never had any concern about heart problems.  OF COURSE that's just anecdotal. :cookiemonster:




According to my watch my HR was in the 90s for my heroic dose, 100+ when I was scared. ~70 resting naturally. Quite a difference.


--------------------
:rastamon::getstoned::rastamon:


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OfflinePrimalSoup
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Korean Jesus]
    #26403477 - 12/27/19 06:43 PM (4 years, 1 month ago)

I've only tripped heavily for the most part when very fit and IME that makes a huge difference.  I don't think I've ever checked my pulse at any time...  But then I don't wear a watch either. :shrug:


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if you stand too close to the machine it'll start to eat you
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OfflineNOUS333
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Re: Why Chronic Microdosing Might Break Your Heart [Re: PrimalSoup]
    #26403696 - 12/27/19 09:13 PM (4 years, 1 month ago)

Quote:

PrimalSoup said:
I've never been able to tell 'cause I can't figure out how clocks work when I'm :trippnballs:

But I've tripped on shrooms well over a thousand times and never had any concern about heart problems.  OF COURSE that's just anecdotal. :cookiemonster:




Over a thousand times.  Thats crazy. 

I cant bring myself to trip again for what would probably be no more than my 10th time.


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OfflinePrimalSoup
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Re: Why Chronic Microdosing Might Break Your Heart [Re: NOUS333]
    #26403809 - 12/27/19 10:53 PM (4 years, 1 month ago)

:lol:  Uhm, really you just do it.  Kind of like swimming.


--------------------

if you stand too close to the machine it'll start to eat you
Primal's simple tested teks and projects: :awesomenod: Wheat Prep 2.0  Acidic Tea Tek  Potency Project! 


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OfflineLoaded Shaman
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Re: Why Chronic Microdosing Might Break Your Heart [Re: BabylonRuleDem]
    #26403933 - 12/28/19 01:33 AM (4 years, 1 month ago)

Quote:

BabylonRuleDem said:
My bullshit detectors are going crazy here:eek:
What was the total number of participants in the 1967 study that had 12 people affected? 100-150ug is not a microdose...and they were giving these doses to 7 year olds?:lolsy:
Taking any drug daily for 35 months is not a good idea, even so this article provides nothing more than anecdotes.

“Of the thousands of people who microdosed, no one has reported any heart valve trouble during their period of microdosing, and many people have been microdosing for over a year. All the people we have surveyed with heart problems had them before they started microdosing”
So why write this article?

correlation does not imply causation, this article is  :shitty:




This right here. If anything I think organizations are getting more desperate to spread anti-psych propaganda as a last-ditch effort with the rise of information on YouTube, blogs, and sites such as this.

It's a trap!!! :cool:


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"Real knowledge is to know the extent of one’s ignorance." — Confucius


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OfflineKorean Jesus
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Re: Why Chronic Microdosing Might Break Your Heart [Re: PrimalSoup]
    #26404134 - 12/28/19 06:24 AM (4 years, 1 month ago)

Quote:

PrimalSoup said:
:lol:  Uhm, really you just do it.  Kind of like swimming.



I'd trip more if I weren't concerned about my vision


--------------------
:rastamon::getstoned::rastamon:


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OfflineNOUS333
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Re: Why Chronic Microdosing Might Break Your Heart [Re: PrimalSoup]
    #26404160 - 12/28/19 07:00 AM (4 years, 1 month ago)

Quote:

PrimalSoup said:
:lol:  Uhm, really you just do it.  Kind of like swimming.




Well. Maybe its different for you.  I get really attached to thoughts and very ‘involved’ with what goes on in my head even when im just sober but especially tripping.  Out of all my trips maybe 1 or 2 were cognitively light and fun experiences. The rest have all been deeply spiritual and transition points in my life that had me processing shit for months if not years.   

The last trip i had was so powerful, 6 years ago, when i thought of tripping again 2 years ago all i had to do was go out and buy a strainer and stuff to make tea, i think i made the tea and took one sip and realized i was fooling myself. I knew what i had to do in my life and i knew the mushrooms were just going to tell me the same thing. I got serious with my self, got serious about listening my higher intuitions and ive really come a long way since. All because i only thought about tripping. 

I kinda wish i could just trip recreationally but whatever spiritual associations ive made in my brain with tripping whether they are false or not have really helped me get my shit together and take life seriously.      I kinda wish i could talk to you in person though, ive never met anyone who has tripped that much....feel like we could have some interesting conversations. 

.


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Offlineazramb
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Re: Why Chronic Microdosing Might Break Your Heart [Re: NOUS333]
    #26404288 - 12/28/19 08:56 AM (4 years, 1 month ago)

Interesting, I understand the concern and it's always good to be looking out for potential side effects but I honestly don't think there's anything to be worried about. I've just never heard of anyone having any side effect like this from long term microdosing. Most people who microdose don't necessarily do it daily though. More like a couple days on couple days off kind of thing. However some do dose daily and still seem to be fine. More legitimate studies should be done but I doubt they cause any real trouble on the heart.


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InvisibleBill_Oreilly
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Korean Jesus] * 1
    #26404403 - 12/28/19 10:03 AM (4 years, 1 month ago)

Quote:

Korean Jesus said:
Quote:

PrimalSoup said:
:lol:  Uhm, really you just do it.  Kind of like swimming.



I'd trip more if I weren't concerned about my vision





dude youre fine, stop with that. You are very new to tripping and if you REALLY had eye problems from tripping just a few times, i would never trip again and go to a doctor.

its all in your head


--------------------
Something there is mysteriously formed,
Existing before Heaven and Earth,
Silent, still, standing alone, unchanging,
All-pervading, unfailing,
I do not know its name; I call it tao.
If forced to give it a name, I call it
Great (ta). Being great, it flows out;
Flowing out means far-reaching;
Being far-reaching, it is said to return.


It's just a shot away..


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OfflineKorean Jesus
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Re: Why Chronic Microdosing Might Break Your Heart [Re: Bill_Oreilly]
    #26404491 - 12/28/19 11:05 AM (4 years, 1 month ago)

Quote:

Bill_Oreilly said:
Quote:

Korean Jesus said:
Quote:

PrimalSoup said:
:lol:  Uhm, really you just do it.  Kind of like swimming.



I'd trip more if I weren't concerned about my vision





dude youre fine, stop with that. You are very new to tripping and if you REALLY had eye problems from tripping just a few times, i would never trip again and go to a doctor.

its all in your head



hopefully bro :smile:


--------------------
:rastamon::getstoned::rastamon:


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