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solo
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Ayahuasca psychedelic tested for depression
Ayahuasca psychedelic tested for depression
Pilot study with shamanic brew hints at therapeutic potential.
Arran Frood
NATURE
06 April 2015
Attachment: phpejw4l2 (766kB)
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It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Chemosynthesis
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Too bad it's an open-label study. Until the placebo controlled trial is published and reviewed, I'm not too excited, though I would not be surprised
to see efficacy.
Placebo implementation will be interesting (possible use of low dose emetics?) It would be nice to later see what combinatorial effects, if any, are
in play if efficacy is demonstrated, as optimizing the ligands to specific receptors without as many side effects would be nice (i.e. MOAI
interactions, blood pressure spikes, some serotonin agonism and anticholinergics causing gastrointestinal side effects and affecting
polydrug/medication use).
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Zombie
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To bounce off Chemosynthesis, Cool!
This is part of what I am attempting to study.
There are many different, yet related idiosyncrasies of the human psyche that can only be accessed thru Psychedelics. It's a saddening state of
affairs that Hippies, and drug addicts got their hands on these compounds in the 60's, because the uses for such drugs / compounds could be the answer
for many of the afflictions people deal with on a daily basis.
Depression, anxiety, addictions, Bi polar disorders, ect all appear to be easily treatable with compounds like N N-DMT, 5-mEO-DMT, 4-mEO- DMT,
Psilocin, Psilocybin, 2-cE, ect. all appear to have HUGE benefits, and very low if any risks or addictive qualities.
Most of you are aware that N N-DMT is found in practically every species of animal tested, as well as being present in many plant species. Every one
of us has this compound in us now. It is produced by our physiology, yet it is considered a Class 1 drug, and has (according to the US Govt) NO
legitimate use.
For the most part the only research allowed (by law) is to determine how bad it is. This being the case, legitimate research as to it's beneficial use
is almost impossible to undertake.
You all sort of have a "feel" for me, and what type of person I am.
I HATE drug addicts. Hang them all. Raping, robbing, welfare leeching, no good bastards. Rush Limbaugh is on my list as well.
Drugs in society are there for real reasons. Complex problems arise from miss-use.
All that said... I have tried practically every drug on the planet at one time or another. I'm no spring chicken, nor am I immune to a good time BUT,
I never fell into the group I deplore. I NEVER took a drug as a crutch or as an escape.
That brings me to this... The one field that I believe needs to be researched in order to better humanity is the science behind EXACTLY what these
compounds do in the human body / brain.
Not just collecting "Trip Reports" but finding what part of the brain is doing what , when these compounds are being used.
In reality MOST of the "anti-depressants" that are prescribed have completely unknown mechanisms. Yet they are shoveled into schools, hospitals, work
places by the TON!
What's worse is there is No known end to treatment.
I have read several studies that indicate addictions of many types can be eliminated in as few as THREE treatments with N N-DMT.
Depression can be treated, and eliminated with low dose Psilocin in as little as 6 months!
Are the doctors, researchers, Big Prarm., and our elected law makers really attempting to get rich by feeding us ineffective CRAP, and allowing the
potential life changing compounds to be swept under the legal rug?
I REALLY don't understand all this but I do know the one field that I choose to study is one of the most difficult fields there is. That is true for
Many reason I have posted here plus more I have not listed for the sake of sparing a rant.
In all honesty... I will never be told what to do, when to do, how to do, or actually Anything I do not freely choose to do. Something like attempting
to help humanity on the most basic level can not be considered a bad thing in any light.
If it is??? They better have me put down.
I work on hunches.
I saw computers before "punch cards'. I saw MP-3 players before 8 tracks. The list is long...
I see the compounds I listed as the saving grace of humanity.
Personally I do not know a single person on any sort of prescribed psychotropic medication that could not do better on the compounds that we are not
allowed to research.
I feel the same about addictions... Coffee, Booze, tobacco, heroin, scratching your butt. Whatever the addiction, it can be stopped.
I for one would like to see changes so that the really smart people could put their efforts into working with the real deal compounds.In fact I'd sell
everything, and buy the stock!
They tried to have me "put to sleep" so I came back to return the favor.
Zom.
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Etaoin Shrdlu
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Hey. I like being addicted to caffeine.
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cyanureeves
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a placebo effect would certainly indicate a troubled person or an imaginative individual with mind reading capability. a placebo that causes visuals
and hallucinations could no way be a placebo unless maybe the patient is told about the drug's effects.even smoking dmt infused banasteriopsis is
different and way more potent than just the dmt alone. i have banasteriopsis and mimosa root bark and i think i could make an ayahuasca brew with just
those two herbs. a 12 hour trip on ayahuasca would be shear terror if a patient was noy told what he was given. i smoke dmt infused banasteriopsis and
and do chill for days afterwards but i think it's just a feeling of appreciation that i am not on a dmt high.the crap is just spooky but as
fascinating as a scary carnival ride is to an unsuspecting child and that boggles an adult.a placebo would not work on me and i can attest that it
does calm me down for days afterwards but so did a good ass kicking when i was young.i guess trauma works! sorry! mispelled bisteriopsis.shoulda
learned grammer instead of smoking.
[Edited on 4-8-2015 by cyanureeves]
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gregxy
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The other thing is that Big Pharma has been aware of these drugs for 50 years. In spite of their class 1 status, I'm sure they have researched the
hell out of them. If there was a way to make them work for depression etc. I think they would have found it already.
Cannabis is another story. It is illegal because Big Pharma and Budwiser don't want competition from something you can easily grow in your yard.
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Zombie
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Quote: Originally posted by gregxy  | The other thing is that Big Pharma has been aware of these drugs for 50 years. In spite of their class 1 status, I'm sure they have researched the
hell out of them. If there was a way to make them work for depression etc. I think they would have found it already.
Cannabis is another story. It is illegal because Big Pharma and Budwiser don't want competition from something you can easily grow in your yard.
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Is the first paragraph your opinion or fact?
I'm not asking to be disrespectful.
To set a "buffer zone" in this thread... I am referring to a regulated dose, controlled fashion use of specific compounds.
You do not need to meet Jesus in order for a compound to have an effect.
while 60 Mg of Valium can be a hoot, I don't think that is what the prescribed use is intended to be.
N N-DMT in controlled / less than threshold doses is what I am talking about, and I believe that is where the research is.
I already mentioned we do not need more "trip reports". We need facts.
In this case the placebo effect is an accountable control for determining some of the effect.
As far as Weed is concerned...
My same approach applies. There is NO NEED FOR AN OUNCE OF WEED when a few Mg's of extracted compound will last a month in controlled doses.
Most people would suddenly get cured if it were only allowed as a 0.45Mg pill that had the same medical effect as 20 "Bong Hits", yet did not get you
high.
I don't even care what ANY pot smoker says. It's about the high. Nothing more. Go bleed in the street. I don't care.
The fact is people have manipulated the use, and effects to the point they are doing the equivalent of 60mg Valium doses several times a day.
Did I mention I HATE stoners as much as any other form of drug addict? I should have.
Like much of YouTube... Addicts, or any sort of abuser help form the poor image of many useful compounds.
For hells sake, you can't even buy battery acid in many parts of the world. Did that happen because we don't need batteries? NO!
Abusers destroy everything in their wake.
This is the fate of Mushrooms, cactus, DMT,
Low controlled doses for specific uses have been shown time, and time again to be beneficial but stoners rule the day.
Find a way to get high on air. I'm tired of it all around me all the time anyway. Air is Soooo annoying . I want it gone.
[Edited on 4-8-2015 by Zombie]
They tried to have me "put to sleep" so I came back to return the favor.
Zom.
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blogfast25
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I could ask the same about your initial long ramble. Maybe (!) tomorrow I might make some time to rebut some of the points you've made so far.
On the positive side, I'm all for controlled research into psychotropic substances, on the 'sub-high' dosage level (for potentially therapeutic
purposes). But substances that have potential hallucinatory side-effects will often not make it onto the 'to do' list of most licensed researchers.
That has little, if anything, to do with 'hippies' or 'raping drug users' or 'stoners'.
By the way, without these 'psychedelic' effects, who would ever have heard of, say Ayahuasca? It's precisely their obvious effects that draw
attention to them and might, potentially, make them interesting subjects of study as therapeutics.
[Edited on 8-4-2015 by blogfast25]
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Zombie
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| Quote: Originally posted by blogfast25 |
I could ask the same about your initial long ramble. Maybe (!) tomorrow I might make some time to rebut some of the points you've made so far.
On the positive side, I'm all for controlled research into psychotropic substances, on the 'sub-high' dosage level. But substances that have potential
hallucinatory side-effects will often not make it onto the 'to do' list of most licensed researchers. That has little, if anything, to do with
'hippies' or 'raping drug users' or 'stoners'.
By the way, without these 'psychedelic' effects, who would ever have heard of, say Ayahuasca? It's precisely their obvious effects that draw
attention to them and might, potentially, make them interesting subjects of study as therapeutics.
[Edited on 8-4-2015 by blogfast25] |
You usually call me out on my over dramatic flair. I will try harder to work on this.
It's akin to the issues with chemistry in general.
The bad apples tend to spoil things for the rest. I've only spent a few months researching this topic but I do have some very interesting information
to date. Trouble is there is not much in the way of actual published research. I say not much but there is some...
Dr Robin Carhart-Harris is one of the better researchers in my opinion.
http://www.pnas.org/content/109/6/2138.abstract
David Nut works mainly on depression, and its treatment with Psilocybin.
Roland Griffiths works mainly with addictions, and treatment...
Quote: CNN
" Initial studies by Griffiths and his team to treat smoking addiction have found 80% success rates in people quitting the habit up to six months
after their treatment. Their studies indicate that psilocybin-based therapy could potentially be quicker and more effective than long-term therapies
such as nicotine "
Just a simple google search reveals thousands of pages on the subject.
https://www.google.com/search?q=psilocybin+depression+treatm...
They tried to have me "put to sleep" so I came back to return the favor.
Zom.
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blogfast25
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Mostly MSM rehashes that feed the echo chamber known as 'the Internet', of course. But as always, it's the few gems that really matter. Will have a
look tomorrow.
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cyanureeves
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i've always lived around dope haters,they will always be around also.the murder rate among coca leaf chewers is not high i bet but somehow we
americans do kill for the coca product.i will always be a doper because the chemistry is awesome.i can swear by dmt but will stand by zoloft because i
have to live among people.i'm feeling a bit depressed and will soon be dancing with chacmool,that scary son of a bitch!
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mayko
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In other recent ayahuasca-related news:
| Quote: |
A chemical called harmine, which occurs naturally in a number of plants around the world, has been shown to regenerate pancreatic cells lost in
diabetes. |
Harmine drug that restores beta cells seen as key diabetes treatment
al-khemie is not a terrorist organization
"Chemicals, chemicals... I need chemicals!" - George Hayduke
"Wubbalubba dub-dub!" - Rick Sanchez
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cyanureeves
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also got that! i should be a happy healthy mug according to latest studies and rats and such. gas is my problem and i swear it started when i used
acid way back.any how i learned how to do acid/base extractions,bought ph meters and learned about none polar solvents,got many dirty looks at stores
while purchasing most the stuff.i dont regret nothing and now i think quite a bit about how i might feel when i'm pumping my last drop of blood when i
die.i think about my old man seeing all kinds of colors and crap he didnt understand when he died.our bodies release dmt when we expire and it is
scary but maybe i will be familiar with all this stuff.i've seen the aztec gods and hope i dont see some weird nordic god when i die because then i'll
know i'm really dead.
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Chemosynthesis
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Do all keep in mind that this was a study utilizing six patients, so there are very clear limitations with sample sizing alone, not to mention the
type of study (open label). As a preamble to a larger double-blind trial (with pre-determined effect sizes and valid statistical testing), it's not
useless, but still very limited. | Quote: Originally posted by cyanureeves | | a placebo effect would certainly indicate a troubled person or an imaginative individual with mind reading capability. a placebo that causes visuals
and hallucinations could no way be a placebo unless maybe the patient is told about the drug's effects. |
I'm not sure what you mean by this statement, as the placebo isn't measured against hallucination. Yes, it's difficult to test psychoactive substances
with a placebo control because it is often readily apparent what the placebo treatment was, which un-blinds the subject, but this is where
methodological critiques come into play (and I am sure I will have issues with the eventual paper, as will the authors publishing it). Placebo doesn't
necessarily have to be totally inert. For example, in ahayusca, harmaline alkaloid MAOIs are administered to make DMT orally bioavailable to the brain
rather than peripherally metabolized. Clearly MAOI drugs have been used to treat depression, so using an MAOI alone in a refractory patient cohort, or
a mildly emetic substance with peripheral muscarinic antagonism and 5HT3 agonist effects may serve as a type of placebo. If the authors claim to have
placebo controls, I want to see the paper they referenced to be published. They may be using an active placebo, which is not uncommon (even in
analgesic studies, which may surprise you), but this would be difficult in such an uncharacterized substance as a plant extract, which is problematic.
Placebo and nocebo are very real and have to be discriminated against, even in psychopharmacology, which is less controllable than most other
disciplines of pharmacology, including neuropharmacology. With some substances, this is clearly difficult to do, as marijuana is smoked, though oral
dronabinol has had placebo trials (http://www.ncbi.nlm.nih.gov/pubmed/21310551). Trials are still conducted with inactive vs. high doses of caffeine or nicotine, and it is obvious
which treatment group gets what drug. Some mitigation of placebo (at least on the part of the anticipatory or researcher driven kind) occurs.
Just because a patient received a treatment, psychoactive or not, doesn't mean the actual drug alleviated depression, that there were not confounding
contributory effects from methodological flaws, nor does it necessarily apply for each patient group since depression is likely a heterologous disease
since it's known that some patients respond better to some treatments than others.
Steady state concentration is dependent on both dose and rate of absorption. Clearly a dilute, ingested leaf versus a purified and snorted/smoked/IV'd
substance will have drastically different pharmacological profiles. That's just an urban legend/potential hypothesis that has never been
substantiated. I imagine that if you were acting is mercurial as your posting has been lately, that people did give quite a few looks.
| Quote: Originally posted by gregxy | The other thing is that Big Pharma has been aware of these drugs for 50 years. In spite of their class 1 status, I'm sure they have researched the
hell out of them. If there was a way to make them work for depression etc. I think they would have found it already.
|
Most biomedical research and drug development takes place in the US.
Much the medical research in pharmacology from 1962 onwards was spent re-testing medication in use but not tested for safety since the 1938 Food,
Drug, and Cosmetic Act. The Controlled Substances Act has been law since 1970, and many countries mimic this regulation through the United Nations and
International Narcotics Control Board, so research isn't necessarily as simple as you may believe.
A lot of paperwork goes into even working with these substances, as in DEA Form 225 approval on top of FDA and local/state compliance and is usually
performed in academic hospital settings with additional funding sources (thus more paperwork, IRB panels, etc.). Additional security and records
keeping is required for these substances, and they are in limited supply depending on the national quotas manufacture.
In order to argue for any clinical trials, you have to supply various pre-clinical sources of data, which are generally lacking for many
psychoactives, and your experimental protocol to be separately approved at each clinical stage. Additionally, each schedule 1 narcotic to be tested
requires a dedicated registered researcher for that substance, as well as a physician registered practitioner for dispensing purposes. These are
special categories within DEA registration, not just any licensed person. Most of the literature with psychoactive substances stopped with animal
model trials, not human ones. It takes an average of 12-15 years to go from optimized lead to completed clinical trials, so you could rule out many of
the psychoactive substances being easily tested in humans before 1970.
Even at large medical centers with concurrent research and addiction treatment aims, there can be trouble enough just administering said substances to
rats. This is a part of why studies on schedule 1 narcotic abusers don't supply the individuals with pure drugs for testing. Basically, no
pharmaceutical company wants to try to invest billions in new drug testing only to then try to lobby to reschedule a drug. That is a losing game,
financially. Not least of which due to the change in patent filing in the US. You either risk getting scooped by waiting until the drug is rescheduled
to file... or you file and lose out on precious patent time lobbying, which might not even be successful.
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Nicodem
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There are many studies that demonstrate psilocybin, LSD other psychedelics reduce the symptoms of depression for long periods, sometimes after as
little as one treatment. One of the latests reviews on the this topic can be found in Therapeutic Advances in Psychopharmacology, 2014, 4,
156-169 (DOI: 10.1177/2045125314527985). There is lately a renaissance of studies related to treatment of depressions, substance addictions, obsessive
compulsions and other psychological conditions with psychedelics, but nearly all of these studies are just a reiteration of studies already done more
than 50 years ago. At that time psychotherapists could still use psycholytic and psychedelic treatments with LSD and other psychedelics, with
remarkable achievements (and misschievements when used in malicious or incompetent hands).
| Quote: Originally posted by Chemosynthesis | | I'm not sure what you mean by this statement, as the placebo isn't measured against hallucination. Yes, it's difficult to test psychoactive substances
with a placebo control because it is often readily apparent what the placebo treatment was, which un-blinds the subject, but this is where
methodological critiques come into play (and I am sure I will have issues with the eventual paper, as will the authors publishing it).
|
The use of placebo can compromise the results of a study with psychedelics, as it will have effects beyond the neutrality. In my opinion, the group
that receives a placebo cannot be used as a control group. Due to the peculiar nature of these drugs, a placebo given group will have unpredictable
consequences as a response to the "treachery" (stress, resentment, etc.) that will undoubtedly affect symptoms. Just imagine a placebo used in cancer
patients, except that the patients immediately realize they received a placebo. Such a placebo will have undesired effects that could negatively
affect the results of the study. A nocebo, or something that has perceivable effects, is more apt to such studies, but only to naive subjects (people
who are not familiar with the psychedelic phenomenon). For example, Pahnke et al, successfully used niacin in the control group in their "Marsh Chapel
Experiment" with psilocybin in the 60's.
For depression studies I would suggest neither a placebo or nocebo, just a large enough control group of randomly chosen subjects with the same
diagnosis to monitor and compare. This is a problem because it means the treated group would better be a comparatively large group of randomly chosen
subjects as well (founding such an expensive study would require a willing government agency - a no go with today’s attitude toward psychedelics).
An alternative to obtaining founds is monitoring the health of religious groups that use psychedelic sacraments (e.g., Santo Daime, União do Vegetal,
or Native American Church) vs. a comparative population that does not partake the rituals. Indeed, some such studies have been conducted, particularly
on the Native American Church where the ritual use of peyote had a dramatic effect in preventing alcoholism. The drawback is that such a study cannot
eliminate certain factors even if the control group is local and of same culture (effects of the community life, religious solidarity, faith induced
effects, personal traits attracting toward such religions that could inhibit the researched illnesses, or other factors that are all church related).
These drugs are therefore nothing like the usual drugs amenable to the typical clinical study protocols. From the numerous studies conducted either
long ago, or in the recent revival years, it could just as well be concluded that it is not the drug that is "active" in the classical clinical sense.
Instead it appears that it is the psychedelic state of mind that causes the beneficial change. Even more, it appears that not even achieving a
psychedelic state is enough and might not even be required, but it is just a state where mystical insight is facilitated.
Most psychologists, especially psychotherapists can tell you that a mystical insight can cause dramatic psychological and behavioural changes in the
subject, particularly in periods of personal crisis (depressions, addictions...). It may therefore not be the psychedelic drug that has the healing
activity, but it is the mind of the subject that does the work. For example, some non-psychedelic hallucinogens were also found to reduce depression
symptoms, or help in treating addictions after single or few treatments (e.g., particularly dissociatives like ketamine and ibogaine). It can be
argued that these non-psychedelics act by totally different physiological mechanisms to achieve the same effect (which might actually be the case for
ibogaine). Yet it must be a strange coincidence that they are hallucinogenic as well. Unless this is further evidence that there is no exclusively
physiological mechanism of action.
All this is in contrast with the classical concepts of pharmacology where the drug itself causes the improvement directly. It might just be the the
mechanism of action of the drug on a cellular level is not what causes the therapeutic change. Hallucinogenic drugs typically provide their
long-lasting effect by acute therapeutic applications, rather than chronic use like the majority of today's drugs. This might be another indication
against a physiological mechanism of action (few drugs improve a chronic illness by acute application, and even these few are mostly some sort of
toxins used therapeutically).
Obviously, with brains it is not easy to determine the cause and effect, because the mind can alter the neuronal physiology and the physiology can
alter the mind. Does one have insight because of the physiological change, or does the insight cause the change in physiology of the neuronal
networking? Obviously, scientists tend to be reductionists and avoid such complex models as long as it goes. For this reason they will be biassed
toward seeing only a one way interaction. Most commonly among the psychopharmacologists is the tendency to assign all the therapeutic effects to the
physiological change. Some psychotherapists will be biassed in the opposite direction. All are too biassed by their desire to obtain a simplified
model.
In view of such a hypothesis, the psychedelic drug as such, given in the clinical setting, might have no direct connection with the medical
improvement. Paradoxically, the drug itself could act as a placebo in some circumstances (providing the psychedelic state, but the mind of the subject
still being unable to achieve insight). Today, there is good psychopharmacological knowledge on how to achieve the psychedelic state (dose, "set and
setting"), but nobody has been able to reliably induce mystical insight (medical doctors are generally not skilled at playing the role of shamans or
witches). Whoever would want to do such a study with such drugs properly, using the scientific method, will have to first give away with the classical
clinical methods and modify the method to suit some hypothetical mechanism of action. There are a number of ways to do this. Groups can be divided by
set and setting, guided or non-guided therapy, psycholytic or psychedelic therapy, and so on. If there are differences - and I suspect there will be,
because studies performed in the 50's and 60's did show plenty - then there is much more to psychedelic drugs than there is to common drugs.
And there is not a slightest chance that an originator pharmaceutical company would go for it and ever register any such drug. Drugs that do not act
as typical drugs have no business in their business. (Perhaps one little but notable exception is a particular mechanism of action of some psychedelic
drugs, particularly DOI, that might be interesting to the big pharma: JPET 327:316–323, 2008, DOI: 10.1124/jpet.108.143461 and PlosONE, 2013, e75426, DOI: 10.1371/journal.pone.0075426)
A quote of Baumeister et al., Therapeutic Advances in Psychopharmacology, 2014, 4, 156-169 (emphasis mine):
| Quote: | | Hallucinogens have been employed entheogenically in human spiritual practice for several millennia, often in shamanistic approaches to healing or as
a gateway for communication with deities. Despite, or perhaps in reaction to, this rich tradition, judicial processes in the 1960s and 1970s
criminalized these substances without a clear scientific rationale, but more as a societal and political response to an emerged counter-culture. A
historical legacy of the United Nations Convention on Psychotropic Substances [United Nations, 1971] has been significant obstacles and hurdles for
scientific research using and investigating hallucinogens, whose neuropharmacology have remained incompletely understood [Vollenweider and Kometer,
2010]. Recently, it has been argued that the scientific community itself must lead the case for change in policies, as current drug laws
severely limit scientific exploration of both neurobiological mechanisms and clinical effects that may prove valuable in the understanding of
consciousness and mental illness, and offer novel therapies [Nutt et al. 2013]. |
For a more general and recent review on the potentials for psychedelics, see DOI: 10.2174/1874473708666150107114927 (and also a few other articles in the same issue of Current Drug Abuse Reviews).
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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solo
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Psychedelics not linked to mental health problems or suicidal behavior: A population study
Pål-Ørjan Johansen1 and Teri Suzanne Krebs
Journal of Psychopharmacology
2015, pgs.1–10
DOI: 10.1177/0269881114568039
Abstract
A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid
diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults,
including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics,
other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past
year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed
to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other
body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see
how prohibition of psychedelics can be justified as a public health measure.
Attachment: Psychedelics not linked to mental health problems or suicidal behaviour- A population study.pdf (262kB)
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Chemosynthesis
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| Quote: Originally posted by Nicodem | | There are many studies that demonstrate psilocybin, LSD other psychedelics reduce the symptoms of depression for long periods, sometimes after as
little as one treatment. One of the latests reviews on the this topic can be found in Therapeutic Advances in Psychopharmacology, 2014, 4,
156-169 (DOI: 10.1177/2045125314527985). There is lately a renaissance of studies related to treatment of depressions, substance addictions, obsessive
compulsions and other psychological conditions with psychedelics, but nearly all of these studies are just a reiteration of studies already done more
than 50 years ago. |
I do believe, personally, that there is reason to suspect efficacious treatment of psychological diseases or subsets thereof with some of these drugs,
or at least optimized versions of them, but with respect, due in part to the lack of uniform FDA guidelines implemented from 1962 onwards that I
mentioned, most of these studies are of dubious use, and the authors of your cited paper state
"The initial surge of clinical research that took place between the mid-1950s and 1960s in response to the synthesis of LSD and psilocybin produced
more than 1000 studies, involving tens
of thousands of participants [Grinspoon and Bakalar, 1981]. However, as pointed out by Vollenweider and Kometer, there were difficulties with
these studies [Vollenweider and Kometer, 2010]: the substances were little understood, their effects were difficult to control and different
therapeutic approaches utilized them in different manners, and therefore the present review will refrain from considering evidence obtained in these
studies." The abstract emphasizes with in "Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their
mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent
data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic actions and the
current limited data on their clinic effectiveness."
(Emphasis mine).
| Quote: |
The use of placebo can compromise the results of a study with psychedelics, as it will have effects beyond the neutrality.In my opinion, the group
that receives a placebo cannot be used as a control group. Due to the peculiar nature of these drugs, a placebo given group will have unpredictable
consequences as a response to the "treachery" (stress, resentment, etc.) that will undoubtedly affect symptoms. Just imagine a placebo used in cancer
patients, except that the patients immediately realize they received a placebo. Such a placebo will have undesired effects that could negatively
affect the results of the study. A nocebo, or something that has perceivable effects, is more apt to such studies, but only to naive subjects (people
who are not familiar with the psychedelic phenomenon). For example, Pahnke et al, successfully used niacin in the control group in their "Marsh Chapel
Experiment" with psilocybin in the 60's.
For depression studies I would suggest neither a placebo or nocebo, just a large enough control group of randomly chosen subjects with the same
diagnosis to monitor and compare. This is a problem because it means the treated group would better be a comparatively large group of randomly chosen
subjects as well (founding such an expensive study would require a willing government agency - a no go with today’s attitude toward psychedelics).
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I believe you're slightly confused about the terminology I'm using. Active placebo, which I mentioned, has a physiological effect other than that
which is being studied. This is different from, though arguably inclusive of a nocebo. Some of the possibilities I mentioned could conceivably serve
to fool some patients, particularly if naive to treatment, by simulating the peripheral effects and some central nervous effects common to validated
MAOI treatment. Patients don't need to be explicitly told what their specific treatment is (assuming no crossover in repeated measures) for informed
consent, nor does it need to be a consistent treatment, so this can assist with the blinding of subjects. The largest risk to single unblinding in
these instances is where a patient has experienced the drug before, and is currently on a drug treatment group.
Placebo control of varying kinds is hardly uncommon in psychopharmacology, though the type chosen does have various limitations, both scientific and
ethical. This is part of why I was open to various designs (refractory to MAOI treatment, which is not a standard first line medication, and could be
considered a last resort, etc.)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161672/
If a patient suffers adverse effects from a placebo not being active, or being active and not treating their condition (which is a risk with any
active drug as well), that is partly on the researcher for poor screening and patient briefing. Sham surgery has also been used as a placebo, and it
could be argued that psychotherapy or religious iconography/theosophy could be utilized in the absence of the drug being tested as a form of placebo
to determine the importance of the drug itself. Analgesic studies commonly use non-analgesic CNS depressants to give a form of psychotropic effect
that mimics sedation with opioids. This is an active placebo. A nocebo is a substance that is physiologically inert but gives subjective deleterious
effects, such as giving someone an inert powder, claiming it is monosodium glutamate, and then having a subject self-report an MSG allergy. Not that
you would design a trial that extremely. Technically, I am sure one could refer to an active nocebo, as I implied way above, but this is still
differentiated from otherwise unspecified placebo in that the subjective subject/patient response is considered undesirable in a nocebo, whereas any
effect is unspecified for placebo.
In fact, the use of a placebo in the situation you describe (a true nocebo in this instance, where a patient suffers negative effects from placebo) is
useful for the very purpose of demonstrating an otherwise unnoticed effect with treatment (a potential lack of negative effect), and can indicate
adjunct therapies or novel targets for investigation that would otherwise be obscured, as well as demonstrating that current modalities of
questionable efficacy may need such investigation to determine if they are harmful in some patient populations similar to the study placebo. It does
raise philosophical issues of clinical vs. research equipoise, though. And actually, some cancer studies do use placebo, though this is usually
relegated to those with no known alternative effective treatment to refer to.
http://www.cancer.net/navigating-cancer-care/how-cancer-trea...
| Quote: | | An alternative to obtaining founds is monitoring the health of religious groups that use psychedelic sacraments (e.g., Santo Daime, União do Vegetal,
or Native American Church) vs. a comparative population that does not partake the rituals. Indeed, some such studies have been conducted, particularly
on the Native American Church where the ritual use of peyote had a dramatic effect in preventing alcoholism. The drawback is that such a study cannot
eliminate certain factors even if the control group is local and of same culture (effects of the community life, religious solidarity, faith induced
effects, personal traits attracting toward such religions that could inhibit the researched illnesses, or other factors that are all church related).
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We agree that observational studies are of more limited use than placebo controlled, double blind studied due to a variety of control factors.
Anticipatory control, confounding variables, etc.
We'll have to agree to disagree on the validity of psychopharmaceutical testing, as I can't address psychotherapy as a non-science. As for
mind/brain/body duality issues, my cognitive psychologist friend would probably debate you for hours just because he could, not necessarily because he
even had an opinion on the matter. The pharmacological perspective would arguably be that there is no scientific rationale for said psychological
treatment being contingent on specific regulated substances, though they may in fact be of benefit. This could be very important in allowing freedom
of choice of psychoactives with specific pharmacokinetic profiles to reduce polydrug interactions, at-risk reactions in some patient groups (age,
blood pressure, etc.), or simply allow for substitution with drugs of a tailored half-life to meet with patient/researcher time schedules. If no drug
at all were necessary, this would lead to decreased fixed costs of treatments and reduced risk of pharmacological interaction (ex. DMT analog active
without an MAOI, the latter of which is kind of a poster child for interactions) all while simplifying patient histories (important in a medical
situation to allow more focus on relevant historical details).
As far as your Nutt quote on scientific regulation with neuroscience/neuropharmacology, that particular part of the quote is a very different matter
from psychotherapy, though the two are both mentioned there. Neuroscience/neuropharm normalizes data in the same way as a placebo. Both could arguably
be advanced with diminished regulatory controls, or at least diminished bureaucracy, since filling out those DEA forms takes time, and even with
non-schedule I substances, can require multiple filings for subtypes of schedules, as I learned much to my chagrin. (Ex. Schedule 3 doesn't
necessarily cover 3A, please submit a new form and wait.)
As far as toxicity concerns with psychedelics that Solo brings up, determining/ruling out adverse cardiac fibrosis risk would top my list rather than
behavioral issues, as one is predictable whereas the other is arguably not. Much like the potential for serotonin toxicity syndrome, it would not only
be beneficial for patients to be studied, but would open the door for additional types of studies, in my opinion.
[Edited on 9-4-2015 by Chemosynthesis]
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cyanureeves
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mercuric twice then shame on me! next time i will buzz first before i do any purchase.i think the banesteriopsis(MAOI) is the actual chemical that is
effective in the ayahuasca study.dmt works without the MAOI but with the banesteriopsis i get stomach contractions just like when i drop acid.dmt
alone is very disassociating but changa(dmt infused MAOI) is not and neither is acid. both changa and acid do give me a calm non worrying feeling for
days afterwards.about that native american church though:i read that a group of natives took peyote and were sitting next to a horse carcass.all the
natives not just one,saw the horse carcass fly to the sky.WTF?skip the placebo AND nocebo and go just straight to satan i think.power of suggestion
maybe?if a person was to read all my crap in this here post and smoke changa then all his findings could be suggested?
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Chemosynthesis
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Testing against an MAOI might allow some form of quantification of efficacy and/or additive/synergistic effects. Serotonin agonism is usually what is
associated most strongly with such GI interactions due to the strong role of enterochromaffin cells, though other receptors also play a role
(muscarinic possibly being of relevance here).
Motility is usually 5HT4 mediated, whereas nausea and visceral sensitivity is 5HT3 mediated. Do note that nausea has several known mechanisms of
activation prior to integration in the brain's nausea center, and that motion sickness is completely different.
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solo
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Reference Information
Cardiovascular toxicity of novel psychoactive drugs: Lessons from the past
Patrick Dawson, James D. Moffatt
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume 39, Issue 2, 3 December 2012, Pages 244–252
doi:10.1016/j.pnpbp.2012.05.003
Abstract
The long use of ephedrine, amphetamines, cocaine, LSD and more recently 3,4-methylenedioxy-N-methylamphetamine (MDMA; “Ecstasy”) allows us to
predict with some confidence what cardiovascular risks are likely to be associated with novel psychoactive substances (NPS). Once the probably
multiple biological activities of a compound are known it is possible to define the likely risks of cardiovascular toxicity. Agonists of 5-HT2A
receptors or alpha-adrenoceptors may cause vasoconstriction and tissue ischemia. Drugs which have agonist affinity for 5-HT2B receptors will probably
promote heart valve fibrosis leading to heart failure. Compounds that interfere with uptake of dopamine or 5-hydroxytryptamine (5-HT) are likely to
also have effects on noradrenergic neurotransmission and lead to sympathomimetic effects on the heart and vasculature. Drugs that cause dopamine
release, or inhibit uptake are likely to be addictive and lead to chronic use. Other drugs (particularly the so-called empathogens) are associated
with weekly usage in social settings; over time such use can lead to cardiovascular harm. Defining which of these effects NPS have is an important
element of predicting the harm they may cause and informing those appointed to introduce regulations to control them.
Attachment: Cardiovascular toxicity of novel psychactive drugs-Lessons from the past.pdf (350kB)
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[Edited on 8-4-2015 by solo]
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solo
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Reference Information
Drug Abuse and Cardiac Problem
Mohammad Shafiqur Rahman Patwary
Medicine Today
2013 Volume 25 Number 02
Abstract
Drug abuse has reached epidemic proportions in many
countries including Bangladesh and threatens to overwhelm
economic, social, and health care systems. In addition to
their effects on the central nervous system, many of these
agents induce profound changes in the heart and circulation
that are responsible for a significant proportion of
drug-related morbidity. Drugs that can affect the
cardiovascular system are cocaine, heroin, inhalants,
ketamine, lysergic acid diethylamide(LSD),
marijuana,3,4-methylenedioxymethamphetamine(MDMA),
methamphetamine, nicotine, phencyclidine (PCP),
prescription stimulants, steroids .This article reviews the
cardiovascular problems associated with drug abuse.
Attachment: Drug Abuse and Cardiac Problem.pdf (179kB)
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Chemosynthesis
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Solo, the problem with current toxicological research in that regard is that there is very little in terms of quantification of risk. Yes, I can look
at a drug and use various SAR techniques to flag a compound for further toxicological study, but without actual toxicological data in a controlled
setting, determining what patient groups are most at risk or what kind of interactions are possible but unlikely to be of clinical concern, they are
limited. Particularly with regard to chronic use, a better understanding of these issues would allow for better drug selection, safer dosing
schedules, or even concomittant administration of prophylactic or "rescue" compounds to reduce harm.
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solo
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| Quote: Originally posted by Chemosynthesis | | Solo, the problem with current toxicological research in that regard is that there is very little in terms of quantification of risk. Yes, I can look
at a drug and use various SAR techniques to flag a compound for further toxicological study, but without actual toxicological data in a controlled
setting, determining what patient groups are most at risk or what kind of interactions are possible but unlikely to be of clinical concern, they are
limited. Particularly with regard to chronic use, a better understanding of these issues would allow for better drug selection, safer dosing
schedules, or even concomittant administration of prophylactic or "rescue" compounds to reduce harm. |
......I only provide references to evaluate choices and decisions, and i agree with you as to the controlled studies, with today's street drugs one
doesn't know what one is consuming, hence its best to make your own or grow your own for safety and long life with colorful perspectives......solo
<a href="http://www.freeimagehosting.net/commercial-photography/texas/dallas/"><img src="http://i.imgur.com/jCIaVSs.jpg" alt="Dallas
Commercial Photography"></a>
[Edited on 8-4-2015 by solo]
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cyanureeves
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oooh, i so suspected that.what i didnt describe was that feeling of being catapulted into space which is very,very physical and not psychological at
all.blasted into space then all of a sudden time stops and colors explode or so it seems.hell my heart could be doing 100 mph for all i know.of sound
mind but of a dying body also maybe. the study does say in small dose though and i believe that ayahuasca if thrown up can fail to give visuals.maybe
the people who throw up do feel better afterwards than those who dont.all the videos i have seen of ayahuasca experimenters seem so calm afterwards.i
have also read of 10 hour long nightmares and some split 50/50 paradise and hell. i bet all were feeling better in the long run though.
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Zombie
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All of the compounds you mentioned in your posts Solo contain stimulants.
This is a different class of drug.
In the past 5-6 posts I have seen one commonality.
The question... Do psychedelics work via direct chemical interaction or do they work via allowing a built in reaction.
You fellas used more big words than I have room for in my pea brain. I did understand all but one... Mercurial. I kind f proud of that.
I work on intuition, and I have the gut feeling that the effects of psychedelics are not a direct chemical action. I do not believe these compounds
cause audio / visual / or any other tactile distortion of reality. Nor do I believe they create any spiritual awareness.
My instinct tells me they bind receptors that open pathways we already have. All of the effects are waiting within us, and are dormant (for lack of a
larger word).
These compounds simply allow us to be us.
This, in a simple way explains how so many seemingly un-explainable results can occur.
You can say that spiritual awareness will help cease addiction or you can say that a balance of priorities will do the same.
Look at rehab groups... Many of them use religion as a tool. Self help groups use re-examining your goals...
So does the chemical "trip" make your brain change, and allow a "chemical balance that allows people to think clearly or does the "chemical balance
occur due to the psyche?
Nicodem addressed these questions without including an opinion.
I am offering my opinion... The compounds allow a part or parts of our brain to activate. This activation allows us to chemically balance ourselves,
release us from mundane false priorities, give us a buffer between nonsense, and reality in a time based fashion, and generally lets us accept the
onslaught of sensory input we have to deal with without constant chemical input or receptor firing in the brain.
Take a fella that works in any high stress job. Constant adrenaline, and lactic acid build up...
Put the same fella back at that job but remove the stress effects,ie: adrenaline, lactic acid...
In which case do you "THINK" he will be healthier, live longer, make better life choices daily.
You fellas justifiably mention placebo, no-cebo, cebo cebo...
Once again I have to add, A Trip is not needed to gain certain results. You don't need to pee brown to acquire the needed effect from vitamins.
A placebo control is 100% as valuable if NO ONE was expected to "trip", see aliens, or run down the hallway naked.
15-25mG of psilocin does not alter reality in any detectable way but it does fire receptors. The effect of lessening anxiety, and depression are
documented at low dose studies.
http://www.gizmag.com/johns-hopkins-psilocybin-study-finds-o...
I can NOT say this often enough... Take tripping out of this!
Use any of these compounds in the minimum dosage required to fire synapsis', and trigger receptors.
There is no need to use a cannon to kill a deer.
They tried to have me "put to sleep" so I came back to return the favor.
Zom.
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