[Alex3917]

It's one thing to use psychoactive drugs on occasion if you're eating healthfully, exercising, getting enough sleep, in good mental health, and using only one drug at a time. I can't even imagine what mixing weed and amphetamines on a daily basis would do to a person. That sounds like a terrible, terrible idea.

As soon as drug use becomes banal you are really asking for trouble.

[eru]

I tend to agree. On the other hand, people seem quite happy taking caffeine and alcohol and daily or near-daily basis. Even mixing the two. So I guess your statement doesn't hold in general?

[Alex3917]

First, you can't really judge a person's happiness just by looking at them.

Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume. Take dopamine for example. If you take a drug that increases the amount of dopamine in your brain, then your brain will decrease its density of dopamine receptors to compensate. If you take a drug that decreases the amount of dopamine in your brain, then the density of your dopamine receptors will increase. If you take a drug that decreases the uptake ability of your dopamine receptors, the amount of dopamine your brain produces will increase. And if you increase the ability of your receptors to bind to dopamine, the amount of dopamine in your brain will decrease. The production/reception system for every psychoactive drug works the same way.

Most people who drink coffee or alcohol on a daily basis are only staving off the low level depression caused by using the substance. (Because if you take a drug that increases the amount of the a neurotransmitter, then your receptor density will for that neurotransmitter will decease. Then once you stop taking that drug then you get all sorts of problems because suddenly there isn't enough of that neurotransmitter in your brain because of your low level of receptors.)

Now I'm not trying to suggest drugs are bad. Just the opposite; we're literally made out of drugs. Everything we do from the moment we get out of bed until we go to sleep is designed to get us high in some way or another. It's literally how we survive and reproduce, and because we're essentially the latest iteration in a 500 million year old line of psychopathic paint huffers our brains are extraordinarily well evolved to prevent us from fucking with them.

The only reason why big pharma is even allowed to release their drugs is because the FDA only makes them show they are safe and effective for six weeks. Virtually every longterm study on every pharma drug shows that you are worse off in the long run than if you'd never taken it at all, but the government and pharma industry go to extraordinary lengths to hide that information from both doctors and consumers.

No matter what you do, in the long run you can't win. You can't even break even. And the worst part of the low level depression induced by something like caffeine or alcohol is that you can't even notice it. Gradually colors will be less bright, jokes will be less funny, emotions will be duller, etc. But you'll never even realize it because it's so gradual and subtle when you're just using daily at these low levels.

Especially with alcohol, because not only do you have the normal receptor adaption, but the alcohol itself also causes the bacteria in your gut to produce inflammatory compounds. If you Google for both alcohol + inflammation, and also cytokine theory of depression, it should be pretty obvious why even small amounts of daily alcohol are really bad news for your mental health. (Although good for your heart and a few other things, so it's a trade off as usual.)

[eru]

> Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume.

I don't know, if that's true in general. I know that I can seriously harm myself using lots of stuff --- so why shouldn't the other way be possible as well? (I don't claim that anybody knows how to achieve the positive outcome.)

[carbocation]

I think Alex3917 is right on the money here. Often, the way that you harm yourself is by depriving your body of the drug you were previously consuming.

Theoretically, what you propose could be possible, but would probably involve multidrug therapy with the goal of inhibiting the regulatory pathways that would counteract the drug of choice.

[eavc]

A lot of strong claims here. Can you provide solid sources?

I have a hard time believing that psychiatrists and psychologists would endorse psychotropic drugs because of some big pharma conspiracy.

If you're right, I'd like to know. But if claims like, "every longterm study on every pharma drug shows that you are worse off in the long run," are so sweeping as to seem spurious.

[Alex3917]

Anatomy of an Epidemic by Robert Whitaker. Also check out this blog post of his that summarizes the largest longterm studies of the mainstay psych drugs:

http://www.madinamerica.com/madinamerica.com/Home/AB86250A-A...

You definitely have to read the book though, it's incredibly well researched.

[eavc]

Thanks for the reply.

[Daniel_Newby]

> Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume.

Not true; this is a common pop-sci myth. Nearly all neurological signal processors have numerous types of inputs and outputs. While it is true that the body usually alters drug sensitivity so as to counteract the drug effect, it simultaneously alters many other signal senders and receivers. (You can read about protein kinases and nuclear receptors, which are famously broad spectrum, to learn more about how complicated things are.)

> If you take a drug that increases the amount of dopamine in your brain, then your brain will decrease its density of dopamine receptors to compensate.

Which, of course, does not mean that the drug effect is magically cancelled out, but rather that the cell becomes less sensitive to sudden bursts of dopamine from its neighbors. The drug might also affect not simply the magnitude of receptor sensitivity, but the rate at which the receptor desensitizes during continued stimulation, as well as the firing pattern of the neuron.

Even the receptors themselves are complicated. Most neurotransmitters are received by a family of several distinct receptor types: stimulating one type may make any imaginable change on the other types. Many receptors are made of several interchangeable subunits: the levels of the subunits can change independently, tuning complex patterns of activity rather than simply compensating for the drug. Many receptors are actually receptor complexes that receive several neurotransmitters at the same time: understanding these is presently a scientific tar pit. (IIRC there are several important dopamine-serotonin receptor complexes. The NMDA receptor complex is famously sensitive to a slew of things.)

> And if you increase the ability of your receptors to bind to dopamine, the amount of dopamine in your brain will decrease.

You might find it enlightening to study the difference between postsynaptic receptors and presynaptic autoreceptors.

> Virtually every longterm study on every pharma drug shows that you are worse off in the long run than if you'd never taken it at all, ...

This is not even remotely true. Many drugs are conclusively proven to be very effective (assuming proper patient selection). Popular stand-bys, like those for inflammation and blood pressure, are popular precisely because they Just Work. For as long as you keep taking them.

The central nervous system drugs work too, although the statistics are less impressive. The main problem is that the available drugs are outnumbered by the brain's possible failure modes, so the efficacy rate tends to lag. A related problem is that the drugs tend to be broad spectrum, so it can be tough to dial up to an effective dose without running into unacceptable side effects.

[Alex3917]

"This is not even remotely true."

I meant psychoactive drugs. I realize that NSAIDs and other drugs stay effective.

"The central nervous system drugs work too, although the statistics are less impressive."

If by work, you mean they have some effect, then yes. However, all the research seems to show that you're worse off in the long term than if you'd never taken the drug at all:

http://www.madinamerica.com/madinamerica.com/Home/AB86250A-A...

(And again, you'd really have to read the book to understand the research he's citing and its implications, but the blog post is at least a quick glance at the results of some of the biggest longterm efficacy studies.)