6 ms·

Vaccine development against methamphetamine drug addiction [pdf] (2020)

58 points by dynm 4y ago

eimrine 4y ago
> In the same study selectivity of MH6 antibodies to bind to AMP, METH, 4-methyl-N-methylcathinone (4-MMC), or methylenedioxy-methamphetamine (MDMA) were evaluated by equilibrium dialysis. I'm glad that 4-MMC meets some studies. I believe this is a next-gen drug with cocaine-like effects and little or no contraindications.
- digdugdirk 4y ago
  Very interesting. I'd never heard of this before. Where do you find research on chemicals/compounds like this?
- water8 4y ago
  There’s basically 2 pathways: the dopamine pathway through amphetamines or the acetylcholine pathway via cocaine
  - zafka 4y ago
    Can you expound on this a bit? As the other commentor indicated, this is very interesting. Thank you for exposing me to this tidbit!
    - water8 4y ago
      Just look up with the neurotransmitters regulate. The key chemicals in stimulation are dopamine norepinephrine epinephrine and acetylcholine. Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence
      - valec 4y ago
        >Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence this is so oversimplified as to be completely meaningless
  - valec 4y ago
    i think you are very mistaken. cocaine and amphetamines both enact their effects primarily by drastically raising dopamine levels in the brain (in particular the striatum in the case of the euphoria they cause). neither of them directly target acetylcholine to any capacity. the main difference between cocaine and amphetamines is that amphetamines are dopamine/norepinephrine(/serotonin depending on the specific amphetamine) releasers, while cocaine is a dopamine/norepinephrine/serotonin reuptake inhibitor. releasers make their way inside the presynaptic neuron either through DAT/NET/SERT or by diffusing directly across the membrane, where they then enter monamine vesicles through VMAT2 and collapse the pH gradient causing monoamines to spill into the cytosol, where it is then transported out of the cell by DAT (and sert and net for serotonin and norepinephrine). it is unclear the exact mechanism that amphetamine causes DAT/NET/SERT reversal. anyways end result is norepinephrine and dopamine spill into the synaptic cleft. cocaine, as a SNDRI, simply blocks DAT/NET/SERT from removing their respective monoamines from the synaptic cleft/transporting them back into the pre-synaptic neuron.
digdugdirk 4y ago
This is absolutely fascinating, but I'd say the title isn't fully accurate. These vaccines seem to be entirely neutralizing methamphetamine in all it's functions. Using alcohol as a metaphor, it'd be like you could drink as much as could fit in your stomach and just never get drunk. So while yes, I can imagine it'd be useful in preventing addiction, does it really mean the same if you're physically/mentally incapable of feeling the effects of the substance to begin with?
- chaps 4y ago
  Not having read the article either, it's probably fair to say that it's not expected to be a perfect vaccine for meth. Perfect being the enemy of good, etc where wanting something "perfect" for addicts sounds like a recipe for failure. So to your point about alcohol -- there are pills that supposedly cause a significant reduction in alcohol in your system. It was discussed on HN recently: https://news.ycombinator.com/item?id=31988338 https://news.ycombinator.com/item?id=31988338
  - water8 4y ago
    No, no in medicine you need to be perfect or you’ll kill people
    - chaps 4y ago
      I'm legitimately unsure if you're joking or not.
      - water8 4y ago
        You can’t play statistics with peoples lives. You can’t put out a drug because statistically it might help some while destroying a few. people don’t have the time or know how to understand the risks and that’s why it is imperative that imperfect treatments be limited to experimental use only
        virgildotcodes 4y ago
droopyEyelids 4y ago
For better or worse, we're entering a new era of human development if parents can choose to 'immunize' their kids to addictive drugs. What a bizarre development. Its even weirder when you imagine these future people would be able to take the drugs without suffering/enjoying the effects. That would make for some odd/dangerous social situations.
- eimrine 4y ago
  As far as I understood the work, this is about taking a vaccine, then taking a drug and no feel of drug effect. And by the way the amount of injected vaccine must be greater than amount of the drug.
  - snovv_crash 4y ago
    The idea is that the two events can be separated by years, though. This means that at the end of rehab the exiting patients can be guaranteed not to relapse for at least a few years.
  - malfist 4y ago
    You're thinking about narcan. It binds with the opiates in your system and pulls them out of your neurotransmitters. This is an actual vaccine, it trains your immune system to respond to the substance. Once that training is done, you don't need any amount of the original vaccine substance to be in your body. Besides, how would that even work if you took the vaccine and a month later used meth? That vaccine isn't in your body anymore.
chrsig 4y ago
I wonder how how this impacts other forms of amphetamines? From the perspective of a person that struggles with ADHD, I'd really hate to think that some overzealous parent immunizes their kid against medications that help them function in the world.
- codyogden 4y ago
  Yeah. This is a great point. I would be absolutely lost in life with ADHD and being without stimulants.
  - to1y 4y ago
    What happens to your tolerance?
    - filoleg 4y ago
      Not the person you are replying to, but if you use it as intended, you don't usually need to worry about it. Once I got prescribed, within the first year, the dosage got adjusted multiple times to get to an adequate stable number (which is 30mg daily for me, half of the FDA recommended max of 60mg). After 7 years of taking that dosage daily (i occasionally skip days once a month or so, or take reduced dosage a couple times a month), I haven't felt the need to increase the dosage at all. The only tolerance I feel I'd acquired is for that initial rush after taking the meds (and that tolerance goes away quickly if i dont take it for a couple of days). But this rush was never a desired effect for someone taking it for its intended purpose, rather than chasing the high. And it still works just as well for the purpose it was prescribed to me for. Note: i skip a day or two a month or decrease dosage not for some intentional planned reason, but on days when i accidentally end up sleeping in too late. Dont want to stay awake for too long and mess up my sleep schedule.
    - gruez 4y ago
      A psychiatrist has written about it. https://lorienpsych.com/2020/10/30/adderall/#8_If_I_keep_taking_Adderall_for_too_long_will_I_develop_tolerance_to_it https://lorienpsych.com/2020/10/30/adderall/#8_If_I_keep_tak...
BurningFrog 4y ago
Can someone summarize by what mechanism the immune system can somehow fight meth addiction? I can't see how those two biological worlds interact.
- Herodotus38 4y ago
  It probably works by the same mechanism that people have used to try and develop cocaine vaccines over the decades. Basically you introduce an antigen to the body so that large amounts of antibodies are created which bind to cocaine and prevent it from being uptaken into the neuroreceptors where it acts. https://en.wikipedia.org/wiki/TA-CD https://en.wikipedia.org/wiki/TA-CD https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/
- StrictDabbler 4y ago
  The vaccine is intended to make you allergic to meth. This is difficult because meth is small and weakly antigenic. The vaccine candidates attach extra groups to the meth to make it seem more like a bioactive compound that the immune system should destroy. (I am describing conjugate vaccines badly) The studies reviewed here suggest that vaccination can produce meth antibodies and reduce blood concentration but it's not clear to me that this would work on a human addict. It seems like the addict would just take in more meth, unless the antibody reaction is supposed to be an unpleasant disincentive. It seems that previous studies on cocaine failed to actually affect behavior so this may well be more like pure research than a practical project.
liampulles 4y ago
There is a great TV series called Traffik (later adapted into a film) which makes the case that drug addiction primarily stemmed from social and not chemical causes... I wonder if that view is infact true. If it is, then I would think that meth users would just switch to another drug if meth were made ineffective. Does anyone knowledgeable know where the evidence seems to point in terms of the root addiction being chemical vs. social (vs ...) based?
- water8 4y ago
  I’ve always found that the opposite of addiction is connection. People turn to drugs to fill a void.
- eurasiantiger 4y ago
  It is a more nuanced issue. Some people get addicted and dependent because they have learned to escape their general life situation by consuming drugs which help them cope with negative emotions. You will find a lot of these people in lower and middle class jobs. Some people get addicted because they have too much free time, too much cash at hand and are generally a person who constantly requires a lot of stimulation and activity. You will find a lot of these people in executive positions. MANY people get dependent because they were in an accident, got prescribed oxycodone or hydrocodone, religiously took their medicine according to the prescribed schedule of two pills every four hours for two weeks, and were then denied a refill and possibly labeled a drug-seeker, leaving them very vulnerable to drug pushers. You will find a lot of these people dead on the street.
  - daniel-cussen 4y ago
    Those doctors violated the 13th amendment. In general the reason doctors determine dosing maxima to be pitifully amount of drugs is because then...the beautiful thing happens...you're addicted to doctors.
- pydry 4y ago
  Probably. Most people who take drugs are just looking for a painkiller - whether that's "social pain", physical pain or both.
water8 4y ago
Vaccine to screw with your motivation system geee what could go wrong?
RobertRoberts 4y ago
Can someone explain the use of the word "vaccine" here? My layman's understanding of medical industry is that a vaccine is only useful against a "virus". Has the word "vaccine" turned into a generic word for "medicine" in many cases? They state "vaccine development strategies" as their motivations, but seem to skip over the idea what the actual definition of a vaccine is, but then allude to it by stating "drug-vaccine conjugation" after already stating (as fact) there is such a thing as "METH vaccine development strategies". Maybe I am just too much an outsider, but the past 20 years I feel like a vaccine can cure more than it could in the past...
- jovial_cavalier 4y ago
  The word has no meaning anymore.
- dylan604 4y ago
  I had the same issue when reading the title. It's like the skincare community's use of the word serum. Just repurpose, say it with authority, everyone will go along
- thehappypm 4y ago
  The word has changed in meaning. It used to be virus-oriented, but that has shifted; after all not all diseases are viral, such as Lyme, which once had a vax. Now it really means a substance that can train the immune system to attack an antigen. Which is much broader but fundamentally the same.
  - collyw 4y ago
    Nah, it's been updated. It doesn't need to attack an antigen, just "produce an immune response". It doesn't matter if that immune response is for a virus that is long extinct, as long as the "vaccine" makes your body produce some antibodies.
- phonypc 4y ago
  It has never been exclusively virus oriented. Foundational work on vaccines was done before viruses were discovered, and many early vaccines were for bacterial pathogens. The definition is now being expanded beyond infectious diseases I suppose.
hahaitsfunny 4y ago

58 points by dynm 4y ago

> In the same study selectivity of MH6 antibodies to bind to AMP, METH, 4-methyl-N-methylcathinone (4-MMC), or methylenedioxy-methamphetamine (MDMA) were evaluated by equilibrium dialysis. I'm glad that 4-MMC meets some studies. I believe this is a next-gen drug with cocaine-like effects and little or no contraindications.

digdugdirk 4y ago
Very interesting. I'd never heard of this before. Where do you find research on chemicals/compounds like this?
water8 4y ago
There’s basically 2 pathways: the dopamine pathway through amphetamines or the acetylcholine pathway via cocaine
- zafka 4y ago
  Can you expound on this a bit? As the other commentor indicated, this is very interesting. Thank you for exposing me to this tidbit!
  - water8 4y ago
    Just look up with the neurotransmitters regulate. The key chemicals in stimulation are dopamine norepinephrine epinephrine and acetylcholine. Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence
    - valec 4y ago
      >Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence this is so oversimplified as to be completely meaningless
- valec 4y ago
  i think you are very mistaken. cocaine and amphetamines both enact their effects primarily by drastically raising dopamine levels in the brain (in particular the striatum in the case of the euphoria they cause). neither of them directly target acetylcholine to any capacity. the main difference between cocaine and amphetamines is that amphetamines are dopamine/norepinephrine(/serotonin depending on the specific amphetamine) releasers, while cocaine is a dopamine/norepinephrine/serotonin reuptake inhibitor. releasers make their way inside the presynaptic neuron either through DAT/NET/SERT or by diffusing directly across the membrane, where they then enter monamine vesicles through VMAT2 and collapse the pH gradient causing monoamines to spill into the cytosol, where it is then transported out of the cell by DAT (and sert and net for serotonin and norepinephrine). it is unclear the exact mechanism that amphetamine causes DAT/NET/SERT reversal. anyways end result is norepinephrine and dopamine spill into the synaptic cleft. cocaine, as a SNDRI, simply blocks DAT/NET/SERT from removing their respective monoamines from the synaptic cleft/transporting them back into the pre-synaptic neuron.

digdugdirk 4y ago

This is absolutely fascinating, but I'd say the title isn't fully accurate. These vaccines seem to be entirely neutralizing methamphetamine in all it's functions. Using alcohol as a metaphor, it'd be like you could drink as much as could fit in your stomach and just never get drunk. So while yes, I can imagine it'd be useful in preventing addiction, does it really mean the same if you're physically/mentally incapable of feeling the effects of the substance to begin with?

chaps 4y ago
Not having read the article either, it's probably fair to say that it's not expected to be a perfect vaccine for meth. Perfect being the enemy of good, etc where wanting something "perfect" for addicts sounds like a recipe for failure. So to your point about alcohol -- there are pills that supposedly cause a significant reduction in alcohol in your system. It was discussed on HN recently: https://news.ycombinator.com/item?id=31988338 https://news.ycombinator.com/item?id=31988338
- water8 4y ago
  No, no in medicine you need to be perfect or you’ll kill people
  - chaps 4y ago
    I'm legitimately unsure if you're joking or not.
    - water8 4y ago
      You can’t play statistics with peoples lives. You can’t put out a drug because statistically it might help some while destroying a few. people don’t have the time or know how to understand the risks and that’s why it is imperative that imperfect treatments be limited to experimental use only
      - virgildotcodes 4y ago

droopyEyelids 4y ago

For better or worse, we're entering a new era of human development if parents can choose to 'immunize' their kids to addictive drugs. What a bizarre development. Its even weirder when you imagine these future people would be able to take the drugs without suffering/enjoying the effects. That would make for some odd/dangerous social situations.

eimrine 4y ago
As far as I understood the work, this is about taking a vaccine, then taking a drug and no feel of drug effect. And by the way the amount of injected vaccine must be greater than amount of the drug.
- snovv_crash 4y ago
  The idea is that the two events can be separated by years, though. This means that at the end of rehab the exiting patients can be guaranteed not to relapse for at least a few years.
- malfist 4y ago
  You're thinking about narcan. It binds with the opiates in your system and pulls them out of your neurotransmitters. This is an actual vaccine, it trains your immune system to respond to the substance. Once that training is done, you don't need any amount of the original vaccine substance to be in your body. Besides, how would that even work if you took the vaccine and a month later used meth? That vaccine isn't in your body anymore.

chrsig 4y ago

I wonder how how this impacts other forms of amphetamines? From the perspective of a person that struggles with ADHD, I'd really hate to think that some overzealous parent immunizes their kid against medications that help them function in the world.

codyogden 4y ago
Yeah. This is a great point. I would be absolutely lost in life with ADHD and being without stimulants.
- to1y 4y ago
  What happens to your tolerance?
  - filoleg 4y ago
    Not the person you are replying to, but if you use it as intended, you don't usually need to worry about it. Once I got prescribed, within the first year, the dosage got adjusted multiple times to get to an adequate stable number (which is 30mg daily for me, half of the FDA recommended max of 60mg). After 7 years of taking that dosage daily (i occasionally skip days once a month or so, or take reduced dosage a couple times a month), I haven't felt the need to increase the dosage at all. The only tolerance I feel I'd acquired is for that initial rush after taking the meds (and that tolerance goes away quickly if i dont take it for a couple of days). But this rush was never a desired effect for someone taking it for its intended purpose, rather than chasing the high. And it still works just as well for the purpose it was prescribed to me for. Note: i skip a day or two a month or decrease dosage not for some intentional planned reason, but on days when i accidentally end up sleeping in too late. Dont want to stay awake for too long and mess up my sleep schedule.
  - gruez 4y ago
    A psychiatrist has written about it. https://lorienpsych.com/2020/10/30/adderall/#8_If_I_keep_taking_Adderall_for_too_long_will_I_develop_tolerance_to_it https://lorienpsych.com/2020/10/30/adderall/#8_If_I_keep_tak...

BurningFrog 4y ago

Can someone summarize by what mechanism the immune system can somehow fight meth addiction? I can't see how those two biological worlds interact.

Herodotus38 4y ago
It probably works by the same mechanism that people have used to try and develop cocaine vaccines over the decades. Basically you introduce an antigen to the body so that large amounts of antibodies are created which bind to cocaine and prevent it from being uptaken into the neuroreceptors where it acts. https://en.wikipedia.org/wiki/TA-CD https://en.wikipedia.org/wiki/TA-CD https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/
StrictDabbler 4y ago
The vaccine is intended to make you allergic to meth. This is difficult because meth is small and weakly antigenic. The vaccine candidates attach extra groups to the meth to make it seem more like a bioactive compound that the immune system should destroy. (I am describing conjugate vaccines badly) The studies reviewed here suggest that vaccination can produce meth antibodies and reduce blood concentration but it's not clear to me that this would work on a human addict. It seems like the addict would just take in more meth, unless the antibody reaction is supposed to be an unpleasant disincentive. It seems that previous studies on cocaine failed to actually affect behavior so this may well be more like pure research than a practical project.

liampulles 4y ago

There is a great TV series called Traffik (later adapted into a film) which makes the case that drug addiction primarily stemmed from social and not chemical causes... I wonder if that view is infact true. If it is, then I would think that meth users would just switch to another drug if meth were made ineffective. Does anyone knowledgeable know where the evidence seems to point in terms of the root addiction being chemical vs. social (vs ...) based?

water8 4y ago
I’ve always found that the opposite of addiction is connection. People turn to drugs to fill a void.
eurasiantiger 4y ago
It is a more nuanced issue. Some people get addicted and dependent because they have learned to escape their general life situation by consuming drugs which help them cope with negative emotions. You will find a lot of these people in lower and middle class jobs. Some people get addicted because they have too much free time, too much cash at hand and are generally a person who constantly requires a lot of stimulation and activity. You will find a lot of these people in executive positions. MANY people get dependent because they were in an accident, got prescribed oxycodone or hydrocodone, religiously took their medicine according to the prescribed schedule of two pills every four hours for two weeks, and were then denied a refill and possibly labeled a drug-seeker, leaving them very vulnerable to drug pushers. You will find a lot of these people dead on the street.
- daniel-cussen 4y ago
  Those doctors violated the 13th amendment. In general the reason doctors determine dosing maxima to be pitifully amount of drugs is because then...the beautiful thing happens...you're addicted to doctors.
pydry 4y ago
Probably. Most people who take drugs are just looking for a painkiller - whether that's "social pain", physical pain or both.

water8 4y ago

Vaccine to screw with your motivation system geee what could go wrong?

RobertRoberts 4y ago

Can someone explain the use of the word "vaccine" here? My layman's understanding of medical industry is that a vaccine is only useful against a "virus". Has the word "vaccine" turned into a generic word for "medicine" in many cases? They state "vaccine development strategies" as their motivations, but seem to skip over the idea what the actual definition of a vaccine is, but then allude to it by stating "drug-vaccine conjugation" after already stating (as fact) there is such a thing as "METH vaccine development strategies". Maybe I am just too much an outsider, but the past 20 years I feel like a vaccine can cure more than it could in the past...

jovial_cavalier 4y ago
The word has no meaning anymore.
dylan604 4y ago
I had the same issue when reading the title. It's like the skincare community's use of the word serum. Just repurpose, say it with authority, everyone will go along
thehappypm 4y ago
The word has changed in meaning. It used to be virus-oriented, but that has shifted; after all not all diseases are viral, such as Lyme, which once had a vax. Now it really means a substance that can train the immune system to attack an antigen. Which is much broader but fundamentally the same.
- collyw 4y ago
  Nah, it's been updated. It doesn't need to attack an antigen, just "produce an immune response". It doesn't matter if that immune response is for a virus that is long extinct, as long as the "vaccine" makes your body produce some antibodies.
phonypc 4y ago
It has never been exclusively virus oriented. Foundational work on vaccines was done before viruses were discovered, and many early vaccines were for bacterial pathogens. The definition is now being expanded beyond infectious diseases I suppose.

hahaitsfunny 4y ago