I would really, really deeply appreciate it if Bryan Roth or anyone else would cite even a single study that shows that LSD has ever caused valvular heart disease. MANY, MANY millions of people have taken LSD over the past more than 50 years and I have never heard of anyone developing valvular heart disease because of their LSD use.
AGAIN: I am just asking for someone to cite EVEN ONE STUDY that has found that LSD has ever damaged anyone's heart valves. I am asking because I took LSD more than 5,000 times, starting in 1969, and have spent most of my time since 1966 researching the subject of LSD and the sometimes SEVERELY negative reactions people can have after taking LSD. (I invented the word "microdose", according to Torsten Passie. I manufactured the first large batch of labeled 5 microgram microdoses in the San Francisco bay area in the late 1980s. Hundreds of thousands of these labeled microdoses [out of a total of more than 400,000 doses] were seized by the DEA in January 1993.) My lengthy "autobiography" may be read here on my Substack.
Bryan Roth is quoted as having said "Any drug in development is tested against this receptor, and if the drug activates it, they throw it away. It’s well-established as a target to avoid." That, and some of Bryan Roth's other warning statements, definitely seems to indicate that people should NOT use LSD!
Because Bryan Roth is far, far better educated than I am, I think it is important for me to listen carefully to what he has to say. (Luckily for the public, after many decades of very, very widespread use, LSD can no longer accurately be called a "drug in development"...)
Alarmism is UGLY and can physically harm people. People who use psychedelics are said to tend to be MUCH more influenced by suggestion than non-users. I think it is possible that the severe anxiety caused by the fear that their use of LSD has physically damaged them that some people may experience after reading what Bryan Roth has said may actually harm them...
Interesting article-it appears that "we don't know how SSRIs work, or psychedelics work in the brain. The former, works on the transmitter site, NOT on the receptor, while the latter works (agonist) on the actual receptor. Is there any evidence that these compounds work on the gut where 90% of serotonin is produced? Do we know of any "patients" that have contracted heart disease from say microdosing, and what is the threshold here? Seems like a lot more research is needed other than comparing a pharma drug two decades ago to natural compounds...
Follow up question for Bryan or Jane, if they'd be kind enough...
Bryan says "The drugs we identified had also caused valvular heart disease in up to 30 percent of patients taking them." Before starting a panic in the psychedelic community, is there any reason to take comfort in the fact that Parkinson's medications or migraine medications are taken frequently, while most psychedelic therapy sessions are few and far between?
Hi Davivid, it sounds like you have had an interesting and colorful journey.
A couple points to clarify. What Bryan Roth is not saying is that people should not use these substances , or that classic Psychedlics and MDMA, etc.. cause cardiac valvular defects . He is saying that based on their pharmacology , they could have this effect. We just don’t know. It’s an appropriate and responsible question to ask (and answer)
A retrospective study could be done trying to correlate past use such as yours and any increased incidence of heart valve defects vs what would be expected in the general population. Costly and time consuming but possible.
I think his concern is more with the potential of microdosing classics on an ongoing basis versus megadose theory. And yes, due to numbers of users in the sixties we probably would have picked up on a relationship to megadose use and defects by now.
Im cautiously highly enthusiastic about the potential of these substances in the prevention/treatment of especially mental health “disorders”, yet harm reduction ,including important questions like Bryan’s , should be prioritized first.
I strongly disagree with your assertion that "...Bryan Roth is not saying is that people should not use these substances..." (I am pretty sure that if you asked Bryan Roth if you should use the highly illegal [Schedule 1] drug LSD, he would say you "should not".)
Many more people are said to use LSD these days than used LSD in the 1960s. (If nothing else, there simply are MANY more people alive now than there were in the 1960s.)
I disagreed with those alarmists in the 1960s who loudly claimed LSD might be "like thalidomide". I disagreed with those alarmists in the 1960s who loudly claimed LSD causes "chromosome damage".
I am an old person. Doctors have studied my heart a lot. And frequently. To the best of my knowledge, none of the high tech imaging, etc. that has been done over the years has shown any sign of damage to my heart valves.
I think I kind of understand what Roth is saying about frequent microdosing. My original detailed written instructions for the use of 5 microgram microdoses of LSD, which came with each packet of 25 microdoses, made it VERY clear that the microdoses of LSD I was manufacturing and distributing for free were NOT intended for casual DAILY use.
What apparently happened was that Fadiman and many others apparently decided they could make a lot of money if they packaged and sold the idea of microdosing and convinced people that they should do it often...
Although I greatly respect LSD and find its use to be amazingly helpful to me, I think that some of the incredibly strong emotions that megadoses of LSD can unleash are capable of possibly having a hand in things like heart attacks. People have been said to "die of fright", although I do not know if anyone has actually been shown to have done so.
I am surprised that this question hasn't come up in these discussions: "What has happened to the prevalence of valvulopathy in the U.S. and other countries since say 1960 and now?" - We have an absolute increase in consumption from almost zero to whatever number. Some of the use seems to have been frequent, i.e. weekly if not daily. Should there not be an increase? Similar question to the one that comes up around cannabis and schizophrenia - if it's causal should there not be an increase.
"In June 2020, Roth's Lab announced a $26.9 million cooperative agreement with the Defense Advanced Research Projects Agency (DARPA) to develop a new class of psychiatric drugs for the treatment of addiction, anxiety, or depressive symptoms."
(Fenfluramine hydochloride is "an amphetamine analogue", according to a 2020 FDA document I read. A 2004 EPA document about fen-phen mentions a daily fenfluramine dose of 30 milligrams.
["The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg."
---from a 1975 NIH document about fenfluramine.]
A 120mg dose of fenfluramine weighs 120,000 micrograms.
A microdose of LSD weighs 5 micrograms.
A 120,000 microgram dose of fenfluramine is 24,000 TIMES LARGER THAN A 5 MICROGRAM MICRODOSE OF LSD.)
Bryan Roth said (about SSRIs) "They work — we don’t know why they work..."
Bryan Roth said "We notified the FDA and drug companies....they ignored our recommendations."
(Perhaps the reason the FDA thought Bryan Roth lacked credibility was because of where he went to school.)
Bryan Roth said "The big concern is with repeated dosing, and lots of people are doing that now with microdosing. That’s extraordinarily risky until the appropriate studies have been done; you’re basically recapitulating the situation that led to fen-phen."
(I am horrified by this EXTREMELY INFLAMMATORY statement. It reminds me of what Kelan Thomas said in The Microdose recently, warning that microdosing could lead to valvular heart diease, which can cause "death". After repeated requests, Thomas also has failed to cite even a single case of someone developing valvular heart disease after using microdoses [or macrodoses] of LSD.)
It is estimated that over the past 60 or so years many, many, many hundreds of millions of people have taken LSD.
IRL I have not seen or heard of any report of any person ever developing valvular heart disease because they used LSD.
THE BOTTOM LINE, OF COURSE, IS ALWAYS "FIRST, DO NO HARM"!!!!
Recommending to people that they take ANY drug, especially an illegal one, for any reason, is something that I have steadfastly refused to do since my first LSD experience in 1969. I am not licensed to practice medicine and I do not do so.
I wonder what it is about psychedelics like LSD, psylocibin and MDMA that seem to be very useful for therapeutic use with their plasticity where the other drugs mentioned are not good therapy drugs?
Mechanism with respect to what effect? SSRIs block Re uptake of Serotonin (among other things) . SNRIs block uptake of both Serotonin and Norepinephrine. If you have a more specific question I am happy to try and answer .
It seems MDMA , in the case of PTSD , and the classic Psychedelics (LSD/Psilocybin/Mescaline/DMT ) in the case of anxiety and depression, have very different mechanisms of a action.
MDMA suppresses Amygdala responsiveness (the “fear” center). This allows some with PTSD to “approach” their traumatic events more directly and see them in a new light which dismantles the need for the fear response that underlies PTSD .
Classic Psychedelics may help some people with anxiety and depression by decreasing the influence of prior beliefs (and thus sense of self and the environment ) while simultaneously stimulating large release of BDNF —allowing for new learning. That’s why integration work focusing on behavioral change directed by more clear motivation is so critical to healing in the context of psychedelic assisted therapy . Note the wording : psychedlic assisted therapy —not therapy assisted psychedelic use!
I would really, really deeply appreciate it if Bryan Roth or anyone else would cite even a single study that shows that LSD has ever caused valvular heart disease. MANY, MANY millions of people have taken LSD over the past more than 50 years and I have never heard of anyone developing valvular heart disease because of their LSD use.
AGAIN: I am just asking for someone to cite EVEN ONE STUDY that has found that LSD has ever damaged anyone's heart valves. I am asking because I took LSD more than 5,000 times, starting in 1969, and have spent most of my time since 1966 researching the subject of LSD and the sometimes SEVERELY negative reactions people can have after taking LSD. (I invented the word "microdose", according to Torsten Passie. I manufactured the first large batch of labeled 5 microgram microdoses in the San Francisco bay area in the late 1980s. Hundreds of thousands of these labeled microdoses [out of a total of more than 400,000 doses] were seized by the DEA in January 1993.) My lengthy "autobiography" may be read here on my Substack.
Bryan Roth is quoted as having said "Any drug in development is tested against this receptor, and if the drug activates it, they throw it away. It’s well-established as a target to avoid." That, and some of Bryan Roth's other warning statements, definitely seems to indicate that people should NOT use LSD!
Because Bryan Roth is far, far better educated than I am, I think it is important for me to listen carefully to what he has to say. (Luckily for the public, after many decades of very, very widespread use, LSD can no longer accurately be called a "drug in development"...)
Alarmism is UGLY and can physically harm people. People who use psychedelics are said to tend to be MUCH more influenced by suggestion than non-users. I think it is possible that the severe anxiety caused by the fear that their use of LSD has physically damaged them that some people may experience after reading what Bryan Roth has said may actually harm them...
Interesting article-it appears that "we don't know how SSRIs work, or psychedelics work in the brain. The former, works on the transmitter site, NOT on the receptor, while the latter works (agonist) on the actual receptor. Is there any evidence that these compounds work on the gut where 90% of serotonin is produced? Do we know of any "patients" that have contracted heart disease from say microdosing, and what is the threshold here? Seems like a lot more research is needed other than comparing a pharma drug two decades ago to natural compounds...
Too bad we can't hear from Alexander Shulgin about this.
Follow up question for Bryan or Jane, if they'd be kind enough...
Bryan says "The drugs we identified had also caused valvular heart disease in up to 30 percent of patients taking them." Before starting a panic in the psychedelic community, is there any reason to take comfort in the fact that Parkinson's medications or migraine medications are taken frequently, while most psychedelic therapy sessions are few and far between?
2000 is 23 years ago. Any receptor research in this decade that moved the science forward?
Hi Davivid, it sounds like you have had an interesting and colorful journey.
A couple points to clarify. What Bryan Roth is not saying is that people should not use these substances , or that classic Psychedlics and MDMA, etc.. cause cardiac valvular defects . He is saying that based on their pharmacology , they could have this effect. We just don’t know. It’s an appropriate and responsible question to ask (and answer)
A retrospective study could be done trying to correlate past use such as yours and any increased incidence of heart valve defects vs what would be expected in the general population. Costly and time consuming but possible.
I think his concern is more with the potential of microdosing classics on an ongoing basis versus megadose theory. And yes, due to numbers of users in the sixties we probably would have picked up on a relationship to megadose use and defects by now.
Im cautiously highly enthusiastic about the potential of these substances in the prevention/treatment of especially mental health “disorders”, yet harm reduction ,including important questions like Bryan’s , should be prioritized first.
I strongly disagree with your assertion that "...Bryan Roth is not saying is that people should not use these substances..." (I am pretty sure that if you asked Bryan Roth if you should use the highly illegal [Schedule 1] drug LSD, he would say you "should not".)
Many more people are said to use LSD these days than used LSD in the 1960s. (If nothing else, there simply are MANY more people alive now than there were in the 1960s.)
I disagreed with those alarmists in the 1960s who loudly claimed LSD might be "like thalidomide". I disagreed with those alarmists in the 1960s who loudly claimed LSD causes "chromosome damage".
I am an old person. Doctors have studied my heart a lot. And frequently. To the best of my knowledge, none of the high tech imaging, etc. that has been done over the years has shown any sign of damage to my heart valves.
I think I kind of understand what Roth is saying about frequent microdosing. My original detailed written instructions for the use of 5 microgram microdoses of LSD, which came with each packet of 25 microdoses, made it VERY clear that the microdoses of LSD I was manufacturing and distributing for free were NOT intended for casual DAILY use.
What apparently happened was that Fadiman and many others apparently decided they could make a lot of money if they packaged and sold the idea of microdosing and convinced people that they should do it often...
Although I greatly respect LSD and find its use to be amazingly helpful to me, I think that some of the incredibly strong emotions that megadoses of LSD can unleash are capable of possibly having a hand in things like heart attacks. People have been said to "die of fright", although I do not know if anyone has actually been shown to have done so.
I am surprised that this question hasn't come up in these discussions: "What has happened to the prevalence of valvulopathy in the U.S. and other countries since say 1960 and now?" - We have an absolute increase in consumption from almost zero to whatever number. Some of the use seems to have been frequent, i.e. weekly if not daily. Should there not be an increase? Similar question to the one that comes up around cannabis and schizophrenia - if it's causal should there not be an increase.
"In June 2020, Roth's Lab announced a $26.9 million cooperative agreement with the Defense Advanced Research Projects Agency (DARPA) to develop a new class of psychiatric drugs for the treatment of addiction, anxiety, or depressive symptoms."
---Christopher Bergland, Psychology Today, 9.17. 2020.
AND:
(Fenfluramine hydochloride is "an amphetamine analogue", according to a 2020 FDA document I read. A 2004 EPA document about fen-phen mentions a daily fenfluramine dose of 30 milligrams.
["The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg."
---from a 1975 NIH document about fenfluramine.]
A 120mg dose of fenfluramine weighs 120,000 micrograms.
A microdose of LSD weighs 5 micrograms.
A 120,000 microgram dose of fenfluramine is 24,000 TIMES LARGER THAN A 5 MICROGRAM MICRODOSE OF LSD.)
Bryan Roth said (about SSRIs) "They work — we don’t know why they work..."
Bryan Roth said "We notified the FDA and drug companies....they ignored our recommendations."
(Perhaps the reason the FDA thought Bryan Roth lacked credibility was because of where he went to school.)
Bryan Roth said "The big concern is with repeated dosing, and lots of people are doing that now with microdosing. That’s extraordinarily risky until the appropriate studies have been done; you’re basically recapitulating the situation that led to fen-phen."
(I am horrified by this EXTREMELY INFLAMMATORY statement. It reminds me of what Kelan Thomas said in The Microdose recently, warning that microdosing could lead to valvular heart diease, which can cause "death". After repeated requests, Thomas also has failed to cite even a single case of someone developing valvular heart disease after using microdoses [or macrodoses] of LSD.)
It is estimated that over the past 60 or so years many, many, many hundreds of millions of people have taken LSD.
IRL I have not seen or heard of any report of any person ever developing valvular heart disease because they used LSD.
THE BOTTOM LINE, OF COURSE, IS ALWAYS "FIRST, DO NO HARM"!!!!
Recommending to people that they take ANY drug, especially an illegal one, for any reason, is something that I have steadfastly refused to do since my first LSD experience in 1969. I am not licensed to practice medicine and I do not do so.
I wonder what it is about psychedelics like LSD, psylocibin and MDMA that seem to be very useful for therapeutic use with their plasticity where the other drugs mentioned are not good therapy drugs?
I have a simple question.. do SSNI have the same mechanisms as SSRI?
Hi Linda
Mechanism with respect to what effect? SSRIs block Re uptake of Serotonin (among other things) . SNRIs block uptake of both Serotonin and Norepinephrine. If you have a more specific question I am happy to try and answer .
Best regards
Hi Chase
It seems MDMA , in the case of PTSD , and the classic Psychedelics (LSD/Psilocybin/Mescaline/DMT ) in the case of anxiety and depression, have very different mechanisms of a action.
MDMA suppresses Amygdala responsiveness (the “fear” center). This allows some with PTSD to “approach” their traumatic events more directly and see them in a new light which dismantles the need for the fear response that underlies PTSD .
Classic Psychedelics may help some people with anxiety and depression by decreasing the influence of prior beliefs (and thus sense of self and the environment ) while simultaneously stimulating large release of BDNF —allowing for new learning. That’s why integration work focusing on behavioral change directed by more clear motivation is so critical to healing in the context of psychedelic assisted therapy . Note the wording : psychedlic assisted therapy —not therapy assisted psychedelic use!