Hi all.
I am someone who used MDMA in the past (last usage was June 2013) roughly about 10-15 times over a 18 month period. I went through a great deal of anxiety and depression for six months until I got better. I have recently had a re-occurance of symptoms, which could just be my anxiety. Anyways I was reading this today and am curious. Source https://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml
Possible Significance of Cognitive Differences and MDMA Neurotoxicity
How severe are these cognitive changes? They do not indicate impairment in day-to-day activities. The differences occur in cognitive tests in which young, healthy people perform well. Thus, these differences are generally small in magnitude despite their statistical significance. In fact, neither the investigators nor the ecstasy-using volunteers themselves appear to be aware of any cognitive impairment in these individuals (McCann, 1999b; Rodgers, 2000). These studies raise questions about whether these ecstasy-using volunteers have experienced serotonergic neurotoxicity that might eventually be associated with more severe symptoms. Such symptoms could become prominent as ecstasyusers age. Additionally, larger impairments in specialized areas of functioning may exist but simply have not been discovered yet.
Studies of individual variation in symptoms associated with neurodegenerative disorders have lead to two relevant concepts. First, there is a threshold of damage that must be exceeded in some brain systems before symptoms develop. This has been primarily investigated with dopaminergic cell loss and Parkinson's disease (Brownell, 1999; Calne, 1985; Di Monte, 2000). There are less data on the serotonergic system. In a rat study using the serotonergic neurotoxin, 5,7-DHT, Hall (1999) concluded that a loss of greater than 60% of serotonergic neurons was necessary to decrease extracellular 5-HT levels in the striatum. Alterations in behavior were seen with slightly smaller depletions (51% or more), possibly due to regional variations in neurotoxicity. One might speculate that even smaller depletions may not affect many serotonergic-related behaviors, although the maximal serotonergic response to drugs or other stimuli is likely to be reduced (reduced electrically-stimulated 5-HT release in MDMA-exposed rats was documented by Gartside, 1996).
Second, the concept of cognitive reserve has been developed to explain why greater education, intelligence, or brain size is associated with less severe impairment in conditions such as Alzheimer's disease, AIDS, and normal aging (Alexander, 1997; Coffey, 1999; Graves, 1996; Stern, 1996). This cognitive reserve may be seen as a surplus of processing capacity that protects the individual against loss of functioning when that capacity is decreased. Cognitive reserve could be the result of more extensive functional brain tissue, density of neural connections, or cognitive strategies for problem solving. Individuals with less cognitive reserve could be expected to undergo larger cognitive decreases from MDMA exposure than users with greater cognitive reserve. Support for this possibility comes from Bolla (1998) who reported a significant interaction between dose and vocabulary (measured with the WAIS-R). ecstasy users with lower vocabulary scores showed greater decreases in delayed visual memory performance, while users with higher vocabulary had largely preserved performance. Although the absolute magnitude of performance decrease was small, this study suggests that cognitive reserve could play a role in expression of MDMA neurotoxicity.
Whether symptoms of MDMA neurotoxicity are likely to increase as users age is difficult to predict. Some have speculated that aging ecstasy users might have increased risk of depression and other affective disorders. From a neurochemical perspective, age-related decrease in SERT density appears modest (estimated at 4.3% per decade in one recent study (van Dyck, 2000)), while 5-HT receptors undergo more complex age-related changes (reviewed in (Meltzer, 1998). One would hope that these changes will not cause ecstasy users to exceed a hypothetical threshold for developing symptoms of neurotoxicity. However, we simply do not understand 5-HT or affective disorders sufficiently to make predictions with any confidence. Late onset affective disorders are probably influenced by many nonserotonergic factors, such as social isolation and cerebrovascular disease.
These are serious and legitimate concerns and there is insufficient research to adequately address them. On the other hand, there is no direct evidence to support these concerns. Neurotoxic phenethylamines have been self-administered by humans for over 60 years. In this time, no evidence has been published suggesting that methamphetamine or amphetamine increase risk of Parkinson's disease, despite damaging dopaminergic axons. In contrast, the link between Parkinson's disease and MPTP, a meperidine analogue and dopaminergic neurotoxin that destroys cell bodies, was rapidly discovered (Davis, 1979; Langston, 1983). This suggests that there may be fundamental differences between neurotoxic phenethylamines, which selectively damage a subset of monoaminergic axons but not cell bodies, and other neurotoxins. Similarly, concerns about the selective serotonergic neurotoxicity induced by MDMA and other drugs are not fueled by a toxic syndrome identified in users. Instead, they are motivated by the intuition that the dramatic decreases in indices of serotonergic functioning must have some adverse behavioral consequences.
Some have suggested that MDMA neurotoxicity may be related to its putative therapeutic effects. Although this is technically possible, there are a number of reasons to doubt this hypothesis. The acute intoxication induced by MDMA is unusual. In contrast, similar serotonergic neurotoxicity can be produced by many other drugs. The events associated with MDMA neurotoxicity occur in rats between approximately 3 and 12 hours after drug administration, when subjective effects are decreasing or absent in humans. Thus, the acute intoxication produced by MDMA appears to be fully separable from long-term serotonergic effects. If MDMA proves useful as an adjunct to psychotherapy, it seems more likely that this utility will be associated with the unusual acute intoxication produced by MDMA than with the chronic serotonergic changes produced by many drugs.
I don't know if I am misinterpreting the information here, but from what I can gather it says that if you acquired some sort of neurotoxicity in the past, then symptoms will get worse with age rather than better? I'm confused if they mean current ecstasy users or abstinent users in this article.
My last hope was that I got better before for a period of time, but now that seems to be out the window? Maybe I'm just being a hypochondriac, I dunno. I never experienced any cognitive decline, but the depression I have definitely experienced, and now that it's back I can barely function.
Any thoughts? I'm not educated in neuroscience so I don't really know what this means.
I am someone who used MDMA in the past (last usage was June 2013) roughly about 10-15 times over a 18 month period. I went through a great deal of anxiety and depression for six months until I got better. I have recently had a re-occurance of symptoms, which could just be my anxiety. Anyways I was reading this today and am curious. Source https://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml
Possible Significance of Cognitive Differences and MDMA Neurotoxicity
How severe are these cognitive changes? They do not indicate impairment in day-to-day activities. The differences occur in cognitive tests in which young, healthy people perform well. Thus, these differences are generally small in magnitude despite their statistical significance. In fact, neither the investigators nor the ecstasy-using volunteers themselves appear to be aware of any cognitive impairment in these individuals (McCann, 1999b; Rodgers, 2000). These studies raise questions about whether these ecstasy-using volunteers have experienced serotonergic neurotoxicity that might eventually be associated with more severe symptoms. Such symptoms could become prominent as ecstasyusers age. Additionally, larger impairments in specialized areas of functioning may exist but simply have not been discovered yet.
Studies of individual variation in symptoms associated with neurodegenerative disorders have lead to two relevant concepts. First, there is a threshold of damage that must be exceeded in some brain systems before symptoms develop. This has been primarily investigated with dopaminergic cell loss and Parkinson's disease (Brownell, 1999; Calne, 1985; Di Monte, 2000). There are less data on the serotonergic system. In a rat study using the serotonergic neurotoxin, 5,7-DHT, Hall (1999) concluded that a loss of greater than 60% of serotonergic neurons was necessary to decrease extracellular 5-HT levels in the striatum. Alterations in behavior were seen with slightly smaller depletions (51% or more), possibly due to regional variations in neurotoxicity. One might speculate that even smaller depletions may not affect many serotonergic-related behaviors, although the maximal serotonergic response to drugs or other stimuli is likely to be reduced (reduced electrically-stimulated 5-HT release in MDMA-exposed rats was documented by Gartside, 1996).
Second, the concept of cognitive reserve has been developed to explain why greater education, intelligence, or brain size is associated with less severe impairment in conditions such as Alzheimer's disease, AIDS, and normal aging (Alexander, 1997; Coffey, 1999; Graves, 1996; Stern, 1996). This cognitive reserve may be seen as a surplus of processing capacity that protects the individual against loss of functioning when that capacity is decreased. Cognitive reserve could be the result of more extensive functional brain tissue, density of neural connections, or cognitive strategies for problem solving. Individuals with less cognitive reserve could be expected to undergo larger cognitive decreases from MDMA exposure than users with greater cognitive reserve. Support for this possibility comes from Bolla (1998) who reported a significant interaction between dose and vocabulary (measured with the WAIS-R). ecstasy users with lower vocabulary scores showed greater decreases in delayed visual memory performance, while users with higher vocabulary had largely preserved performance. Although the absolute magnitude of performance decrease was small, this study suggests that cognitive reserve could play a role in expression of MDMA neurotoxicity.
Whether symptoms of MDMA neurotoxicity are likely to increase as users age is difficult to predict. Some have speculated that aging ecstasy users might have increased risk of depression and other affective disorders. From a neurochemical perspective, age-related decrease in SERT density appears modest (estimated at 4.3% per decade in one recent study (van Dyck, 2000)), while 5-HT receptors undergo more complex age-related changes (reviewed in (Meltzer, 1998). One would hope that these changes will not cause ecstasy users to exceed a hypothetical threshold for developing symptoms of neurotoxicity. However, we simply do not understand 5-HT or affective disorders sufficiently to make predictions with any confidence. Late onset affective disorders are probably influenced by many nonserotonergic factors, such as social isolation and cerebrovascular disease.
These are serious and legitimate concerns and there is insufficient research to adequately address them. On the other hand, there is no direct evidence to support these concerns. Neurotoxic phenethylamines have been self-administered by humans for over 60 years. In this time, no evidence has been published suggesting that methamphetamine or amphetamine increase risk of Parkinson's disease, despite damaging dopaminergic axons. In contrast, the link between Parkinson's disease and MPTP, a meperidine analogue and dopaminergic neurotoxin that destroys cell bodies, was rapidly discovered (Davis, 1979; Langston, 1983). This suggests that there may be fundamental differences between neurotoxic phenethylamines, which selectively damage a subset of monoaminergic axons but not cell bodies, and other neurotoxins. Similarly, concerns about the selective serotonergic neurotoxicity induced by MDMA and other drugs are not fueled by a toxic syndrome identified in users. Instead, they are motivated by the intuition that the dramatic decreases in indices of serotonergic functioning must have some adverse behavioral consequences.
Some have suggested that MDMA neurotoxicity may be related to its putative therapeutic effects. Although this is technically possible, there are a number of reasons to doubt this hypothesis. The acute intoxication induced by MDMA is unusual. In contrast, similar serotonergic neurotoxicity can be produced by many other drugs. The events associated with MDMA neurotoxicity occur in rats between approximately 3 and 12 hours after drug administration, when subjective effects are decreasing or absent in humans. Thus, the acute intoxication produced by MDMA appears to be fully separable from long-term serotonergic effects. If MDMA proves useful as an adjunct to psychotherapy, it seems more likely that this utility will be associated with the unusual acute intoxication produced by MDMA than with the chronic serotonergic changes produced by many drugs.
I don't know if I am misinterpreting the information here, but from what I can gather it says that if you acquired some sort of neurotoxicity in the past, then symptoms will get worse with age rather than better? I'm confused if they mean current ecstasy users or abstinent users in this article.
My last hope was that I got better before for a period of time, but now that seems to be out the window? Maybe I'm just being a hypochondriac, I dunno. I never experienced any cognitive decline, but the depression I have definitely experienced, and now that it's back I can barely function.
Any thoughts? I'm not educated in neuroscience so I don't really know what this means.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")