Vaccine development against methamphetamine drug addiction [pdf] (2020) | Hacker News Reader

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

dynomight.net

58 pointsdynm54 comments

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?

I’ve always found that the opposite of addiction is connection. People turn to drugs to fill a void.

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.

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.

Probably. Most people who take drugs are just looking for a painkiller - whether that's "social pain", physical pain or both.

Wasn't this a famous study on rats called Rat Park?

https://en.wikipedia.org/wiki/Rat_Park

The book High Price came to similar conclusions.

Here is a good article about chemical vs. social causes of addiction. https://aeon.co/essays/theres-no-neural-fix-for-reversing-th...

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?

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

No, no in medicine you need to be perfect or you’ll kill people

I'm legitimately unsure if you're joking or not.

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

Is it your understanding that western medicine currently operates on this model of only allowing perfect drugs and treatments to exist?

What of all the side effects, many life-threatening, of drugs and treatments available on the market?

When you take antibiotics and they don’t work, they don’t destroy your entire motivational system for the rest your life. They don’t mentally castrate you

Penicillin (along with every other antibiotic) is a deeply imperfect treatment in many ways (sub-100% effectiveness, deadly allergies, other side effects). It's also one of the most potent life-saving inventions in history. If the relevant regulatory bodies were run this way, we'd have almost none of modern medicine.

no penicillin doesn’t kill people. It’s the allergic reaction that kills people. A person who does not have an allergy to penicillin yet has never taken penicillin has no fear of dying from it.

"It's not the fall that kills you, it's the landing"

Don't many/most drugs have known side effects and we literally are "playing statistics" with the tradeoff between the good the drug does on one hand and rare, sometimes fatal side effects on the other hand?

When you take antibiotics, are you playing statistics with your life no. The antibiotics themselves will not kill you. you guys are substituting strawman side effects for mental castration should it go wrong?

Quick Google: "Every year, there are more than 140,000 emergency department visits for reactions to antibiotics. Almost four out of five emergency department visits for antibiotic-related side effects are due to an allergic reaction. These reactions can range from mild rashes and itching to serious blistering skin reactions, swelling of the face and throat, and breathing problems."

"C. difficile is a type of bacteria (germ) that causes diarrhea linked to at least 14,000 American deaths each year. When you take antibiotics, good bacteria that protect against infection are destroyed for several months. During this time, you can get sick from C. difficile. The bacteria can be picked up from contaminated surfaces or spread from the healthcare environment. People, especially older adults, are most at risk who take antibiotics and also get medical care."

-https://my.clevelandclinic.org/health/drugs/16386-antibiotic...

Meanwhile 150 people anually die of Tylenol: https://www.theatlantic.com/national/archive/2013/09/150-ame...

Please reread my post. My use of "perfect" was in terms of the effects -- as in, a 100% reduction of methamphetamine's effects, such that it'd be reasonable to call it a "perfect" drug. Not in terms of safety, nor rolling die for people's lives.

Though I suppose you'd be "playing statistics on with people's lives" on a drug that has a 75% effect as opposed to a 100% (ie, perfect) effect. Since the drug isn't as effective as expected, treatment as a whole isn't as effective, so deaths will happen. A statistically better outcome overall, but still a "statistical game" as you call it.

Tell me one drug that kills people and people are like “ehhh it happens every now and then” that’s FDA approved

No need for this hostile, bad faith sort of argumentation. Let me restate your question:

"Tell me one drug that has a known risk of death that, in-line with the article, is used to treat addiction that's approved by the FDA."

Methadone.

Opioids

touche

Can someone summarize by what mechanism the immune system can somehow fight meth addiction?

I can't see how those two biological worlds interact.

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://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/

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.

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

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.

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.

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.

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.

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.

Yeah. This is a great point. I would be absolutely lost in life with ADHD and being without stimulants.

What happens to your tolerance?

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.

A psychiatrist has written about it.

https://lorienpsych.com/2020/10/30/adderall/#8_If_I_keep_tak...

Or immunze them against the naturally occuring nuerotransmitters!

I think this would probably be limited to being used as a treatment in people with drug use disorders, and maybe people at risk for it. Widely deploying a vaccine against any recreational drugs would be ethically suspect and economically senseless. Most people never even try meth, and some people need meth or more commonly amphetamine to treat things like ADHD, narcolepsy and other sleep disorders(non-24), as you point out.

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...

The word has no meaning anymore.

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

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.

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.

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.

> 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.

Very interesting. I'd never heard of this before. Where do you find research on chemicals/compounds like this?

There’s basically 2 pathways: the dopamine pathway through amphetamines or the acetylcholine pathway via cocaine

Can you expound on this a bit? As the other commentor indicated, this is very interesting. Thank you for exposing me to this tidbit!

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

>Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence

this is so oversimplified as to be completely meaningless

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.

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