What the hell are some of you saying, drugs don't just magically travel to the brain alone and hole up there, they are diffused throughout the body. Of course it makes a difference.
It's just that the difference, with many drugs, is typically not significant enough for anyone to bother thinking about it. Weight calibrated dosages like mg/kg type measurements are used frequently in scientific literature and studies, specifically, when controlling as many variables as possible is important to get the most accurate result. However for convenience of the logistics of manufacturing and prescribing it's currently far easier just to settle on agreed upon dosages and increments, usually round numbers, multiples of 10, stuff like that, such as vyvanse / lisdexamphetamine which I believe has manufactured doses from 20mg to 70mg in 10mg increments, rather than calculating the exact optimal dosage to sub-milligram accuracy and manufacturing prescriptions for specific patients with specific doses... it would just be chaos. Equally, people are affected by drugs differently, to a greater or lesser extent, depending on other factors unrelated to their weight, so controlling for their weight would still not lead to a completely uniform response if everyone took drugs according to their bodyweight.
Considering that even the vast resources available to pharmaceutical industries don't do this - even if there was decided to be some advantage - consider the issues this would cause with clandestinely manufactured drugs and friends of different weight sharing a bag of cocaine or something, do you really think anyone is going to agree that the fat one should get a larger proportion of the total quantity, and it should be calculated by the relative sizes of everyone involved? No one is going to do this.
That said - there ARE many drugs where (more responsible) drug users DO take bodyweight into account. I'm sure I've seen it and heard it discussed pretty often that, for example, a relatively slight woman might take like half a pill compared to some hench or maybe just slightly obese dude who needs to take at least 2.
And what about alcohol? You're saying you've never heard of anyone moderating their alcohol intake based somewhat on their weight? It might not be explicitly discussed that often but that's just because most people realise that it is obvious. Someone who weighs 50kg is gonna get a lot drunker on the same amount of alcohol compared to someone who weighs 200kg.
Psychedelics are a wildcard because they are such profoundly altering substances that a lot of the time people don't even know how fucked up they're getting and frustratingly assume they have a lot more self awareness about their own state of mind than they actually do, but the same applies to a 300mcg of acid in the example I just gave with the 50kg vs the 200kg person. It's just that in this case they might both be tripping hard enough that their relative perceptions of their own alteredness compared to their companion is just not something they are capable of considering.