> The human has opioid[1] and cannabinoid[2] receptors.

Yes, much of the reason drugs even have an effect is because receptors for them already exist in the body. That's also the reason why they can be so dangerous; normally endogenous signals are regulated by the body, but externally administered substances are often not. Physical dependence is the body's self-regulation trying to compensate for the presence of external substances that it can't downregulate; a sudden lack of the substance may cause withdrawal symptoms as the body takes time to adjust back to normal. These withdrawal symptoms can be fatal (such as in the case of benzodiazepine withdrawal, or indeed opioid withdrawal). Also, external substances can trigger receptors or permutations of receptors that don't naturally occur as frequently, as strongly, or at all, resulting in undesirable or even potentially fatal effects. Small changes even to substances that are normally unproblematic can nonetheless change their effects significantly enough to cause a problem, as illustrated by the submission.

Absolutely that’s why substance abuse is very dangerous. I would even append permanent destruction of receptors to the list.

Oh, right; I forgot that's also a thing. I try to advocate for the reduction of SSRI use for that reason. It's a known side effect that they can permanently destroy or desensitize serotonin receptors when used for periods that exceed around a year or two (this varies by individual). I wouldn't even go that far, personally, but some people's doctors do not know about that effect of SSRIs and keep prescribing them for five years or more, in which case I usually take it upon myself to educate the person directly if their doctor does not know. I don't tell them to stop taking it immediately or anything, just that they might want to watch how long they stay on it.

(Side note: I don't know what's so special about prescribers when most of them don't even fully understand the substances they're prescribing. It's possible that fully educating myself about what I'm doing might actually have been better than having blindly accepted a prescription for it, at least in some hypothetical future where this stuff can even be prescribed at all. I guess some people associate illegality automatically with immorality/irresponsibility.)

Leeches have cannabinoid receptors, most animals have them; seem to be pretty fundamental.