Kranzler et al, in the April 2014 edition of The American Journal of Psychiatry, show that topiramate 200 mg daily led to very substantial reduction in alcohol use in heavy drinkers, compared to placebo. But this effect was dramatically present only for a subgroup of drinkers who have the CC genotype of the rs2832407 gene. This genotype is carried by about 42% of people having European ancestry.
Topiramate stands out as a very reasonable, safe, and relatively well-tolerated adjunct in the treatment of alcoholism. I don't think it is necessary to test for the genotype--it would be reasonable to offer an empirical trial, and to predict with the patient that there will be about a 40% chance of the medication having a dramatic effect. If it doesn't help, the risks would be minimal. Since topiramate is an anticonvulsant, it could theoretically treat or prevent withdrawal symptoms, even if it doesn't independently reduce the urge to drink.
Wednesday, December 17, 2014
Marijuana: effects on memory
In order to show the effects of cannabis clearly in a research study, it is of course best to have a prospective, randomized, controlled experiment, conducted over a long period of time.
This would not be ethical in humans. In fact, I don't see that it was particularly ethical in monkeys either. But Verrico, Gu, et al. did such a study, published in the April 2014 edition of The American Journal of Psychiatry, giving adolescent rhesus monkeys daily IV doses of THC 5 days per week for 6 months. A control group, matched for baseline cognitive performance, received IV infusions with no THC.
They found significant impairments in spatial working memory in the THC group.
This is strong evidence that marijuana has negative effects on cognition in adolescents. It did not prove that there are lasting cognitive deficits after the THC has been metabolized out of the body.
We can conclude from this study that daily heavy THC use in otherwise healthy adolescents is likely to interfere with optimal cognitive performance, which could impair schoolwork and possibly contribute to cumulative risk of various other developmental deficits.
The study does not address risk to cognitive function in adults. And it does not address the possibility that THC may be useful for managing other symptoms for some individuals, despite the side-effect of spatial memory impairment.
This would not be ethical in humans. In fact, I don't see that it was particularly ethical in monkeys either. But Verrico, Gu, et al. did such a study, published in the April 2014 edition of The American Journal of Psychiatry, giving adolescent rhesus monkeys daily IV doses of THC 5 days per week for 6 months. A control group, matched for baseline cognitive performance, received IV infusions with no THC.
They found significant impairments in spatial working memory in the THC group.
This is strong evidence that marijuana has negative effects on cognition in adolescents. It did not prove that there are lasting cognitive deficits after the THC has been metabolized out of the body.
We can conclude from this study that daily heavy THC use in otherwise healthy adolescents is likely to interfere with optimal cognitive performance, which could impair schoolwork and possibly contribute to cumulative risk of various other developmental deficits.
The study does not address risk to cognitive function in adults. And it does not address the possibility that THC may be useful for managing other symptoms for some individuals, despite the side-effect of spatial memory impairment.
Evolution & Psychiatry
It is richly interesting to consider the impact of evolutionary processes as they pertain to human behaviour and psychiatric phenomena.
This is an area which is, of course, laden with controversy. Yet I find the controversy quite unnecessary, perhaps a reflexive reaction which itself could be understood in evolutionary terms.
Despite having several science degrees, including many courses in biology (including genetics and molecular genetics) I am embarrassed to admit that, during my undergraduate years, I never read major popular books by evolutionary theorists. It is only recently that I have read The Selfish Gene by Richard Dawkins. I was well-versed in textbook science, and even laboratory-based genetics, yet the joy of learning about genetics can be savoured much more deeply by taking a look at some of these popular works on the subject.
I do not find the subject matter of The Selfish Gene the slightest bit controversial. I understand why some find it controversial, but I see this as mainly a product of simple human resistance to adapting entrenched beliefs (some of which have been around for millenia, and considered sacred) in the face of strong contrary evidence. In this case, some of these entrenched beliefs touch on themes relating to religion and ethics. It is similar to renaissance astronomers being met with disbelief or condemnation, following discoveries about planetary motions which were quite different from previous views.
Actually, as with most science, I find the subject of evolution to be delightfully, joyously interesting, and certainly not a threat to the culture's moral fabric, etc. Understanding processes of nature need only increase one's sense of wonder and awe, not somehow render it more "spiritless." My only objection to The Selfish Gene and other similar books is the use of the term "Darwinism." While I admire the work of Darwin very much, I don't find that it is necessary or useful to attach his name to a system of understanding nature. Attaching his name makes the subject sound like some kind of philosophical or political opinion (such as "Calvinism" or "Marxism"), or a type of esthetic or artistic style. The science of evolution is similar to the science of arithmetic, geometry, or physics. We would not call a mathematician or physicist a "Pythagorean" or a "Newtonian."
Evolutionary theory is a simple application of clear logic to a system in which phenomena are replicated. Those phenomena which replicate more abundantly become more widespread in the population. This is a self-evident truth, which leads in more complicated systems to some very interesting mathematics. As Dawkins points out, this type of replication occurs in genes, but also in culture as "memes." The application of game theory analysis to such replicating systems leads to an understanding of equilibria between competing strategies, which can persist in any population or culture. Fluency in mathematics makes an insightful understanding of evolutionary science much more clear.
How is this relevant to psychiatry? An evolutionary analysis of behaviour reminds me a little of a psychoanalytic exploration of "the unconscious" -- it can bring to awareness behavioural tendencies that are favoured "as if" the genes themselves had a selfish motive. Genes, being chemical entities, do not literally have motives, but the fact that they replicate leads to gene frequencies and genetically-based behaviours occurring as if they had motives. Similarly, the "unconscious" could be understood as silent forces within the mind which guide action, outside of awareness. Therapeutically, according to psychoanalytic theory, insight about one's unconscious motives can lead to a greater freedom of will, and to an escape from recurrent traps of symptoms. Similarly, awareness of the "forces" caused by natural selection of genes can help us decide whether to culturally over-ride these forces, for the betterment of ourselves or of society. For example, as Dawkins pointed out, biology itself cannot be relied upon to produce widespread altruism, and to produce an end to warlike or aggressive behaviour; such a state can be shown mathematically not be an "ESS" (evolutionarily stable state). So if we are to aim for widespread peace and altruism, we must culturally over-ride innate biological tendencies, on a personal and population level, and work to teach peace very actively.
For such a project to work, we would have to anticipate its meme-like properties, and be prepared to deal with ensuing problems. For example, in religious cultures, the meme-like nature of associated beliefs and behaviours can cause deleterious cultural changes as a result of "natural selection." While many religious beliefs are characterized by a deep sense of fairness, justice, peacefulness, and altruism, the memetic properties needed for beliefs to "propagate" lead to a high likelihood of negative elements, such as magical thinking, instilling fear of hell, suppressing contrary views despite strong evidence, espousing violent actions as sacred elements of following or defending one's faith, etc. Religious memes can become "symbiotic" with memes for political power or influence, leading as we have often seen to religions and governments combining their influences to dominate a nation's political affairs.
This is an area which is, of course, laden with controversy. Yet I find the controversy quite unnecessary, perhaps a reflexive reaction which itself could be understood in evolutionary terms.
Despite having several science degrees, including many courses in biology (including genetics and molecular genetics) I am embarrassed to admit that, during my undergraduate years, I never read major popular books by evolutionary theorists. It is only recently that I have read The Selfish Gene by Richard Dawkins. I was well-versed in textbook science, and even laboratory-based genetics, yet the joy of learning about genetics can be savoured much more deeply by taking a look at some of these popular works on the subject.
I do not find the subject matter of The Selfish Gene the slightest bit controversial. I understand why some find it controversial, but I see this as mainly a product of simple human resistance to adapting entrenched beliefs (some of which have been around for millenia, and considered sacred) in the face of strong contrary evidence. In this case, some of these entrenched beliefs touch on themes relating to religion and ethics. It is similar to renaissance astronomers being met with disbelief or condemnation, following discoveries about planetary motions which were quite different from previous views.
Actually, as with most science, I find the subject of evolution to be delightfully, joyously interesting, and certainly not a threat to the culture's moral fabric, etc. Understanding processes of nature need only increase one's sense of wonder and awe, not somehow render it more "spiritless." My only objection to The Selfish Gene and other similar books is the use of the term "Darwinism." While I admire the work of Darwin very much, I don't find that it is necessary or useful to attach his name to a system of understanding nature. Attaching his name makes the subject sound like some kind of philosophical or political opinion (such as "Calvinism" or "Marxism"), or a type of esthetic or artistic style. The science of evolution is similar to the science of arithmetic, geometry, or physics. We would not call a mathematician or physicist a "Pythagorean" or a "Newtonian."
Evolutionary theory is a simple application of clear logic to a system in which phenomena are replicated. Those phenomena which replicate more abundantly become more widespread in the population. This is a self-evident truth, which leads in more complicated systems to some very interesting mathematics. As Dawkins points out, this type of replication occurs in genes, but also in culture as "memes." The application of game theory analysis to such replicating systems leads to an understanding of equilibria between competing strategies, which can persist in any population or culture. Fluency in mathematics makes an insightful understanding of evolutionary science much more clear.
How is this relevant to psychiatry? An evolutionary analysis of behaviour reminds me a little of a psychoanalytic exploration of "the unconscious" -- it can bring to awareness behavioural tendencies that are favoured "as if" the genes themselves had a selfish motive. Genes, being chemical entities, do not literally have motives, but the fact that they replicate leads to gene frequencies and genetically-based behaviours occurring as if they had motives. Similarly, the "unconscious" could be understood as silent forces within the mind which guide action, outside of awareness. Therapeutically, according to psychoanalytic theory, insight about one's unconscious motives can lead to a greater freedom of will, and to an escape from recurrent traps of symptoms. Similarly, awareness of the "forces" caused by natural selection of genes can help us decide whether to culturally over-ride these forces, for the betterment of ourselves or of society. For example, as Dawkins pointed out, biology itself cannot be relied upon to produce widespread altruism, and to produce an end to warlike or aggressive behaviour; such a state can be shown mathematically not be an "ESS" (evolutionarily stable state). So if we are to aim for widespread peace and altruism, we must culturally over-ride innate biological tendencies, on a personal and population level, and work to teach peace very actively.
For such a project to work, we would have to anticipate its meme-like properties, and be prepared to deal with ensuing problems. For example, in religious cultures, the meme-like nature of associated beliefs and behaviours can cause deleterious cultural changes as a result of "natural selection." While many religious beliefs are characterized by a deep sense of fairness, justice, peacefulness, and altruism, the memetic properties needed for beliefs to "propagate" lead to a high likelihood of negative elements, such as magical thinking, instilling fear of hell, suppressing contrary views despite strong evidence, espousing violent actions as sacred elements of following or defending one's faith, etc. Religious memes can become "symbiotic" with memes for political power or influence, leading as we have often seen to religions and governments combining their influences to dominate a nation's political affairs.
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