Thursday, August 2, 2012

Neurobiology of Addiction - Dr. Steven Jurd

Neurobiology of Addiction

Dr. Steven Jurd, Clinical Associate Professor, University of Sidney, Australia ( presented  Aug. 2, 2012, IDAA, Orlando

(These are my rough notes from Dr.Jurd's Continuing Medical Education lecture at the IDAA conference. In contrast to the 'dryness' of this material Dr. Jurd's presentation was most engaging, peppered with clinical anecdotes and some very humorous slides that had the hundreds in attendance LOL)

Dr. Jurd hypothesized that as Addiction is a Brain Disease there would be a  neurobiological basis which could be defined, the neurological systems involved could be identified, and the underlying molecular pathology would show. 

He made a strong statement that Addiction was ‘not simply withdrawal’.  He expressed the concern that he still encountered physicians who identified ‘addiction’ with the simple state of ‘withdrawal’.  

In contrast to this outdated idea, he quoted the Diagnostic and Statistical Manual of the American Psychiatric Association which said ‘early remission’ occured up to 12 months after withdrawal.  Addiction persists therefore long after use has stopped.

It is a common problem, with serious social and medical impact and many psychiatric complications.

Thirty six years ago “Alcohol Dependence Syndrome” was reported in the medical literature as involving tolerance,repeated withdrawal symptons, relief of withdrawal by drinking, salience of Drink seeking behaviour, subjective awareness of compulsion  to drink, narrowing of drinking repertoire, and reinstatement after abstinence.

These points were later included in the more extant Substance Dependence used in the DSMIV.

Substance Dependence - DSM IV describing well and succinctly the maladaptive pattern of substance use.

The brain was obviously the site of addiction given the subtle interplay between various brain functions.

Dr. Jurd described  Griffith Edwards  term “salience” which encompassed ‘drink seeking behaviour’ and the tendency of the substance to assume greater importance.

There is a reward  system , hard wired into mammalian brains, which is a good thing but unfortunately it is ‘high jacked’ in addiction. 

All attempts to track this reward system down have identified dopamine as the central neurotransmitter.  Once noted for his significance to the development of psychosis and parkinson’s disorder it’s now understood to be central in the addiction as well.

The “new” dopamine hypothesis states that DA is not merely a vector for production of psychosis. DA is crucial for all reinforcement. DA in the nucleus accumbens causes reward = attention, memory, learning. Addiction subsumes this basic mechanism.

Dr. Jurd showed the complex slides indicating all the effects of the different drugs of abuse and how they have been shown by research to act on dopamine. Then he offered  this simplification. 

“All drugs increase dopamine in the nucleus accumbens
Uppers put pressure on the accelerator
Downers damage the brakes”

Then he said, 
 but “remember that it is tonic not a phasic system’. There is always some dopamine in the process.

Having said this Dr. Jurd went on to discuss what causes relapse stating that three things have now been identified in ‘animal’ models: Stress, Cues and Priming dose.

It was found that 10% of rats like alcohol but this was only the rats that liked pure alcohol.  All rats liked beer and can  over time  be conditioned to drink  the equivalent of 24 cans of beer per day.Once hooked get them to press lever to obtain the alcohol. 
When the spigot is turned off, they eventually go back to other rats. It is then that ‘relapse behaviour’ can be induced with ‘foot shocks’, and example of stress, and also cuing and priming by added a little alcohol to the water. This will result in the rats returning to the lever and spigots even though they’d left them for some time previous. 

Neural Circuitry mediates drug seeking.
The final common pathway goes from the Pre frontal cortex to nucleus accumbens to ventral pallidum.
Cue and stress pathways have also been identified.

Childress in 2008 showed in  Prelude to Passion with functional MRI studies of 22 male cocaine patients that  limbic activation  occurred to ‘unseen’ cocaine and sexual images of 33 milliseconds.
Brain reward circuitry responds to drugs and sexual cues presented outside of awareness.
48 hours later, however, the addicted ‘liked’ visible versions of the same cues.
This study displayed the  unconscious vulnerability in addiction.
(Reward circuitry fired up even though their conscious brain didn’t see)

In addition to this there is ample evidence from Genetics studies of the disease basis of addictions.  Dr. Jurd listed some of the primary studies in his slides showing how even early work had been replicated confirming the reliability of the data.  Some of this research included the following: 

Twin studies (Kaij 1961, Prescott 1999)
Adoptee studies (Goodwin 1972, Cloninger 1979, Sigvaardson 1996, Cadoret 1995)
Longer term follow up (Vaillant 1983, 1995, 2003)

Dr. Jurd then presented the Nano Evidence for brain disease indicated in the genetic research showing :
GABA a2 receptor subtypes associated with alcoholic dependencdence Soyka 2008
A1 allele of D2

Finally he presented studies that showed that both pharmacology had an impact on the disease, with solid research showing Naltrexone and Acamprosate could alter relapse rates. 

Acamprosate works by decreasing the negative reinforcement
Naltrexone blocks the positive reinforcement

There was some discrepancy in the findings of European studies and American which could be attributed to the daily patterns of European drinking versus the more episodic pattern of alcohol consumption in American.  German studies showed that combined the drugs had even greater benefit that either alone.

Animal studies for acamprosate done with technique called alkalinization, putting the rat in vapor chamber and misting alcohol into the chamber , confirmed the effects of the medication on use. 

The fact that pharmacological treatments work certainly supports the disease hypothesis.

In summary: 

Addiction is a disease
Craving is a phenomena
Addicts reward themselves chemically

Several neurotransmitters are relevant
Combination drug treatment may be appropriate
There may be pharmacological subtypes of the disease

Dr. Jurd then went on to quote the research on successful treatments which showed that approximately 80% success rate could be achieved for 5 years. 

Brewster, Kaufman et al (2008) showed in Ontario Physician Health Program , a 5 year follow up of 100 physicians
AA/NA a required component
 71% no relapse while 85% response rate

McLellan, Skipper showed a 75% similiarly good outcome in their studies. 

This roughly 80% recovery rate was seen to be a product of the following key components: 
-contingency management
-frequent random drug testing
-tight links with AA/NA = abstinence
-Intensified treatment and monitoring follows relapse
-continuing care approach
-lifelong recovery focus

Explaining “recovery” Dr. Jurd turned to our present day understanding of “Brain Plasticity”

Synaptic structures are highly dynamic. Synapse count per cell body changes from 2,5000 in infants to 15, 000 in adolescents to 7,500 in adults  
Mature brains can generate new neurons. Exercise increases neural production.
Cells actually move within the CNS.

The Brain is active. It changes, and adapts to circumstances.
Dr. Jurd warned us that during this lecture we were all growing new synapses.

The brain is not a hard wired black box

Recovery is a consequence of new behaviour,new thoughts, new feelings
In new cells, new synapses and pathways are developing. Ultimately, a new microscopic neural architecture develops.

Dr. Jurd concluded by saying, 

Addiction lives in the brain. We can agree on a definition of addiction.  Mainstream medical profession agrees on this.  The relevance of the reward pathway,  it’s biochemistry and pathology have all been demonstrated. Further. we manipulate it with pharmacology and recognise the relevance of  neuroplasticity to recovery

In Sidney we noted that when there was a drought on heroin the uses switched to cocaine and ampetamine so there’s a cross over capability.

At the end of his talk he put in a plug for the Australian Doctors in Recovery annual conference. 
The Hotel Windsor , Melbourne
March 22 to 24 to 2013
One week after grand prix

No comments: