Addiction Information January Newsletter

Introduction
Welcome to the first Addiction Information Newsletter. The object of this newsletter is to give you a monthly overview of what is happening in the world of addiction across a number of fields. You can subscribe to this newsletter and receive an e-mail version by joining our mailing list. Your suggestions are most welcome, and articles for the website or that you would like to have linked to this newsletter can be directly submitted to me by e-mailing shaun.shelly@yahoo.com.
In this issue:
The Motivated Addict, Dual-process models, CBT Ineffective?, Drug Policy, Brain Structure, Meth Psychosis, Transcriptional Mechanisms, Nepicastat & 18-MC Trials, Neuroscientist Marc Lewis, Dr Frankenstein's Cure and "beating addiction"

Psychology
The Motivated Addict
Kopetz and others have published an informative paper, Motivation and Self-Regulation in Addiction: A Call for Convergence. This paper neatly summarises some of the "Big Questions" of addiction from a motivational point of view: What moves an individual from user to addict?; Who is more vulnerable and why?; and What keeps the addict using?. What is interesting is they look at similarities between addiction and other "normal" motivated behaviours. They also touch on the move from the drugs being a means to an end to becoming an end in itself. This fits in nicely with my view of addiction being a form of pathological relationship (more on the neurology of this in a later newsletter). Towards the end of the paper they casually drop a potential bombshell: "addiction is in many ways psychologically similar to motivated behaviour in general, whereas in some rare and extreme cases it appears more like a "brain disease"". Now there's something that can motivate some discussion.

Dual-process Models and Addiction
There is an article that makes interesting reading in the Clinical Psychological Science Journal entitled Cognitive Bias Modification and Cognitive Control Training in Addiction and Related Psychopathology: Mechanisma, Clinical Perspectives and Ways Forward. It examines arguments against and support for dual-process models, using the metaphor of the rider and horse. The horse being impulsive processes and the rider representing the more top-down reflective processes.The article goes on to examine how each of these dual processes can be modified through targeted training. When taken in the context of current findings in neurobiology the dual-process model, can, I feel, provide some good directions for effective addiction treatment. I have certainly found that both the rider and the horse, to extend the metaphor, need work!

Junk Science
Therapy Ineffective for Opioid Addiction?
"CBT is not an effective way to treat opioid dependence". So begins an article in the Yale Daily News that highlights a study by the Yale University School of Medicine: A Randomized Trial of Cognitive Behavioural Therapy in Primary Care-based Buprenorphine. The tone of the article suggests that Buprenorphine is enough to cure heroin addiction. I know that this is not exactly what they say, but as researchers they are well aware that the careful choice of words will determine how the article is reported and absorbed into popular thinking. There are already articles popping up all over the place making sweeping statements such as "the study could change how such dependence is viewed and treated in the U.S. healthcare system". Let's hope not. I feel strongly that this kind of "study" is wrong and have written a more detailed explanation of why I think so: Buprenorphine is enough? I think not.

Drug Policy
Taboo or Not Taboo
The news from around the world has been filled with a variety of articles about drug policy. Sam Branson  (Richard's son) released the film "Breaking the Taboo", which focuses on the harm done by and the ending of the Global War on Drugs. Because of this there has been renewed coverage of the Drug Policy Alliance. This group has the support of such luminaries as Sir Richard Branson, George Soros, Former Surgeon General Joycelyn Elders, a number of former presidents and political leaders....oh, and Sting. Their mission is "advance those policies and attitudes that best reduce the harms of both drug use and drug prohibition, and to promote the sovereignty of individuals over their minds and bodies."

In America there has been a lot of focus on Marijuana Policy and The War on Drugs. Marijuana is now legal for recreational use in Colorado and Washington. It is There is a lot of coverage on this issue, but most of it is not well thought out and written by either side of the lunatic fringe, so, frankly I found none of it worth featuring here. Except maybe for this article by psychiatrist David Nathan who is a clinical associate professor at Robert Wood Johnson Medical School: Why marijuana should be legal for adults. Nathan basically argues that Marijuana should be handled like alcohol and cigarettes. Legal to adults, but children should be taught the risk. 

Illustration by Norma Bar
The debate surrounding the War on Drugs is extremely lively. The Wall Street Journal asks "Have we lost the war on drugs?". Understandably there is a significant economic slant to this article. This is not a new angle. In the late 90's The Economist dedicated a whole issue to the legalisation of all narcotics because it made "economic sense". Here are two articles from 2001 from the same publication: Stumbling in the Dark and The case for Legalisation. Tony Newman, Director of the aforementioned Drug Policy Alliance listed "10 disastrous consequences of the drug war" in the Huffington post. Some of these have little relevance in the local context, but others, such as Racial Injustice, Unsafe Neighbourhoods, Compromising Teenagers Safety and Destroyed Families, certainly do. More on the local situationnext month.

Lord of the Drugs
Across the pond in the United Kingdom the UK Drug Policy Commission wrapped up 5 years of work and published their final report: A Fresh Approach to Drugs. Arguably the most important recommendation is that the political lead for national drug policy be moved from the Home Office to the Department of Health.This recommendation is embraced by the British Medical Association who are encouraging their members to join the debate on drugs policy.

Cries for reform have also been heard in the House of Commons and the House of Lords. Baroness Molly Meacher chairs the All Party Parliamentary Group for Drug Policy Reform, and she is all for the decriminalisation of drugs. The MailOnline make her sound like a raving looney with the headline "Let young have drugs instead of drink says peer as she compares taking substances to drinking coffee". If only that were true!

Downing Street will have none of it however, and have rejected calls for the decriminalising of drugs. David Cameron claims "our current policies are working". That paragon of British press virtue The Sun also seems to think its not a good idea, because a girl called Ocean smoked cannabis and it turned her "into a thieving heroin addict". So there we have it!

Something That Is Working
In amongst all of this I found this article about a program in Seattle that seems to be working, and I really think this LEAD program has some really good points. Basically it enables Police officers to divert those arrested on possession charges directly into housing and treatment facilities, by-passing the criminal justice system. I first read about it in the Seattle Times, and took a look at the LEAD website. There is also a short concept paper. There is great potential in this project, and perhaps it is small projects like these that will change the hearts and minds of the people and result in more effective public policy.

Research
Susceptibility to addiction linked to brain structure?
The paper that seems to be creating the most attention at the moment is Distinctive Personality Traits and Neural Correlates Associated with Stimulant Drug Use Versus Familial Risk of Stimulant Dependence. Building on her 2011 work where Karen Ersche and others found that a sample of cocaine addicted individuals displayed reduced levels of grey matter and anatomical changes in the orbitofrontal cortex compared to non-users, she now examines non-addicted long-term cocaine users (n=27), addicted users (n=50) and the family members of addicted users (n=50), and unrelated healthy non-using volunteers (n=50). She examined these groups both in terms of personality traits and brain anatomy. One of the conclusions drawn from the findings is that cocaine use does not always lead to addiction - something I often have to point out to concerned family members. What is more interesting is that perhaps resilience or vulnerability towards addiction could be predicted according to brain structure, and that some of the structural abnormalities we observe in addicted individuals, although compounded by drug use, may pre-exist the onset of substance use. Maybe the phrenologists of past just needed to dig a little deeper!

Meth Psychosis Confirmed in Study
A recent study published in JAMA Psychiatry confirms what many of us in the Western Cape already know: Meth use causes psychosis. The lead author, Dr Rebecca McKetin studied 278 meth users in Australia. She observed their meth use and psychotic behaviours over a period of 4 years, and the study concludes that Meth use significantly increases incidence of psychosis - 27% likelihood for those that use 1-15 times a month and a massive 48% for those who use16 or more times. Across the board, the chances of having a psychotic episode increased 5 times with Meth use. This particular study listed pre-existing psychotic episodes as an exclusion criteria, so it would appear that Meth may actually cause the psychosis rather than catalyze a pre-existing condition. As Dr McKetin says: "I think this is probably as close as we're going to get to showing a causal relationship between methamphetamine use and psychotic symptoms. There's actually quite a lot of evidence when taken together that suggests that that is the case." Also important to note was that when combined with heavy cannabis and alcohol use psychosis was seen in 69% of the cases.

Transcriptional Mechanisms of Drug Addiction
In his article, Transcription Mechanisms of Drug Addiction, Eric Nestler briefly reviews the growing evidence for the role played by prominent transcription factors in gene expression in addiction. This is an area of particular interest because, in my mind, it is these transcription factors that may affect gene expression that leads to the long-term effects of addiction even after extended abstinence. In this article Nestler discusses Nuclear Factor Kappa B, cAMP and Delta-Fos B. Delta-Fos B has long been linked with the development of spiny neurons in cocaine addicts, but what Nestler doesn't discuss or explain is the increases we see in Delta-Fos B in behavioural addictions. Could it be that increases in Delta Fos-B are not the result of the drug action, but as a result of some internal mechanism that results from addictive behaviour? Could the levels of Delta Fos B perhaps be the biological marker for the move from user to addict? More research is needed to examine the transcription factors in behavioural addictions before we can answer these questions.

A little further down the cAMP line we find CREB (cAMP response element-binding protein). The upregulation of CREB is thought to contribute to the tolerence and withdrawal states of addiction through increased dynorphine transmission.. Elevated levels of CREB in the NAc of rats seem to make the rats less sensitive to the rewarding effects of cocaine. It is thought that further investigation may lead to the development of pharmaco-therapies for stimulants. You can read more about this in the paper Roles of Nucleus Accumbens CREB and Dynorphine in Dysregulation of Motivation.
If you have no idea what any of this is about you may want to read my essay The Neurobiological Underpinnings of Addiction.


Pharmacology
Nepicastat Clinical Trials Target Relapse 
Some of us may be familiar with the work of Berridge, Robinson, Steketee, Kalivas and others in the area of long-term sensitisation of addicts to stress, drug cues and the drug itself, which can lead to the reinstatement of drug seeking behaviours even after long-term abstinence. It is proposed that by inhibiting the enzyme dopamine beta-hydroxylase and lowering norepinephrine levels, the desire to reinstate drug seeking behaviour may be reduced. Pre-clinical trials have shown that Nepicastat doesn't stop rats from administering a steady stream of cocaine, but it does reduce reinstatement after a break, and they do not work as hard to get cocaine when exposed to stress or drug related cues. Interestingly it does not seem to stem their desire for other behaviours, such as getting food or sugar. The double blind clinical trials are being sponsored by NIDA.

18-MC Trials Target Reward System in Addiction and Obesity
NIDA has also made funding available to Savant HWP for the development of 18-methoxycoronaridine as a potential orally active treatment for drug addiction, obesity and other forms of compulsive behavior. 18-MC is an alpha-3-beta-4 nicotinic receptor antagonist that modulates excessive dopamine fluctuations in the mesolimbic system of the brain. It therefore targets the reward system directly by modulating the excessive dopamine fluctuations in the mesolimbic system, but is not drug specific because it is not an agonist or antagonist for the primary receptor site of a specific substance. Interestingly, 18-MC is a derivative of Ibogaine, the controversial underground cure for addiction. The difference between ibogaine and 18-MC is that 18-MC has no affinity for the alpha-4-Beta-2 subtype, NMDA-channels or 5HT transporter. It does have modest affinity for the mu and kappa opioid receptors.

Personality of the Month
Marc Lewis

Marc is a developmental neuroscientist and professor of developmental psychology, recently at the University of Toronto. He is currently at Radbound University in the Netherlands. He has authored over 50 journal articles in psychology and neuroscience. The reason, however, I have decided to feature Marc is because of his personal history of addiction which is documented in his book and his amazing blog, Memoirs of an Addicted Brain.. This blog has some really fascinating posts that stimulate all sorts of conversation, and  the comments are of a far higher standard than we usually see on the web. Marc also makes the effort of responding to many of the comments and he also has a guest memoirs section. Reading these memoirs and Marc's blog brings home the fact that addiction affects all walks of life and that these are people we are dealing with. And that neatly brings me to this month's quotes:

Quotes of the month:

Lee Hoffer criticizes the "overly quantitative presentations on the "behaviors" of drug users that dominate conferences in the field" in his article Unreal Models of Real Behaviour: The Agent-Based Modeling Experience. He goes on to say: 

"The highly personal narratives of participants framed by equally complex social environments are not visible in the numbers. To epidemiologists and other like-minded health researchers, the numbers are the narrative and all that is required for informing and evaluating theories, models, interventions, treatment programs, or policy."
And if that isn't enough for the scientists among us to take things personally, in his article titled Too many rating Scales: Not enough Validation published in the December 26 issue of Addiction, Duncan Raistrick says: 

“Experts and stakeholders are, by definition, selected because they are distinguished in their field, and have opinions and experience to bring to the table. The problem is that opinions are often very strongly held to the exclusion of equally strong science"


Crazy "Cures"
Dr Frankenstein's School of Ablative Surgery
Forget the pharmacological approach, let's just get in there and "vaporize" the nucleus accumbens. For those of you who haven't studied the dark arts, the procedure involves drilling a couple of holes in the skull and inserting long electrodes into the "pleasure center" of the brain. An electrical current is then passed through the electrodes which kills the cells in the nucleus accumbens. A recent paper published in Stereotactic and Functional Neurosurgery reports that 60 opioid addicted patients in mainland China were followed up 5 years after surgery. and 47,4% were seen to be abstinent.On the other side of the coin, memory deficits were seen in 21%, motivational loss in 18% and some changes in personality in 53%. In spite of this the paper concludes: "The bilateral ablation of NAc by stereotactic neurosurgery was a feasible method for alleviating psychological dependence on opiate drugs and preventing a relapse. Long-term follow-up suggested that surgery can improve the personality and psychopathological profile of opiate addicts with a trend towards normal levels, provided persistent abstinence can be maintained; relapse, on the other hand, may ruin this effect.". Hopefully they wont use the same technique to cure my skepticism.

"Beating" Addiction
Those of you who are excited by the prospect of ablative surgery may also derive some pleasure out of the cure described in the Siberian Times (where else): Dr German Pilipenko and Professor Marina Chukhrova believe that their "limited pain exposure" method of treating addictions stimulates the brain to produce endorphins, thereby "making patients happier in their skins". The amazing thing about this "cure" is that it apparently treats depression and obsessions as well. Natasha, one of the success stories says: "I wouldn't keep coming back for this if I didn't think it was working. I know many of my friends think I am mad to trust these doctors. But I want to live. For the first time since I because an addict five years ago, I feel I have a chance. I just want to be like all those thousands of girls who have a normal life - finding a man, getting married, having kids, going through the problems of life together. I want that kind of normal life - and finally I can feel I am coming back to it." Maybe in Siberia a "normal" life involves having the crap hit out of you.

That's it for this month. I hope you found something that met your interest. Once again, comments are welcome. Please feel free to contact me directly by e-mail, and don't forget to subscribe to my monthly reminder.

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