In my last post on cannabis, I reviewed some observational evidence that smoking marijuana could be seriously bad news if you have psychosis or relatives who do, putting you at higher risk for psychosis yourself. Ultimately there will be no gold standard randomized controlled trial - the design for that would be: randomize one group of teenagers at high risk for psychosis to smoking pot (hey, make it multi-arm - some will smoke LOTS of pot, and others less), and have another group not smoke pot, follow them through young adulthood, and see what happens.
Yeah, that's not going to happen. But what we do have as evidence in several epidemiologic studies and some prospective cohort trials is that the more pot and the earlier a teenager starts smoking pot, the higher the risk of developing psychosis. We also have some plausible biologic mechanisms (this study, for example, seems to show that folks with cannabis dependence and folks with schizophrenia have similar brain metabolism in key areas, which were significantly different than non-schizophrenic non-cannabis dependent folks). And in animal studies, where randomized controlled trials can be done, heavy doses of THC seemed to damage the brain.
I feel like music. How about Austin's own Spoon, with Don't You Evah (right click to open in new tab).
Is the news all bad for funny cigarettes? Any time one badmouths marijuana or questions its benefits one will find that a bunch of people pop up with all sorts of miraculous properties of cannabis. And, in truth, cannabis is not just about THC, and is an exceedingly interesting plant with all sorts of intriguing cannabinoids in it. As commenter Erik noted, cannabidiol seems to be neuroprotective and balance some of the more toxic effects of THC, suggesting that "vintage pot" with a better ratio between the two might be much healthier.
I have used cannabinoids clinically (never in psychiatry, however) - there is an FDA-approved synthetic THC called marinol that we used to give out on the cancer ward in medical school, in Texas, to cachectic patients who had no appetite. Back then before the proliferation of a ton of antiretrovirals we saw a lot more advanced AIDS - those patients also seemed to benefit from marinol to increase appetite. I must say I did a number of consults on hospitalized cancer patients in Massachusetts, but never saw marinol prescribed up here. If you look at the link to marinol you will find the DEA page describing that the purified synthetic THC is much safer than cannabis smoked au naturale.
Some of the DEA's points are valid - lord knows what is in the cannabis you might buy from your friendly neighborhood dealer - and certainly in the case of immunosuppressed cancer and advanced AIDS patients, smoked joints could easily be adulterated with natural fungi that grow into big nasty (and deadly) fungus balls in the lung. I saw a case of this fungus ball in medical school in a patient immunosuppresed with HIV who also happened to smoke a lot of pot. It could have been from other sources, of course, but my attendings assured me they had seen it several times in AIDS patients who were heavy pot users. It's not a pleasant way to go, and the treatments are horrible.
(Over time, you see enough cognitively bereft heavy pot users and psychotic heavy pot users and top that off with deadly fungus balls, and you can see why I'm none too fond of the stuff. These types of experiences are anecdotal, but influential to any doctor in practice. Part of being human, I suppose.)
Other DEA points are the same old conventional wisdom and faulty reasoning that led T. Colin Campbell to conclude that animal protein causes cancer from some rodent studies using isolated casein and aflatoxin. Natural cannabis contains a mixture of cannabinoids with different effects - one can't necessarily extrapolate the effects of just THC to marijuana in general (though it seems more reasonable to do so with the modern "skunk" high-THC marijuana). And "purified synthetic THC" could be kinda like casein without the whey in aflatoxin-poisoned rodents - a bad idea for pretty much anyone if you aren't a step away from death via advanced disease + starvation.
So, the lengthy intro aside, let's examine some of the evidence for marijuana that shows positive effects in the human brain. Fortunately we have the Rolls Royce of academic reviews available - a Cochrane Review - Cannabinoids for the treatment of dementia.
So what's the good news for marijuana? Well, cannabis receptor 1 and 2 (CB1 and CB2). CB1 is primarily active in the central nervous system, and CB2 is found more in the periphery, particularly on the white blood cells. Some studies of cannabinoids seem to find them to be, in the whole, neuroprotective. They regulate glutamate transmission (reducing neurotoxicity) and may reduce neuroinflammation. They might protect the brain from toxic injury. THC may also be what is called a cholinesterase inhibitor, which is a class of drugs that are now used to treat Alzheimer's.
Small open label trials showed that marinol (synthetic THC) reduced agitation and helped weight gain in dementia patients. Another small trial of cannabidiol showed it helped with sleep. But, as Peter has been known to say, small, third-rate studies are small, third-rate studies, and do little more than give us a reason to design larger, better studies that might prove a point or two. The great thing about a Cochrane review is those scientists comb MEDLINE and OVID and conference reports and ongoing research trials and PUBMED for the awesome studies. Those that are randomized, controlled, and done with acceptable follow-up and inclusion criteria. And when you comb the literature for that sort of study with respect to cannabis products and dementia, you find one study that wasn't even the greatest of studies (15 patients, using marinol), so the reviewers ultimately have to say there is no reliable evidence that cannabis should be used clinically in dementia patients.
And what about non-dementia, non-psychosis studies - neuroimaging studies, for example? After all, I treat a particular population - one apt to be anxious, depressed, demented, or psychotic. If you are none of the above, are not at high risk for psychosis (ie no family members with psychotic disorders and no personal history), and like to spend the days smoking out on your mom's basement couch - how risky is it to your brain? Well, a neuroimaging review seems to indicate there are metabolic changes in the brain related to smoking pot, but no one is sure what it means. Other kinds of studies of neuropsychologic testing also show mixed results.
What seems to be the consensus when one reads general articles meant for psychiatrists (in Psychiatric Times, for example), is that marijuana in the brain is perhaps best conceptualized as a potent nerve growth factor. In a young, growing brain (a teenager), likely replete with plenty of nerve growth factor, extra nerve growth factor has the potential to be disastrous - lighter fluid on a briskly burning fire. In an older, demented brain (a smoldering, dying fire), nerve growth factor may well be therapeutic, but there isn't enough good evidence to conclude that is the case.
Is marijuana "paleo?" The anthropologists can answer that question far better than I can. Is it healthy? I can name circumstances which encompass the majority of my patients in which there is some reasonable evidence that it is most likely very unhealthy and risky. I'm willing to withhold judgment about it's ultimate therapeutic value in other cases (like dementia) until more evidence is in. And certainly there will, logically, be a difference between artisan variety vintage stuff than the "skunk" high-THC brands of today.
And let's not forget the underlying evolutionary principle - human babies born of natural eating and natural living mothers and fathers are strong and amazing and not broken. We are not automobiles - when left to an evolutionary diet and activities we are likely to thrive, as we always have. And cannabis has the potential to be a potent long-term brain-altering substance. There's an old adage in psychiatry: Don't fix what ain't broken.
In the modern world, well, let's hope the science researchers design and implement some good studies that can answer our questions!
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