Medical Marijuana Helps HIV Pain

There have long been anecdotal reports that marijuana can have pain-killing (analgesic) effects in types of chronic pain which are otherwise difficult to treat. This has led to great enthusiasm about the prospect of "medical marijuana" - but, attractive as that might sound, there has always been a lack of hard evidence showing that marijuana in fact works. Being highly illegal in the U.S.A (more illegal than cocaine in fact), it's hard to study.

A paper out today in Neuropsychopharmacology aimed to test the analgesic power of smoked marijuana vs. placebo and found that it was moderately effective. The work was done at the University of California (where else?) San Diego, and the subjects were all men with HIV. Like many such patients, they all suffered from chronic pain due to nerve cell damage, caused by either the virus itself or certain anti-HIV drugs. The patients in this study had all been diagnosed with "distal sensory predominant polyneuropathy" (DSPN), and were already taking standard painkillers such as aspirin and/or opiates such as morphine. This was pain that wouldn't go away.

30 volunteers were randomly assigned to smoke four times per day for 5 days; they smoked either marijuana cigarettes or placebo cigarettes which were similar in appearance but which lacked the active chemicals of marijana. After a two week break the subjects got the other kind for cigarette for five days (a cross-over design). Most, but not all, of the patients had some experience with (illegal) cannabis previously.

The results - After smoking marijuana, the patients rated their pain as being significantly less than when they were on placebo. The difference was significant although not enormous at first glance - a median difference in pain reduction of 3.3 "DDS points" (starting score median was 11.1) which translated into a standardized effect size of 0.60 ("medium" to "large"). So marijuana didn't completely kill the pain, but it was a decent help, and the effect was comparable to that seen with other drugs used in neuropathic pain such as anti-convulsants.

There was one snag, however. Although the side effects of the cannabis were generally minor, one of the patients, who had never tried cannabis before, developed "cannabis-related psychosis" on the first day they smoked the real cannabis.

One cannabis-naive subject had an acute, cannabis-induced psychosis at the start of the second smoking week; unblinding revealed that he had received placebo during the first week and active cannabis during the second.

Marijuana use has been correlated with an increased risk of psychosis. Whether the link is a causal one is hotly debated, but it's plausible that it could be, so it's something to bear in mind. The problem is that, frustratingly, the authors don't tell us anything about what "an acute, cannabis-induced psychosis" actually means. Is this just their melodramatic way of describing the unpleasant but fairly harmless experience of "pulling a whitey"? How long did it last? Did the patient require psychiatric treatment? Full-blown psychosis from the first dose of cannabis sounds rather implausible. Also, a number of drugs currently on the market can cause psychosis in rare cases, such as L-dopa - it shouldn't be seen as the end of the world for a drug, especially if it's one which fills an important niche.

So, this is evidence that marijuana can be helpful in one form of chronic neuropathic pain. Although it was a small, short study in a fairly narrowly defined group of patients, this is a believable result, given the anecdotal evidence and given the fact that mountains of animal studies show that marijuana-like drugs (CB1 receptor agonists) are analgesic in animals. It's a cliché that medical research papers always end with a call for further study on the question at hand, but in this case, I think that really is warranted. If marijuana can help treat intractable chronic pain, we need to know about it, and that means we need more randomized controlled trials.

Ronald J Ellis, Will Toperoff, Florin Vaida, Geoffrey van den Brande, James Gonzales, Ben Gouaux, Heather Bentley, J Hampton Atkinson (2008). Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial Neuropsychopharmacology, 34 (3), 672-680 DOI: 10.1038/npp.2008.120

Medical Marijuana Helps HIV Pain

There have long been anecdotal reports that marijuana can have pain-killing (analgesic) effects in types of chronic pain which are otherwise difficult to treat. This has led to great enthusiasm about the prospect of "medical marijuana" - but, attractive as that might sound, there has always been a lack of hard evidence showing that marijuana in fact works. Being highly illegal in the U.S.A (more illegal than cocaine in fact), it's hard to study.

A paper out today in Neuropsychopharmacology aimed to test the analgesic power of smoked marijuana vs. placebo and found that it was moderately effective. The work was done at the University of California (where else?) San Diego, and the subjects were all men with HIV. Like many such patients, they all suffered from chronic pain due to nerve cell damage, caused by either the virus itself or certain anti-HIV drugs. The patients in this study had all been diagnosed with "distal sensory predominant polyneuropathy" (DSPN), and were already taking standard painkillers such as aspirin and/or opiates such as morphine. This was pain that wouldn't go away.

30 volunteers were randomly assigned to smoke four times per day for 5 days; they smoked either marijuana cigarettes or placebo cigarettes which were similar in appearance but which lacked the active chemicals of marijana. After a two week break the subjects got the other kind for cigarette for five days (a cross-over design). Most, but not all, of the patients had some experience with (illegal) cannabis previously.

The results - After smoking marijuana, the patients rated their pain as being significantly less than when they were on placebo. The difference was significant although not enormous at first glance - a median difference in pain reduction of 3.3 "DDS points" (starting score median was 11.1) which translated into a standardized effect size of 0.60 ("medium" to "large"). So marijuana didn't completely kill the pain, but it was a decent help, and the effect was comparable to that seen with other drugs used in neuropathic pain such as anti-convulsants.

There was one snag, however. Although the side effects of the cannabis were generally minor, one of the patients, who had never tried cannabis before, developed "cannabis-related psychosis" on the first day they smoked the real cannabis.

One cannabis-naive subject had an acute, cannabis-induced psychosis at the start of the second smoking week; unblinding revealed that he had received placebo during the first week and active cannabis during the second.

Marijuana use has been correlated with an increased risk of psychosis. Whether the link is a causal one is hotly debated, but it's plausible that it could be, so it's something to bear in mind. The problem is that, frustratingly, the authors don't tell us anything about what "an acute, cannabis-induced psychosis" actually means. Is this just their melodramatic way of describing the unpleasant but fairly harmless experience of "pulling a whitey"? How long did it last? Did the patient require psychiatric treatment? Full-blown psychosis from the first dose of cannabis sounds rather implausible. Also, a number of drugs currently on the market can cause psychosis in rare cases, such as L-dopa - it shouldn't be seen as the end of the world for a drug, especially if it's one which fills an important niche.

So, this is evidence that marijuana can be helpful in one form of chronic neuropathic pain. Although it was a small, short study in a fairly narrowly defined group of patients, this is a believable result, given the anecdotal evidence and given the fact that mountains of animal studies show that marijuana-like drugs (CB1 receptor agonists) are analgesic in animals. It's a cliché that medical research papers always end with a call for further study on the question at hand, but in this case, I think that really is warranted. If marijuana can help treat intractable chronic pain, we need to know about it, and that means we need more randomized controlled trials.

Ronald J Ellis, Will Toperoff, Florin Vaida, Geoffrey van den Brande, James Gonzales, Ben Gouaux, Heather Bentley, J Hampton Atkinson (2008). Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial Neuropsychopharmacology, 34 (3), 672-680 DOI: 10.1038/npp.2008.120

The British Media's Favorite Diagnoses

I was bored again last night, so time for some more graphs.
This shows the total number of LexisNexis UK News Search hits in the "UK Broadsheets" category from 1st January of each year to 1st January of the next year, for four terms. A hit represents a broadsheet newspaper article containing the specified string(s). (This article might not be "about" that condition e.g., a report about a crime committed by someone with schizophrenia which be a hit for "schizophrenia".)This is the same data for schizophrenia, bipolar/manic depression and autism/Asperger's, but shown as the ratio of hits compared to the number of hits for "Epilepsy" in the same year. I did this because hits for all conditions increase over time, which probably represents the fact that newspapers are getting longer & maybe that they're getting more interested in health (speculation.) Assuming that coverage of epilepsy is relatively immune to "fashion", which seems plausible, this allows trends in the "popularity" of the other three conditions to be seen more clearly.

What's the story? Firstly, the popularity of schizophrenia has remained fairly stable relative to epilepsy since 1985; this is what you'd expect, since rates of schizophrenia haven't changed much over that time. I was a little surprised that the recent cannabis-causes-schizophrenia theme, which some British papers have been pushing quite hard, hasn't had much effect. Hmm.

Bipolar disorder has become much more popular since about 2000; it's now close to being as popular as schizophrenia. Given that the true rates of these two disorders have probably not changed for 30 years, this points to some kind of cultural, as opposed to medical, trend; bipolar is almost certainly more diagnosed and less stigmatized today than in the past - indeed in some circles it's more trendy than just plain depression. (Note that "bipolar" will also give hits for articles using it in the political sense ("bipolar world"), but this is pretty uncommon.)

As for autism, coverage spiked in 2001-2002, the height of the British MMR-causes-autism scare. So no surprise there, but what did surprise me is that the popularity of autism has continued to increase since, with no sign of having peaked yet. Despite the fact that even the most stubborn armchair developmental neurologists have now largely stopped using the British newspapers to argue that vaccines cause autism, autism still gets more mentions than ever before.

So British newspaper readers can expect to hear plenty more about autism in 2009. Just remember that if you want in-depth discussions of this topic you might be better off reading LeftbrainRightbrain. That the newspapers are devoting increasing space to serious illnesses such as autism and bipolar disorder is in many ways a good thing, but quantity isn't quality, as MMR and the media's deeply uncritical coverage of the Kirsch et. al. (2008) antidepressant meta-analysis showed (more on that soon...)

Feel free to draw more conclusions from these coloured lines, as the mood takes you.

P.S I would have liked to do "depression", but that word has many meanings, e.g. in economics. "Clinical depression", on the other hand, seems to me increasingly old-fashioned; people just call it depression. Any ideas as to the best thing to search for?

[BPSDB]

The British Media's Favorite Diagnoses

I was bored again last night, so time for some more graphs.
This shows the total number of LexisNexis UK News Search hits in the "UK Broadsheets" category from 1st January of each year to 1st January of the next year, for four terms. A hit represents a broadsheet newspaper article containing the specified string(s). (This article might not be "about" that condition e.g., a report about a crime committed by someone with schizophrenia which be a hit for "schizophrenia".)This is the same data for schizophrenia, bipolar/manic depression and autism/Asperger's, but shown as the ratio of hits compared to the number of hits for "Epilepsy" in the same year. I did this because hits for all conditions increase over time, which probably represents the fact that newspapers are getting longer & maybe that they're getting more interested in health (speculation.) Assuming that coverage of epilepsy is relatively immune to "fashion", which seems plausible, this allows trends in the "popularity" of the other three conditions to be seen more clearly.

What's the story? Firstly, the popularity of schizophrenia has remained fairly stable relative to epilepsy since 1985; this is what you'd expect, since rates of schizophrenia haven't changed much over that time. I was a little surprised that the recent cannabis-causes-schizophrenia theme, which some British papers have been pushing quite hard, hasn't had much effect. Hmm.

Bipolar disorder has become much more popular since about 2000; it's now close to being as popular as schizophrenia. Given that the true rates of these two disorders have probably not changed for 30 years, this points to some kind of cultural, as opposed to medical, trend; bipolar is almost certainly more diagnosed and less stigmatized today than in the past - indeed in some circles it's more trendy than just plain depression. (Note that "bipolar" will also give hits for articles using it in the political sense ("bipolar world"), but this is pretty uncommon.)

As for autism, coverage spiked in 2001-2002, the height of the British MMR-causes-autism scare. So no surprise there, but what did surprise me is that the popularity of autism has continued to increase since, with no sign of having peaked yet. Despite the fact that even the most stubborn armchair developmental neurologists have now largely stopped using the British newspapers to argue that vaccines cause autism, autism still gets more mentions than ever before.

So British newspaper readers can expect to hear plenty more about autism in 2009. Just remember that if you want in-depth discussions of this topic you might be better off reading LeftbrainRightbrain. That the newspapers are devoting increasing space to serious illnesses such as autism and bipolar disorder is in many ways a good thing, but quantity isn't quality, as MMR and the media's deeply uncritical coverage of the Kirsch et. al. (2008) antidepressant meta-analysis showed (more on that soon...)

Feel free to draw more conclusions from these coloured lines, as the mood takes you.

P.S I would have liked to do "depression", but that word has many meanings, e.g. in economics. "Clinical depression", on the other hand, seems to me increasingly old-fashioned; people just call it depression. Any ideas as to the best thing to search for?

[BPSDB]

Links You Might Like #2, and a note on Powerwatch

The Chronicle of Higher Education has a must-read piece about the integration of sociology and behavioral genetics. In it we learn that the American Journal of Sociology has just run a special issue devoted to that theme - wow. Looks fascinating (I haven't read it yet). As John Hawks notes, however, the traditional feuding between biological and social theorists of behaviour doesn't seem to be over yet...

There was an interesting discussion of the psychology of philosophy over at The Garden of Forking Paths.

Finally, Powerwatch UK have, very decently, included a link to my December 21st criticisms of a paper about leukemia and power lines, in their coverage of that study.

Links You Might Like #2, and a note on Powerwatch

The Chronicle of Higher Education has a must-read piece about the integration of sociology and behavioral genetics. In it we learn that the American Journal of Sociology has just run a special issue devoted to that theme - wow. Looks fascinating (I haven't read it yet). As John Hawks notes, however, the traditional feuding between biological and social theorists of behaviour doesn't seem to be over yet...

There was an interesting discussion of the psychology of philosophy over at The Garden of Forking Paths.

Finally, Powerwatch UK have, very decently, included a link to my December 21st criticisms of a paper about leukemia and power lines, in their coverage of that study.

Critiquing a Classic: "The Seductive Allure of Neuroscience Explanations"

One of the most blogged-about psychology papers of 2008 was Weisberg et. al.'s The Seductive Allure of Neuroscience Explanations.

As most of you probably already know, Weisberg et. al. set out to test whether adding an impressive-sounding, but completely irrelevant, sentence about neuroscience to explanations for common aspects of human behaviour made people more likely to accept those explanations as good ones. As they noted in their Introduction:

Although it is hardly mysterious that members of the public should find psychological research fascinating, this fascination seems particularly acute for findings that were obtained using a neuropsychological measure. Indeed, one can hardly open a newspaper’s science section without seeing a report on a neuroscience discovery or on a new application of neuroscience findings to economics, politics, or law. Research on nonneural cognitive psychology does not seem to pique the public’s interest in the same way, even though the two fields are concerned with similar questions.

They found that the pointless neuroscience made people rate bad psychological "explanations" as being better. The bad psychological explanations were simply descriptions of the phenomena in need of explanation (something like "People like dogs because they have a preference for domestic canines"). Without the neuroscience, people could tell that the bad explanations were bad, compared to other, good explanations. The neuroscience blinded them to this. This confusion was equally present in "normal" volunteers and in cognitive neuroscience students, although cognitive neuroscience experts (PhDs and professors) seemed to be immune.

But is this really true?

This kind of research - which claims to provide hard, scientific evidence for the existence of a commonly believed in psychological phenomenon, usually some annoyingly irrational human quirk - is dangerous; it should always be read with extra care. The danger is that the results can seem so obviously true ("Well of course!") and so important ("How many times have I complained about this?") that the methodological strengths and weaknesses of the study go unnoticed. People see a peer-reviewed paper which seemingly confirms the existence of one of their pet peeves, and they believe it - becoming even more peeved in the process.(*)

In this case, the peeve is obvious: the popular media certainly seem to inordinately keen on neuroimaging studies, and often seem to throw in pictures of brain scans and references to brain regions just to make their story seem more exciting. The number of people who confuse neural localization with explanation is depressing. Those not involved in cognitive neuroscience must find this rather frustrating. Even neuroimagers roll their eyes at it (although some may be secretly glad of it!)

So Weisberg et al. struck a chord with most readers, including most of the potentially skeptical ones - which is exactly why it needs to be read very carefully critiqued. Personally, having done so, I think that it's an excellent paper, but the data presented only allow fairly modest conclusions to be drawn, so far. The authors have not shown that neuroscience, specifically, is seductive or alluring.

Most fundamentally, the explanations including the dodgy neuroscience differed from the non-neurosciencey explanations in more than just neuroscience. Most obviously, they were longer, which may have made them seem "better" to the untrained, or bored, eye; indeed the authors themselves cite a paper, Kikas (2003), in which the length of explanations altered how people perceived them. Secondly, the explanations with added neuroscience were more "complex" - they included two separate "explanations", a psychological one and a neuroscience one. This complexity, rather than the presence of neuroscience per se, might have contributed to their impressiveness.

Perhaps the authors should have used three conditions - psychology, "double psychology" (with additional psychological explanations or technical terminology), and neuroscience (with additional neuroscience). As it stands, the authors have strictly shown is that longer, more jargon-filled explanations are rated as better - which is an interesting finding, but is not necessarily specific to neuroscience.

In their discussion (and to their credit) the authors fully acknowledge these points (emphasis mine)

Other kinds of information besides neuroscience could have similar effects. We focused the current experiments on neuroscience because it provides a particularly fertile testing ground, due to its current stature both in psychological research and in the popular press. However, we believe that our results are not necessarily limited to neuroscience or even to psychology. Rather, people may be responding to some more general property of the neuroscience information that encouraged them to find the explanations in the With Neuroscience condition more satisfying.

But this is rather a large caveat. If all the authors have shown is that people can be "Blinded with Science" (yes...like the song) in a non-specific manner, that has little to do with neuroscience. The authors go on to discuss various interesting, and plausible, theories about what might make seemingly "scientific" explanations seductive, and why neuroscience might be especially prone to this - but they are, as they acknowledge, just speculations. At this stage, we don't know, and we don't know how important this effect is in the real world, when people are reading newspapers and looking at pictures of brain scans.

Secondly, the group differences - between the "normal people", the neuroscience students, and the neuroscience experts - are hard to interpret. There were 81 normal people, mean age 20, but we don't know who they were or how they were recruited - were they students, internet users, the authors' friends? (10 of them didn't give their age and for 2 gender was "unreported" -?) We don't know whether their level of education, their interests, or values were different from the cognitive neuroscience students in the second group (mean age 20), who may likewise have been different in terms of education, intelligence and beliefs from the expert neuroscientists in the third group (mean age 27). Maybe such personal factors, rather than neuroscience knowledge, explained the group similarities and differences?

Finally, the effects seen in this paper were, on the face of it, small - people rated the explanations on a 7 point scale from -3 (bad) to +3 (excellent), but the mean scores were all between -1 and +1. The dodgy neuroscience added about 1 point on a 7 point scale of satisfactoriness. Is that "a lot" or "a little"? It's impossible to say.

All of that said - this is still a great paper, and the point of this post is not to criticize or "debunk" Weisberg et. al.'s excellent work. If you haven't read their paper, you should read it, in full, right now, and I'm looking forward to further stuff from the same group. What I'm trying to do is to warn against another kind of seductive allure, probably the oldest and most dangerous of all - the allure of that which confirms what we already thought we knew.

(*)Or do they? Or is this just one of my pet peeves? Maybe I need to do an experiment about the allure of psychology papers confirming the allure of psychologist's pet peeves...

Deena Skolnick Weisberg, Frank C. Keil, Joshua Goodstein, Elizabeth Rawson, Jeremy R. Gray (2008). The Seductive Allure of Neuroscience Explanations Journal of Cognitive Neuroscience, 20 (3), 470-477 DOI: 10.1162/jocn.2008.20040