Heart Pressure Medicine for Cocaine Addiction?
Cocaine addiction can be frightfully hard to treat since cocaine affects two key neurotransmitters in the brain: dopamine and glutamate. So investigators have been looking for ways to interfere with the action of the chemicals in key regions of the brain.
Researchers from Boston University School of Medicine and Harvard Medical School have published new data from a rat study in which they examined the impact of a calcium-channel antagonist called diltiazem, a drug used in the treatment of high blood pressure.
Diltiazem reduced cocaine cravings and the research indicates that calcium channels provide critical links between dopamine and glutamate that drives the intense craving associated with cocaine addiction in a region of the brain known as the nucleus accumbens.
This makes sense: we have known for some time that calcium plays an important role in learning, memory and motivation in this part of the brain. In effect cocaine trains the brain using a dysfunctional form of learning that drives the desire to use the drug.
Though it is still early, this is important research that may give us a whole new approach to treatment. It is unlikely that diltiazem itself with be useful in treating humans, since the amount needed to produce the effect in the brain would likely cause a major drop in blood pressure, but any new approach like this should speed up the search for other effective treatments.
National Acupuncture Detoxification Association
I had the pleasure and privilege of being on Scott Cluthe’s show on Lime Radio this evening. It’s on Sirius Satellite Channel 114, and if you are interested in the new holistic worldview that is emerging all over the planet, I highly recommend Scott’s show and, in fact, all the shows that I have heard on Lime. I have also had a link to Lime website for some time now, and it always has a great deal of excellent material.
There were some excellent questions from listeners, and one caused me to do some research. The question was about the National Acupuncture Detoxification Association (NADA). The Association is a nonprofit that conducts training and provides public education about the use of acupuncture as an adjunctive treatment for addictions and mental disorders.
There is a substantial body of research literature on the topic of using acupuncture as part of a package of measures for treating substance abuse, and although it is still considered controversial in some quarters, it is being used in over 1,500 places around the world, and that does not include China and Japan, where I have seen acupuncture used a great deal in addictive disorders.
My own experience has been mixed. I have had little success I treating smoking addiction with acupuncture, though I have many colleagues who say that it is extremely helpful. I have had more success in using thought field therapy and homeopathy for treating smoking addiction, even though there is so far no good research data on the use of either for smoking.
If you are interested in the use of acupuncture as an adjunctive treatment for substance abuse, the NADA website if a good place to start.
Decision Making and Internal Balance
Many of us run into problems when we try to make decisions. In a special section in the October 26 issue of the journal Science, Martin Paulus who is a professor in the Department of Psychiatry at the University of California in San Diego, has marshaled a growing body of evidence that human decision-making is inextricably linked to an individuals’ need to maintain a homeostatic balance.
He goes on to suggest that psychiatrists may need to approach the treatment of psychiatric patients from a new direction: by understanding that such individuals’ behavior and decision-making are based on an attempt to reach an inner equilibrium, in the same way that we try to being our temperature or blood pressure back to a set point. And if the thermostat is broken we may see mental illness and substance abuse.
This makes good sense: in the past decision-making process as a considered series of options and values, but that is not what we see in the clinic. People with addictions and some mental illnesses keep making bad choices, despite being intelligent and insightful.
Recent neuroimaging research shows strong support for the homeostatic nature of decision-making:
The insula is involved in processing interoceptive information: the body’s internal state or sense of balance
Damage to the insula stops addiction to cigarettes
Some of the same brain structures implicated in the urge to take drugs are involved in other biological urges
The question addressed in part by this paper are whether changes in decision-making behavior and associated brain functions are a result of pre-existing characteristics – which may predispose individuals to use drugs – or occur as a consequence of long-term use.
This is certainly an interesting idea, and we shall have to see how it fits as we collect further data.
“The quality of a decision is like the well-timed swoop of a falcon which enables it to strike and destroy its victim.”
–Sun Tzu (Chinese Military Strategist and Author of the “Art of War”, c.400-c.430 B.C.E.)
“The risk of a wrong decision is preferable to the terror of indecision.”
–Maimonides (a.k.a. Rabbi Moses ben Maimon, Spanish-born Jewish Philosopher and Physician, 1135-1204)
“All you have to decide is what to do with the time that is given you.”
–J.R.R. Tolkien (South African-born English Writer, Linguist, Oxford Don and a Member of C.S. Lewis’ Literary Group, “The Inklings,” 1892-1973)
“Decisions are doorway to change and change starts from a moment of decision. One decision can change your life forever!”
–Tony Robbins (American Motivational Speaker and Writer, 1960-)
“Nothing is more difficult, and therefore more precious, than to be able to decide.”
–Napoleon Bonaparte (Corsican-born French Military Strategist, General and, from 1804-1814, Emperor of the French, 1769-1821)
Chocolate, Comfort Foods and Depression
Most people have done a bit of comfort eating from time to time: candies and chocolates are usually the favorites. That’s not a coincidence. Not only do they taste good, but chocolate also contains chemicals that may improve mood, and sugar can have an indirect impact on the uptake of specific amino acids into the brain, where they go on to form the chemical neurotransmitters involved in inter-cellular communication and learning.
On the more serious side, some types of mood disorders, particularly seasonal affective disorder, premenstrual syndrome and the so-called “atypical depression” are often associated with quite sever cravings for chocolate.
So I was very interested to see a paper from colleagues in Australia in this month’s issue of the British Journal of Psychiatry.
Gordon Parker and Joanna Crawford examined links between chocolate craving in people who are depressed and both personality style and atypical depressive symptoms, with a web-based questionnaire completed by nearly 3000 individuals reporting clinical depression.
People accessing a mood disorder consumer information website (http://www.blackdoginstitute.org.au) were invited to participate in an online survey of lifetime treatments for a depressive episode, together with some interesting evaluation tools.
Half of the respondents said that they craved chocolate, and the number was slightly higher in women. They said that they felt that chocolate helped with depression, anxiety and irritability. The ones who said that chocolate helped were more likely to score higher on a “neuroticism” scale, particularly irritability and rejection sensitivity.
Five years ago the same team found that atypical depression was associated with a personality that was especially sensitive to rejection, and also tended to be linked with several symptoms – including food cravings – that tie in with behaviors aimed to try and make us feel better and to maintain internal balance.
The results suggest that people with certain personality styles derive personal benefit from comfort eating. Some research has linked carbohydrate craving to the opioid system in the brain, and it is possible that munching on chocolate may be an example of genuine self-medication. People eat to chocolate to calm down their ability to feel emotional distress.
The trouble is, of course, that although chocolate is yummy and may even be therapeutic, too much can be a bad thing. Weight problems are common in people with chronic depression, especially the “atypical” type.
“Chocolate causes certain endocrine glands to secrete hormones that affect your feelings and behavior by making you happy. Therefore, it counteracts depression, in turn reducing the stress of depression. Your stress-free life helps you maintain a youthful disposition, both physically and mentally. So, eat lots of chocolate!”
–Elaine Sherman (American Culinary Expert, Teacher and Writer, 1938-2001)
“Look, there’s no metaphysics on earth like chocolates.”
–Fernando Pessoa (Portuguese Poet, 1888-1935)
A New Treatment for Alcohol Dependence?
Several news outlets have today picked up on an apparently odd report: topiramate, a medicine used for migraine and seizures, may also help some people who are alcohol dependent.
A 14-week multicenter clinical trial was orchestrated by researchers at the University of Virginia, and published today in the Journal of the American Medical Association.
371 male and female alcoholics, all of whom were drinking heavily at the time of entering the trial, were randomly selected to take topiramate (up to 300 mg/day) or placebo. All of them had a weekly 15-minute intervention with a trained nurse to enhance adherence to the medication and treatment regimen.
Trials of people with substance abuse are always complicated by high non-compliance rates. Some studies skew their results by making the questionable assumption that if someone doesn’t show up, then they must be cured! This study was structured more realistically: dropouts were assumed to have relapsed to their baseline drinking level.
Even when the dropouts were included, topiramate lowered the percentage of heavy drinking days (the number of days in which men consumed ≥5 drinks/day and women drank ≥4 drinks/day, divided by the number of study days) by a mean of 8.44% more than placebo. The topiramate group showed a reduction from 82% to a mean of 44% heavy drinking days during the 14 weeks, while the placebo group had a reduction from 82% to a mean of 52% heavy drinking days.
In a second analysis that tested the study hypothesis for all randomized participants who took at least one study medication dose and had at least one double-blind site visit, topiramate was much more efficacious than placebo, lowering the percentage of heavy drinking days by a mean of 16.19% more than placebo.
Topiramate was more efficacious than placebo, on measures of self-reported drinking and the liver enzyme gamma-glutamyltransferase, which is a sensitive marker of alcohol consumption.
There are some good reasons why topiramate may be helpful: it acts on gamma-aminobutyric acid receptors in the brain, which have been implicated in some addictive behaviors, including over-eating.
A few years ago topiramate was being examined as a possible weight loss agent, since it has effects on feeding and on metabolism.
The trials have been suspended in North America, primarily because of one of the main side effects of topiramate: it may cause cognitive dulling and word finding difficulties in some people. Those side effects sometimes take a few weeks to develop.
A second point is that when it is used for weight management, some people quickly develop tolerance to its effects.
This new study is interesting and may turn out to be very important. We shall have to see whether the effect on alcoholics is robust and sustained over time.
“All excess is ill, but drunkenness is of the worst sort. It spoils health, dismounts the mind, and unmans men. It reveals secrets, is quarrelsome, lascivious, impudent, dangerous and bad.”
–William Penn (English Quaker, Colonizer in America and Founder of Pennsylvania, 1644-1718)
“One reason I don’t drink is that I want to know when I am having a good time.”
–Nancy Lady Astor (American-born British Politician, 1879-1964)
“Hide our ignorance as we will, an evening of wine soon reveals it.”
–Heraclitus (Greek Philosopher, c.540-480 B.C.E.)
“Where the drink goes in, there the wit goes out.”
–George Herbert (English Religious Poet, 1593-1633)
The Curse of Crystal Meth
I have the dubious distinction of living in a part of the United States with one of the highest rates of methamphetamine abuse in the country. Around here most of the first time users are teenage girls who are trying to lose weight.
In the last few years the spread of methamphetamine abuse across the United States has been as rapid as it has been alarming. Until about six years ago, methamphetamine use was seen mostly in the western and rural United States. Then it jumped over the Mississippi and continued its demonic march to the sea and Georgia has been hit like a ton of bricks.
Not only can crystal met ravage the brains of users, they can get a wide range of physical problems including inflammatory and immune problems throughout the body.
Methamphetamine abuse has now expanded rapidly throughout the rest of the country and across different ethnic groups. According to the 2005 National Survey on Drug Use and Health it is estimated that 10.4 million Americans ages 12 or older have used methamphetamine at least once in their lifetimes for non-medical reasons.
There is a new and important study from the Scripps Institute that has shown that long-term methamphetamine use changes circulating proteins in drug users, causing aberrant immune responses. As a result, increased levels of pro-inflammatory cytokines – proteins that are involved in immune responses – may initiate a previously unrecognized molecular mechanism for the development of cardiovascular disorders including vasculitis, an inflammation of the blood vessels.
It appears that methamphetamine can add sugars (a.k.a. “glycate”) proteins. The researchers found that the immune system responds dramatically to this methamphetamine-induced glycation, which may lead to vascular inflammation. There was a direct relationship between methamphetamine intake and the level of circulating antibodies in animal models. This immune response, coupled with antibodies binding to methamphetamine, might make the drug less biologically available leading to an increased need for higher and higher doses, a problem found among chronic methamphetamine users.
The resulting glycated proteins are called advanced glycation end products (AGEs) that modify the function of proteins and are associated with a number of diseases including diabetes and Alzheimer’s disease.
Methamphetamine-AGE proteins not only increased antibody production, but also were strong enough to overcome the drug’s natural immunosuppressive qualities. Furthermore, a wide range of cytokines directly linked to AGE exposure were increased in rats that self-administered methamphetamine.
The study also showed that even limited daily access to the drug was enough to produce an over-expression of vascular endothelial growth factor which is a potent signaling cytokine involved in angiogenesis and vasodilatation.
If you know anyone tempted to dice with this vile toxin, ask them to have a look here.
Mindfulness and Depression
Mindfulness meditation has rightly been receiving a lot of attention recently. It is quite simply a technique in which you become intentionally aware of your thoughts and actions in the present moment, non-judgmentally. Though originally a Buddhist technique, it is something that can be practiced by anyone, and there are, in fact, similar techniques that have been developed by Christian mystics and Sufis.
It has recently been discovered that some of the techniques that were developed so that a mystic or meditator could carry on without distraction, may also have value in treating clinical problems. After all, if a group of people has spent a thousand years developing tools and techniques for managing the mind, it might be a good idea to see what they have discovered!
There have recently been several excellent books on the use of mindfulness in the management of depression:
The Mindful Way Through Depression
Relaxation, Meditation and Mindfulness
Mindfulness and Acceptance: Expanding the Cognitive-Behavioral Tradition
This whole field was moved forward by some research from San Francisco (NR822) that was presented at the end of May at the 2007 Annual Meeting of the American Psychiatric Association in San Diego. The researchers used Mindfulness-Based Cognitive Therapy (MBCT) in a group of 53 people with treatment resistant depression.
MBCT is based on the Mindfulness-based Stress Reduction (MBSR) eight-week program that was developed by Jon Kabat-Zinn in 1979 at the University of Massachusetts Medical Center. Research has show that MBSR can be enormously empowering for people with chronic pain, hypertension, heart disease, cancer, and gastrointestinal disorders, as well as for psychological problems such as anxiety and panic.
Mindfulness-based Cognitive Therapy grew from this work. Zindel Segal, Mark Williams and John Teasdale adapted the MBSR program so that it could be used for people who had suffered repeated episodes of depression.
The results of the study presented in San Diego showed that MBCT was effective in reducing depression when compared to treatment as usual: what we call “TAU.” What seems to happen is that MBCT gives people a set of skills for detaching from the stream of depressive thoughts and feelings. As a result the symptoms decrease. Though the study will need to be expanded and replicated, this is clearly a fertile area for research.
This work is also interesting in the light of recent research showing that mindfulness training may improve the activity of some of the subsystems of the brain dedicated to attention, as well as helping some people with mental illness control their aggressive behavior. Mindfulness training may also help to reduce subjective reduces distress and improves positive mood states. It seems to be particularly good at reducing distracting and ruminative thoughts and behaviors.
And just for good measure, mindfulness may help some smokers quit.
“The purpose of meditation is not enlightenment, it is to pay attention even at extraordinary times, to be of the present, nothing-but-in-the-present, to bear this mindfulness of now into each event of ordinary life.”
–Peter Matthiessen (American Naturalist and Writer, 1927-)
“Meditation is not to escape from society, but to come
back to ourselves and see what is going on. Once there is
seeing, there must be acting. With mindfulness, we know
what to do and what not to do to help.”
— Thich Nhat Hanh Vietnamese Buddhist Monk, 1926-)
“Conscious means “having an awareness of one’s inner and outer worlds; mentally perceptive, awake, mindful.” So “conscious business” might mean, engaging in an occupation, work, or trade in a mindful, awake fashion. This implies, of course, that many people do not do so. In my experience, that is often the case. So I would definitely be in favor of conscious business; or conscious anything, for that matter.”
–Ken Wilber (American Philosopher, 1949-)
Risk-taking in Teenagers
The study of adolescence is in an intersting state of flux.
The expectation that teenagers are rebellious by nature is probably not correct. After all, it is nly recently that adolescence, which more or less corresponds to the teen years, has been recognized at all. As recently as the early 1960, most young people went straight from school to employment, and wore the same clothes as everyone else at work. And of course that is still the pattern in many parts of the world, with the exception of school, which is sadly unavailable to so many. In most cultures teenage rebellion is not recognized at all.
Two years ago Professor Philip Graham, author of an excellent book published by Oxford University Press called ‘The End of Adolescence’ and a leading child and adolescent psychiatrist, challenged the myth that teenagers are trouble. He believes that the social attitudes towards the ‘adolescent stereotype’ that prevail in Western society have significant negative effects on the mental health of young people.
This stereotyping can cause some real problems:
- Low expectations of behaviour are often shared by teenagers themselves, leading to low self-esteem
- at least some of the frustration shown by young people in secondary schools can be attributed to the fact that they are ‘disempowered’ in relation to their intellectual and emotional competence
- The legal position of young people, for instance in relation to the age of criminal responsibility, voting age and the consumption of drugs and alcohol, is wildly inconsistent, and results both in injustice and in inadequate preparation for adult life
- The organisation of mental health services often fails to take into account the need to recognise the ‘young adult’ status of this age group.
The other side of this research is the risky behavior of many young people.
There is an excellent review in this month’s issue of Current Directions in Psychological Science by Laurence Steinberg, Distinguished University Professor and the Laura H. Carnell Professor of Psychology at Temple University in Philadelphia. He is also the Director of the John D. and Catherine T. MacArthur Foundation Research Network on Adolescent Development and Juvenile Justice.
The review points out that over the past 10 years there has been a great deal of new research on adolescent brain development that sheds light on why yonug peple engage in risky and dangerous behavior. And also answer the question about why the educational programs or interventions that have been developed have not been especially effective. According to Steinberg, heightened risk taking in adolescence is the result of competition between two very different brain systems, the “socioemotional” and cognitive-control networks. Both are undergoing maturation during adolescence, but along very different timetables. During the adolescence, the socioemotional system becomes more assertive during puberty, while the cognitive-control system gains strength only gradually and over a longer period of time.
The “socioemotional” system processes social and emotional information, and it becomes very active during puberty, allowing adolescents to become more easily aroused and experience more intense emotion. They also become more sensitive to social influence.
On the other side, the cognitive-control system is the part of the brain that regulates behavior and makes the ultimate decisions, but it is still maturing during adolescence and into a person’s mid-20s and perhaps beyond.
The socioemotional system is not always going full bore. When the system is not highly activated, for example, when individuals are not emotionally excited or they are alone, the cognitive-control network is strong enough to impose regulatory control over impulsive and risky behavior, even in early adolescence.
In the presence of peers, or in situations where emotions run high, the socioemotional network becomes sufficiently activated to diminish the regulatory effectiveness of the cognitive-control network.
Steinberg cites a study in which the presence of peers more than doubled the number of risks teenagers took in a video driving game.
As he says,
“In adolescence, not only is more merrier — it is also riskier.”
“There is a window of vulnerability in teens between puberty and mid-to-late adolescence in which kids have already started to experience the increased arousal of the socioemotional system, but they don’t yet have a fully mature cognitive control system,” he says. “Because their cognitive-control system is still not fully mature, it is more easily disrupted, especially when the socioemotional system is quite excited. And it gets excited by the presence of other people.”
“I don’t want people to think that education should not continue, I just think that it alone is not going to make much of a difference in deterring risky behavior. Some things just take time to develop, and, like it or not, mature judgment is probably one of them.”
Steinberg advocates stricter laws and policies that would limit opportunities for immature judgment that often have harmful consequences. For example, strategies such as raising the price of cigarettes, more vigilantly enforcing laws governing the sale of alcohol, expanding adolescents’ access to mental-health and contraceptive services, or raising the driving age would likely be more effective than education in limiting adolescent smoking, substance abuse, pregnancy, and automobile fatalities.
This is controversial stuff, but is also an illustration of a way in which science can help us make better decisions about how best to help young people to avoid auto-destruction.
Neurologically, teenagers are not just small adults, they are still large children. The problem is heightened because so many young people are constantly multi-tasking and children are being exposed to risky behaviors at ever younger ages, when their brains are least able to handle complex decisions about things that may have long-term consequences for them.
A Very Helpful Website for Parents with Children at Risk of ADHD, Addiction or Anti-social Personality Disorder
Though I’ve said a hundred times that biology is not destiny, there is no question that some genes can predispose us to rect to th environment in certain ways. Some people are genetically-loaded for some specific illnesses. It is not always inevitable that the illness will emerge, and there is more and more evidence that there are strategies that can reduce the risk of many illnesses appearing.
There is a most helpful website maintained by Dr. Liane Leedom. I recently reviewed her book at Amazon.com.
The website is full of helpful advice on helping with people with children at risk for attention-deficit/hyperactivity disorder, addiction or antisocial behavior. Liane’s interest is in parenting strategies for children who have genetic risk for these problems.
Well worth a visit.
Marijuana and Psychosis
A number of my friends and colleagues in London have shown how cannabis (marijuana) may trigger a psychotic illness. A team at the Institute of Psychiatry gave healthy volunteers the active ingredient tetrahydrocannabinol (THC).
They then recorded reduced activity in an area of the brain called the inferior frontal cortex that keeps inappropriate thoughts and behaviors in check. The inferior frontal cortex is part of the self-regulatory systems of the brain that stop us swearing inappropriately, and help us to realize that people are not looking at or spying on us. In other words the inferior frontal cortex checks the environment and stops us jumping to conclusions that could lead to paranoia.
The THC was given to healthy volunteers who had not abused marijuana. The effects were short-lived, but more sever in some people than others, suggesting a genetic vulnerability.
In another study from Yale University, THC was given intravenously. Even at fairly low doses, 50% of healthy volunteers began to show symptoms of psychosis. As expected, people who had a previous history of psychosis were particularly vulnerable to the effects of THC.
A separate study has shown that one of these ingredients – cannabidiol (CBD) – has the potential to dampen down psychotic symptoms, and could perhaps form the basis of new treatments.
Whenever people start talking about the possible association between psychiatric problems and using marijuana, there are always loads of people who protest, “But I’ve used it for years and it’s never done me any harm.”
They may be right, but that objection misses four important points:
- People vary in their sensitivity to marijuana. Mental illness is the result of both genes and environment. Somebody who is very stressed but has no known genetic predisposition may run into trouble, while somebody with strong genetic loading and a minimal amount of stress can get very ill very quickly. And that stress can be anything from marijuana to abuse. There is also a lot of variation in how people respond to specific types of stressors
- If people have already had some psychological trouble, marijuana can be like pouring gasoline on a fire
- The age at which marijuana is used is all important. There seem to be “critical periods” in brain development, when marijuana can be particularly risky. There is a strong correlation between the number of times someone uses it under the age of eighteen and their subsequent risk of developing psychosis later in life. This relationship does not seem to hold with regular cigarettes, alcohol or any of the other street drugs looked at so far, suggesting that this is not just a matter of young people who are self-medicating. We cannot prove “causality” any more than we can “prove” that cigarette smoking causes lung cancer. Trying to prove a single cause for an illness is a tricky business. There are some examples, for instance illnesses caused by a single gene, but they are few and far between
- The marijuana available today is very different from the anemic material that was available in the 1960s and 1970s. Today’s is far powerful
This research provides the strongest evidence yet that modern marijuana can have a significant impact on the brain. Proving a long-term effect would be extremely difficult: it would be neither ethical nor feasible to stimulate long-term psychosis in volunteers.
But clearly if something has an active effect in inducing the symptoms of psychosis after one dose, it would not be at all surprising if repeated use could induce a chronic problem, particularly if someone is genetically predisposed.
