My only concern about the speculative pharmacology that appears on bluelight is that it can distort the way people report qualitative effects. For example, instead of simply saying that x psychedelic is stimulating they might say "x psychedelic acts like a dopamine reuptake inhibitor" or instead of saying they feel euphoria they might say "seems to act as a serotonin/dopamine releaser" or "seems to act as a µ-agonist." Using speculated drug-receptor interactions as a simplistic shorthand for qualitative effects is often a misleading exercise. It doesn't do justice to the complexity of one's subjective experience or the objective methods of pharmacology, in essence it can be the worst of both worlds. This is not to say people shouldn't speculate and I am certainly guilty of it myself, but I think it's not the most useful way to conceptualize a drug effect in the absence of binding data.
If you read PIHKAL and TIHKAL you will see that Shulgin did very little speculation about pharmacodynamics, instead he made a point of rigorously observing his own response to a compound: His heart rate, appetite, erectile function, pupil dilation, etc.
Because of this Shulgin's research is timeless, it will never be dated or obsolete. If Shulgin had been using the prevalent in vitro methods of his day (such as inhibition of twitch response in isolated strips of Guinea-pig ileum) his data would be borderline worthless––and if he had been using the (now obsolete) terminology from those methods as shorthand for his own experience it would have been even worse. We cannot accurately identify pharmacodynamic interactions in our own brain, if things were that easy then there would be no need for electrophysiology or autoradiography or really most of pharmacology as a science.
crOOk said:
When I said "Hamilton" isn't a valid source I was simply saying this because your work is released on either your blog or vice articles neither of which are adequately peer-reviewed to serve as valid sources. I will stick to this statement and hope you will agree to some degree. An article like the one you linked (which I have yet to read entirely) is without a doubt a valid source.
Peer-review is notoriously flawed and subject to reviewer bias, anyone who has spent a good chunk of their life reading (or contributing to) the scientific literature will have no trouble pointing out errors printed in high-impact journals. As a whole scientific literature is certainly a better source for information on drugs than the news media, but each have their strengths and many of the weaknesses in both have a similar origin (a desire to impress readers and reviewers, a desire to publish frequently, a desire to align oneself with social mores, simple human error). It's ironic that you are complaining so much about the shortcomings of non-academic writing and yet seem unwilling to actually read the scholarly journals you treat as the only source of valid information. The answer to all your questions about the pharmacodynamics of MXE have existed in the ACMD literature since 2012, when they were reported by Brain Roth of NIMH's Psychoactive Drug Screening Program, his results were further reported in PLoS ONE: to reiterate MXE does not have MOR affinity below 10,000 nM.
Science should be treated as a method not an abstract symbol of Truth or a talisman to ward off anything that doesn't appear on pubmed. There are things published in Vice that have definite scientific importance but would not be printed in scientific journals (cf. the article "Sea DMT"). Now I write for Harper's and the New York Times Magazine, my next article will contain a broth microdilution assay to determine the MIC of amfonelic acid against E. coli, are the results invalid because they will be published in a literary magazine? The next peer-reviewed article I contributed to, which is currently in press, details the analytical characterization of diphenidine but all the authors learned about diphenidine from non-scholarly sources, does that invalidate our findings? Useful information is everywhere if you have the critical ability to recognize it.
crOOk said:
I did however stumble across the termal decomposition results you present. When I first watched the video I was wondering about the relevance of this product since it formed under conditions that are nothing like smoking. I would've liked to at least hear some details about the results and the conditions other than "oil bath 250°C", e.g. how long was the substance exposed to the oil bath and how much of the efavirenz was converted during that time. Repeating the microwave trial I remember from earlier in the video and analyzing the product would seem to be of more interest, since simulating the conditions of smoking the drug in a pipe yielded no result and the microwave processing step is crucial according to the "manufacturers".
I also wish more could have been included on that experiment, and I am hoping to publish the decomposition data independently. I fight very hard to include as much scientific information as possible, which is difficult when the videos are intended to appeal to millions of viewers, that said you have complained repeatedly about it being "90% entertainment" when it contains the most complete portrait of the psychedelic effects of efavirenz in humans yet created. It includes interviews with street users, chemical analysis of street samples, a description of the psychedelic effects from a medical doctor who conducted self-experiments, interviews with dealers who use the drug professionally as an adulterant, a review of the pharmacodynamics and behavioral effects in rodents (with unpublished footage of the HTR at 1000 frames/sec), thermal decomposition via two different routes, hypotheses regarding the role of expectation and the placebo effect from a UN drug researcher and an anthropologist, and my own description of the drug's qualitative effects at 900mg. If you took all this as pure entertainment then I suppose I should be flattered.
crOOk said:
...you [do not] follow any guidelines for the trials you conduct (single dose, single subject, not double blind, not placebo-controlled, blah blah)
If you think humans ingesting psychoactives and reporting on their effect without a double blind placebo control is invalid then make sure to dismiss everything in bluelight, erowid, PIHKAL and TIHKAL as well as most of information gathered by ethnobotanists and anthropologists. Randomized controlled trials are extremely important, but they are not the only valid measure of a drug's effect.
Nice to see you posting here again, even just a bit.
lol.