Sensitive Topic Opioids –

Content warning
 Many students , family and friends have some experience with drug
use disorders.
 With Opioids especially there are more and more in our society who
have been touched by overdose.
 The discussion of these topic may be triggering.
 Please let me know before or after classes by email at
 [email protected]

1
Opioids Outline:

 Fentanyl – Overdose epidemic

 How Opioids Work
 Opioid Use Disorder
 Withdrawal
 Treatment – Methadone
 Suboxone
 Harm reduction – Narcan
 Dangerous Trends : Tranq Dope (Xylazine), Nitazenes

2
 Opioid Analgesics
Morphine

!
Codeine
Heroin (diacetylmorphine) OD
Fentanyl (Sublimaze) Potent OD
CarFentanyl POTENT OD
Opioid Pain Pill abuse
Oxycodone (Oxycontin)
Hydrocodone (Vicodin,)
Meperidine (Demerol)
Hydromorphone (Dilaudid)
Oxymorphone (Opana)
3
Three Waves
of opioid
deaths -
Largest
Fentanyl
But dropped
10% this year

https://www.cdc.gov/nchs/nvs
s/vsrr/drug-overdose-data.htm

Doa 11 1 2024
5
CDC reports 10% drop in OD
deaths 2024

Why? Not sure

- Less fentanyl on street
– law enforcement

- NARCAN more available

-Xylazine contamination
may make people dose
less often
https://www.cdc.gov/nchs/nvss/vsrr/drug-
overdose-data.htm 6
 More fentanyl
seizures

https://ndews.org/2024/08/19/over-115-
million-pills-containing-illicit-fentanyl-
seized-by-law-enforcement-in-2023/
7
 Yasmine Hamouda
 Dangers of Self Medicating
 A friend, whom I will call "Mike," struggled with depression for a long
time. After experiencing a job loss and a breakup, he began self-
medicating with prescription painkillers he had obtained from his friend.
Mike believed these substances helped him escape his feelings and
provided relief from his sadness. Initially, he felt a sense of euphoria / relief,
which allowed him to forget his problems. But over time, he developed a
tolerance and needed higher doses to get the same effects. This led to
serious side effects, such as mood swings and increased isolation from
friends / family. Mike eventually sought help from a mental health
professional. In therapy, he learned healthier coping mechanisms, such as
engaging in physical activities like hiking and / or running. He also joined a
support group, where he connected with others facing similar struggles.
One key takeaway from Mike's experience is that self-medicating can
provide temporary relief but often leads to deeper issues.

8
Kamran Mattu
 Self-Medication Dangers - oxycodone
 I have a family member, who I will call Bob, who had experiences with self-medication with the use of
Oxycodone. He had a urologic surgery that involved him having to wear a catheter, which greatly limited
his mobility; at times, he would be unable to get out of bed due to the pain. He was thus prescribed
opioids to manage his pain. The surgery recovery process went awry, and instead of having the catheter
in for 3 weeks, he had it in for about 12, and had to reintegrate physical activity into his life. Since physical
activity was a hige part of his life, he was frustrated about having to sacrifice it for so long. Over the
course of more summers and winters, Bob had to undergo 3 additional unplanned surgeries, which
greatly contributed to his developed depression over not being able to live a normal life for over a few
years. He began using the Oxycodone as a pain-reliever as well as a stress-reliever as it was prescribed
in larger and larger doses by convincing his surgeon his pain was worsening. He soon began to rely on
taking opioids even after the pain from surgery recovery was over with, and used it excessively to fall
asleep and do work everyday. After realizing this was an issue, he decided to go to a support group to
help with his addictive behaviors, as well as begin to exercise (such as participate in hiking and skiing)
again to restore the things in his life that brought him actual relief. This moral of this story is that one may
need to restore that which was lost prior to addiction (as well as what the cause was of addiction) in order
for those addicted to certain medications to quit, alongside the use of support groups. Finding other ways
to replace the joy that opioid medications give those who are addicted to them is crucial for eliminating
an addiction.

9
What is
Fentanyl?
NIDA Infographic
 https://nida
.nih.gov/res
earch-
topics/tren
ds-
statistics/inf
ographics/
what-
fentanyl
 Doa 10 31
24

12
Prescription pain
reliever misuse

15
Opioid use disorder .. Short story of
one family
 Youtube, 2 min NASEM (Nat Acadamy Sci
Eng Med) Health and Medicine Division
 https://www.youtube.com/watch?v=aE
Bec2cQ4EQ

 Reference: Nat Acadamies Sci Eng Med

 https://www.nationalacademies.org/our
-work/medication-assisted-treatment-for-
opioid-use-disorder

18
Fentanyl – overdose risk

Opioid drugs mechanism of action

https://www.youtube.com/watch?v=s6
0KzN4GJdQ

19
 What is
Fentanyl?
- NIDA
Infographic

 https://nida.nih.g
ov/research-
topics/trends-
statistics/infograp
hics/what-
fentanyl
 Doa 3 31 2024
20
 Opioid Neurotransmitters:

!
22
Endorphins, Enkephalins
 Behavioral Roles
 Analgesia = pain relief
 Euphoria – runners high
 Gut (GI) - slow motility
 Diseases
 Pain syndromes, acupuncture
 Drugs – Opioid addiction
 Oxycontin (oxycodone)
 Heroin, Fentanyl, morphine

duplicaton
for
N. Wolfe not
property of
Slides
 Medications: Narcan (naloxone), Vivitrol (naltrexone ) for opioid, alcohol treatment
 http://marathontrainingacademy.com/the-runners-high-and-why-we-love-it, http://www.acupunctureofgreer.com/, Oxycontin Image by
Toby Talbot/AP
4 CLASSES OF opioid EFFECTS
CNS Depressant - Sedative Hypnotic
1. Relaxation sedation,"twilight sleep" loss of
anxiety
2. Analgesia
3. Euphoria higher dose
sense of well being-lower dose,
4. Physiology: decreased BP,Heart Rate,
respiration, pupils,GI inh (constipation,
nausea,dry mouth),cough suppression
23
Opioid Receptor actions
 “Delta: analgesia, antidepressant, convulsant, physical
dependence, modulate mu-related respiratory depression
 Kappa: analgesia, anticonvulsant, depression, hallucination,
diuresis, dysphoria, miosis, neuroprotection, sedation
 Mu: analgesia, physical dependence, respiratory
depression, miosis, euphoria, reduced GI motility,
vasodilation.…cough reflex and causing constipation”

 Azadfard M et al 2021 NCBI Opoid Addiction

https://www.ncbi.nlm.nih.gov/books/NBK448203/

24
 Synaptic mechanisms

 Inhibit post synaptic K+ flows out

 Inhibit presynaptic, block Ca++
release
 You Tube, 2 min Neuroscience
 Neuroscientifically Challenged
 Date accessed 4 1 24
 https://www.youtube.com/watch?v=NPlN
CqBHPnE

25
 Opioid Effects in Brain 18-
26

From Carlson and Birkett Physiology of

Behavior, 12th edition Figure 18.12 opioid
receptors in the nucleus
accumbens and ventral tegmental
area are involved in reinforcing effects
of Opioids. Receptors in the preoptic
area are involved in hypothermia.
Receptors in the periaqueductal
gray matter are primarily
responsible for analgesia, and receptors
in the reticular formation are responsible
for sedation.
NIDA
Treatment
Summary

https://www.
drugabuse.go
v/publication
s/drugfacts/n
ationwide-
trends
doa 6 2 16 29
 Opioid Withdrawal 1:
Physical
Symptoms:
 Pain, Cramps, Chills,
 Perspiration ,Priapism, Itch,
 Restless legs syndrome,
 Flu like symptoms, Rhinitis, Yawning, Sneezing,
 Vomiting, Diarrhea, Weakness

 Other rare symptoms but more serious

are: cardiac arryhthmia, stroke , seizure, 30

dehydration, suicide attempts

Opioid Withdrawal 2
 Psychological Symptoms
 Dysphoria,
 Cravings,
 Anxiety/
 Paranoia,
 Insomnia,
 Depression
Panic Attacks,

!
31
Bipolar illness contributing to Heroin
Addiction
Anonymous student 2023
• I had a relative who I will call, MB, who self medicated using heroin. Starting when
MB was very young, around middle school age, he started expressive symptoms of
bipolar disorder. It was found that he had severe bipolar disorder. With this found
out, he was put on a series of medications that were intended to help him.
However, these medications did not help or made him worse. When he took these
medications, he was often described as a “zombie”. He stopped taking his
prescription medication and started drinking alcohol to cope with his disease. This
drug use then spiraled into heroin use. He was taken in and out of rehab multiple
times. There were times where he would get sober, but he always fell back into
heroin use. There were also times where he would get back on his prescribed
medication, but these times never lasted long. He mostly suffered from manic
episodes where he would steal and sometimes end up in jail. He used heroin to
manage his symptoms in the end. Sadly, he ended up overdosing on heroin which
caused his death. He was in his 30s. The take home message is that drug 32
addiction/use can happen because of factors out of our control like mental illness.
 Prescription Pain Killer
abuse
Oxycodone (Oxycontin,
Percoset)
Hydrocodone (Vicodin,)
Meperidine (Demerol)
Hydromorphone (Dilaudid)
Pain relievers for nonmedical
reasons in the previous month.
60 % of vets in chronic pain,
110 million Opioid Rx in 2022
Npr http://hereandnow.wbur.org/2015/01/15/va-
hospital-overprescribing3 2015

https://www.cdc.gov/drugoverdose/rxrate-
maps/opioid.html
Doa 4 1 24
Some 0piate Withdrawal Medications:
MAT= Medication Assisted Treatment
• Substitution Therapies
• Methadone
• Suboxone
• Buprenorphine/naloxone
α2-adrenergic receptor agonists (eg, clonidine and lofexidine).

Newer agents:
tramadol (μ-opioid receptor agonism)
tizanidine (α2 agonism)
Srivastava, A. B., Mariani, J. J., & Levin, F. R. (2020). New directions in the treatment of
opioid withdrawal. Lancet (London, England), 395(10241), 1938–1948.
https://doi.org/10.1016/S0140-6736(20)30852-7
 36

https://nida.nih.gov/research-topics/opioids/medications-opioid-overdose-withdrawal-addiction-infographic DOA 4 1 2024

METHADONE
• synthetic Opioid, like morphine
• taken orally since better absorbed
• slower release, less euphoria
• relies on cross tolerance
• example: 1-2 years then tapered off over weeks
Methadone - 2 min
neuroscience:
Prevents withdrawal,
taken at clinics,
once a day orally
Hard to discontinue
Harm reduction

https://www.youtube.com/watch?v=dw6laQ4-
Zgs
39
Suboxone

 Advantage: MD prescription,
 take at home, not clinic
 Sublingual administration
 4:1 buprenorphine:naloxone
 Interact with CNS depressants/ benzo’s

 Dr. Byrne Describes Suboxone Treatment for Opioid or Pain

Medication Addiction.
 https://www.youtube.com/watch?v=Lm6vN1eNnio
 Industry Promotion of Suboxone Suboxone.com
http://www.youtube.com/watch?v=tOIu77Uha1k
 Reference: Medscape.com/druginfo (suboxone)
40
 Opioid Antagonists:
Harm Reduction:
Narcan = Naloxone
μ-opioid receptor
competetive antagonist
short acting injection 3-5 minute, last 30 min
Autoinjector Naloxone - 2014, (Evzio) for home use
How to use:
Youtue Narcan injection https://www.youtube.com/watch?v=aJmeSezkL1A

Intranasal Naloxone “Rescue Kits”

How to use: 4 min
Youtube Narcan Nasal administration
https://www.youtube.com/watch?v=WnjgrRNMfKM 41
Doa 4 1 24
Fentanyl OD ABC Nightline

• https://www.youtube.com/watch?v=2awPPVKmpRQ 42
 Naloxone (Narcan) and action on Opioids
• Narcan Naloxone saves lives
• E.g 26,500 lives saved in 2014

• NIH
https://www.youtube.com/watch?v=zW
e_lPniEq4

• Date accessed 3 30 2024

43
Prince OD – High concentration of
Fentanyl

 “Prince had "exceedingly high" levels of

fentanyl in his system at the time of his
death, according to a toxicology report.
The concentration of fentanyl in Prince's
blood was 67.8 micrograms per liter …
people have died from as little as 3
micrograms per liter, and as high as 58.”

 https://www.tmz.com/photos/2021/10/11/
stars-whove-died-from-fentanyl/

46
Harm Reduction –
Narcan shot revived Prince 1 week before OD
from Opioid Fentanyl

47
Drug Enforcement Agency DEA
Reports Increased OD
OD rates rose 40% in DC and VA 2021
OD deaths in the U.S. topped 100,000 “for the first
time over a 12-month period”

Fentanyl mixed into almost every illicit drug, and

sold to unsuspecting buyers

https://www.dea.gov/stories/2022/2022-02/2022-
02-16/fentanyl-deaths-climbing-dea-washington-
continues-fight
Actor Logan Williams (Flash) age 18, died of Fentanyl OD
48
 Opioid withdrawal Meds - oral
dissolving : Suboxone Films, Bunavail,
Zubsolv, Subutex
(buprenorphine and naloxone)
 FDA Mar 2014,
 soluble film
 Taste better than tablets
 Strain EC et al Clinical Pharmacology & Therapeutics 89, 443-449
(March 2011) |

 Zubsolv buprenorphine and naloxone sublingual tablets

 COMPARE: Opioid withdrawal
medications
https://www.suboxnashville.com/suboxone-
medicines-compared-suboxone-films-bunavail-
zubsolv-subutex-generic-tablets-and-generic-
suboxone-films/
 DOA 4 2 23

Nicola Wolfe, PhD

49
BUP XR- extended release monthly
injection helps “Sublocade TM
 2017, the FDA approved the use of an extended release
buprenorphine (BUP-XR) under the brand name
Sublocade* as a monthly long-acting injection

 Haight, et al. Efficacy and safety of a monthly buprenorphine

depot injection for opioid use disorder: a multicentre,
randomised, double-blind, placebo-controlled phase 3 trial. The
Lancet. Feb 2019. DOI:https://doi.org/10.1016/S0140-
6736(18)32259-1

 https://www.drugabuse.gov/news-events/news-
releases/2019/02/monthly-buprenorphine-injections-effective-
opioid-use-disorders
50
2023 Crisis “Tranq Dope”
Fentanyl contaminated with “bulking’
animal tranquilizer Xylazine




severe, necrotic crusty skin ulcerations
untreated, they can lead to amputation
“blackout stupor “ – victims of assault..
OD risk – respiratory depression
Not reversable with Narcan,
Not show up in routine tox screens
!
 Why add? May extend the high “Kim Barauskas said that right after she
accidentally injected tranq into an artery, she felt
 FDA alert Nov 8 2022 like her hands had been dipped in acid. Her
fingertips may need to be
 https://www.fda.gov/media/162981/download#:~:text=Xylazine%20is%20a%20non%2Dopioid,may%20share amputated.”Credit...Hilary Swift for The New York
%20some%20clinical%20effectss.
Times

 NY Times 1 7 2023 https://www.nytimes.com/2023/01/07/health/fentanyl-xylazine-

51
drug.html?unlocked_article_code=WdhEKhxfpP2n3B7pHeCFCT138WqQICKKxWB1fO2xuZDdZ-
Fentanyl test strips.. Harm reduction
not always work..
- Not legal in every state
- May get free - health department,
a needle exchange program, or
other community-based
organization.

-buy them online at sites including

dancesafe.org, bunkpolice.com,
and amazon.com, CVS…

https://www.webmd.com/mental-health/addiction/fentanyl-testing-strips
https://btnx.com/HarmReduction#
53
CDC prevent
OD on opioids

!
https://www.cdc.gov/stop-
overdose/safety/index.html

54
NPR on Xylazine ODs 2022

 Narcan not help with

Xylazine so add rescue
breathing if xylazine and
opioid OD

 https://www.npr.org/sections/health-
shots/2022/08/05/1114453468/animal-
tranquilizer-street-drugs

 https://realdealonfentanyl.com/

55
Opioid Trend: OD risk fromNitazenes
No medical use
Recent OD’s in news
Around 800 times more potent than Morphine
40 times more potent than Fentanyl
• Examples:
• Isotonitazene.
• Metonitazene.
• Etonitazene.

• https://health.usnews.com/drugs/articles/nitazenes
• Doa 1 16 2024

56
https://nida.nih.gov/research-topics/opioids/medications-opioid-overdose-withdrawal-addiction-infographic
59
Buprenorphine
helps stay in
treatment
Kakko et al Lancet 2003

+ keeps out of
jail
E.A. Evans, et al. Recidivism and
mortality after in-jail buprenorphine
treatment for opioid use
disorder. Drug and Alcohol
Dependence. DOI: 10.1016/j.drugal
cdep.2021.109254 (2022).
60
Starting Buprenorphine in ER safe
and effective

 NIDA news release 2023

 Onofrio G et al JAMA network 2023
 JAMA network
 https://nida.nih.gov/news-events/news-
releases/2023/03/Buprenorphine-initiation-in-ER-found-safe-
and-effective-for-individuals-with-OUD-using-fentanyl

 Herring, A. A., Vosooghi, A. A., Luftig, J., Anderson, E. S., Zhao, X., Dziura, J., Hawk, K. F., McCormack, R. P., Saxon,
A., & D'Onofrio, G. (2021). High-Dose Buprenorphine Induction in the Emergency Department for Treatment of
Opioid Use Disorder. JAMA network open, 4(7), e2117128. https://doi.org/10.1001/jamanetworkopen.2021.17128

61
Medication Assisted Therapy MAT

62
Reference: NIDA drug screening

 NIDA Drug Screening tool online doa 6 1 16

 http://www.drugabuse.gov/nmassist/?q=qm_json&pageId=questions
_1&pageName=QuickScreen&token_id=1559
65
“Gas Station Heroin” = tianeptine
 2024 News stories
 Pharm: atypical agonist of the μ-opioid receptor
 Atypical Tricyclic antidepressant and antianxiety
 Not regulated - Energy drinks have very high dose 100 times normal
dose
 Several people have died from tianeptine OD
 Side effects: Agitation, Confusion, Dependence (addiction),
Drowsiness, Nausea and vomiting, Rapid heartbeat, Slowed or
stopped breathing.
 Neptune’s Fix voluntary pulled from shelves

70
Reference: Addicted at Birth -
Heroin
 Methadone used

 Youtuve Addicted at
Birth Sky news
 https://www.youtub
e.com/watch?v=X3
UKcHR-2uU

71
Heroin Films
 Voices of Heroin 4 min
 http://www.youtube.com/watch?v=kOPOK24g9Cc
&feature=related

“Gateway to Heroin”
about oxycontin and heroin
epidemic in Boston 44 minutes
http://www.dailymotion.com/video/xjfj
t0_vanguard-gateway-to-heroin-s05-
e01_shortfilms
DOA 3 27 2022
72
NCBI Stat Pearls, Opioid Addiction
Review
 Azadfard M, Huecker MR, Leaming JM.
Opioid Addiction. [Updated 2021 Aug 26].
In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2021 Jan-.
 https://www.ncbi.nlm.nih.gov/books/NBK44
8203/

73
 References

 Substance Abuse and Mental Health Services

Administration (SAMHSA)
 http://www.samhsa.gov

 National Alliance of Methadone Advocates

 http://www.methadone.org/

74
NY Times 2024 article

 https://www.nytimes.com/interactive/2024/09/27/opinion/fentanyl-overdose-
deaths.html?rsrc=flt&unlocked_article_code=1.OU4.2ovd.pJ1r93mX_Xyq&smid=url-share
80
Reference Film:
Abuse of prescription medication
 American Addict 2013
 Available on Netflix

82
Reference :SAMHSA Co Occuring
disorders

 Treatment kit:

 http://www.samhsa.gov/disorders/co-occurring
 Doa 6 13 2020
83
Reference: NIH Opioid Treatment
summary doa 4 2 23

 https://www.drugabuse.gov/publications/effective-treatments-opioid-
addiction/effective-treatments-opioid-addiction
85
Case- Fentanyl addiction 90

 “The new face of fentanyl

addiction: Kati's story
 https://www.youtube.com/watch
?v=BG70kTLfS7w
 Doa 8 22 2023
Reference film

 PBS Frontline Episode 13, 2020

 “ Opioids Inc.”

 About fraud and bribery around

 “ In Sys “ , fentanyl spray
“subaddictive
 Higher doses pushed
 Kapoor - profiteer

91
 Therapies for
TREATMENT –
from NIDA website

 https://www.drugabuse.gov/public
ations/drugfacts/comorbidity-
substance-use-disorders-other-
mental-illnesses

 Date of Access 6 13
2020
92
Buprenorphine start in ER – 93

safe and effective

 NIDA. 2023, March 30. Buprenorphine initiation in the ER

found safe and effective for individuals with OUD who use
fentanyl. Retrieved from http://nida.nih.gov/news-
events/news-releases/2023/03/Buprenorphine-initiation-in-
ER-found-safe-and-effective-for-individuals-with-OUD-using-
fentanyl on 2023, March 31
Catchy Review – I got these tools I 95

use them.. OUD med treatment

https://www.youtube.com/watch?v=eg09sqC4MlA
 Ibogaine re exazmined. NY times 96

Many clinics in Mexico

Schedule I illegal in US

30-60% cure rate

in some studies

Some serious side effects

e.g. heart arrhythmias

NY TIMES 3 5 2024 https://www.nytimes.com/2024/03/05/health/ibogaine-psychedelic-opioid-

addiction.html?unlocked_article_code=1.Wk4.Ef51.VTabM2eMtwxO&smid=url-share
TED Opioid Review 97

Help line 800 662 4357

 Review Video: Opioid Addiction
Mike Davis 2020

https://www.youtube.com/watch?v=V0CdS128-q4 DOA 1 18 2022

99