Thursday, November 3, 2011


Piracetam is a so-called "nootropic" drug, a substance which supposedly helps improve cognitive functioning.  It is available without prescription as a sort of supplement in many parts of the world.  In Canada it is not illegal, but must be imported (such as by ordering over the internet from U.S. suppliers).

The mechanism of action is not clear.   There is no obvious single receptor-mediated mechanism.  There may be various effects on ion channels, cell membrane characteristics, etc. but of course such statements are quite vague.

It is quite clear that there are few side-effect problems or toxicity risks with this agent.  Doses are typically 2-5 grams per day.

I became interested in this agent after encountering a case example of someone who reported quite a dramatic improvement in mood and overall functioning attributed to piracetam supplementation.

Here are the results of my survey through the research literature:  -- a 2005 review  -- a 1991 review looking specifically at its use  in treating  dementia; the data is really not impressive at all for dementia treatment.  -- a 2000 Japanese study affirming the effectiveness of piracetam combined with clonazepam  for treating myoclonus  (myoclonus is a neurological problem in which muscles are twitching involuntarily).  -- a 1996 study from Japan also showing benefit in treating myoclonus;  there were also improvements in motivation, attention, sleep, and mood (possibly secondary to improvement in the movement disorder). -- 2001 study from Archives of Neurology again affirming that piracetam is effective over 12 months of follow-up for treating myoclonic epilepsy. -- this 2000 Cochrane review stated that the data on piracetam are inconclusive, with studies not being of good quality - this 1999 article reviewed studies of piracetam for treating vertigo, concluding that it was useful for reducing frequency of recurrence, at doses of 2-5 grams per day.  -- this is a 2007 randomized placebo-controlled study from The Journal of Clinical Psychiatry,  in which piracetam 4800 mg/d for 9 weeks led to substantial improvements in tardive dyskinesia, with large differences from placebo.  -- piracetam has some antiplatelet function, which could be used in managing or preventing recurrences of vascular disorders.  This is a 1999 review of this subject.  -- this is a broad review of nootropics, published in 1994.  -- this 1987 study from The Journal of Clinical Psychopharmacology shows that children treated with piracetam may show improvements in dyslexia.
Doses were 3.3 grams daily x 36 weeks (dosed twice per day).  However, as I look at the results, I see that there is a statistical difference, but the numbers really look very similar between placebo and piracetam.    The placebo group improved substantially; the piracetam group improved only slightly more.  For example, the raw scores in the Grey Oral Reading Test increased from 17.1 to 22.5 in the placebo group; in the piracetam group it increased from 14.8 to 22.9.   It is true that the piracetam was well-tolerated, with minimal side-effect problems.
this is a 2002 study which attempted to show whether piracetam could prevent ECT-induced cognitive problems.   The dose was 7.2 g/day for a 2-week loading phase, then 4.8 g daily for the remaining 2 weeks.  They concluded that piracetam had no effect on cognition in this group; but the piracetam group did slightly better than the placebo group in terms of overall clinical improvement.
this 2006 study described anxiolytic effects of piracetam which were blocked by flumazenil (a benzodiazepine receptor blocker), suggesting that piracetam has some GABA-like activity.
a Hungarian study describing successful use of piracetam to treat alcohol withdrawal delirium
a 1993 Indian study showing that piracetam has anti-anxiety effects when administered on a longer-term basis in rats.
a 1979 article from Journal of Affective Disorders describing anti-anxiety effects from piracetam similar to a benzodiazepine, but without sedation.
in this 1983 study, piracetam 2.4 g/day or 4.8 g/day was compared with placebo in treating 60 elderly psychiatric patients; the 2.4 g/day group showed increased socialization, altertness, and cooperation, and had some improvement on memory and IQ tests, compared to the placebo group.
in this 1977 study, elderly psychiatric patients were given 2.4 g/day of piracetam or placebo, for 2 months.  The piracetam group did not improve in any cognitive tests or mood symptom scores compared to placebo, but interestingly 52% of subjects in the piracetam group showed overall improvement (CGI) compared to only 25% in the placebo group.
a Cochrane review from 2001 concluding that there is evidence that piracetam may improve the course of aphasia after stroke; however, the evidence was found to be weak.
this 1982 study shows that 40 g of IV piracetam caused greater reduction than placebo in antipsychotic-induced Parkinsonian side-effects.
a small 1979 study which showed that refractory depressed patients improved with the addition  of 2.4 g piracetam.
a look at toxicity risk due to piracetam, when given in higher doses (12 g/day) for 12 weeks, to stroke patients.  The paper concludes that there is no significant toxicity risk at this dose for this population.

In conclusion, piracetam appears to be clearly effective for a few uncommon conditions, such as myoclonus.  There is possible effectiveness for some other problems such as tardive dyskinesia.  The evidence for effectiveness as a "cognitive enhancer" appears to be quite shaky, but not absent.

I am particularly interested in some of the evidence which suggests that it could be useful as a safe, well-tolerated adjunct to treat depression or anxiety.  Some of the studies quoted above appear to support this possibility.  This theme also intersects with my recent thoughts about considering cognitive function in chronic mood, anxiety, ADHD, or personality disorders. A weakness in working memory capacity or executive functioning could substantially interfere with recovery from psychiatric illness; I suspect that a treatment which could specifically help with cognitive function could be a unique angle to augment treatments for these other psychiatric problems.  (see my previous post, which discusses an association between rumination & working memory dysfunction:  Here's another link about this:

I do think it would be worthwhile for research groups to consider doing some new, careful, large trials of piracetam as an augmentation for managing depression, anxiety disorders, etc.


Otte said...

>Nootropil (Piracetam) made years ago by a belgium compagny called UCB and agressively marketed as the (sole) member of the shiny new category called "Nootropics" (was marketed un der the brand name "Nootropil"). Seemed effective in Lance Adams syndrome (post anoctic myoclonus) in high doses (4-6 gram). Disappeared gradually from the medical scene as no lasting EBM evidence could substantiate the claims.

Dr. G. Otte

GK said...

Some of these things that disappeared gradually may still have possible uses; my review of the evidence shows some promising leads, mainly limited by the fact that there aren't very many recent good-quality studies (e.g. of a standard that we would commonly see with other psychiatric drugs), nor have people looked at it specifically as a mood or anxiety disorder augmentation (as opposed to its largely unspectacular role as some kind of dementia treatment).

Otte said...

You may be right and anyway UCB could be interested. Digging up old meds is always attractive. I am absolutely sure that it will cause no harm whatsoever (unless financially). During four to five years in my training I have seen neurosurgeons and neurologists use it extensively at high daily IV doses (minimal dose was 4-6 gram: a lot of ampoules to be cut every day :-).
Some family doctors have continued using it at high peroral dose. Never saw any harm done (nut ,neither does homeopathy...)

GK said...

Your point is well-taken, although I would have to say that homeopathy is not without its risks: on the positive side, homeopathic treatments may usefully exploit a placebo effect. On a negative side, a strong belief or reliance on homeopathic remedies could unreasonably delay people, or bias people against, seeking more effective treatments for serious progressive problems.

Perhaps similar phenomena could occur with questionably effective alternative treatments of other types, including piracetam. But I am curious to explore the possibility of using piracetam as a harmless augmenting agent to try for anxiety or mood patients.

Anonymous said...

Hi Garth,

Interesting post on Piracetam, thank you for sharing.

I live in Toronto and have often wondered about the legal status of Piracetam in Canada (ie. simply importing for personal use) and I've often seen conflicting reports.

Can I ask how you know that it's legal to import? I would love to try some as I think it would greatly help me.

Many thanks in advance,

GK said...

I'm not an expert on legal issues--so perhaps I should not have stated assertively that it is legal in Canada--but I do know of people who have imported piracetam without any problem. Perhaps the laws could vary from one province to the next. For a definitive answer on this one, it might be good to consult a local lawyer who specializes in imports, pharmaceuticals, etc.

Anonymous said...

Re: Chronic cognitive impairment.

Thank you for mentioning this. I wish that more was written about this (I don't necessarily mean on your blog, I just mean in general discussions about mental health). It seems to me that often these complaints are treated as a symptom of depression/ evidence of some kind of cognitive distortion, a belief that needs to be challenged. Or else I think that if they are considered as problems they're often considered to be a side effect of medication, and therefore either something that can be fixed (eg with a change in medications) or as something that in the grand scheme of things is not important if other symptoms are controlled.

For many people probably the most therapeutic and helpful thing is simply having negative beliefs of yourself (including beliefs about your intelligence, talents, abilities, etc) proven incorrect. But what if these beliefs are repeatedly reinforced by your experiences in the world?

I think also that there is a type of therapeutic response that associates concerns about cognitive problems with unhealthy personal or societal expectations. I'm not sure if I'm expressing that well. It's as though these types of difficulties if they exist should not prevent someone from creating a satisfying/ meaningful life, there's a view that our society places too much importance on "achievement" etc (so: problems with academic or professional achievement secondary to ongoing cognitive problems should not become a source of ++ distress because these things should not be so intensely valued). Or I hear about the importance of meaning-making, but there does not seem to be much acknowledgment that cognitive difficulties can prevent this from happening, ie they can prevent you from creating a life that you value (through work or something else), or from engaging in activities that are meaningful to you, etc.

Psychiatric problems in general are supposed to create problems with relationships, but to me the problem often seems specific to cognitive difficulties or to fall-out out because of this. It becomes hard to represent or defend a life that doesn't really reflect your values. This is not necessarily specific to achievement....I think of things like feeling strongly that you value intellectual curiosity or value being knowledgeable about world events, etc, yet if it is difficult to read/ think/ articulate ideas etc it becomes very difficult to be able to reflect these values, to take part in conversations that you want to have. I feel like one major barrier to being with people is not feeling that I am a good representation of who I want to be....again, it seems to go beyond not having the "right" work or other credentials, to having difficulty interacting with people in what I would consider to be a meaningful way. It's not just NOT being able to achieve things because of problems thinking, it's about becoming the kind of person you dislike or don't respect (ie someone who is intellectually lazy, uninformed, complacent, etc). It drives a kind of detachment from your life that in the end seems to become the main problem.