The stoners ought to try to remember the details of this research to think about it next time they take a toke.
Neurons that spend a lot of time firing in some different way in response to a drug probably reconfigure somehow in response to the different pattern of firing. Brains strengthen and weaken connections in response to stimuli, whether those stimuli come from the environment or from drugs or an interaction of the two.
What I'd like to know: What does the THC do to change the development of a fetal hippocampus?
Cocaine Addicts Have Distorted Values For Money
Periodically I like to harp on the damage that addictive drugs do to brains because some libertarians (and not a few economists) imagine that we all have enough free will to make rational decisions about addictive drug use. I take a more evolutionary approach to humans and free will. Our capacity to think rationally is spotty at best and there are elements of our modern technological societies that we are so maladapted to handle that we are like dogs that want to chase cars. When dogs do it they get injured or killed and we are no different. We aren't wired up to handle some products of our societies and it is naive to pretend otherwise.
Here is yet another study showing impaired ability of addicts to make judgements that would seem like common sense to, say, a free market libertarian. Coke heads have impared abilties to perceive awards and control how they respond to rewards.
ATLANTA, GA -- People addicted to cocaine have an impaired ability to perceive rewards and exercise control due to disruptions in the brain's reward and control circuits, according to a series of brain-mapping studies and neuropsychological tests conducted at the U.S. Department of Energy's Brookhaven National Laboratory.
"Our findings provide the first evidence that the brain's threshold for responding to monetary rewards is modified in drug-addicted people, and is directly linked to changes in the responsiveness of the prefrontal cortex, a part of the brain essential for monitoring and controlling behavior," said Rita Goldstein, a psychologist at Brookhaven Lab. "These results also attest to the benefit of using sophisticated brain-imaging tools combined with sensitive behavioral, cognitive, and emotional probes to optimize the study of drug addiction, a psychopathology that these tools have helped to identify as a disorder of the brain."
Some day drug addicts might be treated by stem cell therapies that go in and restore some missing neurons. Imagine the power of such a therapy. If it can fix damaged brains it will also likely be able to alter the way people with undamaged brains form judgements. Development of repair therapies inevitably leads to development of enhancement therapies and also therapies that are not so much enhancement as simply alteration. For good or bad? I guess we'll find out. Probably some of each, hopefully more good than bad.
The addicts and non-addicts had their brains scanned while they were offered rewards and asked to perform tests.
Goldstein's experiments were designed to test a theoretical model, called the Impaired Response Inhibition and Salience Attribution (I-RISA) model, which postulates that drug-addicted individuals disproportionately attribute salience, or value, to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli -- with a concomitant decrease in the ability to inhibit maladaptive drug use. In the experiments, the scientists subjected cocaine-addicted and non-drug-addicted individuals to a range of tests of behavior, cognition/thought, and emotion, while simultaneously monitoring their brain activity using functional magnetic resonance imaging (fMRI) and/or recordings of event-related potentials (ERP).
Coke addicts couldn't react differently to different levels of reward. They lacked a sense of context for their decision making.
In one study, subjects were given a monetary reward for their performance on an attention task. Subjects were given one of three amounts (no money, one cent, or 45 cents) for each correct response, up to a total reward of $50 for their performance. The researchers also asked the subjects how much they valued different amounts of monetary reward, ranging from $10 to $1000.
More than half of the cocaine abusers rated $10 as equally valuable as $1000, "demonstrating a reduced subjective sensitivity to relative monetary reward," Goldstein said.
"Such a 'flattened' sensitivity to gradients in reward may play a role in the inability of drug-addicted individuals to use internal cues and feedback from the environment to inhibit inappropriate behavior, and may also predispose these individuals to disadvantageous decisions -- for example, trading a car for a couple of cocaine hits. Without a relative context, drug use and its intense effects -- craving, anticipation, and high -- could become all the more overpowering," she said.
So glad my brain hasn't been damaged by extensive coke use.
Coke addicts didn't have their prefrontal cortexes light up in a graded fashion to different sized rewards the way non-addicts did.
The behavioral data collected during fMRI further suggested that, in the cocaine abusers, there was a "disconnect" between subjective measures of motivation (how much they said they were engaged in the task) and the objective measures of motivation (how fast and accurately they performed on the task). "These behavioral data implicate a disruption in the ability to perceive inner motivational drives in cocaine addiction," Goldstein said.
The fMRI results also revealed that non-addicted subjects responded to the different monetary amounts in a graded fashion: the higher the potential reward, the greater the response in the prefrontal cortex. In cocaine-addicted subjects, however, this region did not demonstrate a graded pattern of response to the monetary reward offered. Furthermore, within the cocaine-addicted group, the higher the sensitivity to money in the prefrontal cortex, the higher was the motivation and the self-reported ability to control behavior.
The ERP results showed a similarly graded brain response to monetary reward in healthy control subjects, but not in cocaine-addicted individuals.
Why do addicts relapse? They can't accurately judge the relative rewards of drug use and non-drug use. They simply lack the capacity to arrive at judgements that come easy to most of us.
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Randall Parker
2006 October 29
09:21 PM
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2006 July 06 Thursday
THC Primes Rats For Heavier Heroin Abuse
Marijuana really does lead to higher risk of heavy duty drug abuse - at least in lab rats.
To rule out social factors, the researchers turned to an animal model. They dosed some rats with the active ingredient of cannabis and others with a neutral compound during their adolescence (when they were about four to six weeks old). After that, they gave the rats intermittent access to heroin for several weeks, obtained by pressing a lever.
Although all rats helped themselves to heroin, the ones given cannabis's key compound, called Delta-9-tetrahydrocannabinol (THC), during their formative years showed a greater escalation in their self-dosing during the experiment. By the end, rats that'd had cannabis in their 'teens' were pressing the lever that delivered heroin about 1.5 times more than the rats that had previously been drug-free.
I find this incredibly unsurprising. The developing brain develops differently if exposed to drugs that activate brain pleasure circuitry.
Decreased sensitivity leads to greater risk of addiction.
“At first, all the rats behaved the same and began to self-administer heroin frequently,” says Hurd. “But after a while, they stabilised their daily intake at a certain level. We saw that the ones that had been on THC as teenagers stabilised their intake at a much higher level than the others – they appeared to be less sensitive to the effects of heroin. And this continued throughout their lives.”
Hurd says reduced sensitivity to the heroin means the rats take larger doses, which has been shown to increase the risk of addiction.
Earlier use of alcohol in humans is associated with greater risk of alcoholism.
Data from a survey of 43,000 U.S. adults heighten concerns that early alcohol use, independent of other risk factors, may contribute to the risk of developing future alcohol problems. Those who began drinking in their early teens were not only at greater risk of developing alcohol dependence at some point in their lives, they were also at greater risk of developing dependence more quickly and at younger ages, and of developing chronic, relapsing dependence. Among all respondents who developed alcoholism at some point, almost half (47 percent) met the diagnostic criteria for alcohol dependence (alcoholism) by age 21.
The associations between early drinking and later problems held even after investigators controlled for other risk factors for dependence, adding to concerns that drinking at a young age might raise the risk of future alcohol problems rather than being an identifying feature of young people predisposed to risky behavior. The study appears in the July issue of Archives of Pediatrics & Adolescent Medicine, Volume 160, pages 739-746.
Timing of first alcohol use leads to a huge difference in risk
In results that echo earlier studies, of those individuals who began drinking before age 14, 47 percent experienced dependence at some point, vs. 9 percent of those who began drinking at age 21 or older. In general, each additional year earlier than 21 that a respondent began to drink, the greater the odds that he or she would develop alcohol dependence at some point in life. While one quarter of all drinkers in the survey started drinking by age 16, nearly half (46 percent) of drinkers who developed alcohol dependence began drinking at age 16 or younger.
New findings showed that among all drinkers, early drinking was associated not only with a higher risk of developing alcoholism at some point, but also within 10 years of first starting to drink, before age 25, and within any year of adult life. Early drinking was also associated with increased risk of having multiple episodes of alcoholism. Further, among respondents who had had alcohol dependence at some point, those who began drinking young had episodes of longer duration and with a wider range of symptoms than those who started later.
The developing brain gets altered by drug and alcohol use. We do not have free will. If legalization would increase the amount of teen drug use then legalization would lead to much more drug abuse and addiction.
Adolescent brains are at much higher risk because they are still developing. Industrialized societies need to do a better job of protected teenagers from subtstances that will mess up their brain development.
Also see my post Adolescence Is Tough On The Brain.
By
Randall Parker
2006 July 06
10:13 PM
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2006 June 14 Wednesday
Drug Desire Shows In Brain Scans
PET scans show a boost in brain activity when addicts see images of drug usage.
“To make the drug-cues video, we worked with addicts who advised us on how to make it as realistic as possible while simulating scenes involving smoking or snorting cocaine,” said Wang. The scientists also asked the subjects to rate their level of craving while watching both videos, and assessed the severity of their addiction using a standard cocaine craving scale.
Dopamine levels were measured indirectly using positron emission tomography (PET) scanning at Brookhaven’s Center for Translational Neuroimaging. Each subject was injected with a radiotracer designed to bind to dopamine receptors in the brain. During scanning, the PET camera picks up the signal from any bound radiotracer so that levels of tracer bound to receptors can be compared with levels in the blood. As the body’s natural dopamine levels rise, this “endogenous” dopamine competes with the tracer for binding sites, so less radiotracer can bind to the receptors. Therefore, the lower the bound tracer signal, the higher the concentration of endogenous dopamine.
Compared with the neutral video, the cocaine-cues video triggered a significant increase in dopamine in the dorsal striatum, a part of the brain involved in experiencing desire or motivation. The changes in dopamine were associated with the level of craving reported by the subjects and were largest in the most severely addicted subjects.
This finding is consistent with previous animal studies that have suggested a role for the dorsal striatum in cue-induced craving. In those studies, neutral stimuli such as a particular cage environment that had been paired with a drug during “training” sessions later triggered a dopamine increase in both the nucleus accumbens and the dorsal striatum, a response that was correlated with drug-seeking behaviors in the animals.
Frustrated desires for food also cause a rise in brain dorsal striatum dopamine levels.
The finding is also consistent with earlier Brookhaven research documenting dopamine increases in the dorsal striatum induced by exposure to food (see this release). In that study, healthy subjects were allowed to observe and smell their favorite foods, but not eat them; the more the subjects desired the foods, the higher their dopamine levels went.
“Finding this same association between dorsal striatum dopamine levels and cravings for food and drugs suggests that, in the human brain, drug addiction engages the same neurobiological processes that motivate food-seeking behaviors triggered by food-conditioned cues,” Volkow said. This research suggests that compounds that could inhibit cue-induced striatal dopamine increases would be logical targets for medication development to treat cocaine addiction.
These findings suggest to me that compounds which inhibit or reduce desire for cocaine might also reduce cracvings for food. A drug developed to treat coke addicts might also help people to lose weight.
Also, since the vast bulk of us experience food cravings we non-drug addicts probably understand the cravings that drive drug addicts better than many of us realize. Obese people who look down their noses with disapproval at drug addicts ought to go look in the mirror and look at the signs that they have their own very similarly caused cravings which they can not control.
Some day we will gain the ability to tune our desires to better align our daily behavior with our longer term goals. Research into drug addiction, obesity, and other problems with human minds will produce much more than just treatments to suppress desires for food and drugs. We will also gain the ability to mold what causes our minds to feel satisfied, frustrated, impatient, happy, and sad. People will adjust their emotional reactions to make them better able to do tedious work and to pursue longer term goals.
By
Randall Parker
2006 June 14
10:18 PM
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2006 June 04 Sunday
Genetically Engineered Mice Do Not Get Cocaine High
Genetic engineering might one day prevent drug abuse.
COLUMBUS , Ohio – Researchers found that they could eliminate the rewarding effect of cocaine on mice by genetically manipulating a key target of the drug in the animal's brain.
While the researchers aren't suggesting that these genetic modifications be made in humans, the work brings to light the key protein that controls cocaine's effects in the body, which may help scientists develop medications that achieve the same results and therefore help addicts overcome their dependence.
Humans are not evolutionarily adapted to handle recreational drugs. But some day with genetic engineering our offspring might be adapted to resist drug and alcohol abuse.
Howard Gu and colleagues at Ohio State University showed they could genetically engineer mice to be resistant to the effects of cocaine.
He and his colleagues raised laboratory mice with genetic alterations in the gene that codes for the dopamine transporter.
“By doing so we created a dopamine transporter that resists cocaine but also retains its function of taking up dopamine and carrying it back to the neurons,” Gu said.
I am not surprised that an alteraton of a brain protein could produce a different reaction to a drug will at the same time retaining normal function. But what is amazing is that these scientists - using 2006 biotechnology - were able to find an alteration that produces this outcome.
The behavior of the mice with genetically engineered dopamine transporters suggest that they did not get a high off of cocaine
“The normal mice spent more time in the compartment where they had received the cocaine injections,” Gu said. “These animals were seeking more cocaine. However, the mice with the modified transporters showed no preference for either test compartment within the box.”
The researchers used the video footage to measure each animal's activity level after a cocaine injection. The normal mice on cocaine covered roughly five times the distance than the control mice injected with saline (6 meters vs. 1 meter). In contrast, the cocaine-injected mice with the modified dopamine receptors covered about half the distance that the saline-only injected mice covered (roughly 1.5 meters vs. 3 meters.)
“After the cocaine injections, the normal mice ran all over the place, sniffing and checking everything out in the box over and over again, until we took them out of the box,” Gu said. “But cocaine seemed to calm the modified mice, as they sat in a corner for long periods of time.”
“To the modified mice, cocaine appears to be a suppressant, not a stimulant,” Gu said.
Some people argue it will be hard to discover new ways to enhance cognitive function. But using today's biotechnology these Ohio State scientists found a way to reduce the ability of a drug to alter cognitive function. Imagine what tools will be available 20 years from now to use to search for ways to alter functionality in brain proteins.
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Randall Parker
2006 June 04
10:46 PM
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2006 March 21 Tuesday
Genetic Variant Predisposes To Cocaine Addiction
A variant of a neurotransmitter dopamine transporter gene increases risk of cocaine addiction by 50%.
Scientists have discovered that our genes have an impact on our reaction to cocaine and our likelihood of developing an addiction to the class A drug. The research is published this week in the online edition of PNAS, the journal of the American Academy of Sciences. It was carried out at the Medical Research Council (MRC) Social, Genetic and Developmental Research Centre at the Institute of Psychiatry, King’s College London.
Much of our desire to use/re-use drugs and the process of addiction depend on their impact on brain function. Cocaine’s action within the brain is relatively well understood. It strongly binds and inhibits the action of a protein called the Dopamine Transporter (DAT)1.
Addiction Potential
In this latest study, researchers examined the DNA of 700 cocaine abusers and 850 ordinary people and found that cocaine abusers had a specific genetic variation in DAT more frequently than the control subjects. People carrying two copies of this variant were 50% more likely to be cocaine dependent.
Expect a continuing stream of reports of genetic variants that heavily influence human behavior. Do humans have any free will at all? Heck if I know. But I'm not betting on it. My guess is my genes insist to me that I have no free will and I believe what they tell me.
Some day we'll all know our complete genetic profiles. We'll know for which drugs we have a greater risk of addiction. Will that knowledge reduce the incidence of drug addiction?
My guess: preventive treatments will play a bigger role in reducing drug addiction than genetic screening. Give Mom and Dad a vaccine or maybe a nanotech implant that'll eat up heroin, cocaine, ecstasy, and other drugs in the bloodstream and Junior won't get high until he can afford medical treatments that'll reverse the drug-neutralizing technologies that his parents had implanted in him when he was 12 years old.
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Randall Parker
2006 March 21
09:51 PM
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2006 March 19 Sunday
Tokers Get Dumber With Every Joint
He's a toker, he's a smoker, he's a fried out joker.
Memory, speed of thinking and other cognitive abilities get worse over time with marijuana use, according to a new study published in the March 14, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.
The study found that frequent marijuana users performed worse than non-users on tests of cognitive abilities, including divided attention (ability to pay attention to more than one stimulus at a time) and verbal fluency (number of words generated within a time limit). Those who had used marijuana for 10 years or more had more problems with their thinking abilities than those who had used marijuana for five to 10 years. All of the marijuana users were heavy users, which was defined as smoking four or more joints per week.
"We found that the longer people used marijuana, the more deterioration they had in these cognitive abilities, especially in the ability to learn and remember new information," said study author Lambros Messinis, PhD, of the Department of Neurology of the University Hospital of Patras in Patras, Greece. "In several areas, their abilities were significant enough to be considered impaired, with more impairment in the longer-term users than the shorter-term users."
The study involved people ages 17 to 49 taking part in a drug abuse treatment program in Athens, Greece. There were 20 long-term users, 20 shorter-term users and 24 control subjects who had used marijuana at least once in their lives but not more than 20 times and not in the past two years. Those who had used any other class of drugs, such as cocaine or stimulants, during the past year or for more than three months throughout their lives were not included in the study. Before the tests were performed, all participants had to abstain from marijuana for at least 24 hours.
The marijuana users performed worse in several cognitive domains, including delayed recall, recognition and executive functions of the brain. For example, on a test measuring the ability to make decisions, long-term users had 70 percent impaired performance, compared to 55 percent impaired performance for shorter-term users and 8 percent impaired performance for non-users.In a test where participants needed to remember a list of words that had been read to them earlier, the non-users remembered an average of 12 out of 15 words, the shorter-term users remembered an average of nine words and the long-term users remembered an average of seven words.
A longitudinal study would be a lot more convincing. Follow the same tokers for a few years and measure their mental deterioration. Maybe (not that I think this likely) chronic stoners are space cadets even before they become chronic stoners. Or maybe chronic stoners are dumber on average and smarter people decide that getting stoned all the time is just not worth it.
Yeah, maybe. But I doubt it. Heavy duty (multiple times every day) stoner college roommates (not that I ever witnessed criminal activity - this is all hearsay rumours as told to me by other roommates who saw all this while I was at the library of course) whose memories were not first rate came across to me as people who used to be smarter than they were when I knew them. They knew too much about past events and seemed like they once were a lot more together. As kids I figure they didn't used to say "oh wow, I'm supposed to be in class" or "oh wow, I was supposed to meet Lisa for lunch and I like totally spaced". No, I bet they were once a lot more attentive and mentally competent.
If only mainstream left-liberal social scientists hadn't felt the ideological need to collectively decide that the field of psychometrics is the work of Satan some of them would use IQ tests in longitudinal studies of various sorts of drug abusers and we could find out how much damage each recreational drug does to brains.
What practical information I really want to know: Will use of modafinal (Provigil) exact a toll in terms of faster brain aging? Which classes of cognitive-enhancing neuroceuticals won't exact a toll in increased neuronal wear and tear?
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Randall Parker
2006 March 19
05:58 PM
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2006 January 25 Wednesday
Political Partisans Addicted To Irrational Defense Of Their Tribes
Partisan defenders of irrational positions get rewarded by their brains in the same way drug addicts get rewarded by addictive drugs.
When it comes to forming opinions and making judgments on hot political issues, partisans of both parties don't let facts get in the way of their decision-making, according to a new Emory University study. The research sheds light on why staunch Democrats and Republicans can hear the same information, but walk away with opposite conclusions.
The investigators used functional neuroimaging (fMRI) to study a sample of committed Democrats and Republicans during the three months prior to the U.S. Presidential election of 2004. The Democrats and Republicans were given a reasoning task in which they had to evaluate threatening information about their own candidate. During the task, the subjects underwent fMRI to see what parts of their brain were active. What the researchers found was striking.
"We did not see any increased activation of the parts of the brain normally engaged during reasoning," says Drew Westen, director of clinical psychology at Emory who led the study. "What we saw instead was a network of emotion circuits lighting up, including circuits hypothesized to be involved in regulating emotion, and circuits known to be involved in resolving conflicts." Westen and his colleagues will present their findings at the Annual Conference of the Society for Personality and Social Psychology Jan. 28.
Once partisans had come to completely biased conclusions -- essentially finding ways to ignore information that could not be rationally discounted -- not only did circuits that mediate negative emotions like sadness and disgust turn off, but subjects got a blast of activation in circuits involved in reward -- similar to what addicts receive when they get their fix, Westen explains.
"None of the circuits involved in conscious reasoning were particularly engaged," says Westen. "Essentially, it appears as if partisans twirl the cognitive kaleidoscope until they get the conclusions they want, and then they get massively reinforced for it, with the elimination of negative emotional states and activation of positive ones."
The feeling of partisan loyalty is an obstacle to rational thought. Abandon your partisan loyalties and the effect will be to boost your ability to understand political events.
Also, distrust the most partisan commentators who defend the leaders of their factions. Their odds of making sense and being correct are lower than for less partisan commentators.
Addicts of partisanship need treatments that will prevent them from getting high from defending their tribes.
Behavioral data showed a pattern of emotionally biased reasoning: partisans denied obvious contradictions for their own candidate that they had no difficulty detecting in the opposing candidate. Importantly, in both their behavioral and neural responses, Republicans and Democrats did not differ in the way they responded to contradictions for the neutral control targets, such as Hanks, but Democrats responded to Kerry as Republicans responded to Bush.
While reasoning about apparent contradictions for their own candidate, partisans showed activations throughout the orbital frontal cortex, indicating emotional processing and presumably emotion regulation strategies. There also were activations in areas of the brain associated with the experience of unpleasant emotions, the processing of emotion and conflict, and judgments of forgiveness and moral accountability.
Notably absent were any increases in activation of the dorsolateral prefrontal cortex, the part of the brain most associated with reasoning (as well as conscious efforts to suppress emotion). The finding suggests that the emotion-driven processes that lead to biased judgments likely occur outside of awareness, and are distinct from normal reasoning processes when emotion is not so heavily engaged, says Westen.
Political parties harness neural wiring that was probably selected for to encourage tribal solidarity and mutual defense of the tribe. Today it motivates people to defend positions and actions taken by the leaders of their political faction. The human mind was not selected for by evolution to be a perfect reasoning machine.
I feel sorry for the partisans. They are basically drug addicts. But I have greater sympathy for the rest of us who suffer from their actions just as we suffer from the actions of drug addicts.
Update: Think about the pattern of cognitve reaction when people feel loyalties are at stake. Imagine a drug or other treatment could interrupt that reaction. One can imagine why people would want to take such drugs for themselves. One could think more objectively and rationally about business problems or personal problems or political issues. But one can also imagine why governments and other groups would want to avail themselves of neurotechnologies that would allow the disruption of feelings of loyalty.
Millions of people already take drugs to disrupt and prevent feelings of anxiety and depression. The idea of developing pharmaceutical and other medical means to disrupt and prevent other modes of emotional reaction therefore does not seem farfetched. If such disruption can be done with drugs it also probably can be done with genetics to cause offspring to have very different patterns of formation of loyalties. Will people choose to give their offspring different capacities and tendencies to form and defend loyalties? I expect individuals, cults, and governments to do this. I expect humanity to splinter into groups that have greater differences in cognitive function than human groups naturally have due to differences in selective pressures during our evolutionary past.
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Randall Parker
2006 January 25
07:30 PM
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2005 December 14 Wednesday
N Acetyl Cysteine Might Reduce Cocaine Cravings
All still very preliminary.
"Cocaine is highly addictive and can have devastating effects on the health and well being of users," says lead researcher Peter Kalivas, Ph.D., Professor and Chair of the Department of Neurosciences at the Medical University of South Carolina (MUSC). "The discovery that a readily available herbal supplement can reduce the intense cravings associated with cocaine use is an important finding for individuals undergoing treatment for cocaine addiction. Reduced craving might help addicted individuals restrain from abusing cocaine."
In the first phase of the study, Dr. Kalivas and the research team conditioned rats on a regimen of cocaine to establish their addiction. The rats in the treatment group were then treated with NAC. After treatment, the cocaine-addicted rats exposed to NAC were significantly less likely to seek out cocaine than those without NAC. Those treated with NAC ceased to actively seek cocaine, but showed normal food-seeking behaviors.
In the second phase of the study headed by Drs. Robert Malcolm, Hugh Myrick, Steve LaRowe, and Pascale Mardikian in the Department of Psychiatry at MUSC, NAC treatment was investigated in a small inpatient study (n=15) involving non-treatment seeking cocaine-dependent subjects. In this phase of research, subjects were asked to look at pictures that were either neutral (e.g., trees, boats) or cocaine-related (e.g., drug paraphernalia). Those individuals treated with NAC reported less craving for cocaine and spent less time looking at the cocaine-related pictures. In addition, when using a functional magnetic resonance imaging (fMRI) test, subjects treated with NAC had reduced brain activity in the prefrontal cortex, the area of the brain activated during cocaine craving and used to modulate the addictive behavior of chronic cocaine use. An open label trial, which was recently completed, indicated that cocaine-dependent patients could take NAC on an extended outpatient basis, with minimal side effects. More importantly, patients taking higher doses of NAC were more likely to complete the trial, providing further indication of the potential benefits of NAC.
"The potential to use NAC for the treatment of individuals addicted to cocaine is a major finding," emphasized Dr. Kalivas. "For those individuals who have the desire to end their addictive habit, a NAC supplement might help to control their cravings."
A larger clinical trial that will follow 282 cocaine-dependent individuals has just begun in order to further understand and corroborate how NAC works in the brain to reduce cocaine craving. Dr. Kalivas stresses that while the initial findings are very promising, the widespread use of NAC in cocaine treatment is not advised until larger scale studies are complete.
The number of humans involved (15) is too small to know for sure. The bigger study they have begun will provide a more definitive answer.
By
Randall Parker
2005 December 14
07:15 AM
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2005 December 01 Thursday
Bupropion Reduces Methamphetamine Cravings
Addicts participating in a small study at UCL reported less intense cravings for methamphetamine as a result of taking bupropion.
A new study led by researchers at UCLA's Semel Institute suggests the antidepressant bupropion may help treat methamphetamine addiction. No medications presently are approved for treating methamphetamine addicts.
Appearing Nov. 23 as an advance online publication of the peer-reviewed journal Neuropsychopharmacology, the study finds bupropion blunts the methamphetamine "high" and reduces cravings prompted by visual cues such as ambient drug use.
The research team hypothesizes that bupropion reduces the effects of methamphetamine by preventing the drug from entering brain cells, where methamphetamine can produce release of neurotransmitters that cause feelings of euphoria.
The study is the first to examine the effectiveness of bupropion for treating methamphetamine addiction in humans. A multisite Phase II clinical trial led by UCLA researchers is in progress.
Bupropion is found in the anti-nicotine drug Zyban and the anti-depressant Wellbutrin. So meth addicts could easily start trying to use bupropion right now to help them quit. Since a lot of meth users also smoke cigarettes they might also find it easier to quit smoking at the same time.
Drug addiction is a sign that humans are not adapted to the environments they've created for themselves using advances in technology. We were not selected for by evolution to handle the drugs that scientists have turned up. We need to develop technologies which will allow us to adapt ourselves to the elements in our environment which many of us can not handle. Lest you think the "many of us" doesn't include you I have a few questions to ask you: Are you overweight? Do you get less than an optimal amount of exercise? Ever had any problems with addictions or substance abuse? Have any destructive or at least partially disabling cravings? Spend too much time reading on the internet?
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Randall Parker
2005 December 01
10:19 PM
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2005 November 30 Wednesday
Nicotine Vaccine Trial Shows Promise
Picture parents getting their kids vaccinated the first time they smell cigarette smoke on their breath.
A University of Minnesota study indicates that the nicotine vaccine NicVax, which is now being tested in humans, appears safe, well-tolerated, and a potentially effective method for helping smokers kick the habit.
Dorothy Hatsukami, Ph.D., director of the University of Minnesota Cancer Center's Transdisciplinary Tobacco Use Research Center (TTURC), is the lead author on this study. The 38-week study included 68 active smokers who were randomly assigned to receive one of three different doses of the vaccine or a placebo. The findings are published in the current issue of the journal Clinical Pharmacology and Therapeutics.
"The vaccine works by producing antibodies that specifically bind to nicotine and thereby prevent much of the nicotine from entering the brain," Hatsukami said. "This process potentially reduces the pleasurable effects from smoking and reduces the addiction to nicotine."
The vaccine may become a new option for helping the approximately 45 million people in the United States who smoke. In 2004, the rate for smoking in Minnesota was about the same as the national average of 20.9 percent.
"More research needs to be done, but at this point, our results show the vaccine is safe and well-tolerated," Hatsukami said. "We found the vaccine has few side effects on the central nervous system because the antibody itself is targeted specifically for nicotine and does not alter any functions of the brain."
Additionally, she says that while this study was not designed to test the treatment effect, 38 percent of the participants in the high-dose vaccine group quit smoking for at least 30 days.
"This result was an impressive and completely unexpected finding because the study was not focused on helping smokers quit smoking," she noted. "In fact, to participate in the study, smokers had to attest that they did not have a planned quit date for the next six months."
This is really an ideal addiction treatment because it can just as easily prevent addiction as cure it. However, some drugs might not make good immune system targets. In that case what we need are nanobots that are smart enough to recognize and destroy specific drug targets. Nanobots are a more distant prospect than vaccines though. Another possibility would be to develop gene therapies for the liver that would up a liver's ability to break down a drug compound. Make the drug have a very short half-life in the body. Though people could still get high by use of nasal delivery or other delivery mechanisms that take the drugs to the brain without passing through the liver first.
We also need gene and/or cell therapies that will reverse the effects of addictive drugs on the brain. Also, since some people are genetically more prone to addiction we need gene therapies that will modify the brain to make it less prone to addiction.
By
Randall Parker
2005 November 30
07:00 AM
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2005 November 29 Tuesday
Peptide Might Prevent Amphetamine Addiction
A peptide might prevent the development of addiction.
Canadian scientists have developed some clever molecular trickery that is helping to reduce the drug cravings of addicted rats. One of the problems in addiction is that neurons in some parts of the brain lose glutamate receptors from the cell surface, and those receptors are important for communication between neurons. The researchers have sidestepped this problem by crafting a peptide that mimics a portion of the tail of the glutamate receptor and, once inside a neuron, serves as a decoy to prevent the loss of glutamate receptors.
Yu Tian Wang, an HHMI international research scholar, and colleagues at the University of British Columbia in Vancouver report their findings in the November 25, 2005, issue of the journal Science.
In addicted rats, cell-to-cell communication is compromised as a result of certain long-term changes at the level of individual neurons. Their research has produced a targeted drug that tricks brain cells into preventing those changes. "We think this is a good candidate for a drug against addiction that has very few side effects," said Wang, a neuroscientist . Although the initial studies are promising, Wang cautioned that the drug is in the early stages of development and is years away from testing in humans.
One obvious problem with this approach is that peptides are hard to deliver. Diabetics have to take insulin shots because the insulin peptide would get digested and broken up if taken orally. So a peptide treatment would probably have to be taken by syringe. Still, diabetics manage to do this and some addicts have plenty of experience with syringes.
Another potential problem is that the peptide might interfere with normal learning or other normal on-going neuronal processes. But such an interference might be worth it given the damage that amphetamine use causes to people's brains and their lives and the lives of other people around them.
The biggest question I see here is whether the peptide will work on existing addicts. Most people aren't going to go to the doctor and say "Hey, I'm about to spend several months abusing amphetamine. Could you prescribe me that peptide drug that'll prevent addiction from developing?". I suspect the peptide will do less to reverse addiction than it will to prevent it. However, the press release isn't clear enough on the protocol used to tell if that is the case.
The peptide has a piece that looks like the glutamate receptor and so competes with the glutamate receptor for getting pulled into the cell.
Wang's team developed a peptide that serves as a decoy to prevent the cell from pulling glutamate receptors in from their surfaces.
The researchers began by building a peptide – a long molecule made from a string of amino acids – with a structure similar to the tail of the glutamate receptor that is anchored inside the cell. In addiction, cellular machinery tugs on this tail, pulling the entire receptor into the cell. Without its business end sticking out into the synapse, or space between neurons, the receptor no longer works.
Wang's peptide tricks the cellular machinery into tugging on it instead of the receptor's tail. "Once it gets inside the neuron, the peptide competes with the receptor for binding to the machinery," Wang explained. With the cellular machinery otherwise occupied, the glutamate receptors stay on the cell surface, where they continue to receive signals.
The peptide prevented sensitization of the rats to amphetamine and therefore probably would block the development of cravings.
After confirming these results in cell cultures, Wang and colleagues tested the peptide in rats that had been given amphetamine once every other day for 20 days. During this period, the animals displayed stereotypical behavior such as repeated sniffing, licking, and grooming, indicating a craving for the drug. Such behavior parallels the compulsive thought patterns that people addicted to drugs experience, said Anthony Phillips, Wang's colleague at the University of British Columbia and a co-author of the article.
After keeping the rats drug-free for 21 days, the researchers gave the animals a small amount of drug again. The rats immediately displayed intense stereotypical behavior – a sign of behavioral sensitization. The behavior meant that the glutamate receptors in the animals' neurons were rapidly internalized, said Wang. "It's the trigger that leads to sustained motivation to seek a drug."
In contrast, addicted animals who received an intravenous injection of the artificial peptide displayed no sensitized behavior. "The effect was immediate and very noticeable," said Wang.
An ideal anti-addiction drug would allow someone in the early stages of addiction to pull out when they realize they've become hooked. But if such a drug existed how many early stage addicts could be convinced to use it before they racked up a lot of brain damage?
By
Randall Parker
2005 November 29
08:28 AM
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2005 October 07 Friday
Nicotine Leaves Long Lasting Effects On Brain Reward Systems
Scripps researchers Athina Markou and Paul Kenny found that in rodents nicotine causes an elevation in mood that lasts for weeks after the nicotine is gone.
Nicotine induces a long-lasting activation of the brain's reward systems that is not seen after excessive consumption of other drugs of abuse, such as cocaine or heroin. This slight elevation in mood is there regardless of how much nicotine is consumed, and it persists long after the nicotine is gone from the body.
"It's almost a memory of nicotine in the brain," says Kenny, who is now a staff scientist at Scripps Florida. "The reward system becomes hyperactive, even when the nicotine isn't there."
This persistence of reward activity, Kenny adds, appears unique to nicotine among drugs of abuse and is probably crucial in maintaining the nicotine habit. Knowing this may have relevance to prevention of nicotine addiction and smoking cessation programs.
Weeks after the nicotine was gone the effects on rodent brain reward systems remained. Normal pleasures were still enhanced by the long gone nicotine.
In their study, Markou and Kenny looked at the effect of nicotine self-administration on brain reward systems in laboratory rodents. They allowed the rodents to have extended access to nicotine self-administration, and they directly measured the changes in neuronal activity in the brain.
As predicted, the scientists found that nicotine acutely stimulates the brain's reward system and seems to enhance the normal pleasures in the environment for hours. Unexpectedly, however, rather than the depression-like state induced when cocaine and heroin leave the system, nicotine's elevation of mood persists. The measurements of neuronal activity in the brain's reward system one hour after the nicotine consumption looked similar to those twelve hours after consumption.
In fact, this increased sensitivity to reward persists for days or weeks after the nicotine disappears. The excitation of these systems cannot be due to the presence in the brain of nicotine, which is readily metabolized by enzymes in the body so that all traces of it are gone after a matter of about three to four hours.
So if the nicotine is metabolized and cannot be responsible for the elevation in mood, what is the explanation? One possibility is that nicotine leads to an upregulation of the brain receptors to which it binds--the nicotinic receptors. Since the neurotransmitter acetylcholine also binds to these receptors, the elevation in nicotinic receptors due to nicotine may be behind the persistent elevation in mood.
Do addicts of the demon weed tobacco experience increased pleasure from life as a result of smoking tobacco? Had they never started smoking would their average level of experience of pleasure be lower?
What I'd like to see: A study of twins in their 20s (i.e. young enough not to have too much accumulated damage from cigarette smoking) where one member of each twin smokes and the other doesn't. Test them for average level of mood. See if the smoker experiences more daily pleasure than the non-smoker. Perhaps though the toxic effects of the cigarettes cause damage that reduces pleasure other ways. I'd expect that to be the case after enough years of smoking.
In the long run I expect to see the development of wide spectrum long lasting feel good drugs that do as nicotine does but without undesired side effects such as addiction and without a delivery mechanism such as smoke that brings along lots of toxins. One reason that some people are happier than others is that they are wired up that way due to their genes. Those who go through life generally less joyful (and not just those who are depressed) will some day have the option of getting their average pleasure level turned up by adjustment of receptor concentrations in their neurons.
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Randall Parker
2005 October 07
08:14 PM
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2005 September 18 Sunday
Gamblers Seen As Superstitious And Stimulus Cravers
A British study finds gamblers much more superstitious than non-gamblers.
Over 80% of UK bingo players surveyed were generally superstitious - some attributing lucky seats, lucky friends and lucky nights of the week to gambling success.
Just one-third of the larger UK population are thought to be superstitious - the most commonly reported behaviours being: avoiding walking under ladders, touching wood for good luck and throwing salt over shoulders.
Could training in statistics and physics reduce the belief in luck? My guess is those with lower aptitudes for math and physics are more likely to believe in luck. So better training probably would not help much. Future geneticallly engineered neural stem cell therapies for boosting IQ will probably reduce the desire to gamble though.
Another recent study found that alcoholics and gamblers are motivated by different kinds of emotions.
Tavares said that positive emotions and negative emotions are two separate, distinct and independent dimensions, possibly regulated by different brain systems. "We found that alcohol craving was based on the temperament factor responsible for negative emotions," he said. "This suggests that those individuals who are especially vulnerable to negative emotions are the ones who will miss alcohol the most when trying to abstain. Conversely, gambling craving correlated to the temperament factor responsible for positive emotions.
"This suggests that those individuals who naturally lack positive emotions and require intense stimuli to experience elation are the ones who will miss gambling the most when trying to abstain."
As I reported in another recent post fetal alcohol exposure in early pregnancy or during the full length of pregnancy in rhesus macaque monkeys resulted in macaques that had blunted responses to stimuli. Humans exposed to alcohol during fetal development and born with less ability to respond to stimuli might take up gambling as a source of more intense experiences. So alcohol abuse in one generation might lead to compulsive gambling in a successive generation.
If the need to experience an intense stimulus could be met by some other source of a stimulus would gambling compulsion be easier to break? How about putting gambling treatment centers next to amusement parks and taking the gamblers on roller coaster rides? The problem is that it is a lot easier and faster to log on to a gambling web site or do off-site betting on track races than to go to an amusement park. Most people do not live near roller coasters. Could video games provide the craved level of intense stimulation?
Gene therapies and neural stem cell therapies will eventually provide ways to supply neurons that reduce the need for the stimulus high that comes from gambling.
Technological advances are making gambling problems easier to develop (while producing lots of email and blog spam in the process).
Today more young people gamble once a week than smoke, drink or take drugs combined.
"Poker playing seems to have grown to the point where now you've got about 20% of young males, who are either in high school or in college playing poker with their friends on a weekly basis," says Dan Romer, who runs the Annenberg Adolescent Risk Communication Centre at the University of Pennsylvania.
"Of those at least a quarter of them would be exhibiting some form of problem gambling symptoms."
Human beings did not evolve to handle the types of artificial environments that technologies are producing. The range of technologies which humans are not adapted to handle keeps growing. Home methamphetamine labs and internet gambling web sites are just two manifestations of a larger problem: Humans find themselves in technological environments very unlike the environments for which they evolved.
Some humans are lucky enough to have combinations of alleles, embryonic environments, and childhood environments that make them still able to function well in the face of so many potentially harmful activities. Some can gamble occasionally without developing a compulsion to do so. Some can have a drink of alcohol without developing a need for it. Some feel great enough to see no temptation from cocaine or methamphetamine.
But others less lucky are caught up in a growing number of temptations which they are genetically and cognitively ill-suited to handle. The weakening of belief in religious codes that used to justify many restrictions on vices combined with liberal and libertarian views of human ability to exercise free will leave those with neurological vulnerabilities insufficiently defended against a proliferation of ways to develop compulsive, addictive, and destructive vices. Only the acceptance of a more biological view of human nature can restore some of the wisdom about vices lost in the decline of religious beliefs.
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Randall Parker
2005 September 18
12:52 PM
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2005 July 20 Wednesday
Rats Show Cocaine Reduces Ability To Modify Learned Behavior
Addictive drugs are bad for the brain.
Researchers working with rats have zeroed in on the brain circuitry mechanism whose disruption contributes to the impulsive behavior seen in users of cocaine as well as other psychostimulant drugs. The same circuitry has been implicated in such disorders as schizophrenia, depression, and post-traumatic stress disorder, wrote the researchers.
Yukiori Goto and Anthony A. Grace of the University of Pittsburgh described their findings in the July 21, 2005, issue of Neuron. In their studies, they sought to understand the effects of cocaine sensitization on the connections between two higher brain regions--the prefrontal cortex and the hippocampus--and the nucleus accumbens, which is the region in the limbic system involved in processing reward behavior. The prefrontal cortex is involved in processing information, and the hippocampus is involved in learning and memory.
The connections to the nucleus accumbens seem to be bidirectional, said the researchers, and the interactions with the prefrontal cortex and hippocampus could affect the "plasticity" of connections in the neurons of the nucleus accumbens. This means that disruptions to the normal connections could affect behavior.
The researchers' electrophysiological studies of the effects of cocaine on this circuitry demonstrated that the drug did disrupt this normal plasticity. They found that the cocaine induced abnormal enhancement of neuronal connections--a phenomenon called long-term potentiation (LTP).
The researchers also performed behavioral studies on the cocaine-sensitized rats, to explore the behavioral effects of this disruption. In these studies, they placed the rats in a plus-shaped maze. The rats were taught that in response to a visual cue they should turn left or right toward one arm or the other of the maze to obtain a piece of cereal.
Goto and Grace found that, while the cocaine-sensitized rats learned the correct response strategy faster than normal rats, they were significantly less able to change strategies when they were required to ignore the cue and always make a left or right turn to receive the reward.
"Thus, although abnormally induced LTP by psychostimulants at limbic inputs might not interfere with learning a response strategy, it may reduce the capacity of these animals to consider alternate response strategies," concluded Goto and Grace. "In this way, the disruption of synaptic plasticity by cocaine sensitization may contribute to the affective- and context-inappropriate impulsive behaviors that are characteristic of drug addiction."
A drug that increases impulsive behavior in its users creates problems (e.g. crime, poorer relations with friends, neighbors, familiies) for the rest of us. Cocaine addicts have a harder time modifying some behavior or lesson already learned. One can imagine how that would cause them to get stuck in ruts of repetitive behavior that is destructive to themselves and to other people..
Cocaine addicts are more oriented toward pleasure.
“It may explain why cocaine addicts are oriented towards pleasure rather than other goals, and have an impaired ability to make decisions. It could be why addicts go back to taking more of the drug and ex-addicts often become addicted again faster than those who have never taken it,” says Grace
Drugs that reduce cognitive competence increase the costs that users impose on the rest of us while at the same time the drugs make the users less productive. Users simultaneously increase the costs they impose while giving less in return. We need treatments that cure addictions. We also need better drugs that make us more adaptive, not less.
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Randall Parker
2005 July 20
04:28 PM
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2005 June 22 Wednesday
Drug Abusers Suffer Accelerated Brain Aging
Abuse opiates, age your brain.
Young drug abusers are up to three times more likely to suffer brain damage than those who don't use drugs, according to research published online by Neuropathology and Applied Neurobiology.
The brains of 34 intravenous drug abusers, who had mainly used heroin and methadone, were examined after death and compared with 16 young people who had not used drugs.
This revealed that the drug abusers sustained a level of brain damage normally only seen in much older people and similar to the early stages of Alzheimer's disease.
"Our study shows evidence of an increased risk of brain damage associated with heroin and methadone use, which may be highest in the young, when individuals are most likely to acquire the habit" says co-author Jeanne Bell Professor of Neuropathology at the University of Edinburgh.
Damaged nerve cells were identified in the key areas of the brain involved in learning, memory and emotional well-being.
"We found that the brains of these young drug abusers showed significantly higher levels of two key proteins associated with brain damage" adds Professor Bell.
"In a previous study we found out that drug abuse causes low grade inflammation in the brain. Taken together, the two studies suggest that intravenous opiate abuse may be linked to premature ageing of the brain."
The 34 documented drug users had a history of opiate abuse – mainly heroin and methadone – but were HIV negative and had no history of head injury. The 16 control cases had no history of drug abuse or neurological impairment.
The average age in these two groups was only 26 years and included drug abusers as young as 17.
Toxic proteins were found in the brain cells of drug abusers.
Tau protein, which in its soluble form is essential for communication and transport within brain cells, had become insoluble in some cells, causing nerve cell damage and death in selected areas of the brain.
Other nerve cells showed an accumulation of the amyloid precursor protein, which suggests that protein transport had been disrupted and the nerve cell functions affected.
"This study shows that drug abuse can lead to a build up of proteins which cause severe nerve cell damage and death in essential parts of the brain. This is very worrying as there are strong indications that drug use in the UK, in particular opiates like heroin and methadone, has continued to rise in recent years" says Professor Bell.
If you damage your brain with drugs now you will have to wait for decades before stem cell therapies can fix all the damage. Whatever you become after the future damage repair will be someone else different than who you were before you damaged your brain in the first place.
Also see my post "Partial Recovery From Methamphetamine-Induced Brain Damage" and be sure to read the comments by some of the ex-meth users who describe the symptoms of their own brain damage.
By
Randall Parker
2005 June 22
12:32 PM
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2005 June 15 Wednesday
Nicotine And Heroin Activate Same Brain Reward Circuitry
No wonder kicking cigarettes is hard to do.
In experiments with mice, researchers have found that nicotine triggers the same neural pathways that give opiates such as heroin their addictively rewarding properties--including associating an environment with the drug's reward. However, unlike opiates, nicotine does not directly activate the brain's opiate receptors, but activates the natural opioid reward pathway in the brain.
The researchers, led by Julie Blendy of the Transdisciplinary Tobacco Use Research Center (TTURC) at the University of Pennsylvania, said their findings suggest more effective ways that opiate blockers could be used to help smokers quit.
In their experiments reported in the June 16, 2005, issue of Neuron, the researchers administered nicotine to mice and analyzed the levels of a protein called CREB--known to control genes involved in the reward pathway of opiates and other abused drugs. They found that not only was CREB activated in the reward regions of the nicotine-treated animal's brains, but also that the drug naloxone, which blocks the opiate receptors, blocked CREB activation. Also, mutant mouse strains lacking the opioid receptor did not show an increase in CREB activity when they received nicotine.
The researchers also studied the relationship among nicotine, the environment, and this reward pathway. They conditioned mice to associate a specific test chamber with receiving nicotine, finding that the mice would prefer to stay in that chamber when given a choice. The researchers found that just placing the conditioned mice in the chamber activated CREB. They also found that naloxone blocked this conditioned increase in CREB, and that mutant mice lacking CREB or pretreated with naloxone did not show any reward response to nicotine.
However, naloxone did not block the chamber choice of mice conditioned with cocaine, found the researchers, indicating that cocaine activates the brain reward pathway in a different way from nicotine and opiates.
"The present results demonstrate that nicotine-associated environmental stimuli can activate the same molecular signal transduction molecules as the drug itself," wrote Blendy and her colleagues. They wrote that the activation of CREB "is evident not only after acute and repeated nicotine administration, but also following exposure to an environment in which the animal has previously received nicotine."
The researchers noted that clinical studies of opioid receptor blockers to relieve cigarette cravings "so far have produced mixed results, ranging from ineffectiveness at smoking cessation to mild reduction in the desire to smoke."
The researchers wrote that their findings "suggest that the timing and context of opioid receptor antagonist administration are critical for determining the effectiveness of blocking nicotine reward . . . . Given the results reported here, clinical studies designed to evaluate administration of opioid antagonists just prior to cues associated with smoking could lead to a more promising treatment regimen."
The brain reward system is effectively hijacked by recreational drugs. Normally the brain reward circuitry activates to encourage adaptive behavior such as getting food and doing other life-promoting work. Addictive drugs that activate reward circuitry drugs are dangerous because they subvert the purposes of the reward system and reduce or eliminate the motivations for adaptive behaviors.
Note that animals can be conditioned to associate being in a particular room with getting a reward. When medical treatments that control reward responses are developed they'll be used to cure drug addictions. But the understanding of brain reward circuity resulting from addictive drug studies will also point the way toward the development of treatments which can be used to manipulate human behavior in sophisticated ways. Will the greater use of such treatments be by governments and other entities to manipulate the behavior of individuals? Or will individuals use such treatments to manipulate their own behavior?
Self manipulation might sound counter-intuitive at first. But we all end up doing things we think we shouldn't do while at the same time we don't do other things that we think we really ought do so. So will the frontal lobes of our brains choose to administer treatments to ourselvse that realign the motivations of other parts of the b