a medication for mindfulness?

i just got back from the annual CPDD conference.  this was probably the most provocative slide of the entire conference.  i'm pretty sure it was from a talk given by this fella (although with a week having passed since, i can't be sure, and i can't find the abstract), in a really cool session titled "NEW DIRECTIONS IN THE PHARMACOLOGICAL FACILITATION OF PSYCHOTHERAPY FOR DRUG DEPENDENCE."  anyway i thought it was worth sharing, you can probably hit him up for the details.

alphabetamines talk

i gave a talk about the neuroscience of novel synthetic drugs at the 2013 Club Health Conference some weeks ago.  spice, bath salts, that sort of thing.  then i plain-language'd the slides and put them on the internet.  you can download them here.

psychedelics as pharmacotherapy

Two articles in my Google Reader caught my eye this morning:
Ecstasy, the Marriage Counsellor of Tomorrow
Can Magic Mushrooms Help Cancer Patients?
The first reports on a study that argues we're not evolutionarily built to survive romantic relationships because we simply live too long, so why not consider "love drugs" as an aid to make it together to the end. (as an aside: drugs alone are never the answer! although they can be a terriffic adjunct to long-term behavioural therapy.) The second reports on a book/study exploring the use of psilocybin to alleviate the distress associated with cancer diagnosis.

In both cases, the authors surely raise eyebrows by suggesting that currently illegal drugs with "no accepted medical use" and "high abuse potential" may actually have value when used in therapeutic settings. The notion is neither new nor radical to me, but to a public used to a 'Schedule I = bad' mantra, probably pretty racey. But from a neurobio perspective, I don't see a whole lot wrong with it. Neither article advocates using the drug more than a handful of times, and no addiction has ever arisen from a handful of times. Addiction is an acquired disorder that develops with repeated use and eventually turns compulsive -- not likely to happen when used on an irregular, occasional basis. Even the studies of "seasoned" ecstasy or psilocybin users I've seen tend to report patterns of moderate, weekend use, rather than the kinds of compulsive binges you see with other psychostimulants. And nevermind that hallucinogens such as psilocybin have not been shown to have a dopaminergic reward/reinforcement component, so are not likely to result in addiction altogether. With ecstasy, sure, there are cardiovascular risks or the potential for overheating, it's an amphetamine after all; but again, with the doses implied for these purposes, not likely. And brain damage? If you're picturing studies that pit a drug-using against a healthy brain, consider that the drug-using subjects are selected for heightened use duration or severity, and that the healthy comparison subjects in many cases are allowed a handful of occasions of use in their lifetime -- so the marriage-ecstasy/cancer-mushroom brains are going to look more like the controls than the users.

Of course I'm sure the policy implications are tricky (it's probably hard to allow medical use without unleashing a reckless free-for-all), but can we at least ease up on the "no medical value" mantra so we can see if maybe we've been wrong all along? I don't see the harm in at least finding out.

In any case, I wonder if it's a coincidence that both articles appeared on the same day, or if it's a sign of a turning tide.

Weed or Wheel!

Research Article: Weed or Wheel! fMRI, Behavioural, and Toxicological Investigations of How Cannabis Smoking Affects Skills Necessary for Driving


Article here.  Abstract:

Battistella G, Fornari E, Thomas A, Mall J-F, Chtioui H, et al. (2013) Weed or Wheel! fMRI, Behavioural, and Toxicological Investigations of How Cannabis Smoking Affects Skills Necessary for Driving. PLoS ONE 8(1): e52545. doi:10.1371/journal.pone.0052545

Marijuana is the most widely used illicit drug, however its effects on cognitive functions underling safe driving remain mostly unexplored. Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ⁹-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions. Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. We show that cannabis smoking, even at low Δ⁹-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection. In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity. Subjects are more attracted by intrapersonal stimuli (“self”) and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ⁹-Tetrahydrocannabinol. These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving. 

This article recently caught my eye, and it's pissing me off. Mind you, I don't think PLOS One is the most reputable of sources, but this may not be known beyond academic circles, and any policy-maker will be happy to choose this article over another that may be more difficult to access or extract a message from. And therein lies the problem: It's not that the article is bad, per se. The rationale seems sound, the methodology is acceptable, even the results are fine. What's rubbing me the wrong way is the obvious political agenda, and the way it is snuck into the interpretation and discussion -- and undeservedly so. The sweeping, politically charged conclusions are not at all supported by the data, so even though the data themselves are fine, this kind of aggrandization is dangerous in my opinion. I'm surprised to see this coming out of Europe, where I like to tell myself they're more enlightened about drug research. Sigh.

So let's start with the results. In a nutshell, the investigators had subjects smoke pot vs. a placebo joint, and perform an out-of-scanner object tracking task that has shown some relationship to real-life driving, an in-scanner tracking task while brain activity was measured with functional MRI, and self-reports of high, confusion, confidence in ability to drive, etc. Self-reported effects went as expected after pot compared to placebo, and performance on the tracking tasks decreased. During the in-scanner task, a lot of brain regions predictably involved in task performance showed lower activity after pot vs placebo, and a few showed higher activity. And in some of those regions, activity correlated with self-reported confusion. I may have missed a few, but that's the basic gist of it.

The point of contention is with the statements they make in the interpretation of the data. The abstract alone (which, presumably, is all a policy-maker will read before making a decision) feels like a heap of half-truths and manipulation.
"Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task." I don't think this is a fair description of the rationale for the study. They may well have wanted to investigate the effects of cannabis on brain networks involved in a tracking task, but everything in between is pure conjecture. We don't know if the tracking task has ANYTHING to do with driving ability, in the absence of a test that involves.....actual driving. The out-of-scanner tracking task they use has a "moderate correlation with real-world driving," but that's not the one that was used in the scanner, and they never test if performance on the two tasks correlates with each other, let alone actual driving.
"We show that cannabis smoking, even at low Δ9-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition." This statement isn't entirely unfair, but I don't see how it deserves to be applied specifically to driving. The evidence suggests that subjects were feeling more generally "confused" after cannabis, which could also impair their ability to walk on a crowded sidewalk, or mow their lawn, or play chess. Why isn't the article focused on those?
"Subjects are more attracted by intrapersonal stimuli (“self”) and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance." This statement is the authors' interpretation based ENTIRELY on the brain regions that were activated/deactivated. But brain regions tend to be involved in more than one thing (including, but far from limited to, the thing that is convenient for the interpreter), and it seems overreaching to make it sound like a sure result in the absence of having tested any of these things.
"These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving." This is the one that got me. I mean, what?! Until someone gets a research subject high and puts them in a driving simulator, this is a HUGE leap in logic. How does decreased performance on an in-scanner tracking task translate to real-world driving behaviour? It can't be the only factor that goes into driving, and maybe people can recruit other resources to compensate for impairment when their safety is actually on the line, and just as there is a low blood alcohol level that is considered "safe" for the roads (but surely impairs task performance too), shouldn't it be tested if there is a dose-response relationship for cannabis too before calling for a zero tolerance policy? (I mean, don't get me wrong, I am NOT in favour of impaired driving, and firmly believe that no one has the right to make their intoxication anybody else's problem. But I am equally not in favour of skewed statements with little basis. If you're going to broadcast claims to the world, they should at least be backed up.)

Also, I find the conclusion of the manuscript entirely schizophrenic: "...we failed to find any quantitative correlation between the THC levels measured in whole blood and either the BOLD signal or the psychomotor performance. These results bolster the “zero tolerance policy” that prohibits the presence of any amount of THC in the blood while driving." If self-reported confusion correlated with outcome measures, but THC in the system didn't.....wouldn't it make more sense to call for a zero tolerance policy on confusion?

In all seriousness, though, the paper certainly deserves a spot in the Journal of Proofs of Concept with Potential Implications for the Real World; it's not groundbreaking, but it IS the sort of thing that policies should be built on. But to scoop up a bucket of sand and call it a sandcastle is not just unprofessional, but in this case, potentially detrimental to evidence-based policy progress.