Cannabis as Antidepressant? Thinking Outside the Box

It’s time to reassess the way we treat depression.

If we are to believe statistics, then we are a nation of stressed-out, hapless sods.   The annual American Psychology Association “Stress in America“ survey consistently reminds us that a good 75% of Americans report being either “physically or psychologically” stressed.  As an antidote to chronic stress and the depression that frequently ensues, the prevailing panacea is in the form of an antidepressant, most commonly in the form of an SSRI (Selective Serotonin Reuptake Inhibitor) which is thought to work by increasing levels of the chemical messenger serotonin.   Healthy serotonin levels are credited with promoting the sense of well-being we all want.  Fix the chemistry and fix the problem.

One out of eight Americans takes a prescription anti-depressant (yes, you read that statistic correctly) and it is the leading cause of disability. In recent years usage has skyrocketed.  The number of Americans who say they’ve taken an antidepressant over the past month rose by 65 percent between 1999 and 2014.

By its widespread usage, it would appear that we love our antidepressant prescriptions.  And to be fair, there may be valid reasons to explain why so many Americans take them – more people are seeking help, mental health no longer carries such a social stigma, and (at least one would hope) people feel better on them.

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But an ill wind is blowing in the world of Prozac and its sisters.  The controversy runs deep and there is no shortage of argument on both sides, an argument that I suspect will carry on for years.

For starters, the drugs’ efficacy has been hotly debated and some studies have indicated that these drugs don’t work much better than a placebo.  While there are plenty of favorable studies of antidepressants in peer-reviewed literature, critics argue that the positive studies are much more likely to be released and published, while the studies with negative results are tucked away in a desk drawer.  More recent large-scale meta-analysis (an analysis that combines results of multiple studies) of drug trials have borne out this phenomena which is known as “publication bias.”

Then there are the side effects that so many patients complain about – weight gain, fatigue, loss of libido, and many other unpleasantries.    But what troubles me most is that some of these drugs are very, very hard to quit.  In some cases, even a single day off the drugs can be a harrowing experience.  One patient told me that she forgot to refill her prescription and spent the day off the drug “shaking and raging.”

From my perch as a nurse, I’m starting to hear from various sources about possible alternatives – both conventional and controversial – to treating depression.  My therapist colleagues strongly stand by a form of talk therapy called Cognitive Behavioral Therapy (CBT), in which patient and therapist collaborate to identify negative thought processes and responses.    A compound pharmacist has just sent me an email and research about intranasal ketamine, a drug commonly administered intravenously for anesthesia but also appearing to relieve depression as a side effect.   Nutritional supplement companies send me catalogues herbal mood- adjusting formulas – there’s even one called “Happy Camper”.  Yet another recommendation (and this one may sound really out-there but bear with me) comes from Michael Pollan’s latest and fascinating book “How to Change Your Mind:  What the New Science of Psychedelics Teaches Us about Consciousness, Dying, Addiction, Depression and Transcendence.”   Pollan describes research on using psychedelic drugs to effectively jolt the brain out of its rumination loop known as the Default Mode Network, the ceaseless background banter of unfocused thoughts we all have inside our heads.

Mushrooms anyone?

All of this has me musing about using cannabis for depression or at least as an adjunct to treating depression.    Looking back in history, cannabis has been used to treat depression for centuries.  In the 1600’s, English clergyman Robert Burton makes mention of its use in his book The Anatomy of Melancholy.  During the same period doctors in India actively used cannabis to treat their patients’ depression.

Proponents of using cannabis for depression point to its faster-working response as it stimulates the endocannabinoid system, promoting growth and development of nervous tissue with little to no side effects. The biggest conundrum for cannabis researchers these days is figuring out which particular compounds and strains of cannabis are most effective.  A study from 2006, for example, discovered that THC in low doses can serve as an antidepressant by producing serotonin.  However, high doses of THC could actually worsen depressive symptoms.

A new study that caught my attention was published earlier this year by researchers at Washington State University.  It found that adults reported a significant reduction in depressive symptoms with just a single puff of cannabis that was high in cannabidiol (CBD) and low in in tetrahydrocannabinol (THC). I liked this study because it involved over 12,000 responses and it pulled data from people using medical marijuana as they really use it, not in tightly controlled, artificial environments.

How, you may ask, did the researchers glean such information from so many?  The answer is in the form of a simple and straight-forward mobile app with the fitting name” Strainpoint.”   Here’s how it worked: Before using cannabis the participants entered the name of the strain and rated the severity of their symptoms (in this case symptoms of depression, stress and anxiety) and then 20 minutes later they entered  how many puffs they took along with a new symptom rating.

The results of the study were generally positive but are not without a few caveats.

The encouraging results:  Most users experienced positive effects, at least initially. The majority (over 89 percent) reported a before-and-after decrease in symptom severity for depression, with similar results for stress and anxiety.  As far as how the concentrations of THC and CBD affected symptom severity, the team found that just one puff of high-CBD, low-THC cannabis was enough to lower depressive symptoms, while two puffs of any form of cannabis were tied to a reduction in anxiety. Interestingly, this study also supported the earlier research finding that higher CBD formulations produced the best effects, not THC.

However, this study also concluded that although depression symptoms were alleviated temporarily with cannabis usage, the long term usage of cannabis did not, in turn, mean a reduction of symptoms over time.

One big limitation before conclusions can be drawn from this particular study is that there was no control group and thus no “placebo effect” measurement which is generally considered de rigueur protocol.  Also, although the app enabled a high number of responses to be elicited, the participants were not at all monitored so a margin of error must be incorporated into the results.

Patients usually tell me that they prefer not taking a prescription drug for any condition unless it’s absolutely necessary.   So my takeaway from this study is that it gives us a glimpse of how cannabis may give offer relief from depression with just a tiny micro-dose and without serious side effects.  Perhaps the results of the study are still unclear on how we can use cannabis in mental health but it opens the door to future, more rigorous research.   In my view, offering another alternative to treating the epidemic of depression, however transient the effect, is a welcome breakthrough.

And that’s something we can all cheer up about.

Going Low and Slow: Dosing and Cannabis

From the get- go in nursing school, we nurses learn the “five rights” of medication administration:  right time, right patient, right medication, right route and, so very important, the right dose.  A medication error can have grave consequences and it’s easy to miss something when doling out drugs on a busy shift.  Fortunately, the pharmacists have our back and they endeavor to make the instructions and packaging incredibly clear.  And if there’s any question about a drug being mis-labeled or wrongly prescribed, I’ve got my trusty Mosby Nursing Drug Manual, 2018 edition, which occupies a permanent spot in my nursing tote.

But I’m learning that with medical cannabis, even with non-psychotropic formulas, we are in the Wild West of discovery.  What dosage exactly?  From pioneering practitioners in the medical cannabis realm, the answer seems to be “it all depends” followed by the mantra “go low and go slow.”

For example, a company that sells practitioner-only hemp-derived CBD has been courting my business with their new pharma-grade tinctures and pills.  The product literature is clear about the number of milligrams in each dropper or capsule but the “recommended dose” is vague – it just states that it depends upon the person, their metabolism, health factors and how their CB receptors are clustered in the body.

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Looking at using cannabis for any medical purpose takes some re-thinking for both practitioner and patient.  We are accustomed to higher doses generally resulting in a stronger therapeutic effect (along with the higher likelihood of adverse effects).  This is called a monophasic dose-response relationship.

But cannabis doesn’t work this way at all and the dosing range is broad.  Some patients benefit from “micro-dosing”, which is taking the tiniest amount possible to reap the desired benefits.   Micro-dosing is growing in popularity.  In fact, taking small amounts of cannabis, whether it’s THC-heavy or primarily CBD, can sometimes produce a superior therapeutic effect than taking a larger dose.

Go figure.  The “less is more” approach is possible because of the highly sensitive endocannabinoid system (ECS) that is part of our own physiology, a system designed to maintain balance above all else. When the cannabinoid receptors become overstimulated by higher doses, the cells retract, where they are either recycled or degraded. As cannabinoid receptor levels diminish, the effects of cannabis also decrease, especially when the dose is ramped up.

The experience of a drug becoming less effective as it’s taken more frequently and in higher doses is not uncommon to anyone who’s taken a prescription medication.  It’s known as “tolerance-building” and can be true for cannabis usage as well.

The solution for tolerance building is called a “tolerance break” in cannabis language.  In the medical world for tolerance building and other reasons, we call for a “drug holiday.”  Just like it sounds, a tolerance break, sometimes called a t-break, is just that – a short-term break from cannabis to clear one’s head and body of cannabinoids. Some consumers benefit from reducing their rate of consumption, while others choose to abstain completely for a set duration.  Even just a few days without cannabis will result in a return of more profound effects, while abstaining for a week or two will get the person “over the hump.”   To really clear out the system, especially the stubborn THC, at least 30 days is advised.  It all depends upon the person, their consumption patterns and what they are trying to achieve.

An ideal dose, be it for cannabis or for certain types of drugs, falls in what’s called the “therapeutic window”.  That’s the range between the lowest effective dose and the dose that produces unwanted side effects. People who are new to taking cannabis usually have a very narrow therapeutic window; for regular users the window is wider.  People build tolerance to the various effects of cannabis at different rates. By adding CBD to THC, the therapeutic window becomes even wider.

Interestingly, cannabis can produce the opposite effect when giving the same dose and strain to different people. For example, anxious people who take cannabis may relax and feel sleepy while non-anxious people who take the same dose can become anxious and more alert.

For all of these reasons, dosing medical cannabis can be tricky since it is so very individual.  So here are some starting recommendations if you’re a bit lost in the vast landscape of botanical medicine.

For dried flowers, a good measure of a “dose” is 0.25 to 0.5 grams of either high-THC or high-CBD cannabis. When just starting out, many people find that consuming about 0.25 grams is an easy way to test their reaction to the herb.0.25 grams (about half of a pre-measured rolled marijuana cigarette.)

A single dose of an edible is 10 mg of either THC or CBD. After testing out a single dose, most medical cannabis patients are recommended to increase in increments of 5 mg until the desired effects are achieved.  But be careful, depending on how your body metabolizes the cannabis, it can take between 30 minutes and two full hours before the effects of the edible present themselves. The enticing gummy edibles may look innocuous enough but orally-ingested cannabis is powerful.  Talk to anyone who has overdone edibles and you’ll hear a woeful tale.

Full-extract oil is considered one of the most potent forms of medical cannabis.  It’s highly concentrated, which means that it can have powerful effects on the brain and body. When first starting out with full-extract medical cannabis oil, most patients take a tiny grain-of-rice-size droplet. At this small dose, the dose might be repeated three to four times per day. For the most part, a standard dose of an oral CBD extract begins at 10 mg.

For self-help, the web is awash with useful calculators for determining the optimal dose based on the particular content in the bottle and the person’s weight.  However, the options for patients who are shop at dispensaries are limitless – should you vape, inhale, eat or rub a salve into the skin?  Products are not standardized so higher doses might be easy to miss and packaging labels can be confusing.

One day cannabis will make a proper place for itself in my Drug Reference handbook, sandwiched somewhere between Calcium Carbonate and Carbamazepine.  There I will be able to quickly find recommended dosage, interactions and side effects, all prudently color-coded to cut to the chase.  I look forward to reading that chapter.