Neurobiology of Addiction - Dr. Steven Jurd

Neurobiology of Addiction

Dr. Steven Jurd, Clinical Associate Professor, University of Sidney, Australia (http://sydney.edu.au/medicine/addiction/staff/academics/profiles/sjurd.php) 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In contrast to this outdated idea, he quoted the Diagnostic and Statistical Manual of the American Psychiatric Association which said ‘early remission’ occured up to 12 months after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. www.ausdocsinrecovery.org 

The Hotel Windsor , Melbourne

March 22 to 24 to 2013

One week after grand prix

Progressive Nature of Alcoholism and Addiction

In meetings of Alcoholics Anonymous people who relapse describe their descent into the abyss of addiction by saying "when I was in the rooms of AA, my disease was in the parking lot doing push ups."  Returning to the struggle with alcohol they went from the plan of 'drinking like a gentleman" or 'drinking like a lady" to the all consuming animalistic life of serving the god of the bottle.
Millions of people come to AA but don't stay, simply using the success of AA to initiate their recovery in some other form.  AA showed the world in the 1930's that Alcoholism and Addiction could be 'cured' through abstinence and 'one drunk helping another'.  The 'self help movement of 12 step programs with the essential spirituality of a 'god of your understanding' ie no longer making yourself and your own desire God but rather joining group and community for a consensus reality, has served countless others with compulsions of wide variety. The recognition was the Aristotelian idea that one couldn't 'think themselves into new action but rather needed to act themselves into new thinking".  The cognitive behavioural therapy of the 12 step program as opposed to the 12 step fellowship showed individuals through action that their belief in the benefits of alcohol were cognitive distortions induced by the insaniety of addiction.
Untreated alcoholism progressed to institutions or death.  Once a person passed a certain point the so called up elevator or down elevator place, the future was either a slow or fast descent depending on how one 'controlled' the drinking, all paths downward being at best 'harm reduction' .  The only cure to date in chemical addictions remains the abstinence which causes so many addicts to say "I don't like AA because......."  Those who themselves achieve abstinence by any means see the value of AA and don't disparage it. Those who don't achieve abstinence will likely condemn all programs which come between them and their drug of choice with the passion which most recognise when we say, "the lady protesteth too much."
A tenet of AA is that once an alcoholic, always an alcoholic.  This is certainly evidenced by scienttfic research which to date has not be able to identify those who won't relapse to previous levels and worse.  Vaillant's research showed that relative to the general population, an alcoholic 5 years sober was 'statistically' no greater risk of drinking dangerously than a person who never drank. This is important in the work place but on an individual basis no one sober knows if he or she could pick up a drink "safely".  A Montreal study of 'controlled drinking' showed that despite 5 years of abstinence of those who returned to drinking 50% within the year drank alcoholically.  I believe it was a Dutch study that showed that 30% of those 15 years abstinent returned to drinking alcoholically.
The research suggests that there is a decreasing risk after 3 years of abstinence of people returning to their previous behaviour but that the risk of this even at 15 years sobriety is that a third risk death or institutions for the sake of a drink.  The World Health Organization designates only 'abstinence' as a cure and requires all other programs be called 'harm reduction".  Further it recommends that 'harm reduction' programs only be used in the context of a stepping stone towards abstinence not as an 'end in themselves' .
This suggests that the insaniety itself persists.  People with simple 'allergies' don't decide I'll try taking something that once caused a horrible rash, again.  Yet people who broke out in police and divorces seem to somehow figure 15 years of good living later that picking up alcohol is again a good thing.
The progressive nature of alcoholism has been the principle reason for people explaining that with relapse a person returns to previous level of abuse much more quickly than the first time. People who drank 'normally' for 20 years then drank abusively for 2 abstain only to relapse and find themselves drinking abusively either immediately or a year or so later.
Personally I remember smoking an occasional pipe or cigar for 10 years before becoming a pack a day cigarette smoker for a year.  Quitting somking on 2 separate occasions with the intent of just having a weekend smoke or at most one or two a day I was back to smoking a pack a day within six months.  Quitting again then I found the next time at six months in the week before I quit I was smoking 2 packs a day, a truly exponential increase. It's almost 15 years since my last smoke and still I occasionally 'romanticize' an 'occasional' cigarette.
Functional MRI studies of gamblers have shown that the addiction is not driven by reward associated with the 'win' but rather by the 'dice' being in the air 'just before the 'decision' of 'win or lose'.  The 'thrill' for the brain is that moment of uncertainty.  Psychoanalytically the addict has been seen as having failure in primary relationships and seeking to re enact that 'moment of abandonment'. Melanie Klein described this as the 'good breast, bad breast' moment for the infant.  The infant wants food and the 'good breast' is the one that delivers it. The 'bad breast' is the breast that doesn't appear 'on time'. The longer the delay in a child having basic needs met, ie the period of neglect, the greater the division between the good breast and bad breast.'  This explains to some extent those who are at greater risk for addiction though to date no one appears to be immune to addiction. As one cocaine researcher said "some of us might not sell our grandmother's for crack in the first week of addiction but all of us would after a few years." Addiction itself causes reversible or permanent brain injury with increasingly loss of the more human motivational structures seen in Maslow's research with the devolution over time to the 'animal' and finally 'lizard' brain of the McLean triune brain model.
All research to date on persons who develop alcoholism or addiction shows them as being inherrently 'immature' psychologically especaily around the issue of  'gratification'.  Despite this the head of the Supreme Court of Canada's alcoholism was a serious concern for the high court only decades past.  No doubt some of the early work of Beverly McLaughlin, present supreme court head of Canada was undoing that 'wreckage of the past'.
The more 'instant' a substance has for providing 'gratification' the greater the risk of addiction. This is shown in the 'addictive' potential of crack which smoked or injected has greater addictive potential than coke which is 'snorted'.  The addictive potential of injected and inhaled substance is greater than that which is ingested. This is one of the distinctions which separate the marihaua or cannibis addict from those who want cannibis for 'medicinal' purposes. The addict must smoke the cannibis whereas the healing benefits of cannibis are equal and more medicinal if taken as a tea.  Those wanting it for medicinal purposes, a highly significant minority, despite the eupheminism of "medical marijuana' the precurser of 'medical prostitution', are therefore not those who insist it only 'works' for them if it is 'smoked'.
Following on this progressive disease of addiction it's been said that the sex addict who has made a life of orgies,   doesn't truly thereafter, want to hold just hands with a nun.
The brain of the addict is demonstrably changed on a whole range of neurochemical measures. Dopamine pathways associated with the nucleus accumbens, the pleasure centre of the brain, are changed and the change persists.  Frontal lobe utilization of sugars, the food of the brain, is altered on MRI studies for 3 months after the last use of cocaine.  Marijuana remains detectable and active in the system for 6 weeks and possibly 3 months.  Alcohol influence on the liver is detectable days and weeks later.  The minimum true test of abstinence and once a diagnostic test of addiction was the abstinence from a substance or behaviour for 4 seasons or one year.  If a person couldn't stop gambling despite negative consequences, or drinking despite dui's, this was pathognomic of inherrent addiction.  Marijuana smokers who say they can go a days or weeks without a 'toke' are akin to alcoholics or  who say they can go a few hours without a drink.
There is permanent organ damage with addiction as well.  Women are much more susceptible to the physical deterioration of addiction which is a kind of poisoning of the system physically and obviously spiritually.  Spirituality is likened to Freud's 'eros' or life drive as opposed to his 'thanatos' or death wish.  The dice in the air or really 'playing with death' seen in the 'adrenaline junkie' and 'compulsive risk taker'.
The definition of addiction is that it is unhealthy and hastens risk of death whereas a behaviour such as AA attendance, normal work or church or sports or any recreation moderately followed is by definition not an 'addiction'.  The term addiction is used for 'unhealthy' substances and endeavours.
The other factor which obviously plays a role in the apparent progressive nature of alocoholism is the aging of the host.  A person will drink to a steady state they may maintain at a younger age but this drinking behaviour is 'hard' on the 'body'.  When a person abstains or takes a break it's a bit like an athlete who leaves and returns to the sport.  The alcoholic now has an older liver, older lungs, and older brain.  Addiction is a burden at the best of times.  A common time for 'relapse' is with early retirement when one has means, loss of life  structure and there's just so much golf one can play. These executives who stopped drinking often 20 years earlier begin to drink excessively in their late 60's. Alcoholism is a principal cause then for the heart disease and illness and death seen specifically in this population.  It's not so much that the 'disease' is 'stronger' it's that the 'host' is older.
The neurochemical explanation for the apparent 'progressive' nature of the disease and the high risk of return to previous level then worse for addiction is that the addiction has established an information 'highway' in the brain.  Not using the highway results in the development of other 'tracks' for neurochemical communication. However the 'highway' remains and can quickly be brought back into use. Much like we say about learning to 'ride a bicycle' .  Once one 'learns to be a drunk or addict' it's like 'riding a bicycle', the learning is always there to return to and build on.
Further if the 'thrill' or 'adrenaline rush' is of the 'dice in the air' then the death wish of addiction is to go further than one's worst last drunk.  So if a person crashed a motorcycle drunk at 70 mph  and lived maybe this time one's unconscious wish would be to 'crash a motorcycle drunker at 80 mph" and see if one lives..
Certainly that's the picture that the sex addicts give in their simply 'pleasure' driven experience so well described in  the snuff movie 9mm starring Nicholas Cage.   Only increasing risk and degradation gives the same 'high' so more and more of a thing is sought in the ancient adage of heroin addiction when one is forever 'chasing the tail of the dragon.'
Thankfully abstinence resolves this issue if the alcoholic or addict can 'surrender' to the notion that this is not their 'war' and there are countless alternatives in life worthy of such intense endeavour.  Addicts and alcoholics not surprisingly when they change their focus from death resulting activities to life enhancing ones commonly go on to great contribution and amazing success and altruism.
 It's well recognised  today that one doesn't need to take the elevator to very bottom of society but rather can get off any at any basement floor.   That then can  become one's'personal bottom' and  the basis for the springboard into a life that has been called for may 'the 4th dimension'.  Peace, bliss,  joy, happiness,  love and meaning  are  far different from the frenzied withdrawal and driven  pleasure lust of addiction.

Nanoseconds

If you believe you are first
Remember that experience
Of belief, or self
That grokking whatever
Took nanoseconds to know
Neurochemical synapses
Take time
So I am but an after thought
Of that first thought.
In the Beginning...