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I just went through and performed a full rewrite/reorganization of the article to make it more readable as well as more informative. I need to rest for tonight (spent almost 4 hours researching and rewriting the article), and I will be adding references by Monday morning. Thank you for starting the article. I strive to make this Wiki a better, easier to read, more well organized, and more informative place* :-).
- Although if ease of reading must come at cost of information, I can not abide ;-).
- Good work. I've been wanting to see this article expanded for some time. I should note that I disagree with some of your content though. For instance, alcohol is reinforcing/euphoric even in non-anxious people, unlike benzos and most other GABAergics. Dissociatives like ketamine and phencyclidine are dopamine reuptake inhibitors and nitrous oxide has opioid effects, likely underlying their abuse potential. They're in contrast to psychedelics like LSD and such which, like you said, seem to potentiate whatever mood the person is in. Also, nicotine is not a dopamine reuptake inhibitor (I believe that was a mistake/typo), and I think the very last paragraph is unnecessary/unrelated to the main subject. I hope that you'll fix the page so I don't have to. In any case, please don't take my criticisms the wrong way -- I very much appreciate your work and I hope you do more. Thank you. el3ctr0nika (Talk | Contribs) 22:08, 6 March 2010 (UTC)
- I proofread and rewrote the page, being less tired this time, and included a third section, "drugs of a mixed mechanism of action", to expand upon the last paragraph that was out of place. A mixed mechanism of action is very related to the main subject, to show how the same drugs in different dosages, or different isomers, can have completely different effects upon the brain - using methorphan as an example, one isomer is a dissociative hallucinogen, and the other isomer is a potent opioid analgesic. I understand that most of the drugs mentioned, and most of all drugs, have a mixed mechanism of action (defined as: affect more than one neurotransmitter or receptor subsystem [except for many opioids, which are pure mu-agonists]), but I have included ones that have a very distinct profile of effects at different doses or have very unusual effects for their respective classes. I've been busy this week, but you can contact me on my talk page as well. I'm currently employed as an information security consultant, but have doctorates in psychology and pharmaceutical science (and BS in O Chem) - what the hell! Talk about the work not matching the education :-D (It's a long story). I'm not sure if it's ethical to reference my own published articles or case-studies, or studies I co-authored - my name might as well be "et al." :-) L Marchese Ph.D. D.Pharm.Dip.Sci. 126.96.36.199 (talk) 08:08, 9 March 2010 (UTC)
- Thanks for the further contributions. I still think the article needs quite a bit of straightening out though -- I'm a bit of a perfectionist you see. A few things:
- 1) As I said above, ketamine and phencyclidine are very mixed drugs, acting not only as NMDA antagonists, but also varyingly as dopamine reuptake inhibitors, opioids, sigma agonists, and anticholinergics. Nitrous oxide is mixed with NMDA antagonist, GABA agonist, and possible opioid effects as well. The reason I bring this up is because from what I've read, [more] selective(-ish) NMDA antagonists are actually rather dysphoric (e.g., memantine, MK-801, and DXM perhaps) and are not euphoriants by definition. It seems that additional actions like direct dopaminergic or opioid effects are necessary for NMDA-mediated dissociatives to actually be 'enjoyable'. On their own they just seem to blunt affect.
- 2) This is a matter of personal opinion, but I think cocaine's potential for psychosis is much more related to D2 activation rather than sigma affinity (if at all), similarly to amphetamine and methylphenidate.
- 3) Tramadol is actually a serotonin releasing agent, not reuptake inhibitor (I can provide citations if necessary). This likely plays a major role in tramadol even having the capacity for euphoria (compare SSRIs and MDMA as a crude example). It's also a norepinephrine reuptake inhibitor, 5-HT2C antagonist, and weak NMDA antagonist (I'm sure you probably knew most of this already, but just noting), and some or all of these properties may contribute to its mood-lifting effects as well. As an example 5-HT2C antagonism disinhibits dopamine release in the mesolimbic pathway and augments the effects of various reinforcing drugs like amphetamines and opioids.
- 4) Kappa agonists are definitely not considered euphoriants, but dysphoriants (speaking from personal experience, they're morbid substances). In scientific studies they've been shown to inhibit dopamine release and self-administration of reinforcing drugs like amphetamine and cocaine as well. Though, I should ask, does pentazocine also have affinity for mu- or delta-opioid receptors? I'm unclear on that. If so agonist action at those sites could possibly balance it out.
- 5) I'm not sure how much of a role sigma activity plays in DMT's effects.. so many drugs are sigma ligands.. SSRIs, heroin, cocaine, methamphetamine, MDMA, and PCP to name a few, yet we almost never even consider this property in their overall effects and mechanism of action. Also, DMT is a strong D1 agonist with much higher affinity for this receptor over 5-HT2A (something like 10-fold I believe), so this likely plays a major role in any rewarding effects it may produce as well.
- Anyway, once again, thank you for your work. I think there's much to do though. Further expansion is necessary and the page could be divided into subsections. I'd like to write a part on euphoriants and their effects on the pleasure centers as well. I may put this article up on WikiProject Pharmacology for review later so we can get some assistance from other editors.
- Oh I almost forgot, you can use this tool which automatically generates reference templates via PubMed IDs, ISBNs, and URLs. It's very convenient and saves us editors quite a bit of work. On Wikipedia you'll always want to properly format your citations using the ref template over mere plain text. el3ctr0nika (Talk | Contribs) 09:09, 9 March 2010 (UTC)
Lead definition of euphoriant
At the top of the article it defines a euphoriant as "a type of psychoactive drug which induces feelings of physical and/or mental euphoria, the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush." this seems to contradict the very word which appears to mean a substances that simply induces euphoria. C6541 (T↔C) 00:27, 10 March 2010 (UTC) I have found several definitions that define a euphoriant as a substance which tends to induce euphoria, nothing more. C6541 (T↔C) 00:29, 10 March 2010 (UTC)
Inclusion of deliriants
I have serious doubts about this. The overwhelming majority of reports on Erowid describe a very negative, dysphoric, and often terrifying experience associated with deliriant use, including datura and diphenhydramine. I suggest that, with out a realiable citation, this section be removed entirely. Attys (talk) 23:49, 29 October 2010 (UTC)
It is noted that deliriants are by their very nature dysphoric and dangerous, and the citation I added, specifically about datura, supports this. By its very nature it is required, as hallucinogens are divided in to three subsections or types in scholarly study: dissociatives, deliriants, and psychedelics. To have one or two without the other one or two is incomplete. Do you believe the dangers of deliriants, and the dysphoric nature of them, should be worded more strongly, or in less erudite terms?188.8.131.52 (talk) 18:08, 12 February 2011 (UTC)
Methadone - available forms
There is a clear mistake regarding the availabilty of Methadone-based preperations. In the section about the mixed agents, the opioid drug Methadone is listet as a mu-agonist and NDMA-antagonist, mentioning that one of the actions is developed by the L-isomer and the other action by the R-isomer, and that however only racematic preperations of Methadone are commercially available - and this is definitely wrong! Isolated Levomethadone (the levorotary form, that inherits the opioid-agonistic properties) is commercially available and well known, one commonly in substitution used and widely spread commercial preperation is "L-Polamidon" (with the "L-" indicating that this product solely contains the l-isomer Levomethadone, regarding to the formerly available preperation "Polamidon" containing the racematic form). In many countries L-Polamidon is yet the only commercially available Methadone-based preperation, while the racematic form is exclusively manufactured in pharmacies on demand / request by a doctor and no longer sold as an already manifactured preperation.
http://en.wikipedia.org/wiki/Methadone - in the 4th passage
The euphoric effects of cannabinoids are not due to their extremely mild psychedelic effects, but through an entirely different mechanism. In fact the psychedelic property is most commonly described as dysphoric due to the accompanying anxiety and paranoia that such a high dose would elicit. Their effects are more similar to dissociatives than psychedelics, but could also fit under CNS depressants. I think they belong in their own category like Opioids. — Preceding unsigned comment added by 184.108.40.206 (talk) 04:39, 1 February 2012 (UTC)