Opiates and serotonin delpletion.

[MeDieViL]

I'm pretty sure opiates are serotonergic as they can contribute to serotonin syndrome. It would be interesting to see how they did this if they didn't affect serotonin levels!


While it's currently against general ethical guidelines to, say, give someone MDMA everyday for a year and look at their brain, the mass of anecdotal evidence says that repeated use of MDMA likely has some long-term detrimental effect on neural health (as do most other drugs, including but not limited to benzos, DRAs, alcohol, etc). Pure MDMA probably has less effect than many people, particularly those who use themselves as yardsticks, would imagine, since many pills are cut with speed (or pipes, or some weird shit), and I wouldn't be surprised to find amphetamine increases MDMA's neurotoxicity (beyond, and possibly far beyond, what you'd see with either one alone) since it seems to cause MDAI to become neurotoxic where it wasn't before.

That said, primate brains have been more resistant than rat brains to e.g. Olney's lesions, at least so far.

J Psychoactive Drugs. 2007 Mar;39(1):31-9.Links
Is recreational ecstasy (MDMA) use associated with higher levels of depressive symptoms?
Guillot C.

University of Southern Mississippi Hattiesburg, MS, USA. [email protected]

Due to potential serotonergic deficits, 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) may cause long-term mood disruptions in recreational Ecstasy users. The purpose of this review is to evaluate the evidence for a relationship between recreational Ecstasy use and higher levels of depressive symptoms. Eleven out of 22 studies initially have reported significantly higher depression scores in Ecstasy users in comparison to control participants. However, only three studies ultimately have revealed significantly higher depression scores in comparison to cannabis or polydrug controls. Furthermore, most studies have suffered from methodological weaknesses, and the levels of depressive symptoms that have been found in Ecstasy users have not been shown to be much higher than those found in normative groups. The evidence for an association specifically between Ecstasy use and higher levels of depressive symptoms is currently unconvincing, but the frequent concomitant use of Ecstasy and other illicit drugs has been shown to be associated with higher levels of depressive symptoms. Possible causes include polydrug use in general, MDMA-induced serotonergic deficits, individual effects of illicit drugs besides Ecstasy, combined effects of MDMA and other illicit drugs, and preexisting differences in the levels of depressive symptoms in Ecstasy users.

PMID: 17523583 [PubMed - indexed for MEDLINE]

Drug Alcohol Depend. 2007 Mar 16;87(2-3):303-11. Epub 2006 Oct 30.Click here to read Click here to read Links
Anxiety, depression, and behavioral symptoms of executive dysfunction in ecstasy users: contributions of polydrug use.
Medina KL, Shear PK.

Department of Psychiatry, University of California at San Diego, 3350 La Jolla Village Drive (151B), San Diego, CA 92161, USA. [email protected]

BACKGROUND: Given ecstasy's (MDMA) potential serotonergic neurotoxicity, it is plausible that regular ecstasy users would have an elevated prevalence of behavioral executive dysfunction or mood symptoms. However, recent studies have found that the relationship between ecstasy use and psychological symptoms was no longer significant after controlling for marijuana use (e.g., Morgan et al., 2002). The goal of the present study was to examine the relationship between ecstasy exposure and self-reported executive functioning and psychological symptoms after controlling for gender, ethnicity, and other drug use. METHODS: Data were collected from 65 men and women with a wide range of ecstasy use (including 17 marijuana-using controls). Participants were administered the Frontal Systems Behavioral Scale, State-Trait Anxiety Inventory for adults, and the Beck Depression Inventory-2nd edition. RESULTS: Although 19-63% of the ecstasy users demonstrated clinically elevated psychological symptoms, frequency of ecstasy use did not predict the psychological symptoms. No gender differences or interactions were observed. CONCLUSIONS: These results revealed that, although ecstasy users demonstrate elevated levels of psychological symptoms and executive dysfunction, these symptoms are not statistically associated with their ecstasy consumption. Instead, other drug use (alcohol, marijuana, opioids, and inhalants) significantly predict psychological symptoms in this sample of polydrug users.

PMID: 17074449 [PubMed - indexed for MEDLINE]

Polydrug use is a big issue, however the evidence that mdma use itself causes long term problems is not very convincing.

 

[onmyway]

of course, people who are already genetically prone to depression would likely be drawn to a drug like MDMA. there is obviously some type of relationship between drug use in general and depression. discerning the casual from the causal relationships is one of the challenges.

 

[MeDieViL]

of course, people who are already genetically prone to depression would likely be drawn to a drug like MDMA. there is obviously some type of relationship between drug use in general and depression. discerning the casual from the causal relationships is one of the challenges.

Well, when seperating poly drug use from MDMA use, no evidence of increased psychological problems where found.

BACKGROUND: Given ecstasy's (MDMA) potential serotonergic neurotoxicity, it is plausible that regular ecstasy users would have an elevated prevalence of behavioral executive dysfunction or mood symptoms. However, recent studies have found that the relationship between ecstasy use and psychological symptoms was no longer significant after controlling for marijuana use (e.g., Morgan et al., 2002).

CONCLUSIONS: These results revealed that, although ecstasy users demonstrate elevated levels of psychological symptoms and executive dysfunction, these symptoms are not statistically associated with their ecstasy consumption. Instead, other drug use (alcohol, marijuana, opioids, and inhalants) significantly predict psychological symptoms in this sample of polydrug users.

 

[MeDieViL]

Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety symptoms are associated with polydrug, not ecstasy, use.
Bedi G, Van Dam NT, Redman J.

School of Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne, Australia. [email protected]
Abstract
Although previous studies have examined anxiety and depression in ecstasy (+/-3,4-methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms are associated specifically with ecstasy or with polydrug use in general. We compared mean symptomatology and clinically significant symptoms in 45 ecstasy polydrug, 48 cannabis polydrug and 40 legal drug users, who completed standardised self-report anxiety and depression symptom measures. We further examined whether group differences were secondary to increased somatic symptom reporting, which may reflect acute/subacute drug effects. Anxiety and depression scores were higher in polydrug than legal drug users, with no difference between ecstasy and cannabis groups. There was no difference in numbers meeting criteria for clinically significant depression or 'moderate' or 'severe' anxiety, but the polydrug group contained more individuals reporting at least 'mild' anxiety symptoms than the legal drug control. Multivariate analyses indicated that anxiety alone was sufficient to discriminate groups. Polydrug users reported more somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy polydrug users may be associated with polydrug rather than ecstasy use. Higher ratings in polydrug users appear to be secondary to increased somatic symptom reporting, suggesting possible impacts of drug effects on symptom endorsement.

If anyone has any studies showing long term problems where polydrug use has been sepperated from MDMA use id be glad to see it.

 

[Psychedelic Jay]

The danger of poly drug use lies not in use alone, but overdoses.

 

[Amberthefrog]

Oleney's lesson experiments neither support nor disparage the idea of extrapolation from animal data - the doses of NMDA antagonists used in the aforementioned studies, were greatly in excess of those humans have ever been subjected to in studies. Not surprising that the resulting lessons haven't been observed in humans.

 

[Deleted member 137730]

I'm still convinced that SOME, maybe not much serotonin is at one stage necessary for opiates to work. Here is an article that states rats without serotonin neurons lost all opiate analgesia. I have found other articles stating the same thing in rats treated with serotonin transporter neurotoxins AKA amphetamine derivitives. Just do some searches if you wanna read more. Heres one below on how serotonin is needed for opiates to exert analgesia. It does say that the rats with depleted serotonin still got addicted to opiates, but im not so sure that was because it caused a pleasurable response. They could of continued taking them for other reasons.

http://news.wustl.edu/news/Pages/9876.aspx

I have done MDMA at high doses and I no longer get analgesia from opiates or HIGH at all in the least bit even if i take 80 mg plus of oxycodone with no tolerance.

Before I did MDMA i could always get high and have analgesia.

Im absolutely convinced lack of serotonin can render opiates more or less useless.

On another note, its not uncommon to hear how MDMA use changes the experience of other drugs based on the re-wiring of the serotonergic system after neurotoxic damage and repair.


Any thoughts.

And to atara if you meant to post that, yes i have tried it with little success. Inisitol is much better for this.

 

[atara]

Have you tried Saint John's Wort?