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More long-winded pedantry about drugs - Tactical Ninja

Apr. 3rd, 2013

10:34 am - More long-winded pedantry about drugs

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You might remember that last week the lecturer for the course I was so critical of sent me some references so I could check for myself. Last week I looked at the statement that 500,000 users of heroin in the US in the early 1970s was reduced to 200,000 by 1974, and that this was due to the influence of this dude. While I couldn't find evidence to support that exact figure and discovered that exact figures on this are pretty much impossible to produce, I did find support for the idea that the number of heroin users dropped significantly in the early 1970s. I also found a number of reasons for that drop, the most likely being the cessation of the Vietnam War meaning that addicted soldiers were no longer being introduced to the population at a high rate, a swing to a preference for other drugs in the population (mostly cocaine from what I gathered), a shortage of heroin due to policies implemented in the Middle East and Asia, and targeted interventions such as the methadone program. I am less sure about the Maharishi, as I couldn't find anything at all about that.

However, the reference supplied by the lecturer on a reduction in the number of heroin users was supported in principle, if not in direct evidence. That's good enough for me to accept the first part of that argument.

The other set of refs he sent me were related to research into the effects of long term heroin use on the brain. The lecture slide claimed that long term drug use damages the brain, and I had asked for references, mostly because of the generalisation of 'drug use', because I know this is not the case for all drugs. However, I was personally unclear on whether heroin was a culprit or not, so I read the references. Now my brain hurts. I should write an article on how reading about the neuroscience of addiction damages the brain. *snerk*


The first one was Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers.

This study compared amphetamine users with heroin users and control subjects on a battery of cognitive tests. It found that while both amphetamine users and opiate users were impaired, it was in different ways - the amphetamine users were impaired on extra-dimensional shift tasks, spatial working memory, and pattern recognition memory (associated with temporal lobes). Heroin users were impaired in learning intra-dimensional shifts, spatial working memory, and strategic performance - they struggled to learn how to strategise a test even after training, and tended to repeat behaviours.

They concluded that different drugs may lead to different types of cognitive impairment, that amphetamine seems to be associated mainly with loss of 5-HT from the orbitofrontal cortex, and they mention that their results stand in contrast to previous studies that heroin abusers do not exhibit typical frontal-executive deficits - which implies they think there's a frontal association there too, but it seems unclear.

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: Evidence for monoaminergic mechanisms.

This one compared amphetamine users with opiate users, and also with people with lesions on their prefrontal cortex, and finally people in a tryptophan-depleted state; using a cognitive decision-making test. They found that amphetamine users made suboptimal decisions and made them slowly, whereas opiate users made good decisions but made them slowly. The prefrontally damaged people showed results similar to amphetamine users, and also the lowered tryptophan people.

They associate prefrontal cortex activity with decision making, and conclude that both depleted tryptophan and chronic amphetamine abuse can lead to behaviour consistent with impaired prefrontal cortex function. Opiate use, on the other hand, demonstrates a different type of impairment, and they say this about it:

"Thus, the increased deliberation times shown by both the chronic amphetamine and opiate abusers in our decision-making task is consistent with altered neuromodulation of the circuitry incorporating ventral areas of PFC, ventral striatum, and amygdala, associated with the abuse of these substances. Moreover, the absence of any relationship between this particular impairment and years of abuse suggests that this deficit does not necessarily reflect an enduring or cumulative disruption of this circuitry. Additionally, in the case of opiates, it is possible that chronic abuse may directly alter opioid receptor functions in the PFC itself (Mansour et al. 1988)."

This is interesting. I think it's trying to say that this impairment shown by opiate users is not consistent with cumulative damage to the prefrontal cortex, but instead with the function of the opioid receptors - but I'm finding it a bit hard to interpret that sentence, not being a neuroscientist. Anyway, the study itself focuses mainly on amphetamine and its effects being similar to the other test subjects, with the heroin associations being somewhat less focused-on.

It mentions that further research is needed to ensure that the correlation between the different drugs and associated behaviour patterns is fully understood - that poor decision making may lead to amphetamine abuse, for example, rather than the other way around. This is good to see - so many researchers draw a causal conclusion when it's drugs being researched, and don't even entertain the possibility that it may be more complex. So this makes their study much more credible in my opinion.

You'll note that the first two studies had a bunch of crossover in terms of authors and researchers, and also that these studies involved performing tests designed to measure cognitive function and drawing conclusions from the results. The next study, they actually looked inside (sort of) people's brains.

Brain Disintegration in Heroin Addicts: The Natural Course of the Disease and the Effects of Methadone Treatment. I have to say the title of this one makes me go *gnng*, especially after you read the article and discover that at no point is anyone's brain actually seen to be disintegrating. However, I'll cut them some slack for English not being their first language, and also for going for the shock-value title - I've done that myself. But, it does set it up to appear as if they are firmly in the 'drugs are bad' camp, and brings their objectivity into question.

Anyway, so these researchers used EEG to measure activity in the brains of chronic heroin users and control subjects. They found abnormal electrical activity in the central brain area, starting in the left hemisphere and moving to right hemisphere, correlated to the length of time using heroin. They related this to cognitive function (unspecified) and craving for heroin.

They also found that short term heroin users did not differ from 'normal' people on cognitive tests associated with prefrontal activity, but that individual variations were found in patients who injected a larger amount of heroin immediately before entering the clinic (well duh). Weirdly enough, they used this lack of difference to assume that these people had prefrontal dysfunctions and that caused them to self-administer more heroin, as opposed to perhaps assuming that having just injected heroin might affect one's performance on tests. Hmm..

In terms of long term use, they found that patients with a longer history of heroin use gave a significantly poorer performance on orbito-frontal neuropsychological tasks than 'normal' subjects. They also mentioned in their discussion of 'concomitant brain damage' that a significant number of long-term users had suffered non-fatal overdoses, which can lead to oxygen deprivation in the brain, which can cause injury. These appear to be mostly associated with posterior brain 'disintegration' - I think here they mean lesions, since in the discussion they compare it with types of lesions caused by brain diseases, injury, and age.

Apparently they also found that methadone maintenance patients had more severe cognitive impairment than heroin users.

So what can I conclude from all this? Well, first I'd like to say that due to time constraints, I haven't looked at any other refs than these ones, to see if there is research that comes to different conclusions. However, I think we can be fairly sure that long term heavy heroin use can lead to cognitive impairment that is at least in part consistent with changes to the prefrontal cortex. I would not go so far as to say 'damage' after reading these articles, but there's definitely something going on in there. Also, I couldn't conclude that it was specifically the prefrontal or frontal cortex that appear to be affected - again, not a neuroscientist, but the observed changes in cognition appear to have been spread more widely in the brain. My brief look at alcohol-related impairment seemed to show a similarly wide spread with alcohol - here acknowledging that I haven't researched this in depth.

Now, in the lecture, what I said was that as far as I knew alcohol and methamphetamine were acknowledged culprits for affecting the brains of users, and that I wasn't sure about heroin but I didn't think so. I stand corrected there, obviously, and I'm happy to acknowledge that publicly. I should also point out that in one of those articles up there, there's a discussion of cocaine that points out mild impairments having been demonstrated in long term cocaine users too, but that another article (the ones with the similar authors) says there is no evidence for the neurotoxicity of cocaine - which implies any changes in the brain due to cocaine use have a more complex correlation than simply 'cocaine use causes x'.

Anyway, this whole thing came about because in the lecture, the lecturer's slide simply said (something along the lines of): "Long term drug use damages the brain." And I took exception to that, asking for references to support the statement. The reason for this is that in the field of drug policy, the first thing you learn is that 'drug' is an arbitrary term and that it's extremely unwise to talk about 'drugs' as a monolith. For a start, it causes people to assume one drug is like another, which can be dangerous if you're talking about people assuming that heroin is the same as marijuana (the lecturer did touch on this elsewhere to his credit). Secondly, if you want policy to be based on evidence instead of moralising or assumption or ignorance, you have to be specific about what evidence relates to what drug.

The idea of 'drugs' as the scourge that's destroying our society is an old one, brought into focus by Nixon and his War on Drugs. He didn't differentiate between different drugs, and our drug law and policy is a product of that, complete with a great deal of harmful misinformation and mythology (like the gateway theory or the concepts of 'hard' and 'soft' drugs) that is accepted as true by the majority of people who have grown up immersed in Drug War rhetoric. "Long term drug use damages the brain" is part of that rhetoric. This type of statement is harmful because it reinforces this mythology in people's minds, and causes people to just accept the continuation of policies that have been so harmful in the past, because it's 'common sense'. This makes it very difficult to implement harm reduction policies in the face of the ignorance and knee-jerk reactions of politicians and the voting public. We need specifics and we need evidence, and I care a great deal about making sure these specifics and evidence get to as many people as possible.


So what should that slide have said? Well, I reckon something like "Long term chronic use of certain drugs can cause cognitive impairment." Underneath this in brackets (eg alcohol, amphetamines, heroin). Spoken: Long term heavy use of these drugs has been shown to produce cognitive impairment consistent with changes to the brain, such as.. etc etc etc.. And at the bottom of the page, footnotes linking to the studies.

That's how I'd do it anyway. The lecturer has told me he's changed the slide in question so it no longer makes that broad statement, so credit to him for that. I realise the statement above does not have the same impact, and that the next step of the argument was drawing a relationship between the effects of transcendental meditation on the brain and its potential for use in rehabilitation therapy. But if that's the case, then showing the specifics and producing evidence for how this therapy works to target the specific impairments, all backed up by research and evidence that pedants like me can look up, will make the argument stronger. And if the evidence isn't there, then not making the argument will make the lecture stronger. In my opinion, obviously.

So there you have it. The lecturer produced the refs I asked for, I read them, and learned something about heroin, while he has made an improvement to his lecture series by removing a generalisation. Win/win again. Sweet!

Comments:

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From:bekitty
Date:April 2nd, 2013 11:18 pm (UTC)
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Right. Can we get David Nutt to explain those papers, please? I've heard he's quite good at that.

Also, ibogaine! :)
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From:tatjna
Date:April 2nd, 2013 11:21 pm (UTC)
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David Nutt's talking at the conference I'm going to, but a) he clashes with a talk I'm really keen on and b) he's talking mostly about the work of the Beckley Foundation. I wonder how he'd feel about me thrusting those papers at him and going "EXPLAIN PLZ!"

Also, I'm trying to work out which talks to go to now we're getting closer to the time, and it feels as if quite a lot of what I'm choosing is based in questions raised by people here, so I can come back and go "This is what is happening in that field" about a number of topics.

SO HARD TO CHOOSE
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From:_fustian
Date:April 3rd, 2013 07:42 am (UTC)
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These studies seem to take no account of the possibility that the neurodegenerative effects they're reporting are caused by adulterants or opportunistic infections--or, as you mention, oxygen starvation--rather than the heroin itself. (Where is the control study of patients prescribed diacetylmorphine for long-term pain management?) I guess that's outside their scope, though; after all, street heroin is what most opiate users are administering. But that consideration would seem to be highly relevant in the formulation of harm-reduction policy.
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From:tatjna
Date:April 3rd, 2013 08:05 am (UTC)
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One of the studies (either the first or the second one, can't remember) attempted to factor in things like education level and social status to their findings, which in some respects can be a useful indication of the potential for confounding factors. The Russian study mentions that at the time, a significant percentage of heroin addicts were children of wealthy middle class families, as heroin use was 'taking off' there at the time. This would suggest that they at least considered the potential effects of poverty in relation to their findings. However, you're right in that none of them acknowledged it as a significant factor in their findings.

Likewise, the stress, nutritional deprivation and violence associated with the lifestyle of addiction to an illegal drug are not factored in as potential influences on cognitive function here. In one respect I think that's a huge failing, in another it's almost impossible to separate a drug of addiction from the lifestyle associated with it if the drug is illegal. The scales of harm produced by David Nutt and his crew have the same problem. If you're wanting to see if addiction is associated with cognitive impairment, then the lifestyle is currently part and parcel, since legal, pure heroin (and amphetamine) are not generally available. And none of the studies claim that 'heroin causes X' so they are covering their arses as far as making causative claims goes.

In terms of prescribed medications, I guess the question is, are you studying addicts? And if you're studying addicts, how many of them will still be on their prescribed medication? Apparently what normally happens is that the person becomes addicted, doctors stop prescribing, and they move on to street drugs - and then end up in studies as addicts, again with all the associated lifestyle co-factors.

I would be interested in seeing a study done on long-term patients of prescribed heroin programs in Switzerland. I expect that sort of research will start emerging pretty soon, if it doesn't already exist.
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From:_fustian
Date:April 3rd, 2013 08:32 am (UTC)
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it's almost impossible to separate a drug of addiction from the lifestyle associated with it if the drug is illegal

Indeed. So studies like this are always likely to be analogous to investigating the effects of a gluten-rich diet on people who collect wheat from rail sidings: more anthropology than pharmacometrics.

I would be interested in seeing a study done on long-term patients of prescribed heroin programs in Switzerland.

Sure; that would eliminate a few of the confounding factors. The UK still prescribes heroin for chronic pain management though (thus my ref. to diacetylmorphine). Mind you, those patients aren't likely to be free of confounding factors, either. Animal studies would have seemed to be a more direct route, were there no ethical considerations. I guess there are things we just can't be study directly.
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From:tatjna
Date:April 3rd, 2013 08:40 am (UTC)
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It's a failing of research on drug users, in my opinion, that it's almost entirely focused on problem drug use. On one hand, I can see why - if it's harm we're trying to reduce, then harm is where we should look. But on the other, it entirely ignores the 85-97% (depending on who you ask) of illegal drug users who don't suffer harm, and I think that ignoring this group is ignoring a valuable resource for comparison.

I intend to remedy that. ;-)
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From:helianthas
Date:April 3rd, 2013 08:16 am (UTC)
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Interestingly, ADD/ ADHD -- characterized by executive function deficits including difficulties with prioritization and decision making and thought to be controlled by the pre/frontal cortex-- is *treated* with amphetamine. The class I took said that these areas in folks with ADHD but not taking amphetamine at the moment look abnormal on fmri scans, meaning there is lowered activity. I'm assuming the amphetamine increases the activity in these regions while taking it (it's short acting.) these studies seem to imply that the amphetamine causes the impaired decision making deficits, but as you're saying above in terms of correlation vs causation, maybe folks drawn to amphetamine use have deficits in these regions to begin with. </p>

I'd hate to think that amphetamine given as medicine could be causing further deficits in brain function...

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From:tatjna
Date:April 3rd, 2013 08:42 am (UTC)
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That's an interesting point and one that I unfortunately know little about. I believe that people who use amphetamine for ADHD don't achieve the same sort of high as neurotypical users, is that right? Definitely implies there is something different in the brain, but I don't know whether the differences are the same as the ones found in heavy meth users. I suspect there's research out there about this though.
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From:siobhan63
Date:April 3rd, 2013 03:12 pm (UTC)
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My husband has aspergers and ADHD and does take ritalin now and then (not regularly). It doesn't make him agitated or hyper or "high" - just able to focus (although sometimes too intently and if he gets focused on something he shouldn't, it can get ugly). He can also drink shitloads of coffee without being the least bit affected by the caffeine.

He also has an Rx for medical pot for the Aspergers - he doesn't act or seem the least bit stoned in the usual pot sense - again, it makes him MORE focused and calmer and even more alert.
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From:Will Marshall
Date:April 4th, 2013 01:29 am (UTC)
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Pretty much.

Amusingly, A: ADHD is commonly misdiagnosed in hyperactive kids, and B: diagnosed kids are often prescribed amphetamines.

As you can imagine, this does NOT end well.
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From:jaelle_n_gilla
Date:April 3rd, 2013 08:32 am (UTC)
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Sounds logical, that different drugs damage the brain differently. After all, that's why we take drugs - to make us feel better different. Each drug makes you feel different from the next drug, so obviously they target different areas or synapses of the neural system. And continued use of said drugs are bound to have a lasting effect on exactly those cells they target.

Of course that means "drugs" in the sense of "illegal substances" but also alcohol and tobacco. Although with tobacco I guess you kill yourself with lung cancer before the brain actually suffers significantly. Oh well.

I just saw a documentary on crystal meth. Granted, it was from the propaganda side with a raised finger but the before-and-after pictures of such drug users of under a year sometimes where shocking. Dear gods those people had the most terrible facial disfigurements! Can quite put you off such things for good.
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From:tatjna
Date:April 3rd, 2013 08:53 am (UTC)
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From what I understand, tobacco doesn't cause any significant changes in the brain, even after heavy long-term use. At least, according to the chapter I just read in a book about it. ;-)

I think it's important to acknowledge that not all drugs change the brain in any chronic way (obviously psychoactive ones affect the brain when under the influence) - so actually continued use is not bound to have a lasting effect, it depends entirely on the drug in question and a number of other factors such as method of administration, associated lifestyle, dosage rates, and the like. Many illegal drugs are not associated with brain damage, and many legal ones are, like alcohol as you point out.

Meanwhile, the shock/horror anti drug campaigns are quite scary aren't they? Unfortunately, they don't seem to reduce uptake of drugs (not an academic study, but mentions where more info can be found if you're interested). Apparently they put some people off, but those people tend to be people who wouldn't have tried meth in the first place, and it seems young people tend to see anti drug campaigns as a joke.

Despite this, I thoroughly agree that crystal meth isn't something I'd be interested in getting into. Dopamine-based psychoactives = yeah nah.
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