36 replies to this topic

[circuitblue]

nootropikamil,

As you have pointed out, I also have seen no data on any "smart drugs" increasing facets of cognition in controlled experiments with healthy volunteers. And with regard to your comments on conventional stimulants, there is also scant data on deleterious effects of long-term use. I'm assuming that the wikipedia entry information cited above was probably from the drug manufacturers to attenuate liability, rather than being data from human patients. Scientific rigor is the only method for separating nebulous rants on psuedo-scientific amplifications of marketing mumbo-jumbo from these drugs manifesting true efficacy. Drop me a line if you perchance find any compelling studies of nootropic efficacy (eg. more than the bullshit-EEG criteria) or stimulant-induced pathologies.

best,
-chris
http://psypharm.blogspot.com
http://www.neopharmacology.com

[dopamine]

It would be absurd to say there are no negative long term effects from using stimulants, as it is clearly the case with substances such as amphetamine and methamphetamine. Many of the people on boards of this type are seeking relief from such damage, including Adam if I recall correctly. Amphetamine-induced neuronal toxicity is a well known phenomenon and is often used as a model of chemically induced neuronal damage in experimental research. The warnings and precautions in the PDR and various other drug references relating to amphetamines are there for scientifically sound reasons - not because of some government conspiracy.

It is true that Piracetam's mechanism of action is largely unknown, and it's efficacy in healthy humans is questionable. Amphetamines and various stimulants are certainly effective in enhancing various parameters of cognitive performance under certain circumstances, but there is a point of diminishing returns and tolerance to the initial acute effects. This severely limits their therapeutic potential for otherwise healthy individuals.

Donepezil would certainly be a safer alternative to traditional psychostimulants, but it's efficacy in healthy humans is also questionable. The long-term effects of acetylcholine esterase inhibition are largely unknown, so one must weight the relatively unknown risks against the relatively known benefits. The advantage of Piracetam is that it's safety is fairly well established and has no known toxicity level, while at the same time eliciting some suggestive research in terms of it's efficacy in healthy volunteers.

[emerson]

It would be absurd to say there are no negative long term effects from using stimulants

I agree, but mostly due to how broad that catagory is. It's true much in the same way that "It would be absurd to say there are no negative long term effects from pills whose binding agents are coloured green." Within the umbrella of each of those statements are far too many different mechanisms of action to hold up as a predictive force of long term effect. Certainly, saying that long term use of stimulents would have a negitive effect feels very true on an intuitive basis. But intuition is a pretty bad road map. Caffeine is a substance which springs to mind immediatly which is a stimulent, studied from hell and high water by this point, and shown to give a pretty miniscule effect on lifespan from lifelong use.

[doug123]

nootropikamil,

As you have pointed out, I also have seen no data on any "smart drugs" increasing facets of cognition in controlled experiments with healthy volunteers. And with regard to your comments on conventional stimulants, there is also scant data on deleterious effects of long-term use. I'm assuming that the wikipedia entry information cited above was probably from the drug manufacturers to attenuate liability, rather than being data from human patients. Scientific rigor is the only method for separating nebulous rants on psuedo-scientific amplifications of marketing mumbo-jumbo from these drugs manifesting true efficacy. Drop me a line if you perchance find any compelling studies of nootropic efficacy (eg. more than the bullshit-EEG criteria) or stimulant-induced pathologies.

best,
-chris
http://psypharm.blogspot.com
http://www.neopharmacology.com

I don't think the current nootropics are all that effective. Would I take them, if I was assured of their quality and the cost is marginal? Of course! But in my experience interacting with many individuals from this and other Internet forums, over 75% have untreated ADD/ADHD and don't get what they are looking for in the conventional nootropic dietary supplements. The other 25% have consisted of folks already performing top notch and are looking for ways to enhance their performance.

I investigated your website and see that you have a pretty good understanding of medicine. We could use more feedback from individuals such as yourself in this forum. Also, please visit my forum.

It would be absurd to say there are no negative long term effects from using stimulants, as it is clearly the case with substances such as amphetamine and methamphetamine. Many of the people on boards of this type are seeking relief from such damage, including Adam if I recall correctly. Amphetamine-induced neuronal toxicity is a well known phenomenon and is often used as a model of chemically induced neuronal damage in experimental research. The warnings and precautions in the PDR and various other drug references relating to amphetamines are there for scientifically sound reasons - not because of some government conspiracy.

It is true that Piracetam's mechanism of action is largely unknown, and it's efficacy in healthy humans is questionable. Amphetamines and various stimulants are certainly effective in enhancing various parameters of cognitive performance under certain circumstances, but there is a point of diminishing returns and tolerance to the initial acute effects. This severely limits their therapeutic potential for otherwise healthy individuals.

Donepezil would certainly be a safer alternative to traditional psychostimulants, but it's efficacy in healthy humans is also questionable. The long-term effects of acetylcholine esterase inhibition are largely unknown, so one must weight the relatively unknown risks against the relatively known benefits. The advantage of Piracetam is that it's safety is fairly well established and has no known toxicity level, while at the same time eliciting some suggestive research in terms of it's efficacy in healthy volunteers.

I have a similar feeling about the potential dangers of long term amphetamine administration in humans. However, I cannot find too much data suggesting amphetamines are unsafe for individuals under care of a competent licensed physician. If someone has a weak heart, for example, amphetamine is likely to cause trouble -- or even death. Individuals whom might be suffering from an attention related disorder should start with non stimulant medications such as Strattera, Provigil, or Wellbutrin before trying the amphetamine derivatives. Some doctors don't agree with this approach due to the volume of data supporting their use that suggest such therapies are more effective -- and safe -- in such disorders.

Regarding modafinil: whose analogue has been used clinically to treat loss of vigilance in elderly patients since the mid 1980 -- it appears to be very safe and I am unaware of any evidence that suggests Adrafinil or Modafinil -- or its mechanism of action -- is dangerous for any patient or population (except for some individuals suffering from acute psychosis). (1, 2)

Donepezil appears to currently be the most well researched and proven therapy to positively affect the memory and learning of a healthy subject. Most other purported cognitive enhancers have no evidence supporting their use. Hell, there is more evidence supporting the use of nicotine gum in healthy subjects than any of the currently available nootropics.

1. Israel L, Fondarai J, Lubin S, Salin B, Hugono R. L’adrafinil (Olmifon) et patients âgés ambulatoires.
Efficacité, versus placebo, de l’Adrafinil sur l’éveil dans les activités de la vie quotidienne.
Psychol Med 1989;21:1235–1255.

2. Jouvet M. Une nouvelle famille de médicaments pour améliorer l’éveil: les eugrégoriques. Journ
ées d’étude sur le vieillissement, organisées par l’ORPHEM, Marseilles, France; March 25–26,
1987.

Kohler F, Lubin, S. Étude en médecine générale de l’intérêt thérapeutique d’Olmifon chez des
malades présentant des symptomes précoces de vieillissement cérébral handicapant leur activité
quotidienne. Étude ouverte pragmatique chez 304 patients. La Vie Médicale 1990;2:335–344.

[circuitblue]

I have a similar feeling about the potential dangers of long term amphetamine administration in humans.  However, I cannot find too much data suggesting amphetamines are unsafe for individuals under care of a competent licensed physician.  If someone has a weak heart, for example, amphetamine is likely to cause trouble -- or even death.  Individuals whom might be suffering from an attention related disorder should start with non stimulant medications such as Strattera, Provigil, or Wellbutrin before trying the amphetamine derivatives.  Some doctors don't agree with this approach due to the volume of data supporting their use that suggest such therapies are more effective -- and safe -- in such disorders.

Regarding modafinil: whose analogue has been used clinically to treat loss of vigilance in elderly patients since the mid 1980 -- it appears to be very safe and I am unaware of any evidence that suggests Adrafinil or Modafinil -- or its mechanism of action -- is dangerous for any patient or population (except for some individuals suffering from acute psychosis). (1, 2)

Donepezil appears to currently be the most well researched and proven therapy to positively affect the memory and learning of a healthy subject.  Most other purported cognitive enhancers have no evidence supporting their use.  Hell, there is more evidence supporting the use of nicotine gum in healthy subjects than any of the currently available nootropics.

My old boss is an accomplished neuromedicinal chemist, and I had been curious for a while about deleterious effects due to long-term amphetamine usage given their extensive use in World War II. Asking him about related data he noted that most vets quit using amphetamine as soon as they got home, and conflicting variables (eg. heavy drinking) can obfuscate trying to collect accurate data. Regarding their use under the care of physicians though, it should be noted that physicians used to prescribe amphetamine for well... everything. You're lacking confidence? Have some amphetamine. You're overweight? Here's some amphetamine. Lethargic? Amphetamine. Desite knowing a lot more about related toxicology (which I won't claim to be any sort of expert on), physicians main guide for prescribing them is still the DSM-IV, a crude crude guide given its utterly subjective nature, which I would argue leads to almost arbitrary diagnosis given the weak methodologies it encompasses. But even if you take the DSM-IV as an accurate guide for diagnosis and treatment, there are a lot more putative side effects from stimulants, such as exacerbation of free radical generation due to metabolism of greater concentrations of catecholamines like dopamine, and more importantly the oxidative metabolism of the drug itself. In a nutshell, I've found no good solid reviews of long-term amphetamine toxicity... I'm either missing them in the myriad of amphetamine-related articles or there is a uttter lack of data.

With regard to adrafinil, it's been a while since I read many specifics, but I remember reading that long-term adrafinil use was associated with liver toxicity.

With regard to all serious psychoactive substances, we know very little in general... Dr. Breggin is a counterpart author to Dr. Kramer ("Listening to Prozac") and writes fairly eloquently on how virtually nothing is known about long term effects or how these drugs really affect neurophysiology (eg. pharma companies say SSRI's increase levels of serotonin and correct a "neurochemical imbalance" in people that have "disorders"... this is a *complete* fabrication in every sense. We have very little idea about how these drugs influence the neurophysiology of people). I'm not one to say what people should or shouldn't do (after all, desite it being mostly anecdotal, usage is what spurs along many objective scientific studies), but don't take solace in the medical discipline's endorsement of these drugs where there isn't blatant, repeated, high-quality data to back it up...

I tried to organize an objective study with piracetam back in college but couldn't find the proper psychological tests to use... there are a number, as was said before, that you can choose from to evaluate various facets of cognition from visual acuity to short term memory to spatial reasoning etc... Applying these established tests with healthy volunteers in controlled experiments with these drugs is what really needs to be done to really call any of them "smart drugs" or nootropics. The scale the that inventors of piracetam created (ie. increased blood flow, increased communication between the two hemispheres, EEG-modulation defining these substances) seems more like a marketing gimmick than scientific methodology. Hopefully someone will eventually fund the aforementioned studies.... if we find they have efficacy in some we'll have some great leads. If not, we'll have to let them go...

So I clicked your link and was greeted by a website encouraging me to buy supplements... out of curiosity, is it legal now to resell piracetam in the states? I shall be checking out the forum...

Best,
-chris

[doug123]

My old boss is an accomplished neuromedicinal chemist, and I had been curious for a while about deleterious effects due to long-term amphetamine usage given their extensive use in World War II. Asking him about related data he noted that most vets quit using amphetamine as soon as they got home, and conflicting variables (eg. heavy drinking) can obfuscate trying to collect accurate data. Regarding their use under the care of physicians though, it should be noted that physicians used to prescribe amphetamine for well... everything. You're lacking confidence? Have some amphetamine. You're overweight? Here's some amphetamine. Lethargic? Amphetamine. Desite knowing a lot more about related toxicology (which I won't claim to be any sort of expert on), physicians main guide for prescribing them is still the DSM-IV, a crude crude guide given its utterly subjective nature, which I would argue leads to almost arbitrary diagnosis given the weak methodologies it encompasses. But even if you take the DSM-IV as an accurate guide for diagnosis and treatment, there are a lot more putative side effects from stimulants, such as exacerbation of free radical generation due to metabolism of greater concentrations of catecholamines like dopamine, and more importantly the oxidative metabolism of the drug itself. In a nutshell, I've found no good solid reviews of long-term amphetamine toxicity... I'm either missing them in the myriad of amphetamine-related articles or there is a uttter lack of data.

Amphetamines are addictive, first off. Second, they tend to cause marked changes in the Central Nervous System, can dramatically raise blood pressure, alter heart rate, etc. They do have definite potential for serious side effects; and death is possible in many more cases -- at least the data exists in correlation with Adderall and Ritalin it seems:

Study: ADHD Drugs Send Thousands to ERs: http://abcnews.go.co...tory?id=2000936, http://nootropics.ip...-1136523291.jpg

By LINDA A. JOHNSON

May 24, 2006 (AP)— Accidental overdoses and side effects from attention deficit drugs likely send thousands of children and adults to emergency rooms, according to the first national estimates of the problem.

Scientists at the U.S. Centers for Disease Control and Prevention estimated problems with the stimulant drugs drive nearly 3,100 people to ERs each year. Nearly two-thirds overdoses and accidental use could be prevented by parents locking the pills away, the researchers say.

Compare those values to the amount of herbal poisoning exposures in 2003 due to contaminated supplements in 2003 (24412-3100 = a difference of 21,312!!!) Which is more dangerous: taking herbal dietary supplements, or ADD drugs? Geez...

Journal of Pharmacy Practice, Vol. 18, No. 3, 188-208 (2005)
DOI: 10.1177/0897190005277217
© 2005 SAGE Publications

Children’s Hospital of Michigan Regional Poison Control Center, Wayne State University, College of Medicine, Department of Pediatrics, Detroit, Michigan

Herbal poisoning exposures reported to poison centers increased by 344% after passage of the Dietary Supplement Health and Education Act, with 24412 exposures reported in 2003. Increased toxicity is speculated to be related to lack of child-resistant packaging, new issues of contamination, proliferation of multiple ingredient products, excessive concentration of active ingredients, and discovery of new drug-herb interactions. This review addresses contamination issues such as heavy metals, pharmaceuticals, homeopathic remedies, microbes, insects, environmental chemicals, and mis-identification of one plant for another. Toxicity issues covered include carcinogenicity, delay in seeking medical treatment when using herbs to treat serious illness, toxic components, hypersensitivity reactions, hepatotoxins, nephrotoxins, epileptogenic compounds, cardiac toxins, gastrointestinal toxins, and hematologic toxins. Common drug-herb interactions are discussed. The pharmacist plays an important role in patient education and evaluation of potential toxicities related to herbal supplements.

With regard to adrafinil, it's been a while since I read many specifics, but I remember reading that long-term adrafinil use was associated with liver toxicity.

Data on long term use of Adrafinil has never been published; however, modafinil, Adrafinil's primary metabolite -- has been much more extensively researched.



All of the research I have read on Adrafinil has been for three month intervals in elderly subjects (45-88 years of age). The dose used primarily in that research was typically 600mg before breakfast and 300mg around lunch time. Liver values appeared to stay normal within the studies referenced starting page 13 of this paper. There might have been some data I missed that suggests Adrafinil can change values in certain liver enzymes; I just have not seen it.

With regard to all serious psychoactive substances, we know very little in general... Dr. Breggin is a counterpart author to Dr. Kramer ("Listening to Prozac") and writes fairly eloquently on how virtually nothing is known about long term effects or how these drugs really affect neurophysiology (eg. pharma companies say SSRI's increase levels of serotonin and correct a "neurochemical imbalance" in people that have "disorders"... this is a *complete* fabrication in every sense. We have very little idea about how these drugs influence the neurophysiology of people). I'm not one to say what people should or shouldn't do (after all, desite it being mostly anecdotal, usage is what spurs along many objective scientific studies), but don't take solace in the medical discipline's endorsement of these drugs where there isn't blatant, repeated, high-quality data to back it up...

I tried to organize an objective study with piracetam back in college but couldn't find the proper psychological tests to use... there are a number, as was said before, that you can choose from to evaluate various facets of cognition from visual acuity to short term memory to spatial reasoning etc... Applying these established tests with healthy volunteers in controlled experiments with these drugs is what really needs to be done to really call any of them "smart drugs" or nootropics. The scale the that inventors of piracetam created (ie. increased blood flow, increased communication between the two hemispheres, EEG-modulation defining these substances) seems more like a marketing gimmick than scientific methodology. Hopefully someone will eventually fund the aforementioned studies.... if we find they have efficacy in some we'll have some great leads. If not, we'll have to let them go...

So I clicked your link and was greeted by a website encouraging me to buy supplements... out of curiosity, is it legal now to resell piracetam in the states? I shall be checking out the forum...

Best,
-chris

The forum is mostly just research from different compounds. Of course the data is biased to only show the bright side of the story. When I made all those crazy colors and fonts I was clearly out of my mind. I need to go lower those fonts...That site is connected to the store and I do not make any particular product claims -- I do not want any problems claiming and have the government pay me another visit. The dietary supplement business in the USA is deregulated, so anyone can get involved. Obviously having the market unregulated makes it victim to quality issues...

Yes there are some diagnostic tests that can be used to test cognition. One of the tests used by Dr. Danielle Turner, the researcher who published this and this paper on effects of modafinil in healthy and ADD patients used something called -- I think -- the tower of London planning task.

There are several modern tests of cognition that are computerized now. I am interested in learning more about obtaining Danielle Turner's (Department of Psychiatry, University of Cambridge, School of Clinical Medicine) methodology. We should buy her software suite...I'd like to meet her... [bl:)]

Psychopharmacology (Berl). 2003 Jan;165(3):260-9. Epub 2002 Nov 1. 

Cognitive enhancing effects of modafinil in healthy volunteers.

Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ.

Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.

RATIONALE: Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. OBJECTIVES: The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. METHODS: Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. RESULTS: Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. CONCLUSIONS: These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder.

    Publication Types:

        * Clinical Trial
        * Randomized Controlled Trial


    PMID: 12417966 [PubMed - indexed for MEDLINE]

[doug123]

I'm bumping all manic and sh*t. I hope this data can, over time, be consolidated and pinned to the top of the board.