Evidence of global neurological deficits caused by chronic opiate abuse

[Bucklecroft Rudy]

Ive been using subutex for the past year and a half (DHC for 4 years and Pods for 1.5 years) and have been noticing a thick fog starting to gradually consume all my synapses. This led me to a google search (opiates + gray matter/white matter) which in turn led me to the following studies:

http://www.ncbi.nlm.nih.gov/pubmed/16369836

RATIONALE:

There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects.
OBJECTIVES:

The objective of the current study is to explore gray matter density in opiate-dependent subjects.
METHODS:

Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM.
RESULTS:

Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28).
CONCLUSIONS:

This study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects.

http://www.ncbi.nlm.nih.gov/pubmed/21070508

Heroin addiction has been associated with impaired neuronal connectivity and cognitive deficits. One mechanism that potentially explains these findings is alterations in white matter connectivity secondary to chronic opiate use. However, few studies have quantitavely examined white matter deficits in opiate addiction (OA). Here, we investigated white matter microstructure in OA using diffusion tensor imaging (DTI). We performed voxel-wise analysis of fractional anisotropy (FA) in 24 participants with OA and 29 healthy controls. The OA group showed reduced FA in multiple pathways including the corpus callosum, thalamic radiation and inferior longitudinal fasciculus. This FA reduction was mainly the result of increased radial diffusivity (λ(⊥)), indicative of myelin pathology. Longer duration of OA was also associated with axonal diffusivity (λ(1)), most robustly in superior longitudinal fasciculi and right frontal white matter suggesting axonal injury in long-term users. Together, the findings indicate that chronic OA use has widespread and diverse effects on neuronal connectivity and function.

Both studies implicate opiate use in the diminishment of white/grey matter density over time. Now obviously the sample examined heroin addicts who often suffer from concurrent health conditions such as malnutrition etc however the evidence would seem to be too compelling to simply wave away. The studies also fail to mention the specific charecteristics of each user's addiction thus we cant know whether the affected individuals were 20 year+ veterans.

 

[endotropic]

Both studies you linked actually include the duration of use (table 1 in both). Average duration of use is 17 years in the first study (grey matter), 9 years in the second (white matter). They also claim in the second study that white matter deficits increase with duration of use.

Now I'm no expert on white matter/human brain imaging, but one line in the white matter report makes me very suspicious:

Six from the clinical (ed: opiate) group were excluded because of abnormalities detected in their anatomical MRI scans (five with prominent white matter hyperintensities, one with meningioma).

It sounds like they excluded 5 people from the opiate group because they had more white matter than expected. That could be some legitimate sensor malfunction, or a case of eliminating results that don't match the hypothesis, I don't know which, but it makes me suspicious.

The group that published the grey matter paper also found an INCREASED white matter density in opiate dependent subjects in another report: http://www.ncbi.nlm.nih.gov/pubmed/15313520

With those conflicting reports I wouldn't put too much faith in the white matter findings. As far as the grey matter paper, I can't immediately find any holes to poke in it. The good news is they suggest that changes in grey matter should reverse with abstinence.

 

[Bucklecroft Rudy]

The increased white matter density study you posted would actually shore up my initial suspicions since wm hyperintensity is associated with cognitive disorders of various kinds (please correct me if im wrong). From what ive seen thus far the elimination of the patients exhibiting abnormalities was simply a precaution to prevent extremes throwing off the results.

The PFC, SMC and CC (particularly
the anterior CC) play important roles in cognitive
control,
23–25
which is critical to the goal-directed
behavior. Cognitive control involves the ability to
coordinate thought and action in accordance with
internal goals.
26,27
The active maintenance of PFC
activity indicates the representation of goals, assign-
ment of valence and selection of action to achieve
them.
24,28
The SMC is active before movements occur
and seems to be crucial for linking cognition to
action.
25
Individuals with anomalies in the PFC, SMC
and CC may be impulsive and prefer immediate
rewards to delayed, but more beneficial, conse-
quences.
3
Thus, drug addiction is characterized by
compulsive and persistent drug-taking behavior
despite serious negative consequences

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1819.2009.01989.x/pdf

 

[Bucklecroft Rudy]

There are a number of medications and practices which have been shown to increase white and grey matter its worth noting however:
http://www.sciencedaily.com/releases/2007/03/070307080827.htm
http://www.ncbi.nlm.nih.gov/pubmed/17996370
http://freud.psy.ohio-state.edu/lab/CNL/Publications_files/Colcombe,2006.pdf
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002669
http://faculty.washington.edu/losterho/mechelli_l2_vmb.pdf
http://www.readcube.com/articles/10.1038/427311a?locale=en
http://f1000.com/prime/reports/b/1/78
http://users.fmrib.ox.ac.uk/~douaud/VB_vbm.pdf

(The aging brain and the opiate brain would seem to have similar mechanisms at play)
Its likely that the grey/white matter loss is a consequence of hypoxia. None of the scientists seemed disposed to speculating as to a cause. This would seem to be suspect and indicates an assumption that the opiates are solely to blame as opposed to a secondary/downstream process.

The good news amidst all this is that grey and white matter represent the totality of the brain's tissues. The brain is highly plastic (See above links) thus it should be quite possible to reverse any opiate mediated decline.

 

[sekio]

A subjective feeling of "fogginess" or lethargy doesn't neccesarily mean white/grey matter loss or dysfunction.

Also, there are a modicum of environmental factors that effect the amount and ratio of white/grey matter, including novel environments, tobacco usage, stress, socioeconomic standing, etc. Hence, you have to be careful drawing conclusions in studies about heroin addicts matched against "controls", because opioid usage rarely occurs in a vacuum.

More generally, make sure you are not deficient in any vitamins or major amino acids, you're not getting ill, getting aerobic excercise, and that you're getting enough sleep.

 

[Bucklecroft Rudy]

"More generally, make sure you are not deficient in any vitamins or major amino acids, you're not getting ill, getting aerobic excercise, and that you're getting enough sleep. "

V. true. Malnutrition ravages the brain quite profoundly. I remember reading a study where stress caused magnesium deficiency which in turn led to cognitive decline. Alcohol induced brain damage is inpart caused by B12 deficiency.

Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of AD and may have therapeutic potential for treating AD in humans.

 

[desertshore]

"More generally, make sure you are not deficient in any vitamins or major amino acids, you're not getting ill, getting aerobic excercise, and that you're getting enough sleep. "

V. true. Malnutrition ravages the brain quite profoundly. I remember reading a study where stress caused magnesium deficiency which in turn led to cognitive decline. Alcohol induced brain damage is inpart caused by B12 deficiency.

No, it's caused by B1 deficiency (Korsakoff's syndrome). And, as you say, there are studies that show that in anorexia/malnutrition there is atrophy of different brain areas.
I don't want to discuss the fact that chronic opiate abuse can be damaging to the brain. It would be more interesting to see if chronic opiate use can be damage the brain. See if in people that must take opiates for years (i.e. for pain management) but that are followed by doctors, eat properly and generally conduct an healthy lifestyle (well, as much as they can) there are similar decreases in WM/GM volumes.

More in general (and I'm saying this as a researcher in this field), I believe that the contribution of this kind of scientific work to our knowledge is very close to zero. I did not read in full the article you linked (I'm at home now), but it looks like in the juggling article they found a change in brain volume that disappeared when the people stopped juggling (so what? I thought everyone knew about adult brain plasticity by now), in the paper about lithium they cannot rule out osmotic effect. Scientists do this kind of research because that's where the money is now

 

[Bucklecroft Rudy]

Cheers for the correction there I always thought B12 was implicated but it is indeed Thiamin. I also concur that the same investigation with a clinical sample consisting of pain patients would be far more informative since the comorbitdity factor in addicts is very high. Most addicts dont sleep very well for instance. Sleep architecture is disrupted significantly by opiates with REM sleep being curtailed. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784658/ Sleep deprivation (which this effectively is) has also been indicated as a factor in grey matter loss.

The lnks I posted are merely to illustrate Neural plasticity and the range of activites that can influence it. I do however agree that the juggling paper could perhaps have been better employed in the bathroom. Any novel experience or engagement with learning enables plasticity. Far more interesting are chemical methods of accomplishing neural growth

 

[Bucklecroft Rudy]

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059645

This study suggests that the grey matter loss is indeed reversible and is related to the behavioural changes observed in addicts

 

[pofacedhoe]

tobacco use is a big confounding variable- i haven't read the study but did they exclude tobacco users?

 

[Hammilton]

I think that the wm hyperintensities were localized, and indicative of another problem as opposed to a global thing. Hyperintensity is associated with its own issues, of course. 5 subjects with hyperintensity seems like enough to to suggest opioid use may be associated with them too. It would be interesting to know where the hyperintensities were located.

I would tend to think the deficits in white and grey matter could be explained by the fact that chronic heroin users are probably experiencing chronic bouts of hypoxia. However I can't think of a process that would make hyperintensities more common, making it far more interesting.