The Neurobiology of Street Drugs and Addiction

Joe Gilboy PA-C

Hoag Hospital Emergency Department

Irvine and Newport Beach, CA

Your brain is a complex neural network

“What fires together wires together”

Neuroplasticity

I want you to leave with more questions and less answers

Let's go back to school and learn some neurobiology

Presynaptic Cell

Postsynaptic Cell

Synaptic area

Uptake pumps

Dopamine

Dopamine receptor sites

Normal day

Ventral tegmental area

Reward System

Limbic SystemDopamine (Reward Chemical)

Remember this area is your hard drive level

Caudate Nucleus

Regulation of movement

Remember these drugs are working at a prehistoric wiring level

Respiratory center

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Accumbens

Amphetamine

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AccumbensCocaine

Time After Drug

Morphine

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Nicotine

Effects of Drugs on Dopamine Release

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Accumbens

0.51.02.510

Dose mg/kgmg/kg

mg/kgmg/kg

Methamphetamines

Stimulation of dopamine in the limbic systemCan be snorted, smoked, or injected

Highly addictive and tissue tolerancestrong cravings

“Tweakers” are highly agitated and paranoid

Amphetamine

Methamphetamine

What’s the difference??Generation Adderall A version of this article appears in print on Oct. 15, 2016,

New York Times Sunday Magazine

Psychosis with Methylphenidate or Amphetamine in Patients with ADHDMarch 21, 2019

N Engl J Med 2019; 380:1128-1138DOI: 10.1056/NEJMoa1813751

https://www.dea.gov/press-releases/2019/02/14/whitinsville-woman-faces-20-years-prison-adderall-distribution

cAMP

Meth

S

Dopamine receptor site breaks down after chronic use

Mitochondrial breakdown because of glutamateAnn N Y Acad Sci. 2008 Oct;1139:232-41. doi: 10.1196/annals.1432.028.

Methamphetamine changes NMDA and AMPA glutamate receptor subunit levels in the rat striatum and frontal cortex.

Memory

Emotions

Thought

MRI of a Methamphetamine Addict

Opiate receptor sitesMethamphetamines stimulates dopamine receptor sites in the Nucleus accumbens

Nucleus accumbens

End result stimulation of the reward system

Narcotics/OpiatesHeroin,oxycodone, Vicodin

It was brought to China by Arab traders in the eighth century

The British, East India Company became a chief supplier and promoter of opium for the Chinese

market

In England heroin is mixed with alcoholcocktail to terminally ill cancer patients

No competition more stimulation of dopamine receptor sites (Mu can grow when stimulated)

Heroin/opiate

Mu receptors

Opiate Binding Sites

Nucleus Accumbens

Memory

Movement

Respiration

End result stimulation of the reward system

Treatment for Heroin Patients

1st Line Subutex (buprenorphine)

2nd Line Suboxone (buprenorphine+ naloxone)

Can use methadone prefer to give at methadone clinics where it is dispensed as a liquid to prevent abuse

Chasing Heroin PBS Frontline Special

The worst drug crisis in American history

• Death rates now rival those of AIDS during the 1990s

• Overdoses from heroin and other opioids now kill more than 27,000/year

What started the fire • Pain 5th vital sign

• Originated in the VA hospital system late 1990s and became a Joint Commission standard in 2001.

• Purdue Pharmaceutical

• OxyContin, introduced in 1995, was Purdue Pharma’s breakthrough palliative for chronic pain

How bad is the opiate problem??

• In 1999, there were more than twice as many motor vehicle deaths as fatal drug overdoses. By 2014, those numbers had flipped

Chasing Heroin PBS Frontline Special

Kim Jadda’s vaccine works a bit like a sponge it sucks up the heroin and prevents it from reaching the brain

the vaccine prevents the drug from reaching the brain at all. Narcan in a vaccine

One way to look at it is that addiction is the compulsive repetition of getting “a reward” despite life damaging

consequences

Do they work?

What is the standard rehab success rate?

There is no standard definition of rehabMany base their success rates on unreliable metrics:

• Completion of the program• Sobriety rates immediately after treatment• Client interviews• Internal studies

• Dr. Lance Dodes spent more than 20 years studying and treating addiction. His latest book:

• The Sober Truth: Debunking the Bad Science Behind 12-Step Programs and the Rehab Industry.

AA Success Rate 5-10%

• And to its credit• AA describes itself as a

“brotherhood rather than a treatment”

Drug & Alcohol Rehabilitation Clinics industry trends (2014-2019)Average industry growth 2014–2019: 4.6%

700 Billion: Nation annually in costs related to crime, lost work productivity and health care

3x: The amount the business of recover increased in the last 25 years

14,000: The amount of addiction treatment facilities

$35 billion: annual revenue generated by the addiction treatment industry

Lyft -- $15.1 billion

Source: Substance Abuse and Mental Health Services Administration

Sober living home average about $1,500-2,500 per month. Missing a payment can result in expulsion from the home.

Source: Substance Abuse and Mental Health Agency (SAMHSA)

In the end rehab facilities don’t work $$expensive$$

www.thebusinessofrecovery.com

Generally, the price tag for rehab is:

•Outpatient: $3,000 – $10,000 for 90 days

•Inpatient: $5,000 – $20,000 for 30 days

•Luxury: $30,000 – $100,000 for 30 days

Here’s a bright idea!!

Neuroplasticity

Neuroplasticity

the potential that the brain has to reorganize by creating new neural pathways to adapt, as it

needs

Changes being made in the brain as the brain's way of tuning itself to meet your needs

Formerly held belief that the adult brain was pretty much a physiologically static organ

hard-wired after critical developmental periods in childhood

your brain is much more plastic during the early years and capacity declines with age

WRONG: plasticity happens all throughout your life

Neuroplasticity• Ability of the brain to change structure and

function based on input from repeated behaviors, emotions, and thoughts

“What fires together wires together”

Shackleton-Jones, Nick (2019-05-03). How people learn : designing effective training to improve employee performance. London, United Kingdom. ISBN 9780749484712. OCLC 1098213554

O'Brien CP. Neuroplasticity in addictive disorders. Dialogues Clin Neurosci. 2009;11(3):350–353.

Shaffer J. Neuroplasticity and Clinical Practice: Building Brain Power for Health. Front Psychol. 2016;7:1118. Published 2016 Jul 26. doi:10.3389/fpsyg.2016.01118

In Donald Hebb's (1940s) memorable words:

What fires together wires together — neurons that activate each other become more strongly connected —

through adjustments (increased efficiency) in their synapses. Neuroplasticity is the brain's natural starting point for all learning processes — processes that might

include not only addiction but also recovery

Brain plasticity is a two-way street; it is just as easy to generate negative changes as it is positive ones

What fires together wires together

Why do people become addicts??

Epigenetics

Mu receptorsAddiction vs dependenceEnvironment

Neuroplasticity

• Recent studies provides strong evidence that stimulant addiction may result in large part from underlying, inherited genetic abnormalities in brain structure that encourage impulsive behavior and impaired control.

• Ersche KD et al. Abnormal brain structure implicated in stimulant drug addiction. Science2012 Feb 3; 335:601.

Complexity to a level nobody understandsLets all agree what we have been doing

doesn’t work

time to look for a new way

Neuroplasticity

• Ketamine improves mood disorders within hours not weeks

• Repairing damage connections • SSRIs may be wrong

Depression may be the result os stress-induced damage to brain cells that control mood

The use may lead to newer drugs

• National Institute of Mental Health (NIMH)

Neurons with budding after Ketamine

About 99 percent of genes in humans have counterparts in the mouse 80%have identical, one-to-one counterparts

What fires together wires together

LSD and Anxiety in Cancer patients

• Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer

• J Psychopharmacol. 2020 Feb;34(2):155-166. doi: 10.1177/0269881119897615. Epub 2020 Jan 9

LSD and nicotine addiction• Johnson, M.W., Griffiths, R.R. Potential

Therapeutic Effects of Psilocybin Neurotherapeutics 14, 734–740 (2017)

• South America• Ibogaine is converted into a noribogaine• targets the areas of the brain affected by drug-seeking and

addictive behaviors• Noribogaine “rewires” these areas, allowing the brain to

restructure itself to a state similar to before addiction was triggered.

• Belgers, M., Leenaars, M., Homberg, J. et al. Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Transl Psychiatry 6, e826 (2016).

• Rat Park (environment)

• was a study into drug addiction conducted in the late 1970s (published in 1980) by Canadian psychologist Bruce K. Alexander and his colleagues at Simon Fraser University in British Columbia, Canada

• The researchers built a rat colony

• (Rat Park) which was 200 times the size of a normal laboratory cage

• Housed between 16 – 20 rats of both sexes.

His neural connections are healthy, and his wiring is working well

What fires together wires together

So the opposite of addiction is not sobriety

It is human connection

Neuroscientist Marc Lewis argues that addiction – or dependence, is the result of "deep learning", probably

triggered by stress or alienation.

It can duly be unlearned by forging stronger synaptic pathways via better habits.

What fires together wires together

The Biology of Desire: Why Addiction Is Not a Disease by Professor Marc Lewis

Nearly fifteen years ago, Portugal had one of the worst drug problems in Europe

1 percent of the population addicted to heroin

They had tried a drug war, and the problem just kept getting worse

So they decided to do something radically different. They resolved to decriminalize all drugs

They transferred all the money they use to spend on arresting and jailing drug addicts and spend it

instead on reconnecting them to their feelings, and to the wider society

The most crucial step they secure housing, and subsidized jobs so they have a purpose in life, and

something to get out of bed forBottom line it works

The 15th anniversary of the Portuguese drug policy: Its history, its success and its future

Tiago S Cabral First Published January 1, 2017 Research Article

Want to Win the War on Drugs? Portugal Might Have the AnswerBy Naina Bajekal | Photographs by Gonçalo Fonseca

August 1, 2018

Neuroplasticity

Maybe your genetics affects your body’s response to drugs, foods, medicine and maybe addiction

“Dare to Think” Maybe it’s the cage the patient is in along with genetics and

the cure is neuroplasticityWhat fires together wires together