Podcast: Your Burning Questions About Marijuana, CBD, and Mental Health

Episode Transcript

Jenn: Hey everyone, welcome to Mindful Things.

The Mindful Things podcast is brought to you by the Deconstructing Stigma team at McLean Hospital. You can help us change attitudes about mental health by visiting deconstructingstigma.org. Now on to the show.

Good morning, good afternoon, good evening. Wherever you are joining us from, thank you so much for joining today for “Ask Me Anything About Marijuana, CBD and Mental Health.” I’m Jenn Kearney, and I am a digital communications manager for McLean Hospital.

And I’m just going to say it right off the bat, the brain is a really complicated organ, so much so that we’ve been studying it for what feels like forever, and yet we still have so much to learn about it.

So, we introduce substances to our bodies, our brains functions can either be enhanced or impaired. So, depending on the person and their use of marijuana, both the mind and the body can be impacted in a variety of ways.

So, I’m thrilled to have Dr. Staci Gruber here with me today to discuss all of the myths and misconceptions about marijuana, its impacts on our mental and physical well-beings and to answer more burning questions about cannabis.

So, Staci Gruber, PhD, is the director of the Cognitive and Clinical Neuroimaging Core and the Marijuana Investigations for Neuroscientific Discovery Program at McLean Hospital. We refer to it as MIND. MIND was launched in 2014 by Dr. Gruber to clarify the specific effects of medical marijuana use on a number of outcome measures.

And as if she didn’t already have her hands full enough, Staci also works to educate policy makers and the general public about the neurobiologic differences between adults and adolescents, as well as additional factors that contribute to the impact of marijuana on the brain.

So, Staci, hi, I’m super excited for you to join me today, so thank you so much for doing so. I want to get started by asking what do we even mean when we talk about cannabis? What’s the difference between all the terminology?

Staci: So, first of all, it’s a pleasure to be here and thank you so much for facilitating this. And it’s a great question. We tend to use one term, cannabis or marijuana and we use it to refer to almost anything that comes from the plant Cannabis sativa L, that’s its name.

And it is a complicated plant, rather magically complicated actually. And it’s comprised of literally hundreds and hundreds of different compounds. When we talk about cannabis or marijuana, most people are interested in talking about the primary constituents of the plant that are called phytocannabinoids.

Phytocannabinoids are things in the plant that interact with our own brain and bodies system of receptors and chemicals, the endocannabinoid system. And the two main players here are Delta 9 THC, this is the primary intoxicating constituent of the plant, in other words, what gets you high. What a recreational or adult users are typically looking for when they want to change their current state of being, let’s just put it that way.

The other really well-known compound these days is cannabidiol or CBD. It is a primary, non-intoxicating constituent. So, it does not get you high, but it’s often touted for its potential therapeutic benefits. Let me just say one other quick thing.

There are lots of other cannabinoids in the plant, not just these two. I think of these as sort of your two main, your main players, right? Like in a theater production, these are two stars. There’s lots of co-stars and supporting cast members, other constituents that are cannabinoids.

There are also things like terpenoids, the essential oils that give cannabis its scent and flavor profile. Interesting, neither THC or CBD have a scent or flavor, that comes from terpenoids. These essential oils that actually on their own, appear to have their own bio-behavioral health effects. There’s flavonoids, lots of stuff in other words, in this plant.

So, when we talk about cannabis, I want to be very clear about what we mean and what we don’t mean because some people talk about cannabis and they really mean synthetic or man-made THC or analogs. And some people mean whole plant full spectrum flower, so we’re going to be very clear going forward but I’m ready if you ask me anything, so we’ll go from there.

Jenn: So, could you talk a little bit about the major differences in the chemical components and the differences in the psychiatric effects that they might have on a person? Oh, I think you’re still muted.

Staci: Oh, there we go. Back to our two main players starting with those, because that’s really what’s on everybody’s mind. You can’t turn on the TV or take up a newspaper or a magazine or be online and not hear something about what the latest greatest is, right?

So very basically Delta 9 THC, again, the primary intoxicating constituent of the plant has been used, again, this plant has been used for thousands of years. The first documented use of cannabis goes back to about 2,700 BC or even before that for medical purposes.

So, when we think about the constituents and their effects and what they may mean for us, Delta 9 THC again, is often used for people to change their current state of being. And we often hear stories about individuals who are exposed to cannabis because they’re looking to take the edge off, to feel a little bit more relaxed or calm.

And it appears that for THC, there is a dose dependent relationship. That is low doses, very small amounts of THC have been shown to be anxiolytic. It reduces anxiety, in some people. Let me say this very clearly and probably not the only time I’ll say this, everybody has a different response to different cannabinoids.

We are all different, we are not all created equally when it comes to our neurocircuitry, that’s a myth, so let’s dispel that right now. So, but in general, studies have demonstrated that lower doses of THC are primarily associated with things like reduced anxiety, reduced stress. Higher doses actually have the opposite effect, the opposite of it.

So, it can actually make you incredibly anxious, paranoid. The so-called psychotomimetic effects, the things that people are not generally looking to have. No one really sets out and says, ooh, I want to smoke a little and get really paranoid and hallucinate, no one says that. Not that I’ve heard anyway, and I’ve been doing this about three decades.

When we talk about the other primary constituents that I mentioned, cannabidiol, again, it’s been touted for a number of therapeutic potential indications. So, for things like anxiety we have some great data from preclinical and clinical studies demonstrating CBD may actually help reduce anxiety or stress, it’s been shown to be an effective anti-epileptic drug.

It was actually approved by the FDA for kids with pediatric onset intractable seizure disorders, Dravet syndrome, and Lennox-Gastaut for example.

This actually changed the nation’s I think, perspective on cannabis, all those studies and actually before the official studies were done, sort of the anecdotal findings of people using whole plant full-spectrum products highlighted the effects of cannabidiol on folks with seizure disorders.

When we think about behavior and here we are at the very oldest psychiatric hospital in the country, it’s very important to remember that everybody has a different effect or may have a different effect depending on their exposure, how much they use, what else is “onboard,” because trust me when I tell you that’s important, route of administration, all of these things make a difference.

So, it’s not such a one size fits all approach, but it comes to what happens when you use THC for, let’s say anxiety. Again, dose dependent, your own experience counts, what else is on board and your route of administration for example.

Jenn: Can you talk about any knowledge behind interactions of typical pharmaceutical drugs and marijuana use?

Staci: So, it’s a great question. So when we think of conventional pharmaceuticals, and there’s a lot of work to be done in this area and the reason for that is that both THC and CBD, again the primary, but not the only constituents of the plant, both interact with the cytochrome P450 enzyme system. This is the system in the liver that allows us to process medications, right?

So, it’s very important that we don’t inadvertently increase or decrease the amount of other conventional medications individuals might be taking. And that is actually a real concern in certain patient populations, for example our older patients, who may have slowed metabolism for example.

And who on average are on somewhere between four and five medications once they hit the age of 65 or so, very, very important. There are certain classes of drugs that individuals want to be mindful of.

And actually, again, since we don’t want to be in the business of telling people, hey, this is what to do and this is what not to do. It’s important to really consult your primary care provider, your PCP with regard to the medications you may be taking or your patients may be taking and potential drug-drug interactions.

For example, we do not necessarily want to include people in our clinical trials where we’re giving folks a custom formulated product that’s high in CBD, people who may be taking something like warfarin, something like a blood thinner.

So, these types of different categories are very, very important to consider. Again, strong inducers or inhibitors of the cytochrome P450 enzyme system, very, very important considerations here. Most often, you don’t hear people talking about it, they say, “oh, you know it’s just weed, what’s the difference?” But if you’re taking something that is passed to the liver, this is a very, very important consideration.

Jenn: I would love to know, what is the actual truth about marijuana being physically or mentally addictive?

Staci: So that’s a great question, and I think there’s been a fair amount of work in this area, but I do want to make one quick comment about it. It’s very important to understand the differences between individuals who use cannabis frequently, maybe your medical cohorts who are using it every day for XYZ, one, two, three, and individuals who are using it in high amounts multiple times a day for other reasons.

And the potential liabilities of “addiction” or having what I would call a misuse, or what is really more often termed according to DSM-5 as cannabis use disorder. Is it possible to develop cannabis use disorder?

Absolutely, absolutely it is. It’s possible to develop a use disorder with almost anything because when it begins to get in the way of your life, your ability to interact meaningfully for both educational or employment purposes, et cetera. When it begins to have a negative effect on your life, you may have a use disorder.

And so, it’s important to remember that, like anything else you can develop a use disorder. I would also remind people that, again frequency and magnitude of use is not analogous to having a use disorder. So just because someone’s using something every day in the way that one might use a medication doesn’t mean they have a diagnosed use disorder, really important.

Jenn: Okay, so what would you define as being either a low dose or a high dose of cannabis?

Staci: Excellent question. Let me just make one other quick comment though about substance use if I could. I also want to be very clear about something, we’ve spent well over 20 years looking at the impact of cannabis, on recreational cannabis use, specifically, on what we would consider our more vulnerable individuals, so adolescents or emerging adults.

When we are young, that is our brain is neurodevelopmentally vulnerable. We are more likely to have difficulties with the impact of cannabis that’s because our brain again is, I like to say in cannabis speak, half-baked, right. It’s still under construction. And so, rates of misuse or use disorder are disproportionately higher in those who begin using earlier. I just wanted to make that clear, just in case.

Okay, so back to the next question about what do you consider a low dose? Not me necessarily, but unfortunately there is no commonly accepted lexicon for the following terms. Ready? You’re not going to believe it. Regular cannabis use, what does that mean? We define it in our group, and every scientific paper should define it but people don’t. Typically, a consistent pattern of use, once a week or more is consistent use.

So, what’s a high dose? Most people at this point, I think use the guideline of something that was actually crafted by Governor Hickenlooper in Colorado, many years ago. 10 milligrams of THC was considered a single unit dose, and so as a result, the laws in Colorado dictated that you could not have, for example a pack of gummy bears that were 20 in a package, each at 10.

You had to have individual unit dose packs, individually wrapped up to prevent people from inadvertently or perhaps intentionally having too much, or to try to prevent that from happening. So many people use the standard of 10 milligrams of THC as a standard dose, if there is such a thing.

I think that’s a little bit high as a standard dose personally, because if you’re not familiar with cannabis or you are not somebody who’s used it a fair amount, a single 10 milligram dose can absolutely have some very significant and perhaps undesirable effects.

Low dose is typically considered anything less than five milligrams per serving. And when I say typically again, this is anecdotal, we don’t have a lexicon. There’s no book, we go, yup, that’s the dose. Nope.

For our studies, and we do clinical trials at this point as well as longitudinal observational studies, cross-sectional studies and surveys studies and collect a lot of data. I would say a low dose for our group and in our studies is anything less than 1 and a 1/2 or so milligrams of THC in a survey.

And just as a way of example, the very first custom formulated first time ever actually that it’s ever been done, we had the very first whole plant full spectrum high CBD, low, but not no, THC sublingual solution for folks with anxiety. We’re doing that at McLean right now, come sign up. It’s a great study, open-label phase is complete, double blind is underway.

But when I say low dose, what I mean is each milliliter, so each ml like a dropper full, that our patients take has less than 0.3 mg of THC. So, it’s a three time a day dosing schedule, they actually get less than one milligram per day.

That to me is a low dose, that to me. I’m conservative, you can always add, you can never take it away, once it’s in, it’s in. So just remember that, but low dose, I tend to think of lower doses as less than two milligrams, sort of.

Jenn: So, there are a ton of studies out there about marijuana use in younger people, and I know that MIND has done a lot of them as well but is anybody studying the effects of regular marijuana use in older adults?

Staci: So, I just realized I could hit the space bar, and temporarily I can mute myself. Look at that, high tech. So, there’ve been a lot of studies looking at the impact of cannabis on the developing brain to your point, and the ABCD Initiative is actually collecting data on over 11,000 healthy, 9- and 10-year-olds.

And we’ll follow them prospectively to look at the ways in which cannabis as well as other substances, alcohol, et cetera, change the ways our brain develops, et cetera. So, to your point, the idea of looking at the impact of cannabis use in older adults is critically important. There are not nearly enough data at this point.

We actually have a study funded by NIDA to look at the impact of cannabis use in older adults with chronic pain who decide to use or to add medical cannabis to their regimen, versus those who don’t. The reason it’s so important to look at older adults, older adults are the fastest growing consumer group of cannabis users in the country. So, whosever asked this question, kudos to you, thank you, I feel like I owe you a check.

The numbers are really quite staggering and you can understand why, but it’s a very, very important cohort to look at and yet we have very, very little data. And again, this particular group is also really, really interesting and important because of potential drug-drug interactions, which we know very little about, and things like reduced metabolism.

And the idea is that very often our older patients at least in our longitudinal studies, very often our older patients are not interested in using methods or modes of use that include things like inhalation. They’re not looking to vape or smoke, they tend to gravitate towards ingestible forms of the product, and you’ve all heard stories about quote, “inadvertently” having too much, it was a half a cookie, how high could I be?

But the answer is very high and that’s a problem, but it feels a little bit less like you’re using quote “drugs.” For some people if they’re using ingestibles, whether it’s a beverage or a consumable, or even a lozenge.

So, it’s a very, very important thing to study in individuals over 55, 65, every tier. Again, given changes in metabolism, drug-drug interactions, the fact that you choose a route of administration that has what we call the longest rise time.

It absolutely takes the longest time to get an effect when you use something that’s a consumable, not just edible but consumable, sometimes up to two hours. So, in that two hour period, what we often hear is, ugh, I’m sure I could have more, I’m obviously, I’m immune to this, I better take more.

Well, then it’s a very big problem about two hours and 15 minutes later when they’re pretty high. So, all these factors make it an incredibly important group to study, and that’s why we’ve invested so much in looking at our older adults.

Jenn: So, I know you’ve touched upon some of the products available now, but it seems like everywhere we turn, there’s a new CBD infused something, it’s topical, it’s smokeable, it’s ingestible. I got an ad for a cannabis-infused seltzer the other day.

So how are we supposed to know what products are right for us and for the conditions that we have? And how can we tell when to separate a quality brand from kind of a snake oil salesman?

Staci: Another really great question, it’s actually two questions. So, let me take the first one first. So, CBD, in and of itself is everywhere, that’s because of the 2018 law that was passed making cannabis strains with less than 0.3% THC by weight, again, THC is the primary intoxicating constituent.

So, any cannabis strain with less than 0.3% THC by weight legally is considered something called hemp. The so-called hemp derived products are the things that are proliferating all across the country and in fact, the globe, because they’re legal and you can buy them everywhere, not just at places like specialty stores.

But because they’re legal, they’re not really typically sold in dispensaries. Dispensaries typically take their real estate and use it for things that are cannabis based where you have to have a different set of parameters in place.

But the so-called hemp derived products, the CBD products. Let me say this, CBD is also not one thing, when we say, oh yeah, I took CBD today. Okay, CBD on its own, an isolate versus CBD within the context of other constituents of the plant and terpenoids, whole plant full spectrum including THC, whole plant broad spectrum, everything but THC versus an isolate.

So, all of these things are important. Again, the route of administration is important too, it has very, very low bioavailability when you consume it, when you just swallow it. So, the actual amount that gets quote “in” to do its job is lower.

So very, very important to consider these things. And again, the proliferation of this marketplace, these thousands and thousands of products, everywhere you turn at the gas station. What’s the likelihood that all of these products are exactly as they purport to be? The answer unfortunately, is not so high. Huh? Get it, not so high, a little cannabis joke.

So, in my group, we’re actually taking a very close look at the differences between stated label claims, so what does it say versus what’s in the product? We call it the, what’s in your weed factor.

Our patients come in and after they’re on a regimen of products over a period of time, we actually have their products tested because in those studies it’s not a clinical trial, I’m not giving it to them. And we find that, in fact, there’s usually a pretty big disparity between what they’re told is in the product or what they think is in the product, and what’s actually in the product.

That’s very important. Not just because you may be plunking down a lot of money to get something that you’re thinking is 20 or 30, let’s say milligrams of CBD per ml. But because of what’s in it, that shouldn’t be in it.

Things like heavy metals, pesticides, yeast, mold, these types of things that we don’t want because they are illegal under the 2018 Farm Bill, which is something that we all have to keep in mind. These products are not FDA regulated, so they hit the market and there is no oversight or regulation.

Some companies do a tremendous job, tremendous job. They are remarkably consistent despite the fact that they manufacture products that are botanicals, and there’s a lot of variability inherently in botanicals. Other companies, not so much.

We had one patient come in that was pretty convinced and she spent, I think, 80 or $90 on a one ounce bottle of something that was supposed to have 20 or 30 milligrams of THC, excuse me, CBD in her bottle. It had less than one, that’s a big problem. Sometimes people go without other things to pay for these very expensive products.

So, the big thing I would tell you to your second point how do we know? Snake oil or really good product? So, remember the old adage, buyer beware, I would say, buyer be aware. What you want to do is be aware, ask for something called a certificate of analysis for that product.

Every reputable vendor, every reputable product really truly should be able to give you a certificate of analysis. You can also have the products tested. Trust me when I tell you, it’s not so inexpensive.

Even at my level, it’s expensive, but it’s important because you’re going to put it in your body. And if you’re going to use it for health and wellness or to treat a symptom or condition, as most of our folks do, it’s important to know what it is and what it isn’t.

Jenn: So, I imagine that prior to increased legalization it was really difficult to start performing studies that were related to THC and CBD. Is that changing as the legalization is increasing at state levels, or do you find that you’re still encountering pretty big federal challenges?

Staci: So, I think the landscape has shifted quite a bit. And again, cannabis has been around for thousands of years and we’ve had studies of cannabis use using individuals who self report their cannabis use. And for better or worse, here in the Boston area, we’ve had no shortage of individuals coming forward to be a part of our recreational studies.

I mean, I know it’s a shock, but in a place that has the greatest density of colleges and universities in the world, probably, we don’t have difficulty getting folks in who are interested in being part of those studies.

When we look at the ability to actually administer products or to look at the effect of certain types of products, cannabis at the federal level remains illegal. It is illegal. There is no federal program like in Canada for example, as a result when we attempt to do studies that utilize cannabis, separate apart from hemp derived products, let’s leave those on the side for a moment.

When we’re talking about cannabis derived products, we are relegated to sourcing from a single place which is the University of Mississippi, Ole Miss. NIDA, the National Institute on Drug Abuse supplies all of us with products to be used. I will say this, they have expanded their drug supply program exponentially over the last decade, they’ve been amazing.

They still do not have anything or anywhere near what dispensaries have available to our patients and our recreational consumers, not even close. In fact 98% or so of the products available from NIDA are flower, flower based.

And of course, we know that with the proliferation of things like concentrates, products that are designed specifically to give consumers or patients “big bang for the buck” with regard to high THC, we don’t have those ready.

We don’t have sublingual solutions ready at NIDA, we don’t have candies or brownies or anything. It’s up to the investigators, the poor investigators researchers like me to create those things from their base products if you’re so inclined. Requires a fair amount of tenacity, I have to tell you.

So that’s one area that is a significant limitation currently, we don’t really have the ability to study products that are currently available in dispensaries and are being used, or even online by consumers or patients in a clinical trial model.

If I wanted to study the number one hemp-based product that people are buying all across the world and say, I’m going to do a clinical trial, I want to see how people really do, let’s see if there’s anything to this efficacy claim. I can’t, I can’t. You can buy 50 bottles of it, Jenn, but I can’t give you one drop as your study doctor.

So in order for it to be eligible for a clinical trial it has to be something that we can register with ClinicalTrials.gov, and if it’s currently for sale in the marketplace you can’t use it in a clinical trial because then it’s considered a drug.

So, it’s an interesting quandary. With the Farm Bill of 2018, we do have some more flexibility which we are delighted to have and I think that people are starting to understand we need to have multiple ways of assessing the impact of these products on our patients and consumers.

Jenn: So, I know we’ve made a bunch of progress, but it still feels like there’s a lot of that old air “Reefer Madness” mentality with a lot of folks. Because even when we talk about the work being done in the space, there’s still a large amount of the population that thinks that all cannabis proponents are just folks who want to get high. How do we help educate people in positions of power to the value of research like yours?

Staci: So, I think it’s important to remember that to your point, despite the fact that people have, at least I like to say the nation or maybe the world, has begun to warm, if you will towards the idea of cannabis as part of our culture and perhaps as medicine.

I would remind people that it was actually a part of the U.S. Pharmacopeia, way back when in 1850. So, you didn’t get a recommendation or a certification for using cannabis, you got a prescription, and it was for various conditions. It was not just for one thing.

I have some amazing slides that demonstrate our history, and I have a lot of stuff from the late 1800s, early 1900s. It fell out of favor and “Reefer Madness,” so to speak, and by 1935 it was out, and by 1942 it was illicit. And in 1970, it was placed in the most restrictive class, in the Controlled Substances Act.

But it’s important to remember this because that perspective persists in many areas and arenas. And despite the fact that it was legal, and now it’s sort of kind of legal again for medical purposes in the majority of states and for adult recreational purposes, again in a growing number of states.

It’s important to remember to keep your eye on the science. What does the data tell you? I always like to tell people, it doesn’t matter what I personally think or feel about cannabis or even you, it matters what the data and the science shows.

And to say that the FDA has approved a cannabis or cannabinoid plant-based, cannabis or cannabinoid product for the treatment of pediatric onset intractable seizure disorders, Epidiolex. It’s 99.2 or 3% purified CBD, has been shown to be highly efficacious in kids with these horrific seizure disorders.

That should give us some clue, some indication that at least some constituents of the plant are worth pursuing with regard to their potential therapeutic benefits. And we can’t treat the plant as if it’s all just bad or junk. I always say, it’s not all good or all bad, right? We’re interested in the truth, so you have to consider all of it.

Jenn: So, in trying to consider the truth, how do we find reputable studies about THC and CBD? There’s so much information out there but it gets really easily muddied and it can be hard to trust when there’s a ton of contradicting news around the subject.

Staci: Another great, great question. So, I think most scientists at this point, agree that policy has outpaced science. In most of the types of things that we spend our time thinking about in terms of medicine or psychiatry, we’ve had lots of studies and then patients follow suit here.

Many of the clinical researchers and even preclinical researchers are basically taking their lead from patients who try cannabis or cannabinoids for something, and then we go oh, great, maybe we should try that, we should see if it works. That’s how we design studies, it’s exactly the opposite.

And in this case, I would say that the media has absolutely had an influence in terms of cannabis and the increased interest in seeing reputable research studies. In 2017, the National Academies of Sciences, Engineering, and Medicine put out a paper.

Basically the health effects of cannabis and cannabinoids and found that there was evidence for cannabis or cannabinoids to be helpful for what we call the Big Three + 1: Chronic pain, muscle spasticity as a function of MS and nausea and vomiting as a function of chemotherapy.

The plus one is the intractable pediatric onset seizure disorders. And there were lots of other indications explored but wasn’t quote, “enough evidence.” That doesn’t mean there isn’t some evidence, it doesn’t mean that there won’t be, it means that we’re in early days.

So where do you go to find the latest, greatest? I can tell you that we spend a lot of time looking at lots of different indications and conditions and patient cohorts using a multitude of approaches and clinical trial type ideas to get these questions answered.

I think it’s important to look when you see a finding that’s highlighted in the news, click on the link. Don’t just take the bullet, click on the link, read the study, at least read the abstract. Was it a peer reviewed journal? Was it a peer reviewed study? Was this just something that somebody thinks is probably true?

These things all make a difference and you know for what it’s worth, it also makes a difference how these things are purportedly reported to you, right? So, when you hear someone say, look we know cannabis is actually good for absolutely everything.

Okay, maybe we want to take it with a grain of salt. The same is true for, we know cannabis is really pretty great for pretty much everyone. Again, if it sounds too good to be true, it probably is.

Jenn: So, before we get started on, we’ve got a ton of folks asking about what can be used to treat certain psychiatric conditions. But before we jump into all those questions, could you just provide a quick overview of the difference between THC and CBD? So, when we refer to it throughout the rest of the session, folks aren’t feeling overwhelmed by acronym madness.

Staci: You got it. So once again, THC or delta-9-tetrahydrocannabinol is the primary intoxicating constituent of the plant. Overwhelmingly, this is what our recreational or adult users are looking to have a high amount of in their product to “get high” or to change their current state of being.

It’s also the constituent that has been linked to decrements in performance on certain cognitive tasks, we see changes in certain aspects of brain function for example. It’s the aspect of the plant that most people are concerned about when they think about “the impact on psychiatric symptoms and conditions.”

On the flip side of that, sort of its country cousin I might say, cannabidiol or CBD is a primary non-intoxicating constituent of the plant. Doesn’t get you high, and it may in fact have tremendous therapeutic benefit for things like, but not limited to, anxiety, chronic pain, PTSD, again, epilepsy or seizure disorders. Lots of different indications have been touted as perhaps being helped by the use of CBD.

So those are the basic differences, CBD has not been shown to have negative or adverse effects, it’s generally recognized as safe, is really the term that we use, which is incredibly helpful as we move forward into these things.

Also one quick fun fact in case our audience doesn’t know, CBD can also potentially mitigate or reduce the less desirable effects of THC, so if you want to have a scenario where someone perhaps wants to avoid psychoactivity, I don’t want to get high but I need a little THC.

Pre-treating with CBD or making sure there’s enough CBD “on board” in conjunction with the THC can reduce the amount of psychoactivity from that THC, that’s important.

Jenn: So, we’ve got a ton of folks asking about trying CBD to help manage their anxiety. Lot of providers are either not knowledgeable or don’t have the information on suggested doses, and there’s a lot of contradictory information based on whatever website you land on.

So how do we know where to start in terms of dosages? And I guess a follow up question would be, what can we share with our primary care providers, that’s reputable legit research around why we should try it?

Staci: So, I think there’s good reason to be interested in exploring the potential use of CBD for anxiety and anxiety related conditions. We actually have, as I mentioned a number of studies at McLean that look specifically at that using a clinical trial, the very first of its kind.

We have a cannabis based study looking at folks with moderate to severe anxiety using technically a cannabis product, but it’s very, very low THC, and then we have a hemp-based product.

So, in terms of doses and dosage, it’s a very, very important point. And when people read the literature about “pure CBD” or let’s say Epidiolex, they find that the dose required to get an effect, and again, the effect here is reduction in seizure activity, not anxiety, they are different.

And it’s very likely that different indications and conditions will require different approaches that is a different dose range, and a different mode or route of administration, just remember that. So, you see these doses that are used in the hundreds for folks using Epidiolex.

And that’s, remember a single purified compound. I would go out on a limb and say, it is very likely and in fact, we are hoping to prove this point in the next eight months, that the effect that you get from a single extracted compound when CBD is an isolate, that is nothing else, it’s purified CBD.

You will get a different effect and require a different dose of that product compared to a whole plant full or broad spectrum product because you have the other constituents. For example, a whole plant full spectrum product that contains quantifiable amounts of things like CBC, or cannabichromene, also shown to be an effective anxiolytic and anti-inflammatory.

Or cannabigerol, CBG or cannabinol, CBN or tetrahydrocannabivarin, any one of these things. They all exert their own effects, so you get a bigger bang for the buck across a wider spectrum. And it’s very possible, again, we hope to demonstrate this. There’ve been no studies, no studies so far published that look at the single extracted compound versus whole plant or broad spec, whole plant full spectrum or broad spectrum.

And they certainly, we should. But it’s very likely that you need a lower dose of a whole plant full or broad spectrum product than a single extracted compound.

Jenn: So if you’re considering using marijuana to treat anxiety, there is a growing amount of information out there that says that edibles and smoking are pretty common options, but does the dose in an edible vary, and is there any control in terms of dosage when it comes to smoking?

Staci: So yes, there’s a huge amount of variability. And again, an edible is not an edible, is not an edible, right? So, our studies, for example use a sublingual solution. So, we have folks administer it by putting let’s say a whole ml of this product under their tongue and they hold it.

And they actually have absorption, the salivary just under your tongue is a very, very rich area for absorption. So, you don’t actually have to swallow it, wait till you digest it, and then you have it passed through the liver and then you get an effect. And that’s how most “consumables” or edibles work.

So, the dose in an edible is very, very important to consider and the rule of thumb is always the same, start low, go slow. You can always add, you can never take away, even, I heard somebody say, well, I could just throw it up. No, you can’t, it doesn’t work that way.

So better to just know that you can add, so try starting at the absolute lowest dose and moving forward. Most people acknowledge at this point, that again, lower doses of THC are indicated for people with difficulties, with anxiety, higher doses of CBD, right?

So, you want more CBD to THC in this realm, and you don’t necessarily have to have a mega dose of CBD to get a clinical benefit, we’re exploring that right now. So that’s important to know.

And can you get an accurate measured real “dose” when you’re smoking or vaping? The answer actually is yes. There are products now available that have pre-metered or measured doses. It depends on what state you live in, California is well ahead of the curve and certainly ahead of us here in Massachusetts.

Washington state has some products available as well. We have, I think, one or two available here but you absolutely can “titrate” or figure out about how much you’re getting if you look at exactly what the product is that you’re using. Whole plant products, that is flower that you’re vaping or smoking.

Again, these things are tested, if they’re sold in a dispensary they have to be tested by law. And you can ask for a certificate of analysis. If you know about how much you’ve gotten and you know about how much your, let’s say you’re smoking from a bowl, you can sort of guesstimate how much THC, CBD, all the other constituents are in that bowl, and go from there.

You know about how much you’re taking in, how long does it take you to go through a bowl, it’s a weird way of doing it and it’s not the way we’d like it, but for now I think you want to be mindful of about how much you’re being exposed to.

And remember, you can add, you can always have another hit, you can always take more drops, you can always have another piece of a cookie or a brownie. But once you’ve had it, you can’t not have it.

Jenn: Can you talk a little bit about any existing evidence around medical use of THC for psychiatric disorders?

Staci: Sure, I think people are very, very interested in understanding the ways in which THC, CBD and lots of other constituents may be helpful for individuals with different psychiatric conditions. I will say that I don’t know that we have a ton of data available in terms of what we understand to be the potential benefits of THC.

Again, for anxiety, it appears that individuals who use very low dose THC may get a clinical benefit in terms of having a reduction in anxiety. I think those are most likely products that are combined with CBD, even at a one-to-one ratio is better than no CBD. The so-called concentrates with very, very high amounts of THC, not necessarily indicated here, right.

But when we talk about other products, and I will tell you the reason I got into this in the very first place long ago and far away, was I was doing a range of studies in patients with bipolar disorder. And what I noticed was, patients with bipolar disorder use cannabis at a disproportionately high rate it seemed.

In fact, it’s the second most commonly used substance if you have bipolar disorder. And I would ask our patients, I’m just curious, why do you use it? And I heard this, you know when I’m feeling depressed or down, I take a hit or two and somehow, I don’t know, I feel better, I get this lift. On the other side, I heard patients who would say, yup, if I feel like I’m cycling towards mania, I’d take a hit or two and I feel chill.

So, I didn’t know necessarily, that there was anything else out there that would give you that range, sort of opposite end of the spectrum type effect. And that was one of the things that was most intriguing to me about this.

Much of that likely has to do with “what’s in your weed.” What are the constituents in the products you’re using? And one of the areas of interest that we’re so invested in exploring is how can we improve the quality of life of our patients who are using cannabis?

I mean, it’s a misnomer to say, well, you know all of our colleagues, my psychiatrist try and say, it’s great but none of my patients are using it. I asked them, they say no. And I always say, do they say no because they don’t want to tell you or do they say no, because they’re not using it.

And we’ve had scenarios where we recruit folks and we recruit them into the control group because they’re not cannabis using, and then within 30 seconds, I say, so have you ever tried it? Well, I mean, I don’t use it a lot. Maybe, not that often once, twice a week, not maybe three. Okay, maybe four times. And all of a sudden you know you’re off to the races.

So, I think people use it for lots of different things. I don’t know that we have enough at this point to say that it is absolutely clearly helpful for this particular indication or that indication with regards to psychiatry. I think most people are more concerned with the potential detrimental effects of being exposed, especially given the proliferation of high THC products on the market.

Does that mean it’s not helpful for people with mood disorder? No, not necessarily. Does it mean it’s not helpful for people with any range of things, PTSD for example, it’s very, very common. No. Right now the evidence suggests we need more data, and I couldn’t agree more.

Jenn: Could you talk about if there’s been anything proven scientifically about the connection between marijuana use and the onset of psychosis?

Staci: Sure, so this is another area that’s incredibly important and there’s been a number of publications that have highlighted the association between cannabis use and psychotic disorders or psychotic symptoms.

And that’s very, very important because the very last thing anybody would want to do is exacerbate a system that’s already in place or to make something that is really pretty uncomfortable or absolutely not what we want, worse. We don’t want that.

There’ve been a number of studies that have published a finding suggesting that higher potency products, like higher potency TH... products with higher amounts of THC are more likely to exacerbate psychotic symptoms, or in fact, perhaps create psychotic symptoms.

The question is association is not causation. And in some of these studies, it’s not clear that these individuals did not necessarily have a biological predisposition. I think in some of them, they’ve taken care of this.

Again, the question is when you look at somebody with a first degree relative or a family history of psychotic disorders, or who themselves have had a history of psychotic disorders who turned to cannabis to feel relaxed or take the edge off, where is that fine line between using to some clinical benefit and then tipping the scales and making things significantly worse, and actually creating a psychotic episode?

I think it’s very, very important for individuals with family histories of psychotic disorders, to be mindful. I think it’s very important for anybody with a genetic liability for any condition to be mindful of this. And again, you lose nothing by, again keeping this in mind. I think we are, again, we’re not all created equally and the effects for one are not the effects of another.

Also remember that products change and evolve over time. Something like a Granddaddy Purple here in Boston is not the same as Granddaddy Purple in Tuscaloosa, Alabama, or in Los Angeles or San Francisco.

With that said some of these publications that have talked about and highlighted the very, very importance of looking at the association between cannabis use and psychosis, also rely on reports of their cannabis from the subjects or patients.

I’ve never met anybody who said, yeah, I used really crappy weed, it was low potency. Everybody’s pretty convinced they have high potency, great “stuff.” Not really stuff, that’s not the word they use. I would encourage additional research efforts to actually analyze the products that patients and subjects are using so that we can more clearly understand the association.

Again, associations is not causation, but for many individuals with a predisposition, it is clearly contraindicated. So, you want to make sure when you’re thinking about people who are using, you don’t use before a certain age because you’re neurodevelopmentally vulnerable, and for people with inherent potential risk, you want to be mindful.

It doesn’t mean that everybody with a psychiatric history or a first degree relative of somebody with a psychiatric disorder can never use it, it means you want to be mindful.

Jenn: So, we’ve got a ton of folks on with us who work with kids and their families. Are you aware of any user-friendly reviews of the impacts of cannabis on children and teenagers?

Staci: Yes, I think we’ve actually written a few. So, some of our colleagues and I think our website, which is themindprogram.com or drstacigruber.com, you can probably find a bunch of ours. And we probably should, I think we have, or we may have a link to our colleagues’ papers as well.

There’s been a fair amount in this area, and it’s a really, really important area to stay on top of, especially for our kids and adolescents. Remember, the dialogue that we’re all having about cannabis for medical purposes, sort of undercuts their concern about cannabis as being harmful.

How could it be harmful if my Aunt Sally is using? How could it be harmful if my next door neighbors are using it? I don’t understand. And that’s something that is really, really very important to explain to kids.

And I think we all agree that the “just say no” approach almost never works. We always like to say just not yet, in terms of even trying anything. But being clear on individuals who are using for medical purposes, who are beyond a certain age versus those who are using for other purposes, who are very, very young and perhaps more vulnerable to the negative effects.

That’s the important distinction to draw. So, check our website. And if we don’t have links to our colleagues, I will talk to our team about getting those up there too.

Jenn: We had a couple of folks ask about working in child welfare where case managers are seeing an increase in parents that have medicinal marijuana prescriptions, but it doesn’t seem like there are a lot of resources to help folks in child welfare judge if a parent’s use of marijuana is actually affecting their caregiving capabilities. Do you have any suggestions?

Staci: So, it’s a really, really difficult one, right? In terms of caregiving and caretaking capabilities and the use of any substance, we want to be incredibly mindful and conservative. And I think as we see increasing numbers of individuals using cannabis and cannabinoid based products, we want to be mindful of the environments within which they’re using these products, and what we do and don’t.

So, it’s sort of do’s and don’ts with regard to children, and adolescents, really, really important to keep in mind. I think whenever there’s a question of somebody and their ability to take care or to have what we call inherent competence, err on the side of conservatism.

And it doesn’t mean that people who are using cannabis for medical purposes, and again, we have this catch-all term. Very often we say medical cannabis when we mean somebody who is using primarily whole plant full spectrum product that’s high CBD, super low or no THC. Should we be concerned? Probably not, right.

We don’t see anything, in terms of impairment really in these folks. But do we want to be mindful about what exposure there may be, especially for the most vulnerable in the household? Absolutely, so I think oversight and being clear, facilitating an open and honest dialogue is really your very, very best approach here I think.

When people feel judged, they don’t talk, we know that. So better to come at this with a, we understand, we want to be accepting but we want to put everything into its correct context, so let’s have an open discussion.

Jenn: Do you know if there are any studies that look at the effects of natural cannabis versus the stuff that’s genetically modified?

Staci: I don’t know that I understand what the term genetically modified means in this case. So, what I think you might be referring to is, some sort of natural cannabis, so plant-based cannabis products perhaps compared to, I can think of two comparisons.

One, the so-called concentrates that are created, they’re often very natural. You can use solventless approaches to get a concentrate, you can actually make a concentrate with a hair straightener. So, for all those parents who have kids with hair that’s this long, and you see a hair straightener.

Yeah, be mindful, that’s not what they’re doing. Or the so-called true synthetic products like K2/Spice, they’re very, very different. I’m going to take that for a second. When we talk about synthetic, the so-called synthetics, again the difference here is K2 and Spice, these things that are unbelievably dangerous. Let me say this again, unbelievably dangerous.

They’re absolutely very little or no resemblance to the plant. Okay, they’re binding affinity at the, remember I talked about the endocannabinoid system, our own system of chemicals and receptors. So CB1 and CB2 receptors or cannabinoid receptors, K2 and Spice, these so-called synthetic cannabinoids have exponentially greater binding affinity at those receptors than any plant cannabis product, okay.

The other type of synthetic cannabis you might be talking about is something that’s “pharma grade.” So, the man-made THC analogs, so things like Marinol, again very, very different. And I think when you talk about comparing the effects, there’s certainly been studies that compare whole plant flower to people who are taking, let’s say dronabinol or nabilone, and they actually find higher efficacy with plant-based products.

And people feel more symptom relief extensively from plant compared to the “synthetics” but I want to draw the comparison between “other synthetics,” the K2 and Spice. They really almost shouldn’t even be part of the conversation, it’s a shame that they’re the “synthetic” cannabinoids, because they really, it’s a very, very complicated picture and they really are not at all similar to the plant.

Jenn: Are there any ways for folks that are in recovery from drugs and alcohol to successfully use cannabis products as part of their care plan?

Staci: So, another really, really great question. And I think that people are very, very invested in exploring this very topic, because there have been some interesting and rather compelling findings for example, with CBD.

CBD may actually be a very helpful part of a “step-down regimen” for folks, for example with opioid use disorder. And since we’re still in the midst of an opioid crisis which got significantly worse during the pandemic, wouldn’t it be nice to be able to utilize these types of things?

So, I think that there are small pockets of individuals and clinics across the country who have done different types of programs with patients who are coming off of different types of drugs. And instead of those drugs, they do a substitution therapy approach.

For example, they use high doses of cannabinoids and very often high THC. The idea is no matter how high it is in THC, it’s not going to kill you. THC doesn’t shut down the brainstem like opioids unfortunately do, I’m just going to use that as an example.

So, people have done that, I don’t believe there’s been any controlled studies that have looked at this. I prefer to have some real scientific data as opposed to anecdotal findings but I know people are very invested in this.

And I would say that, for example things like the non-intoxicating constituents which confer a fair amount of benefit when used in conjunction with terpenoids and other constituents may be a way of exploring that at a relatively low risk. But again, it’s something to be mindful of.

Jenn: So, we’ve talked about all the different ways that people consume cannabis, eating, smoking-

Staci: We haven’t, we forgot suppositories, I’m just kidding, go on.

Jenn: So, is one way of taking it more effective than other ways?

Staci: So again, it sort of goes to condition and desired effect. When we’re talking about, I assume you’re talking about medical use. And so, for medical use, we have inhalation that’s vaping and smoking, that’s the fastest onset of effect by the way.

So, you inhale either vaping or smoking and it’s into the lungs, into the blood stream, into the brain very, very quickly, minutes really. So the rise time is very low, the overall duration of effect is a little bit shorter than let’s say the next one, which might be a sublingual solution or something that is a slowly dissolving product or rapidly dissolving, let’s say, strip under the tongue.

Then you have things like edibles that have a very, very long rise time, takes a long time to get an effect but the effect lasts a lot longer. Capsules and tablets, again you’re swallowing these things so you have to wait for digestion and past the liver to get an effect.

Transdermal or topicals, very low bioavailability, so you may need a very different approach when it comes to that. Suppositories, highly efficient way of administering these products. Is one better than the other?

For people who need very, very rapid onset of symptom relief, they often turn to routes of administration that include inhalation. But more and more people do not want to use these routes of administration, in terms of vaping or smoking.

So, they’re looking for something that, again is like a rapidly dissolving strip or lozenge or sublingual solutions. So, is one more efficacious than the other? Depends on what the indication is. Lots of folks use maintenance products that are consumable because they can take a tablet or a capsule or even a sublingual solution around the same time every day to keep a steady state.

Jenn: Aside from epilepsy, which we had talked about before, is anybody doing research on the positive impacts of younger folks using cannabis-based products as part of their treatment plans?

Staci: It’s actually a great question. And I am not aware of too much in that area, it’s interesting. We have a when I give talks about, pediatric samples being sort of excluded except for those with epilepsy and related syndromes.

There’s been a fair amount of work actually in autism, people are very, very invested in children and adolescents with autism or autism spectrum disorders, and how cannabis or cannabinoids may actually help individuals with social interaction and with anxiety. Anxiety appears to be a very, very critical aspect of autism and ASD for at least some. And so, the idea is can you reduce that?

And does it make a difference, so there’s a fairly concerted effort in that area with regard to children, adolescents. There’s a whole program dedicated to it actually in New York state, very, very important. But other than that, I’m thinking about other indications and conditions, I think kids with chronic pain.

Very often you don’t hear about it because parents perhaps understandably so, will do anything and try anything for their kids when there’s really no hope left. But in terms of empirically sound studies on children and adolescents outside of the epilepsy and related seizure disorder issue, there’s some work in tuberous sclerosis. Other than the autism and ASD realm, I’m not really aware of too much in terms of kids.

Jenn: Is there any research that you know of that would back up that cannabis is helpful in treatment plans for physical pain, whether it’s chronic like fibromyalgia or something that’s sporadic but recurring like menstrual cramps.

Staci: So, another really great question, actually again, chronic pain was in one of the “Big 3” from NASEM. So according to our own federal government sanctioned study, the National Academies of Sciences, Engineering, and Medicine that publication said, cannabis or cannabinoids may be indicated in chronic pain in terms of being helpful.

There’s substantive or conclusive evidence that cannabis or cannabinoids are helpful for chronic pain. Different types of pain, neuropathic pain, musculoskeletal pain, menstrual pain, these are all different.

We’re actually doing some survey studies and some quasi clinical trials with these types of products to assess that very thing. But certainly, we have heard a lot of individuals come forward and say that cannabis or cannabinoid based products, hemp or cannabis based, absolutely positively are part of their regimens.

They have allowed them to cut down on conventional medications, including opioids and other medications, and they appear to get a clinical benefit. We need more empirically sound data to back that up from a clinical trial model, which we actually are approved for and hope to launch, I guess the second half of the next year.

Jenn: My last question for you is, tell me what’s happening that you want to share about from the MIND program? And how do we get involved? Asking for a friend.

Staci: That’s right. Nope, right, just a friend. So, the MIND program is an incredibly busy program and it started off as a single longitudinal observational study of people using cannabis. And we have them come in over periods of time and we assess how they’re doing.

We don’t tell them what to use or how to use it, we just keep track of it. And then we assess their products and see what the relationships are. Cognitive, clinical, sleep, sex, measures of brain structure functioning, you name it, we’re measuring it.

That study continues, and it is the only one of its kind and it has really helped to inform some of our clinical trial models of which we have many either in process or about to launch, including that chronic pain study I just alluded to. We have several studies that are ongoing for anxiety for example.

The MIND program also has a study, excuse me, a program dedicated to women. It’s called Women’s Health Initiative at MIND, WHIM, that looks at conditions and indications disproportionately or exclusively affecting women.

Things like menopause related disorders or menstrual related disorders. We have a program dedicated to look at the impact of cannabis and cannabinoids in our veteran population, Serving Those Who Have Served.

We have a number of different projects. If you go to our website, themindprogram.org, wait, or is it .com? I forget, go to drstacigruber.com or the mindprogram., I think it’s .org, and you’ll see more. You can also, I think get to that website from my page on the McLean website.

But it absolutely will tell you how you can get involved, for yourself or a friend or friends of friends. There’s no shortage of opportunities to be involved, even with survey studies, whether it’s medical cannabis use during COVID or cannabis use again, for different types of indications or conditions. We’re delighted to have you participate.

Jenn: Dr. Gruber, this has been the most mind blowing hour. So, I cannot thank you enough for all of the info, yeah, no pun intended. For all of the information that you’ve shared with all of us today, I know how valuable your time is, and thank you so much for taking an hour of it, to hang out with me and answer everybody’s questions about marijuana, CBD and just about everything in between.

And if you’ve joined us, this actually concludes our session. So, Staci, thank you again so much, I appreciate this incredibly much. So, thanks folks and until next time, be nice to each other and do your research. Thanks so much.

Staci: Do your research, buyer be aware, and thank you, it’s been a real pleasure.

Jenn: Thanks for tuning in to Mindful Things! Please subscribe to us and rate us on iTunes, Spotify, or wherever you listen to podcasts.

Don’t forget, mental health is everyone’s responsibility. If you or a loved one are in crisis, the Samaritans are available 24 hours a day at 877.870.4673. Again, that’s 877.870.4673.

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The McLean Hospital podcast Mindful Things is intended to provide general information and to help listeners learn about mental health, educational opportunities, and research initiatives. This podcast is not an attempt to practice medicine or to provide specific medical advice.

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