One would think the easiest, simplest idea would be to avoid harm.  Who wants to be hurt, who really wants others to suffer?

If a substance is invented or discovered that seriously hurts people, shouldn’t it be easy to avoid getting hurt?

But when it comes to substances, or chemicals, that alter how our mind works, the stories situation always seems to get complicated.

A few weeks ago, the great journalist/author, Malcolm Gladwell, returned to the pages of The New Yorker, with an incredibly thought-provoking re-think on the issue of marijuana.  He asks a tough question: “Do we know enough about marijuana?”  After reading this essay, the answer is clearly, no.

https://www.newyorker.com/magazine/2019/01/14/is-marijuana-as-safe-as-we-think

Gladwell asks two questions as the nation heads in the direction of making marijuana use far more common.

The first question he asks is: Does marijuana work as a medication?

The second question he asks is:  If we had a million people start using marijuana, would any harm occur?

His most important finding on both questions is a resounding:  We don’t know.

Does marijuana work as a medication?

This question came as a surprise to me, after all so many states, including the our own fairly cautious state of Ohio, have legalized the use of marijuana as a medication.  One would think, at least hope, that authorities in charge of such a process would due some very detailed study of the evidence before drafting legislation to formally make us of marijuana as a medication for various conditions a policy of the state.

Gladwell cites a recent National Academy of Medicine study from 2017 that did an exhaustive review of the evidence of how well marijuana works as a medicine, and how safe it is as a form of recreation.  This review was authored by 16 scientific experts and was 468 pages in length.

On the question of what the evidence is for how well marijuana works for various medical needs, here is what the report stated:

• To diminish nausea from chemotherapy: “there are no good-quality randomized trials investigating this option.”
• To treat pain:   There is “evidence for marijuana as a treatment for pain but very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products in the United States.”
• To treat epilepsy:  “Insufficient evidence.”
• To treat Tourette syndrome: Limited evidence
• To treat ALS:  Insufficent evidence
• To treat Huntington’s disease: Insufficent evidence
• To treat Parkinson’s syndrom:  Insufficent evidence
• To treat Irritable Bowel Syndrome: Insufficent evidence
• To treat Dementia:  Probably not effective
• To treat Glaucoma: Probably not effective
• To treat Anxiety:  May be effective
• To treat Depression:  Probably not effective

These conclusions from the experts reviewing all available evidence in a National Academy of Science report were very surprising to me.

I shared the impression that many of us have that marijuana is established as one of the very best treatments for the nausea of cancer and its chemotherapies and for glaucoma.  I am quite sure many, many people with these conditions have used medicinal forms of marijuana and experienced quite real, often dramatic relief.  So how can the National Academy of Science come to such a conclusion?

The answer is ultimately that the evidence, to date, provides no clear evidence for marijuana working, or not working, well as a drug for these listed conditions.

One could now ask, why not?  Goodness knows plenty of people use marijuana, plenty of doctors prescribe it, the evidence should be easily at hand.

The answer to this question is that it turns out to be very hard to tell if a drug works, or does not work.  If I have a problem and swallow a pill, one of three things will happen to my problem- it will get better, it will get worse, or it will remain the same.  It is very easy to tell which of these three things happen after I swallow that pill, but determining what role the pill played in any of these outcomes is hard to prove.

Let’s say I get better, maybe I would have without the pill, same could be said for any outcome after I take the pill.

One way to sort it out is to simply ask a huge number of people who have swallowed the pill what happened to them afterwards.  If everyone got better, and up to that time, no one did before the pill was used, that suggests the pill works.   This is the level of evidence for most understanding for how well marijuana works, or does not work, for various conditions.

The problem with this approach is that knowing you took marijuana in itself can impact how you feel.  So to try to eliminate that influence the randomized blinded trial was developed.  In this approach, we take a big number of people with a problem, and give them all the same looking pill.  But for half, and no one knows who is in this half, the pill is the drug, and for the other half it’s something inert like starch.

If everyone knows they are in a marijuana study, and if everyone gets better, the starch group and the marijuana group, then it was not the marijuana that worked.

Another problem is raised in the report’s findings on pain.  Take a close look at that list.  It says we don’t know much about how well marijuana works across a large number of questions.  Questions like, what’s the right amount to take (dose), if it works how well does it work (efficacy), it is better swallowed/smoked/misted/by IV (route of administration)?   These are incredibly important questions.  Take dose, for every drug, it is very important to take the smallest dose that works for two big reasons:  first, if you take less than that amount nothing will happen, secondly, if you take much more than that amount you explode the chances some bad side effects will start happening.

So putting all this together, what I learned from this part of the article is that if marijuana was any other drug, we would not be so enthusiastic about its use as a drug, we simply don’t know even the most basic information about if it works and how to use it to make it work well.  This does not mean it does not work, we simply do not know.

Is there enthusiasm for its use?  Surely.  Are there people whose lives have been dramatically improved by its use?  For sure.  But the history of the use of drugs is littered with a long list of substances that many people swore by that over time were found to be more boosters of enthusiasm than actually effective.   The fact that a report from a deeply trusted source, authored by a number of people with varying perspectives, looking closely at all the evidence concludes that we simply do not have the proof of this drug working very well gives me pause.

Is marijuana safe?

This is a fundamental question for any substance, drug, action, really anything we do.  For marijuana, safety is an issue in two settings- its use as a medication, and its use as a recreational drug.

Gladwell does a great job placing the question in the context of a spectrum of danger for the most common drugs in widespread use across the United States.  On one end is a drug that all agree is as safe as anything could be: coffee.  Coffee may in fact be the only mind-altering drug that has not ruined anyone’s life, mentally or physically.  Not for lack of trying, for there are hundreds of studies trying to find something harmful about using coffee.  Aside from headaches and jitters, nothing has stuck, it appears to be a very safe drug.

Gladwell uses heroin as the opposite end of the spectrum, a drug that clearly kills.  I would have selected cigarettes.  Heroin is deadly for its misuse- overdose, dirty needles, lacing with super-potent opioids etc, all of which have killed nearly 80,000 people last year.  But plain old cigarettes kill 500,000 Americans every year.   In any case, we do have a range of danger in the use of mind-altering drugs, coffee is safe, cigarettes are not.

Where does marijuana fit in?

Another surprise:  No one knows.

I was quite surprised at this conclusion that Gladwell draws.  How is it possible after 5,000 years of use we don’t know the answer to this question?   But Gladwell presents convincing evidence for lack of evidence on this question.

One source of confusion is a problem that is seen in the use of all mind-altering drugs, purity.  Thousands of years ago, the only way to use alcohol was to drink yeast-fermented sugar solutions such as beer, wine, cider.  The only way to use opium was by smoking the poppy juice.  Other mind-altering drugs were also the product of simple processing of various plants such as the peyote.  Typically use of these substances was socially tightly regulated, many societies allowed access to them only in the use of secretive religious activities, or very limited social settings.

It was only 2 thousand years ago in India, China, and Europe that distillation of naturally fermented brews allowed for the creation of high concentrations of alcohol.  The modern era saw the explosion of purification chemistries that have allowed us to synthesize and crystallize essentially 100% pure forms of the most potent mind-altering chemicals, such as the uber-opioids fentanly and cam-fentanyl, and the breeding of uber-THC-concentrated marijuana breeds.

These ultra-potent, ultra-pure preparations now alter our minds with far, far greater force than anything humans have experienced in our entire history.   That makes them far, far more desirable for anyone wanting to alter their mind, and far. far more dangerous.  Alcohol hit this purity, as  noted, about 2 thousand years ago, but now our market is flooded with many, many more drugs of pure potency.

For marijuana, the ultra-high THC concentrations found in current breeds means we are talking about a very different drug than the marijuana of even 15, or more, years ago.

As noted above, as the dose of a substance goes up, the chance of a bad side effect goes up too, a very basic law of any active drug.

In Washington state, the first state that legalized marijuana for recreational use, the most common form the drug is delivered is by use of high concentration extracts for inhalation.  Old marijuana in reefers typically delivered a smoke that was 3-5% THC, the new forms most widely used in Washington state deliver vapor that is 65% THC!

When it comes to the safety of marijuana, the most upsetting observations have to do with the chances that people using it will develop schizophrenia and/or violent behavior.

These observations fly in the folk thinking that marijuana is a calming drug, calming the buzzing mind, how can it make one schizophrenic or  violent?

We don’t know the answer to this question, but here are the observations:

• Some psychiatrists are reporting that now that use of marijuana is the US is about double of what it was not too long ago, a new type of patient with schizophrenia is showing up- they are older, and from the stable middle-class professional class who have used only marijuana.
• In Finland, where marijuana use is widespread, the incidence of schizophrenia has doubled since 1993
• In Denmark, widespread marijuana use has been associated with a 25% increase in the prevalence of schizophrenia since 2000.
• In the United States, where marijuana use has doubled recently, ER admissions for schizophrenia have gone up 50% since 2006.
• In the United States emergency rooms, if you count schizophrenia as a primary or secondary diagnosis, ER admissions went from 1.26 million to 2.1 million since 2006.
• A 2013 paper in the Journal of Interpersonal Violencestudied 12,000 high school students in the United States.  For kids who used only marijuana, they were 3 times more likely to have violent behavior.  For students who only used alcohol the number was 2.7
• In the state of Washington, US, marijuana was legalized in 2014.  The state’s rate of murder and aggravated assault rose 40% between 2013-2017.

What to Do?

We started this essay by observing, shouldn’t it be easy to decide to avoid harm?  The story of marijuana is no different from any other drug people desire, the avoidance of harm turns out to be wildly complex.  When harm faces desire, desire often wins.

With this in mind we can look at some options.

The most complete solution is to end the harm.

This also turns out to be the one solution that is closest to impossible.   How could ending harm happen when it comes to harmful mind-altering substances?  The way to do this is actually quite simple.  For the #1 killer of people in the United States, the way to end the harm is to stop growing tobacco or the importation of any tobacco or nicotine containing products.  That would save about half-a-million lives a year.  Nothing else in the history of medicine, or the horizon of research, would save so many lives.  But we all know this will never happen.

We tried this solution with alcohol, it was called Prohibition.  Just the word Prohibition conjurs up foolish overreach.  But during Prohibition the rate of dying from alcohol dropped 50%.  Today in the US about 100,000 people die of alcohol every year, still far more than the opioid epidemic, but no one dare even talk about ending use of alcohol, even though about 100,000 people would avoid dying every year if we did this entirely.

I find the fact that ending the existence of drugs that kill completely unacceptable the clearest evidence of the power of desire over harm.

There is something about the distress of the adult human mind that almost absolutely demands relief.  Every society we know of has developed mind-altering drugs, as well as rituals and practices to soothe our aching minds.  No power on earth has ever effectively taken away drugs that offer this relief.

And so the tactic of ending the harm is not doable.

Reduce the harm

If we cannot eliminate the harm, perhaps we can limit it.

There are steps that have worked to reduce harm.  Until the explosion of the vaped nicotine devices, we saw anti-tobacco campaigns working. For over 100 years about 25% of American kids graduated from high school smoking cigarettes, that number is in real decline for the first time, so we know making some drugs illegal under a certain age and persistent messaging can limit the harm.

For some drugs, the strategy chosen to reduce harm is to make use a crime.  This is the strategy currently in use for cocaine and heroin in all states, and marijuana is a shrinking number of states.  This strategy has had limited impact, but in the case of marijuana, removing this strategy clearly boosts use.

As for cigarettes and alcohol, and in a growing number of states for marijuana, the legal strategy is to outlaw its use under the age of 18 or 21.  These laws clearly have some impact.  Amongst high school seniors, about 51% used alcohol sometime in their life in 2018, down from 82% in 1997.

BOTTOM LINES

1. At Advanced Pediatrics, we always ask two basic questions whenever we look at whether to recommend any medication, procedure, even consultation:  Will it help?  Will it hurt?
2. The United States is right now following a tremendous surge of interest in marijuana, as a medication, and as a recreational drug.  The trend is clearly set towards legalization and the emergence of great numbers of marijuana medical programs.  Use of marijuana in the US is on the rise.
3. Malcolm Gladwell comes to us with an essay that gives at least me pause.  In an era in which the presumption of innocence of marijuana is strong, Gladwell dares to pause and ask the two questions we favor:  Does marijuana really work as a medicine?  Is marijuana really safe to use?
4. On the question of whether marijuana works as a medication, with the exception of anxiety, a thorough review of the evidence of its ability to really work in 12 conditions where most of us assume it does work concludes- the evidence that it works simply does not yet exist!
5. On the question of safety, a real question of rare but real risk of developing schizophrenia and also of becoming violent (NOTE: these are two very distinct and likely completely unrelated conditions) does exist, we do not know the answer to whether the risk is for sure, but neither do we know the risk is not for real, yet.

I remember many years ago people used to say, how can cigarettes kill, I had an uncle who smoked a pack a day and lived to be a very healthy 100 years old.  The answer was always simple.  Take a gun, put one bullet in the six chambers, spin the chambers, and then ask, is it safe to point the gun at your head and shoot?  Well, for five of six shots, some would say yes.  I would say no, for every shot.  You just don’t know which chamber is pointing at you when you pull the trigger.

For full disclosure, I have never smoked a cigarette or used THC or marijuana in any form.  I of course know many who have done both or either, and seem perfectly fine, but as we now know very well for cigarettes, a substance can cause harm so serious that even if it only befalls a minority of users, it would be smart not to put yourself at risk.

This report tells me that as of today, surprisingly, we simply do not know enough about THC and marijuana to endorse its use, either as a medication or as a recreational drug.   For children, we actually know enough to know it can permanently damage brain development, and so we fully support the AAP policy clearly stating no child should use marijuana or marijuana products recreationally.

As with any substance, we do hope that soon we will find evidence for use of cannabis products that work safely in the relief of as many conditions that cause suffering as possible.

But, the burden of proof rests squarely with any substance or action that proposes to alter our bodies and minds to prove that it does, in fact, help, and does not hurt.

To your health,
Dr. Arthur Lavin