Sunday, April 1, 2012

Interview with Cognitive Neuropsychologist Keith Laws

LSD, E, CBT, and “Mind-Pops.”

Our latest participant in the “Five Question Interview” series is Dr. Keith Laws, professor of cognitive neuropsychology and head of research in the School of Psychology at the University of Hertfordshire, UK. Dr. Laws holds a Ph.D. from the Department of Experimental Psychology at the University of Cambridge, and is the author of Category-Specificity: Evidence for Modularity of Mind. He has written extensively on cognitive deficits resulting from certain types of neurological injury, and has won several awards for his research on cognitive functioning in schizophrenia. He also maintains an active interest in the challenges of functional brain imaging. Professor Laws is frequently quoted in the British media, and is the author of more than 100 peer-reviewed articles. He is a Chartered Psychologist and an Associate Fellow of the British Psychological Society. And recently, Professor Laws became a blogger, launching the LawsNeuroBlog. He maintains a web homepage, and is virtually unbeatable in the category of obscure British rock trivia.

1. LSD is back in the news, with a rehash of several old studies on acid and alcoholism. A lot of people would like to revive research interest in LSD, MDMA, magic mushrooms, and other psychedelics. What’s your view?

Keith Laws: Yes, “re-hash” is an appropriate phrase—we are witnessing a rebranding of “counter-culture” as “over-the-counter-culture.” The history of LSD research is frequently retold as if grand therapeutic advances were halted because hostile governments criminalised LSD. The bottom-line, however, is that most studies of the 50s and 60s produced little worthy of further scientific pursuit. The recent meta-analysis of 60s studies examining whether LSD reduces “alcohol misuse” is a case in point.

That meta-analysis consisted of 6 trials—none of which produced a significant effect, but their total pooled effect suggested some impact on alcohol misuse. In my recent post on this study, I highlighted a series of points, including: how it is likely that further negative studies have been gathering dust in the file drawers of researchers over the years; how some samples consisted of people with serious comorbid mental health and neurological problems (schizophrenia, epilepsy, organic brain disorder, low IQ); and crucially, how the authors made the totally unfounded assumption that anyone dropping-out of the studies had relapsed into drinking. This had a large and disproportionate impact on the control samples in those studies—as many more dropped out from control groups. Combined with the lack of significant effects in any one study, doubts exist about relying on these data as a justification for starting large-scale trials of LSD for alcoholism. We should certainly skeptically regard statements by some, such as Professor David Nutt, that LSD is “as good as anything we’ve got for treating alcoholism.”

2. Tell us about your research interest in the effect of Ecstasy (MDMA) on memory.

Keith Laws: First, I think its crucial not to confuse E and MDMA. Studies of MDMA in humans are few, and mostly examine acute effects via self-report. The vast majority of studies though, including our work, examine the residual effects of street-E in abstinent users i.e. taking largely unknown compounds mixed with varying degrees of MDMA. For me, the real public health issue relates to street-E since most people outside of the lab rarely get to consume pure MDMA.

In 2007 we meta-analysed 26 studies that had examined memory on standardized tests in over 600 ecstasy users and 600 non-users and found significant long and short-term verbal memory impairments in 75% of users. Intriguingly, E was unrelated to visual memory problems; however those who also smoked cannabis did display significant visual memory impairment. A key finding of ours was that the lifetime number of E tablets consumed was unrelated to the degree of memory impairment. This led to a host of misrepresentations in the media and amongst E users who saw it as license to take as many Es as they want. I view this finding, however in a much starker light—taking E is akin to playing Russian Roulette with your memory. Some may tolerate 100s or even 1000s of E tablets, but for others far fewer may lead to memory problems—we can predict that 3 in 4 users will develop memory problems, but not which 3 or after how many tablets. Of course, ecstasy (like Cannabis) is often advocated as a safe-ish drug because it rarely kills. Indeed, metrics of drug harm developed in the UK emphasise physical and social harm, but fail to explicitly acknowledge the cognitive problems associated with E and other recreational drugs. Given that as many as 500,000 young people in the UK use E each week and 75% are affected, then that’s 375,000 young people developing significant verbal memory problems!

3. You’re not convinced by the findings of a recent study of magic mushrooms, where the researchers documented an overall decrease in brain activity. What else could account for this effect?

Keith Laws: Well, the surprising thing about the Carhart-Harris et. al. psilocybin study was the general pattern of brain deactivation, which contrasts with the findings of activation in others such as Vollenweider and colleagues in Switzerland who find increased activation. The decreased activation especially in the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC) were curious and reminded me of the similar deactivation in these areas linked both to anxiety and to the anticipation of unpleasant events. It occurred to me that the prospect of tripping in a scanner may be quite anxiety provoking, and several features of the study led to me to think this may have been the case. First the order of testing was always the same - participants received the placebo scan always before the psilocybin scan and so, could always anticipate the trip— potentially heightening anxious anticipation in that condition. Second, Carhart-Harris et. al. measured “anxiety” and “fear of losing one’s mind” and both multiplied many fold in the psilocybin condition. Interestingly and subsequently, Vollenweider and colleagues pooled date from 23 studies and found that experimental settings involving scanning most strongly predicted unpleasant and/or anxious reactions to psilocybin - converging directly on my suspicion. Although nobody would deny that hallucinogens such as psilocybin impact brain function - the question is which parts reflect the “trip” and which parts reflect “anxiety about the trip”?

4. You have also looked at the matter of using cognitive behavioral therapy for various kinds of mental disorders. How does CBT measure up, in your opinion? Is it useful for addiction?

Keith Laws: Yes, unlike any other country, the UK endorses using CBT to treat psychotic symptoms and to prevent relapse in schizophrenia. Indeed, “NICE” (the National Institute of Clinical Excellence), which decide which treatments are made available to UK patients, suggest that we offer CBT to “all people with schizophrenia”. Anyway, we meta-analysed the data for whether CBT reduces symptomatology or prevents relapse and came to the conclusion that the evidence supports neither. Crucially, CBT only appeared to “work” when the therapists were not blind at outcome assessment i.e. they knew to which group the patient was assigned (CBT or control)! The irony is that CBT therapists sing the mantra of evidence-based practice!

In terms of the use of CBT in people with substance abuse problems, it produces a small impact on abstinence with opiates, stimulants and cocaine, but has little or impact on alcohol use; and as one might expect, these effects disappear across time. Some evidence also suggests that women respond better to CBT than men. Perhaps the most intriguing finding in this area is that CBT has had much greater success in reducing cannabis use, with up to 80% showing significant reduction in use.

5. What else have you been investigating recently? What are you excited about?

Keith Laws: Over the past 3 years or so I have been doing more work with individuals suffering from the obsessive compulsive syndrome of disorders i.e. OCD, Body Dysmorphic Disorder, Trichotillomania, Schizo-Obsessive disorder, Tourette’s, and Perfectionism. Our work is looking at phenotypes that might be expressed through this range of disorders and in their first-degree unaffected relatives. 

Other things we are working on include what we call “Mind-Pops”—those little thoughts, words, images, or tunes that suddenly pop into your mind at unexpected times and are totally unrelated to your current activity—described long ago by novelists such as Marcel Proust and Vladimir Nabokov.  We have just published a paper showing that verbal hallucinations, the core symptom of schizophrenia, may be related to the mind-pop phenomenon that almost everybody experiences, but just manifests itself in a different way.


Ryan said...

There is a clinical trial of magic mushrooms (psilocybin) for smoking cessation going on right now at Johns Hopkins. Also, there is a clinical trial of LSD for anxiety in Switzerland. Native Americans have said for generations that psychedelic substances like peyote (mescaline) and ayahuasca (DMT) help with alcoholism and drug dependence. There will likely be increasing clinical interest in psychedelic treatment of addiction and other emotional disorders.

The historical reasons for why these medications have been ignored is not really the issue, the question is whether psychedelics can help people now. What are the risks and benefits?

Dirk Hanson said...

"There will likely be increasing clinical interest in psychedelic treatment of addiction and other emotional disorders"


I am sympathetic to this line of inquiry,but I think psychedelic advocates are kidding themselves about the applicablity of a trip on LSD, MDMA or psylocybin for most alcoholics or addicts. Being shot out of a cannon into an alternative reality is not an unmitigated good--it is terrifying and traumatic for many. Bad trips happen. It would help if advocates would admit this.

Ryan said...

The recent clinical trials of LSD and psilocybin, as well as MDMA, have all been approved by review boards and national governmental authorities (FDA or equivalent), the same as for any clinical trial. This involves an evaluation of the evidence for risk by physicians and scientists unconnected to the studies.

Everything has risks, including psychiatric medications, also meditation or hiking in the mountains. When evaluating psychedelics, as with anything, it's important to take an objective view of all the evidence and not be too biased by anecdotal stories, either of harm or benefit or "didn't do snything for me".

You might find it relevant to read this 2011 harm assessment of psilocybin mushrooms, commissioned by the Minister of Health of the Netherlands, where psychedelic fungi are legally sold in shops. Spoiler: they note cases of harmful consequences but conclude that these are rare given the amount of use and thus there is no public health reason to ban sale of magic mushrooms. If you search up the authors, none of them appear to be "psychedelic advocates". Harm potential of magic mushroom use: A review

Dirk Hanson said...

In the end, The Netherlands decided to ban the sale of magic mushrooms, nonetheless.

Ryan said...

The 2011 harm assessment was written after the Dutch "ban" on magic mushrooms, which was pushed through by the ruling Christian Democratic Party against the recommendations of the expert drug advisory committee -- this is described in the updated, English-language harm assessment.

Commercially-grown psychedelic psilocybin fungi continue to be openly sold in Dutch "smart shops", not "mushrooms" only "truffles", but it's the same thing. So despite all the news, there wasn't truly a ban at all. (Politics: don't expect it to make sense.)

An entertaining video about the current psilocybin situation in the Netherlands: Hamilton and the Philosopher's Stone

Dirk Hanson said...

I wondered about that, since I've clearly seen 'shrooms being sold in shops in Amsterdam since the ban.

Ryan said...

The UN 1971 Convention on Psychotropic Substances calls on countries to restrict psilocybin to scientific and medical use, but it does not cover preparations of psychedelic plants and fungi, like magic mushrooms, mescaline cactus, or ayahuasca. It is entirely up to individual countries whether or not to restrict magic mushrooms, whether fresh, dried, or otherwise prepared.

The 2005 UK ban on magic mushrooms, which seems to have been an actual ban, was not done with the approval of the Advisory Council on the Misuse of Drugs (ACMD). Chairman David Nutt had asked the Blair government to give the ACMD a heads up if mushrooms were to be debated, but then the ACMD was only given a couple days notice, not enough time to put together a report.

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