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Comment by throwaway835174 | Hacker News Reader

> Nonetheless, it’s widely recognized that individuals who occasionally use ketamine find they need significantly higher doses than when they first started, even after prolonged periods of abstinence.

Sorry for the slight divergence from the focus on ketamine, but more generally, does anyone know if this applies to other medications that alter the brain's function?

I've noticed the same phenomenon with the adderall I am prescribed for ADHD, and despite the tolerance buildup and the offer from my psychiatrist, I refuse to bump up the dose further due to fears of long-term changes in the brain. Honestly, I'm considering ditching it altogether after about a decade of prescription because I become more paranoid over time about unknown, long-term effects. Posts like this about ketamine don't help my suspicions.

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>Sorry for the slight divergence from the focus on ketamine, but more generally, does anyone know if this applies to other medications that alter the brain's function?

Tolerance is a phemomenon where after using a drug regularly for enough time, you will eventually need higher doses to achieve the same effect. A tolerance effect exists for many classes of medication, but in this case there is something specific to Ketamine.

With Ketamine, it can (reportedly) be much harder to reverse this built-up tolerance. That's what they mean by "even after prolonged periods of abstinence". Heavy abusers of Ketamine report having stopped for several years, and finding that the tolerance comes right back the first time they use it again.

With stimulants, this tolerance goes down after a period of abstinence (e.g. switching to a n̶o̶n̶-̶s̶t̶i̶m̶u̶l̶a̶n̶t non-amphetamine ADHD medication like Metylphenidate for a few weeks is known to lower tolerance to other ADHD drugs).

I would generally not worry about tolerance to stimulants at prescribed doses. You should try to avoid taking medication you don't need, but if you need the stimulants to function, the cost/benefit of stimulant medication for ADHD is highly favorable. Even if there is a slow tolerance effect, it can be reversed.

Taking stimulants for ADHD is not dangerous like taking Ketamine for partying is dangerous. Stimulants have the highest efficacy of any known drug in psychiatry. The medical interventions with the lowest NNT are things like insulin for diabetus, or not very far down, stimulants for ADHD. It's more than fine.

Methylphenidate is a stimulant medication [0]. Maybe you meant something else, like atomoxetine?

[0] https://en.wikipedia.org/wiki/Methylphenidate?wprov=sfti1#

You're right, of course. There is a difference between methylphenidate and other amphetamine-class stimulants for ADHD, but I didn't know what to call it.

I should have said it's not a direct agonist. Instead of directly causing dopamine release, it acts as an allosteric modulator on DAT to affect reuptake.

I had a study in mind that found switching to MPH was effective at lowering the equivalent dose (the tolerance did not carry over), but my Googling is failing me right now. Appreciate the correction.

Thank you for the clarification. I didn’t know about the differing mechanism, and you’ve sent me off on a research rabbit hole. Always a happy result of an HN thread. I appreciate your follow up!

I looked into this a while back, and found some reviews from some branch of the Canadian health authorities, that said that euphoric effect of methylphenidate fades more with tolerance than the therapeutic effect.

So you will still be getting some adhd related benefits from it, even if you're not feeling that little rush that you felt when you first started taking it.

Like the other commentator, I do like to skip some days occasionally (mostly on weekends). I usually see on day 1 that I was most definitely getting some benefit from it the day before, even when it didn't feel like it.

In general you should listen to your doctor for these things; if they say that an increase in dosage is recommended, listen to them. Although I am not very sure about the word "offer". What do you mean "offer" from your psychiatrist?

If you are worried about long term effects of stimulant medication (which is a very valid worry), you may want to ask your doctor for an intermittent schedule. Sadly, as we know, many of us need the medication to function reasonably in daily life. However, if you are building tolerance to the medication, it is probably worth it.

I think the Sackler family destroyed most people's trust regarding listening to their doctor about their prescriptions. You can't really come back from that...

Doctors themselves are at least partially, if not mostly, responsible for that lack of trust. The Sacklers might have been pushing on the doctors but the doctors were the ones writing the prescriptions and ultimately responsible for the health of their patients.

The Sacklers gave docs the wrong guidance on how habit forming it is. A doctor is busy and needs to be able to trust the experts- those who make the drug.

^ horrible advice here. In general you should take agency of your oqn health. Educate yourself and make informed decisions instead of relying on the advice of a doctor who may or may not be confident and may or may not give any kind of a shit about you.

In my case, doctors recommended that I "just keep taking xanax until I feel better" which ended in a 24+ hour blackout. So yeah, dont necessarily just listen to your doctor

No, it is not horrible advice, it is good advice. If you have no confidence in your doctor, choose a better doctor. If you cannot trust any doctor, fair enough; do whatever you like.

Well we will agree to disagree ut far too many times ive seenpeople prescribed contraindicated meds because the doctor wasnt paying attention and the patient wasnt aware enough of their own healthcare to even list the pills they were taking daily.

Certain doctors will keep ramping up your adderall script until your on 200mg a day. No one needs that shit. Its horrible for you. So to just say "listen to your doctor, they know best!" As a general statement is asinine

As someone who has been medicated for mental illness for several decades and went through this dance countless times, I can assure you that this is the worst advice to give somebody.

Psychiatrists aren't evil, of course, but they're not going to tell you (or are always aware) of all the minutia of long term effects treatment can have.

It is up to the patient to decide if the risk is worth it to them.

The adage of trust but verify applies here as well. You should start with the assumption that they know more than you, trust, but they can still make mistakes or have gaps in knowledge that could be very impactful to you, so verify.

>Psychiatrists aren't evil, of course, but they're not going to tell you (or are always aware) of all the minutia of long term effects treatment can have.

This, I help a family member with their medication and occasionally they'll have side effects that are obviously a direct result of one or more of the medications and the doctors will often ignore that until it's brought up over multiple appointments, even then they often want to add an additional medication to the 6-7 they already prescribe instead of working to lower dosages of the ones causing issues.

My brother was on ADHD meds most of his early life and started having heart issues that doctors seemed to have no ability to figure out, despite it being one of the listed side effects of his medication.

I have a friend who is pretty convinced that his wife won't live much longer because the dose of her medications is one that is known to cause liver and kidney damage long term.

You also regularly see psych patients gain tons of weight in a short amount of time from some of the medications like Seroquel, but the typical doctor response is "better to be fat than dead" while totally ignoring the long term health issues, including things like depression that the medicine was original prescribed to treat, stemming from ongoing unregulated weight gain.

People really need to advocate for themselves and often aren't in a place to do so.

When it comes to things like this, as cliche as it may sound, your best bet is to probably bring up those fears with your psychiatrist to evaluate the pros/cons with them.

Like most things, there is most likely a tradeoff - but your doctor also most likely prescribed the dosages based on the pros outweighing the cons, but only you can bring up how you feel about specific cons to the doctor.

If you give it a break the adderall tolerance goes away. It’s good to regularly skip days. Ketamine abuse is particularly dangerous compared to so many things, particularly amphetamines taken at therapeutic doses which is safe to the level of no particularly clear long term effects.

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