T Nation

Non-Responders : What's the mechanism at work, and can it be overcome?


It seems like some of us are just non-responders. And it feels pretty universal: HOT-ROX never made me feel jittery (or anything), I've never felt a "caffeine high" or jitters, I rarely (less than a drink a week) drink but still have a very high-tolerance, back in college I tried a couple recreational drugs: non of them did anything for me (a couple made me sleepy), I've been taking sudafed for the past few days to unclog me: again nothing.

Hell, even when I broke my collar bone and they shot me up with morphine (I kept asking for more hoping to feel something and "enjoy the ambulance ride"): nothing. I don't even mess with OTC pain killers for anything, because they don't do anything.

The ONLY thing that has ever consistently altered my mood or performance has been long-term diet and exercise habits.

What's the deal? I know I'm not the only non-responder on these boards.

Does anyone have a good grasp of the mechanism at work here?

It seems almost universal: nothing works. Is there an upside here?


Maybe you're better at metabolising it. Maybe you don't have as many receptors. Maybe you smoked oregano.

You sometimes need time to realize that there's this new cool thing in the body that the cells haven't seen before, so they need to start making receptors n shit, which takes a day or more to work.

And maybe you're just a freak :wink:


there is no one mechanism of action at work for all the different things you listed. for example caffeine works on adenosine receptors. A2 receptors make you sleep, A1 receptors when turned on activates A2, leading to sleep also, so caffeine can bind to A2 receptor and shut it off, making you awake. Or caffeine can bind to A1 receptor, shutting it off so that it cant turn on A2 receptors.

morphine acts on opiod receptors, particullary the mu receptor, and inhibits pain in the form of an action potential to traavel from nociceptors to the brain.

It's way more involved then that but you get the point, different receptors and different mechanisms of action are involved for each drug in your body, so theres really no 1 mechanism of action that can be said to be responsible


So is it possible to "short out" multiple receptors, through exposure to something as a child? Or diet? Something like that?


Really don't have anything to add but...the first 5 times i smoked weed i didn't get high. The sixth time however..bam, i was baked (Don't smoke anymore). Not saying you should try morphine multiple times but it's something to add to the subject.


I had a similar response to alcohol. For a couple weeks I would drink 6-8 shots of vodka (I was around 115lbs at the time... skinny fat... untrained) and I wouldn't feel anything. After about a month... I drank one of those alcohol/energy drink combos... a 'Tilt'... I got so drunk off of just one 16oz drink it was ridiculous. Then ever since then everything makes me drunk to hell.

Not such a bad thing though. :slightly_smiling: I only need 1 or 2 and I'm good.