The 3-HO-PCP opioid activity isn’t as well established empirically as many people assume. From what I can recall, it actually is not confirmed if 3-HO-PCP is an agonist or antagonist on opioid receptors, there is just some research that suggests that it binds to opioid receptors more than other PCP analogues which may be enough to be potentially clinically significant. However, there isn’t enough research to conclusively state just how much this opioid receptor affinity contributes to the effects (it may not be relevant at all, but maybe it is, 3-ho-pcp does not seem to produce physical withdrawals, histamine release, or significant respiratory depression typical of opioids) and whether or not the activity is agonistic or antagonistic.
I have never heard of O-PCE being linked to opioid activity. I would be interested in learning more about that though should the connection exist. I have done both 3-HO-PCP and O-PCE as well as a number of opioids and i did not notice any significant signs of opioid effects that could not be explained away as confirmation bias and psychological priming of effects (i.e., “this dissociative feels warmer than others, i heard it id more active on opioid receptors than other dissociatives so that is likely the cause”, this is flawed in that your expectancy of opioid like effects can lead to you noticing effects that remind you of opioids more regardless of whether those effects would be noticed or even felt if you had not known about that connection).
There is some interesting structural connections between NMDA antagonists and opioid agonists though. Like methadone binds fairly strongly at NMDA receptors, and dextromethorphan, which does not display significant opioid activity, has a stereoisomer, levomethorphan, which acts primarily as an opioid and not a dissociative. Some other dissociatives such as those in the diarethylamine class are also closely structurally related to opioid agonists. NMDA antagonism also seems to potentiate opioid effects as well as lower opioid tolerance to some extent.
Overall though, most drugs taken for their dissociative effects do not seem to display enough opioid effects to be worried about. It is just good to be a bit extra cautious about combining an opioid with a dissociative like 3-HO-PCP and to avoid overusing it since maybe there could be some more unforseen dangerous/uncomfortable side effects and interactions present, but this extra caution should be exercised with all novel psychoactive substances since they largely are all poorly understood at the time they hit the markets. I wouldn’t consider 3-HO-PCP or o-PCE uniquely dangerous for the potential of their opioid activity but moreso for their tendency to produce mania and their high potency relative to other dissociatives. They’re still pretty awesome and worth doing if you’re careful, knowledgeable about harm reduction techniques and proper dosing, and can maintain self control with dissociatives.
