Opioid dependence & opioid use disorder

Opioid dependence & opioid use disorder


Worldwide, opioids are the most common cause
of drug related deaths. The number of individuals abusing them has
quadrupled in the last 20 years, with an uptick in heroin use, an even bigger uptick in prescription
opioid use, and a large group of folks abusing both. Because of their potential for addiction and
overdose, opioids are regulated substances in a lot of countries. As a class, opioids share one thing in common—they
bind to opioid receptors in the brain, spinal cord, and gastrointestinal tract. Some are endogenous, meaning that they are
produced naturally by the body, like endorphin, short for endogenous morphine. But others are exogenous, meaning that they
come from the environment, like heroin and morphine because they come from the opium
poppy—a flowering plant that oozes out a milky white liquid, while others like fentanyl
are synthesized in the laboratory. To understand how opioids work, let’s zoom
into a region of the brain tissue that has opioid receptors. Normally, in the absence of endorphins, inhibitory
neurons secrete a neurotransmitter that prevents nearby neurons from releasing the neurotransmitter
dopamine. Now, let’s say someone goes to play a rigorous
game of badminton. Exercise releases endorphins which activate
the three major opioid receptors located on the inhibitory neurons, called the mu, kappa,
and delta receptors. As endorphins binds to these receptors, they
block the inhibitory neuron from releasing neurotransmitters, allowing the dopamine secreting
neurons to freely unload dopamine. The dopamine then gets picked up by a third
neuron in the same area. When dopamine release takes place in pain
processing regions of the brain like the thalamus, brainstem, and spinal cord, the result is
feeling less pain. When dopamine release takes place in reward
pathway regions like the ventral tegmental area, nucleus accumbens, and prefrontal cortex,
the result is a calming effect that feels good. So that’s how it works normally. But when a powerful exogenous opioid binds
to the opioid receptors, the result is a massive flood of dopamine. This helps with pain control, but it can also
cause an incredible state of euphoria within the regions of the brain involved in the reward
pathway, which is an emotional “high”. Now remember, the purpose of the reward pathway
is to train the brain to repeat activities that cause dopamine-mediated pleasure, so
when opioids stimulate this reward pathway, the brain learns to do that behavior again
and again. With exogenous opioids there are multiple
routes to get the drug to the brain. One way is by ingesting it, but that route
is the slowest. A faster route would be inhalation, because
the drug is rapidly absorbed through the lungs. The fastest route, though, is direct injection
of the substance into the blood. Typically, the faster the exogenous opioid
reaches the brain the stronger the relationship between the behavior and the reward. Now over time, people that are consistently
using a drug, even when taking them as exactly as prescribed, can develop tolerance which
means that with repeated use, they have a reduced response, and therefore an increased
dose is needed to achieve the original response. At a cellular level, there are two theories
that explain why this might happen. One theory is that opioid receptors might
become less sensitive to a drug, and the other theory is that the neurons may remove opioid
receptors from the cell wall in a process called down-regulation, leaving less receptors
available for binding. In either scenario, tolerance leads to the
need for higher and higher doses of a drug, and often times that tolerance remains for
a long time even after tapering from the drug. Alright, so now let’s say that you’re
at rest, there aren’t any drugs or anything stimulating your reward pathway. In this situation, your brain keeps your heart
rate, blood pressure, and wakefulness in a normal state, called homeostasis. Now, let’s say that your secret crush sends
you a text. All of a sudden you may feel sweaty and flushed,
your heart rate may jump a bit. You’re now above your normal level of homeostasis,
because something has changed, right? But it doesn’t stay that way for long, and
after the text message, your brain brings things back down to this baseline. With repeated drug use, a few things start
to happen. Let’s say you take the drug at a specific
time and setting, like 3pm in the bedroom, and, being a depressant, it makes everything
go lower, heart rate, blood pressure, and wakefulness. Your brain being the smart brain that it is,
will pick up on the pattern. Now, next time, at 3pm in the bedroom, the
brain preemptively increases each one, since it knows that when you take the drug, everything’s
going to decrease again. Now, let’s say 3pm in the bedroom rolls
around, but there’s no drug…In that situation, the brain still increases everything..but
the changes aren’t countered with the effects of the drug, and so the person can feel awful,
and these are called withdrawal symptoms. These symptoms can persist to the point where
a person may need drugs just to feel normal, and if that’s the case, they are considered
to be dependent on that drug. Now, on the flip side, let’s say that you
use the drug in an unfamiliar setting, like at 11pm at a party. Well in that situation, your body’s not
ready for the drug and there’s no physiologic “counterbalance” to help offset the effect
of the drug. When that’s the case, it can lead to overdose,
even on a dose that the person’s been normally taking, and that’s often times what happens. The symptoms of opioid withdrawal include
anxiety, shivering, tremors, yawning, body aches, vomiting, diarrhea, abdominal cramps,
runny nose, sneezing, sweating, and an increased heart rate and blood pressure. These symptoms can feel really awful, and
often prompts people to use opioids again; a process called negative reinforcement, since
you’re removing the drug, which causes withdrawal symptoms which reinforces more drug use to
avoid those symptoms. There is also positive reinforcement from
the dopamine-induced euphoria, again leading to more drug use. Together this positive and negative reinforcement
leads to opioid addiction also known as opioid use disorder. The DSM-5 or Diagnostic and Statistical Manual,
the 5th edition, defines opioid use disorder as causing at least two of the following behavior
patterns within a year: 1. Using more opioids or using them for longer
than intended. 2. Being unable to cut down on the use of opioids. 3. Having opioid use take up a significant amount
of time 4. Having cravings to use opioids. 5. Having opioid use affect responsibilities
at work, school, or home. 6. Using opioids even if they cause recurrent
interpersonal problems 7. Giving up important activities in order to
use opioids. 8. Using opioids in physically dangerous situations. 9. Using opioids even if its worsening a physical
or psychological problem 10. Becoming tolerant to the opioids. And finally 11. Feeling withdrawal symptoms from opioids. Having 2 or 3 of these symptoms is considered
mild, having 4 or 5 is considered moderate, and having 6 or more is considered severe. In addition to ruining a person’s life,
opioid addiction can also end it in an overdose. Most often, an opioid overdose causes severe
cardiac and respiratory depression, to the point where a person may have pinpoint pupils
and simply stop breathing. In that situation, the most important thing
is to performing rescue breathing, giving supplemental oxygen, and administering naloxone. Naloxone is an opioid antagonist that powerfully
binds to opioid receptors, and rather than having a direct effect, it blocks other opioids
from binding and activating the receptor. This works because at any given moment, opioids
are binding and unbinding to receptors which means once an opioid releases its hold on
a receptor, the naloxone can simply sneak in and bind more strongly. When naloxone given intravenously it can reverse
the effects of opioids within minutes, potentially saving a person’s life. Generally speaking, high doses of strong opioids
carry the greatest risk of addiction and death, and when paired with other substances that
can cause respiratory depression, like benzodiazepines, they’re more likely to cause overdose because
they can act synergistically to cause respiratory depression. It’s clear that opioids have strong addictive
potential, so their use should be limited and well defined. They have a role in controlling acute pain,
for example, but the goal should be to use short-acting opioids at the lowest effective
dose for just a few days, and slowly increase their dose only as needed. When opioids are used for chronic pain, they
should be weaned off as soon as possible, ideally at a wean rate of 10% of the dose
per week. In general though, chronic pain should be
treated with non-opioid approaches. These include exercise and biofeedback as
well as other types of medications such as acetaminophen and NSAIDs like ibuprofen. There are also disease-specific treatments,
like for migraines use triptans, or for neuropathic pain use gabapentin, or for joint pain topical
pain treatments like capsaicin. For people with opioid dependence, the most
effective treatment is a combination of therapy with medications. Specific therapies that work include motivational
interviewing, which can be used to understand why an individual wants to stop using opioids
and identify specific barriers to treatment. Also cognitive-behavioral therapy can help
an individual learn about withdrawal, discuss the thoughts, feelings, and behaviors that
lead to opioid usage, and create a plan to navigate triggers for usage. Another form of therapy are peer-support programs
which use group discussions to help individuals commit to ending the use of opioids and by
holding one another accountable. In addition, the evidence strongly supports
the use of medications, which reliably decrease cravings and reduce withdrawal symptoms. Methadone is a full opioid agonist with a
long half-life that slowly builds up in the tissues over time, allowing it to reach a
steady-state level within a week. Steady-state refers to the situation where
the overall intake of the drug is more or less in balance with its elimination, so that
the body is exposed to a stable level. In contrast, buprenorphine is a partial agonist
that is sometimes given in combination with naloxone, forming an agonist/antagonist combination. Buprenorphine has a ceiling effect, meaning
that above a certain dose it does not have any more of an effect, which reduces the chance
of an overdose. These medications can competitively bind to
the opioid receptor without producing the same euphoria as the opioids they take the
place of. Since they have opioid effects, though, they
can cause side effects like constipation, insomnia, weight gain, hormonal changes, and
cardiac arrhythmias. The good news is that over time, an individual
can safely taper their use of opioid treatments altogether, and this approach is more likely
to succeed than simply stopping opioids without these treatments. Another medication called naltrexone, can
be used for people who are already abstaining from active opioid use. Naltrexone is a mu-opioid receptor antagonist
that blocks the effects of opioids and helps maintain abstinence. Finally, all of these approaches work best
when an individual has a strong network of family and friends offering support. Opioid use still carries heavy stigma because
usage is still tied to a notion of individual choice and moral failure, even though we now
know that opioid use is a consequence of biological, psychological, and social factors—all of
which need to be addressed to maximize the chances of recovery. Alright, as a quick recap, opioids stop inhibitory
neurons from releasing inhibitory neurotransmitters, which allows dopamine to flood the ventral
tegmental area, nucleus accumbens, and prefrontal cortex, and causing euphoria. Long-term use can cause tolerance which is
the need for increasing doses to achieve the same effect, as well as dependence which is
the reliance on the opioid to function normally. The most effective treatment is a combination
of therapy and medications, with a lot of love and support from family and friends. Thanks for watching, you can help support
us by donating on patreon, or subscribing to our channel, or telling your friends about
us on social media.

57 comments

  1. Whoah the animations on this video are amazing, I just uploaded a video on Caffeine on my channel, check it out if you're interested!

  2. Osmosis, If you guys expect to have subscribers from Non-English Speaking Backgrounds such as China, India, France, Brazil, for god sake can you make these videos with little less talking speed? I think Khan Academy has understood this point now, but not you guys. Thanks.

  3. I mixed Methadone with Naloxone in the exam, I just need some cocaine to forget it. Great video and narrative, thanks.

  4. I have been so impressed in the past with your product — this one however is beyond absurd — I would suggest not doing such a video if you cannot maintain your standard — you do not have to make any "social scientific" statement just do not go near the subject to begin with. The science and chemistry "suddenly becomes ambiguous" is tragic in this video — you actually sound like one of those silly drug commercials with happy smiling people while the narrator speaks of organ destruction and suicidal side effects……… unless the Sacklers pay you directly …. get back to being you please.

  5. Since the major projection of dopaminergic neurons in the reward system is the mesolimbic pathway, does that mean ΔFosB is also similarly induced thereby causing desensitization from repeated drug challenge?

  6. Amazing! Love the speed, clarity, and helpful visuals. Much more detail than KhanAcademy in less time. These videos are helping me so much for the MCATs and for my internship at the hospital.

  7. Isn't the decreased perception of pain mediated by inhibition of inhibitory neurons in regions of the brain like the periaqueductal gray and therefore increased serotonergic activity from the Raphe nuclei not by dopaminergic neurotransmission?

  8. Thanks Osmosis! I recently weened off Tapentadol (palexia) which was really rough. I was on the drug for 10 months. I'm doing better now, however.

    COULD YOU PLEASE DO A VIDEO ON SEROTONIN SYNDROME! I suffered from this a year ago after perhaps ODing on a SSRI drug (even though i was on a small dosage). A video on this topic would be greatly appreciated.

  9. Im writing an essay and would like to use this as my reference, however, my uni does not give good marks for video references. May i know what research or study u used for your video? Thanks. Are there such thing as peer reviewed videos? Thanks

  10. The pry about someone overdosing because they took there medication at a different time of the day than usual is complete bs

  11. they ought to outlaw all opiates and arrest all chronic pain patients and doctors who prescribe these powerful addicting drugs ! t is the same as heroin!! take naproxen or ibuprofen or try to use bio feedback, thinking positive thoughts physical therapy ect people can't really be in that much pain sooner or later chronic pain gets better right? if you take these drugs you will die cause my brothers cousins nieces aunt died!! she was in the hospital for pneumonia and they gave her 15 mg,s of morphine'dope" and three weeks later she died! from opiate overdose said the coroner!! I am a law enforcement officer and i'll bust everybody on pain killers! i will never take on of them hardcore prescription opioid drugs even for surgery! if you take this legal heroin you are an addict!! and if you take even one pill you will die! you can't tell if the pharmacy pills have hydrocodone or heroin in them I have heardon T.V. news!

  12. very useful information thanks. can anybody tell me if someone is addicted to opioid and trying to stop how long will it take for withdrawing to ease off or disappear? thank you .

  13. Great videos, Osmosis! Can you do a video on ehlers danlos? And how the genetic condition causes opioids and anesthetics unable to work

  14. According to all the information I gathered, inhalation is a faster route of administration than IV when it comes to psychoactive substances. One source I can quote from the top of my head is prof. David Presti from Berkley.

    Would be great if you could verify this information and, if I'm right, correct this part.

    Apart from that a wonderful and well-made video!

  15. Wait, Let's get back to the reason I ask my Doctor for something stronger than Tylenol. PAIN! If I did not have Pain from Osteoartheritus in my joints and Lower Back, I wouldn't be taking Hydrocodon-Acetaminoph or any other Opioid.

  16. This is really helpfulll and your all other videos too,the way you describe everything make every topic so easy to understand and intersting.Thanks 🙂

  17. I have a question. Kaplan pharmacology says opioid-induced respiratory depression is treated by naloxone and should not be treated with oxygen because the patient has little response to pCO2. Is that right? Thanks: )

  18. There are also the physical effects of taking drugs – such as infections from dirty needles, breathing difficulties from smoking, and choking caused by vomiting.

  19. Tolerance is a "Nice" way of saying addiction! I was prescribed 450mg a day for many failed back surgeries, NONE of your information is going to help myself nor other chronic pain SUFFERS!

  20. Opioids work very well for many types of chronic pain.You should consider doing more research.Seriously what do you think dr.s were doing prescribing opioids for atrotious diseases ?Try redoing that part of your video.IT IS A GOOD VIDEO

  21. What alternative treatments do you recommend when the NSAIDS have started eating your GI tract and liver or kidneys. Exercise can cause more damage. Some alternative therapies are just too expensive for many. No one has really studied chronic pain treatment, so it is mainly speculation as to what works. Most of this was good, but the DSM guide gets changed for political reasons and to get insurance to pay for treatments, I find much of it suspect. Not all that long ago a woman could be involentarily put in a mental institution for menopause symptoms. There is big money to be made by labeling all chronic pain patients as addicts. The recovery business is booming and what better way to make more money and bilk insurance than to change the definition of substance use disorder.

  22. I've lived with pain constantly  since  1994. started with a popped disc, c6 c7 fused . I've had to add both knees and lower and mid back. my left elbow was relocated to my left shoulder, now my left hand is hyper sensitive , warn is hot, cool is freezing .I have a hard time finding my meds, I do not expect a high, just slight relief . I hope every politician including  trump ends up in agony with no relief , just like me. the assholes deserve it.

  23. LETS GO AFTER THE PHARMACEUTICAL INDUSTRY! HOW ABOUT THAT. THE GOV DOES NOT WANT TO FIGHT THEM AT ALL!!!! THEY RATHER FIGHT AGAINST THE SMALL GUYS TGAT HAVE NO CASH FOR LAWYERS. THIS IS TOO MUCH ALREADY. THE BLAME IS GOING ONTO THE WRONG PEOPLE.

    THE PHARMACEUTICAL INDUSTRY STARTED THIS HEROIN BOOM!!! THEY DID IT CENTURIES AGO AND THEY IT DID AGAIN!!!

    DI YOU GUYS SEE WHAT THE PLAN WAS????? VERY SIMPLE!!! LETS GET AMERICA HOOKED WITH NARCOTIC MEDS THEN ONCE IT BLOWS UP LETS BE THE HEROES BY SUPPLYING THE ANTIDOTE WHICH THEY CALL THE ANTIDOTE "METHADONE, SUBOXONE, SUBUTEX AND MANY MORE" THEY LOOK LIKE THEY ARE TRYING TO HELP BUT THEY ARE NOT!!!!!! ALL THESE OTHER MEDS ARE AS DANGEROUS AND ADDICTIVE AS HEROIN!!!! ASK YOURSELF THIS " IF THEY ARE TRYING TO GET PEOPLE OFF HEROIN AND OPIODS THAT THEY CREATED IN THE FIRST PLACE.

    WHY WOULD THEY RECOMMEND OR ALLOW ADDICTS TO STAY ON METHADONE AND ALL OTHERS FOR THE REST OF THERE LIVES!!!!!???? YES THE REST OF THERE LIVES!!! ITS NOT RIGHT!! IF YOU ARE. TRYING TO GET PEOPLE OFF YOUR MESS/PRODUCTS YOU PUSHED INTO 90% OF AMERICANS HOME/LIVES WHY NOT MAKE IT JUST A TEMPORARY THING???? 3 TO 6 MONTHS OR A YEAR THE MOST, BUT NO. THEY ARE THE DRUG DEALERS THAT WANTS THEM AS A CLIENT FOR THE REST OF YOUR LIFE.

    THE PHARMACEUTICAL INDUSTRY WANT THE HEROIN DEALERS TO BE SHUT DOWN SO THEY CAN STEP IN AND SELL THERE PRODUCTS!!! AND IF ITS HELP THEY WANT TO DO WHY NOT PROVIDE IT FOR FREE??? HECK THEY MADE BILLIONS OF US WITH THE NARCOTIC MEDICATIONS LIKE OXY, DILADID, PERCS AND SO ON!!! THEY HAVE THE CASH TO DO SO!!!!! BUT AGAIN THE GOV DOESN'T FORCE THEM BUT THEY GO AFTER COMPANIES LIKE THE TABOCCO INDUSTRY TO PROVIDE FREE HELP, WELL TRUTH BE TOLD THAT DIDN'T LAST EITHER LOL

    THIS IS NOT RIGHT AND THIS GOV IS TAKING ADVANTAGE OF THE PEOPLE FOR THERE OWN CROOKED AGENDAS!!! WE NEED TO FIGHT PEOPLE!!!!!!WE MUST OR IM SORRY TO SAY TJAT OUR KIDS AND THERE KIDS, KIDS WIL SUFFER THE CONSEQUENCES THAT WE ALLOWED TO HAPPEN BY ELECTING THE WRONG PEOPLE OR EVEN ELECTING PEOPLE THAT HAS LIED TO US ON A REGULAR BASIS!!!!!!!!!!!!! PEOPLE!!!! WE MUST CHANGE AND CHANGE NOW!

    AND PLEASE REMEMBER PEOPLE, THE AGENDAS OF THESE POLITICIANS IS VOTES AS WE KNOW. DONT BE FOOLED WHEN THESE PEOPLE PROMISE THEY WILL FIGHT THIS!!! THEY JUST WANT VOTES AND I CAN PROMISE YOU THIS "THEY WILL BACK DOWN OR MAKE A DEAL BEST SUITED FOR THE PHARMACEUTICAL INDUSTRY AND THE POLITICIAN. THIS WAR NEESS TO BE FOUGHT BY US!!!! WE NEED TO TAKE ACTION ONTHEM NOT THESE SNAKES THAT ALLOWED THIS TO HAPPEN IN THE FIRAT PLACE. REMEMBER WHAT I SAID!!!! THE DAMAGE IS ALREADY DONE, NOW THEY MUST PAY FOR ALL THE LIVES THAT THEY RUINED!!!!! AND WHEN I SAY PAY" ITS NOT FOR THEM TO KEEP SUPPLYING OTHER OPIODS THAT KEEP ON MAKING THEM MONEY AS METHADONE AND OTHER DRUGS LIKE SUBOXONE.

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