About cannabis oil and pain relief

There is no doubt that after sheer curiosity, the most common reason people become interested in cannabis oil is pain. Pain is terrible. It interrupts our lives, occupies our minds and emotions, and becomes the boss of everything. Pain takes the last of our will to do things that limit our activities and is emotionally crushing as it repeats incessantly that things are out of our control, and that we are living in a broken body.

All the drugs commonly prescribed by Western doctors offer little help, cost a great deal and in the end, often leave us craving and addicted physically, which just adds to our feeling of powerlessness. It doesn’t matter if you have carpal tunnel or broken back and incurable disease, or just too sore from working in the garden. Pain limits us and weighs on us emotionally. But prior to prohibition, the American pharmacopoeia was filled with uses for cannabis to fight a variety of pain. Humans have been using cannabis oil for pain and discomfort for generations. And it worked. But now that prohibition is unravelling, we have access to cannabis medicine like never before. It is incredibly safe, far safer than prescriptions and can be grown and prepared at home.

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About Dr Adie Rae, PhD and cannabis researcher for pain

You are listening to shaping fire and I’m your host Shango Los. Today my guest is cannabis pharmacologist Dr. Adie Rae PhD is a National Institutes of Health funded neuroscientist who has been studying cannabis opioids and their interaction for her entire career. She has a strong publication record in chronic pain, addiction and harm reduction.

Dr. Rae is currently an assistant scientist at Legacy Research Institute in Portland, Oregon, and holds a joint faculty appointment at Washington State University. She is also co-founder of Smart Cannabis, a data driven cannabis consultancy focused on connecting all humans with the best cannabis for their needs. They also produce one of America’s most respected cannabis competitions and education events, the cultivation classic in Portland, Oregon.

Transitioning from opioids to cannabis oil for treating pain

Today, we’re going to talk about transitioning from using opioids to cannabis oil for treating pain. Welcome to the show.

Thank you Shango It’s so great to be here.

I really appreciate you sharing some of your valuable time with us. I know that even during a pandemic, you are busy, busy, busy. So, thank you so much for joining us. You bet. So, let’s get right into it. You know, since we’re going to be talking a lot about how opiates and cannabis moderate the experience of pain, I think we should probably get all on the same page about what pain is and how we experience it biologically. So, let’s start with that what’s going on physically in the brain that senses pain?

An introduction to pain

Sure. Pain is a very useful phenomenon. It is a feedback system that our body uses to keep us alive. If we didn’t have pain, we wouldn’t know that we are encountering things in our environment that are potentially hazardous to our tissue into our lives.

A great example of this is people who have congenital insensitivity to pain. So that is you know, they can walk over coals and they can break their arm and they can burn their hands and have absolutely no idea. And these individuals end up living very short lives, because we actually need that feedback from our environment to protect our tissue in our lives. Pain is the phenomenon where our central nervous system, our brain registers noxious information from our environment.

Phantom limb pain

Now, that’s all well and good, but there are a lot of conditions under which that system goes haywire. For instance, if you have an individual with an amputee, that individual can often end up developing phantom limb pain, that is they have pain in the absence of that biological thing that the pain is trying to protect. So that example tells us that there’s something more than just, you have nerves out in your fingertips and in your arms. And in your skin, we’re transferring information about the environment into the spinal cord. And that signal is being sent up to the brain. And the brain is putting together a picture of what the environment is like. It’s more complex than, merely a sensory system that is integrating information inside of our brain. The brain really has a powerful role in constructing what the environment and what the body is going through. So, pain, although it is a useful thing, can really go haywire. And there are a lot of those things that go wrong happen at the level of the brain, not necessarily at the level of the tissue.

Pain is in the brain

That phantom limb example that you gave I find extraordinarily interesting. It has been explained to me before that, that pain is takes place in the brain. And you know, I normally find that to be kind of a semantic difference. That’s not incredibly helpful to patients. But it is very interesting when talking about succession of pain with opiates and cannabis. And yet, occasionally I’ll come across a healthcare worker who says that describing that pain is in the brain is very helpful to for patients, because it allows them to have an understanding that they can manage their pain with thought, and perspective, and with drugs, instead of they are a victim to their hip, or whatever. Right? Yeah, really complex thing.

It really is. And you’re absolutely right that pain does take place in the brain. And we have a whole network of brain structures that are involved in constructing that picture for us.

Pain is a disease

When I was early postdoc, my first year as a postdoc in Sydney, I went to a talk that was given by a number of folks who were involved in clinical pain work. And at the time, Australia was really cutting edge in their view of pain, because they actually gave chronic pain its own disease category. Pain is a disease. Chronic pain is a disease. And that still doesn’t really have chronic pain doesn’t have that kind of recognition here in North America. And so, I’m at this talk, as you know, budding pharmacologist and physiologist.

My job was to measure neurotransmitter release that was being released from neurons and brain slices. Hardcore physiology and pharmacology. Drugs interacting with the brain receptors. And then, changes happening in neuron activity. And I’m watching this talk, and I’m seeing these patients, and I’m hearing them describe their lives and how they’re able to have these absolutely debilitating injuries. And yet, they wake up every day and they say, yeah, my pain’s out about an eight today, sitting here in front of you in this chair, and you’re like, what? How can you be physically registering so much bodily sensation, and yet totally nonplussed just completely fine with it?

The cognitive component of coping with pain

From this talk, I really began to understand that the cognitive component of coping with pain, walking with pain, living beside pain, that ability resides wholly in our brain that is totally within our control. And it really is a testament to the power of our thoughts, the power of our cognition, and our attention, what we pay attention to grows and magnifies. And it’s not that you necessarily turn your attention away from the pain. Although that is one coping strategy. It’s more about shifting your attention to something else. As a pharmacologist, I’m asking, Well, what the heck am I doing? I’m trying to make better pain therapies and make better drugs. And all we need is meditation and coping strategies and cognitive behavioral therapy and biofeedback. What? Okay, I quit.

So, you’re absolutely right. Pain lives in the brain, and we have an enormous amount of power and control over it, if we can learn the tools to harness it. We’ll talk a lot more about cannabis as a distractor later on, but I want to double down on your experience with the powerful mental capabilities of pain patients. I’m very grateful that I haven’t had a lot of pain in my life, except when I had an injury and rotated my L5, and was in a hysterical amount of pain, more than I’d ever been in my life where I was just squirming on the doctors table, because my mind was just all bright.

Patient’s experiences with pain

And when I meet patients through teaching about cannabis medicine, and traveling for it, and everything, and I meet these folks, and, like you said, they’re having an eight day, but they are presenting themselves as calm, cool and collected at a talk or whatever. And then we get together kind of like, on the side, and we sit next to each other, and we talk and I’m trying to understand the nature of their pain.

So, I can make some sort of recommendation to them? Because that’s what they’re there for. And the more we talk about it, it brings them mentally away from their, I don’t know, let’s say, meditative life, where they’re just they’re focusing on doing this thing called life, and intentionally distracting themselves from the pain. But as they describe it more in detail, you can see the defences coming down. And you know, very often, by the time we’re done, understanding the nature of their pain, they are shaking and in tears, and the only thing that’s changed is that part of us doing what we were there to do was they needed to let down their guard and be vulnerable for a moment. And when they let down their guard, I got to truly see the pain expressed through them. It’s very difficult as somebody who’s trying to help somebody to not get sucked into that experience of compassion with them and start crying too, right?

I gotta tell you, working with pain patients and getting to know them, and being one for a while in a small way, really has given me huge respect for people who deal with chronic pain every day.

Giving chronic pain attention

Absolutely. There’s a couple of things in there that I want to unpack, one of which is that of attention. When you’re paying attention, and you’re really digging in and looking at it, and describing it, and putting words to it. I’m going to talk about that. Let’s start there.

So, in that attention, I worked with a fibromyalgia patient once who told me I noticed that on my worst pain days, those were the days I was taking my opioids, and I couldn’t tell if I was taking the opioids because it was my worst pain day, or if my pain was worse because I was spending so much time thinking about. Should I take a half a pill or should I take a whole pill today? So, just the body scan, the physical body scan, of looking for the pain, that’s what makes the pain real. So, she was going through her process of waking up in the morning and doing her body scan, and just by paying attention to it, that’s what fed the need for her pain relievers. That makes total sense. And it is so sad.

Could you think about like how many individuals are doing that this morning? Waking up and going, oh, boy, what kind of day is it going to be today, and really going in and looking for it, and digging into those things. And if you’re over 35, you can you can find that within your body. If you really want to, there’s some spot that ails all of us because that’s what it’s like to have a body.

Physical and emotion pain are inseparable

But the other component that you’re talking about is that emotional component of pain. So, my colleagues and I at Washington University in St. Louis, we put out a paper in the journal Neuron last year. It was in mice, and some of it was in rats. But, what we demonstrated is that the physical, the bodily sensation of pain, and the emotional or affective component of pain are inseparable. They are two symptoms of the same phenomenon that are being driven by this little network in the brain. So we have been going about treating pain from the bodily sensation of it for many decades. That’s the whole reason that opioids exist as we’ve been trying to anesthetize the physical sensations of pain with this drug.

But our work demonstrates that you can’t just ignore the emotional component of pain, because it is literally wrapped up in the exact same brain areas and the exact same mechanisms that are happening with the bodily sensations of pain. And we see this roughly 80 plus percent of patients with chronic pain also experienced some kind of mood disorder like anxiety, depression, or both. So, it’s no surprise that people who are in chronic pain also have depression, because that is literally the manifestation of chronic pain. It has both a bodily component, and an emotional component. Whatever we do to treat pain, chronic pain, we have to think of the organism holistically. We have to think of the emotional well-being as well as the physical well-being of the body.

Describing different kinds of pain

I really liked the fact that you are you focus so much on the vocabulary of pain as well. And it’s interesting. People who are new to their pain often struggle to describe it because luckily, up to this point in their life, they haven’t had to describe it. Whereas, people who have had lifelong pain, they can describe it on a numbered chart, and they’ve got all these different flavours of it. It’s like they’ve got like a Crayola box of descriptors.

So let’s talk about that for a moment. Because, so often people who are coming to cannabis for pain, one of the challenges that they have is delineating between the types of pain, either for themselves, like in their pain journal, or to the doctor. And we know that there are different types of pain, right? There’s that there’s a big difference between the sharp and stabby pain from a fresh fracture, versus the kind of like mind-boggling-everywhere-experience when you’re having a flare up of rheumatoid arthritis. Right. I don’t actually know anything about this part of the process. What do you use as a range of how to describe pain?

Pain descriptors

Well, you’re right. No one’s pain is like anyone else’s. So, it seems important to think about is this throbbing? Is it stabbing? And in the clinic, those kinds of things are really useful from a diagnosis perspective, because you can say, ah, these kinds of descriptors would indicate an inflammatory condition, which means we need to treat it in this way, versus, those kinds of descriptors indicate some kind of neuropathy, or some kind of damage to the nerves, or some kind of problem with the transmission of the nerve signals, so, those kinds of pain are better treated with these modalities. That kind of vocabulary is really important in the clinic for diagnosing a path forward for treatment.

However, on the other hand, I tend to make the argument that , once you’ve gotten past that initial, diagnosis stage and you know what kind of pain you’re dealing with then it doesn’t really matter, because it’s all subjective. It’s all only happening to you inside of your own brain from your perspective. And no one’s pain is similar. You know, you can have two individuals who have the exact same injury, like a rib fracture, right, same rib, same spot, and yet they’re descriptions of the pain, how much the pain bothers them, how that pain interferes with their life. It’s all totally different. And so yes, on the one hand, being able to have words for your experience is really helpful. And when you’re in a community setting and you’re getting support from other people who have the same kind of ailment that you do, it’s really validating to hear Oh, yes, that’s exactly what I feel. And it’s so comforting to know that another human being feels what I feel. But on the other hand, it’s totally subjective and irrelevant, because all that matters is how you feel. And so, if you’re feeling bad in any way, whatever those bad words are, then that’s a starting point for how can we start feeling better. How can we shift the attention, the conversation, the treatment, the therapy your way? How can we shift all of that so that whatever descriptors you’re using, you start to feel better?

Invalidating someone else’s pain

Let’s follow up on that because it is so common your I like your example of the same disclose dislocated rib in the same place and two people will have different experiences of pain, it is so incredibly common, that the person who’s experiencing more pain, whereas other people experience less pain, are written off as being a wuss, like they can’t handle it, like they’re immature, they’re being a baby about it. And I always think that invalidating somebody else’s pain is not legitimate. And certainly there, there are situations where we want to encourage someone to not focus on their pain, which is a different thing. But invalidating a patient, or having their pain invalidated by friends, family, or even a health practitioner, is just wrong. And I just want to hear what you have to say about that.

I mean, to me, like, the perfect example is like the hysterical woman. For how many hundreds of years women do experience more chronic pain. Women have more painful things that are associated with childbirth and reproduction, hormonal imbalance, and for many hundreds of years, that was completely invalidated. We were seen as the weaker sex and we were shunned by psychotherapists, and that is the most extreme example of totally invalidating someone else’s experience. And I feel very grateful that now we live in a time where we are slowly being able to recognize that each individual’s reality has as much value as anyone else’s reality. You know, I’m really inspired by my undergrad students who come through the laboratory. These are privileged white kids who go to a private school. At the same time, they go, Oh, I’m sorry, I can’t talk about that. That’s a trigger for me and everyone respects that. Wow. This is the next evolution in humanity we’re talking about here. So I’m really encouraged by this idea that we’re all coming to accept that if this is real for you, then it’s real for you. Right on.

What are the different types of pain?

Imagine that you know in a chronic pain textbook in the school, there’s a chapter on the different types of pain. And there’s a section on inflammation, and there’s a section on nerve damage. And you study chronic pain intensely and for years. And so, will you give us a general understanding of the different categories of chronic pain?

Yeah, certainly, for me, they fall into three big buckets, two of which you mentioned already – the inflammatory pain and the neuropathic pain. So that is some kind of damage or dysfunction in the nervous system that is causing pain. And then we have this other weird one, which is like this mysterious sort of central pain, something like fibromyalgia, where you can’t really pin down exactly what’s going wrong with any particular part of the physical biology of the organism. And yet, the organism is still reporting that they’re in severe pain. So those are the three broad categories – the inflammatory, the neuropathic, and then the centralized pain. And there can be a lot of transition from either inflammatory pain to Central pain or neuropathic pain to central pain for instance. Where you have an injury that totally resolves – there’s some kind of car accident or work-related injury, the injury is totally resolved, and yet the brain for potentially the rest of its life still keeps registering some kind of discomfort. So, there can be a transition from one of those two types to centralized pain.

There tends to be an inflammatory component to even neuropathic pain, especially in the early days of the development of neuropathic pain. So, for instance, chemotherapy induced neuropathy. People who often survive cancer will beat their cancer, but they’ll be stuck with this neuropathic pain that was induced by the chemotherapeutic drugs attacking the central nervous system or the peripheral nervous system. When I say peripheral, that’s everything outside of the brain and spinal cord and central nervous system is the brain and spinal cord itself. So you know, chemo drugs will attack the nerves throughout the body and leave the cancer survivor with this lifelong pain. But in the very early days of the development of chemotherapy induced neuropathy, there is an inflammatory component, right? Those chemotherapeutic drugs, pull in the brain’s immune system, I’m sorry, the body’s immune system and all of our processes that we have for fighting off pathogens, and the it recruits our inflammatory processes to start repairing the damage to the nerves. Yes, you can sort of put things roughly into these buckets of inflammatory pain, where you have all of these, the body recruits certain molecules to draw blood and draw attention to some invading process or pathogen. You get swelling, oedema, redness, soreness, there’s more fluid on joints, for instance. That’s a very molecular process where there’s just a whole lot of molecules flying around going crazy doing their jobs, hustling and bustling to try and keep this organism alive. To the extent that it is somewhat maladaptive, we have so much of the body trying to protect itself that it is actually really painful for the person who has the body. So, although you can put inflammation in its own bucket, there is largely an inflammation, an inflammatory component to neuropathic pain, and then either one of those things can develop into a central pain, once the inflammation has gone away, once the nerve has totally regenerated or whatever other neuropathic thing might have happened.

Replacing opioids with cannabis oil

Let’s change directions a little bit now that we have established what playing field we are on with pain, and that pain is experienced in the brain. Let’s talk about opioids themselves. We’re not going to spend a whole lot of time talking about the pharmacology of opioids, because that’s not really what we’re about. I think anybody who’s here and listening has already made the decision that that they already want to move away from opioids.

However, if we’re talking about replacing opioids with cannabis, we certainly need to have an understanding of what opioids do and what their method of action is, so that later on in the show, we can compare that to cannabis. Would you give us an understanding of what opioids are doing? And why there is a belief that that decreases pain?

I think that you’re right, that a lot of your listeners are here, and a lot of Americans and Canadians and people all over the world are interested in cannabis oil because it is so obvious that you know, opioids are nasty drugs. And that is true. We clearly have a huge overdose epidemic on our hands. However, the opioids are really good drugs under very few conditions. The whole reason they exist is because they are profoundly good at turning off the bodily sensations of pain. They’re profoundly good at somewhat anesthetizing the body and not allowing it to experience the physical sensations of pain. They are really good at that because they act in the brain itself to shut off the sensations of pain that are coming in through the spinal cord.

If you can imagine your nerves are like little tiny highways of information, and all those highways are headed in one direction into the spinal cord. And that spinal cord becomes like the central hub. That’s the main highway, and all of the information coming through those tiny little arteries are coming through the center for a highway of information. And then going into the headquarters switches the brain. Opioids shut off the sensation of pain at the headquarters.

Pain in the periaqueductal gray

My academic work has always been focused on one particular brain area called the periaqueductal gray. This really is the brain’s pain headquarters. Because if you put an opioid directly into the periaqueductal gray or the PAG, if you put an opioid there, you shut off pain throughout the entire body. And if you put opioids everywhere else, but you block them only in this brain area, then you don’t get any pain relief at all. And so, we know that this is a critical component in controlling or modulating the sensation of pain throughout the entire organism. This tiny little brain area, it’s fascinating. What’s really interesting about this brain area also is that it’s where the body or the brain develops tolerance to opioids as well. So again, if you repeatedly give the brain, just this PAG region, if you repeatedly give it opioids, it will develop tolerance. But if you block opioids here, but continue to give the whole rest of the body opioids, the organism never develops tolerance.

This is a really critical brain region. And we’ll talk more about it when we get to the cannabinoid control over pain. But opioids bind to receptors in this brain region, so you can think of it as a lock and a key. These locks, these receptors, are studding the outside of our neurons. So just little padlocks waiting for their keys to come floating by. And those keys, the drugs, the opioids themselves come in, they float along, and they lock into the binding sites on these proteins. And they turn on certain intracellular signaling cascades. These are molecules that once they become activated by the binding of the opioids to these proteins, they go off and they do some other job, they control neurotransmitter release, they turn on genes they control other proteins. It’s a whole very sophisticated set of intracellular, and between cellular, communications. The sum total of all of those, like hundreds of thousands of millions of little protein interactions, the sum total of that, is the organism not experiencing pain, because it has been shut off at the level of the brain itself.

Wow, Adie. that was awesome. That was that was the best explanation I have ever heard. I don’t know if you… I know you’ve got a PhD. And at some point, you probably had to teach classes, you’re probably an awesome teacher.

Oh, thank you. I really enjoy being in the classroom. But I feel like conversations like ours, where we get to talk to the lay person. I think that’s equally important.

Yeah, well, that explanation is a very nice balance of using accurate, scientific, let’s say like, how it actually works, while also using vocabulary that we’re all familiar with, so that you don’t sound like a textbook. So that’s great. Let’s use me for a straw man for a minute. Because at your description, opioids actually sound like they’d be really effective, right? Like, like listening to your description. I’m like, well, maybe these actually work. Is all this trash I’ve been talking about opioids, I’m not justified? And the problem is actually more of the abuse than the fact that they don’t work. But in my own personal experience, and like I said earlier, I haven’t had a lot of experience with pain. But, but after I had my ACL surgery after a skiing accident, they gave me opioids to help with the pain. And I’m a psychonaut. I’m really cool, I’m gonna get to try something new, you know. And so I used it and my experience was, it really did not do anything to help with the pain, but it made me feel like the pain was maybe down the hallway. It kind of distanced me from the pain a little bit. And I certainly found it to be a bit of a fun distracting like it was it was a novel mind state. That was interesting. But after the first day, it’s not helping and mostly it made me sick. Stupid for everything else I wanted to do. So is my experience typical? Or is my experience more fringe?

Opioid Receptors in the Brain

I think that it might be a little bit of both. When you asked the question like, Hey Adie, you make this sound phenomenal, and these are really powerful drugs. Yes, that’s true. However, you have to keep in mind that the PAG is not the only place where these opioid receptors live. They live on lots of other brain structures, and they live in lots of other important places in our bodies. For instance, in the brain stem, the area that’s like our old evolutionary lizard brain, the thing that keeps us you know, ticking automatically, keeps our breathing going. That’s the area where you also have opioid receptors. And if they get hit over the head too hard, they will shut down your breathing. And that’s how people die. So respiratory depression is essentially what happens in an overdose. People’s breathing rate slows down so much that it stops entirely. And that process is controlled by the brainstem by the same receptors. So the same receptors that are in your PAG turning off pain for your whole body are also in your brainstem, controlling your breathing rate.

It’s not only those two areas, but, like you said, I stopped taking these drugs after my ACL tear, because I felt stupid. They were making me dumb. And the reason for that is these receptors are also in your prefrontal cortex. All of your brain regions that are used for making decisions, and being a functional human. If you turn off all the brain activity at the level of the opioid receptor there, then of course, you’re going to get some cognitive impairment. And this is something that we unfortunately don’t talk enough about with the opioids.

You know, like, I was testifying in the State House in Jefferson City, Missouri one time. And one of the chairman was asking me, Well, what about all the cognitive impairment that comes from cannabis like people driving while high and all of this stuff that they were worried about. No one ever talks about how many people in this courtroom right now took an opioid before they got in their car and drove 60 miles to get here. This element of cognitive impairment that you’re talking about is a very real side effect of opioids.

Opioids and Addiction

Opioids would be great drugs if they only acted on the descending pain pathway, but they have all of these other unintended consequences… constipation, respiratory depression, cognitive impairment, addiction, because they’re binding to receptors that are not just in the brain’s pain pathway, but they’re binding to the receptors indiscriminately. Especially that last component, the addiction component, opioids are better than any other substance that are totally hijacking the brain regions that are involved in reward and reinforcement. So those are very fundamental brain processes where if something activates this circuitry, this reward circuitry, the perception at the level of the organism is, ooh, that was good. I should do that again. Right? So that’s the reward. And the reinforcement is continuing to engage in that behavior because of the reward. So, opioids are particularly good at hijacking those processes so that the opioids feel better, and over time become more important than anything else that activates that system. Naturally the opioids become more important than food, opioids become more important than lasting relationships, opioids become more important than you know what your neighbors think of you. Opioids become more important than your job. So you know, that’s where all of these unintended consequences happen from pain control is that the opioids aren’t just binding to the brain’s pain receptors, they’re binding to all the receptors that control all of these other very important processes.
Well, now you’ve totally unraveled all the impressiveness I had earlier for it, because now it just sounds like a messy drug.

Totally. It is. It’s a super messy drug.

The medical establishment is turning away from opioids

So, before we go to our first commercial break, people started turning against opioids, or at least in publicly in the media, when people started getting an understanding of the level of abuse in our country and how quickly people were moving from pharmaceuticals to street drugs because they were more of portable and in many places more accessible since you don’t need a prescription. People realize that our country has got a chronic addiction problem with opiates. But then that seems to have created an environment where some in the medical establishment have finally kind of taken the risk of saying, Oh, yeah, and they don’t really work. And you really have to dig for that. It’s not usually something that’s in the first paragraph or the first couple paragraphs of an article. It’s down in paragraph 10, right? And they said, Oh, and by the way, is it true that the medical establishment is starting to kind of turn away from the efficacy of opioids?

I think finally, yes. I think for a very, very, very long time there were us fringe weirdo scientists on the side saying, hey, opioids cause hyperalgesia – that means they make pain worse. Hey, opioids actually have all of these other negative side effects. They outweigh the benefits. But you know, like our little fringe voices that are clearly based on the evidence that we’ve been collecting for a long time, our voices don’t matter much in the face of really hot pharmaceutical reps and lobbyists with a lot of money, and doctors who don’t have the time to devote to being skeptical and digging through the literature themselves. And they’re relying on the standard of practice from their clinic, and the recommendations of the American pain society. And they’re relying on these pharmaceutical reps to give them the best tools to do their job in the shortest amount of time possible, because they only have an average of 13 minutes with each patient. So, yeah, I think that for a long time we knew that opioids weren’t effective over the long term and that their side effects outweighed their benefits. We knew that there were some fundamental pharmacological problems with them. You know, the basic neuroscientists knew that oxycodone at the molecular level is no different than heroin. And yet it took a crisis of this magnitude to wake everybody up to the reality that it doesn’t matter if you’re using heroin or if you’re using oxycodone, the results are the same. Your body becomes physically dependent and you have to have some other strategy if you want to have a sustainable and healthy management of chronic pain over the long term.

Well, that sounds like a perfect place to end our first set Thank you at so we’re gonna take a short break and be right back. You are listening to shaping fire and my guest today is cannabis pharmacologist Adie Rae.

Introduction to cannabis oil as alternative to opioids

Welcome back, you are listening to shaping fire. I’m your host Shango Los and our guest this week is cannabis pharmacologist Adie Raw. During the first set, we made sure that we were all on the same page about what pain is and how it functions in the body, and what opiates are attempting to do in in providing some relief. But we’re all here because we want options other than opioids. And so, that’s what we’re going to go to in this set. Adie, I know that you have a expertise in how cannabinoids function in the brain, and specifically decreasing the experience of pain. And I think that I just want to start just by tossing you the mic, if you will, and saying, what are the main methods or modes of operations, that some of the cannabinoids that we are familiar with, at this point, are acting in the brain to provide relief in different ways than opioids?
How does cannabis oil, THC oil, provide pain relief?

Yeah, you bet. So let’s start with how they’re similar. Before the break, we talked about the mechanisms by which opioids relieve pain. They bind to this area of the brain that I focused on my entire career, the PAG, the periaqueductal gray. Opioids float along and they bind to their receptors like locks fitting, or keys fitting, into their locks. And cannabinoids work, especially Delta Nine THC. THC works in the exact same way. THC floats along into the PAG and binds to its receptors studded along the outside of these neurons. And what’s really fascinating is that the Mu opioid receptor, which is the primary pain-relieving target, and the CB1 cannabinoid receptor, they are cousins. They’re both G protein coupled receptors. That’s the kind of protein they are. They have an extremely similar structure and an almost identical function. They’re both coupled the inside of the cell. They talk to the same sets of messengers, GIGO proteins. You can imagine on the left hand and the right hand you have the Mu opioid and the CB1 cannabinoid receptor, both sitting there, like locks waiting for their keys to come along. When those keys bind, the locks change shape a little bit and then release their messengers. And those messengers are identical. Isn’t that fascinating? That’s totally cool. I had no idea. Yeah, the same brain region, the same kind of protein, the same second messaging system. And the result is also the same. You have a change in neurotransmitter release, and a change in the descending control of pain. And that’s really the primary way that delta nine THC relieves pain, it’s acting in the exact same place by the exact same way that opioids are working. The difference is everything else.

Cannabis oil is not addictive

We’ve talked about how you know the opioid receptors don’t just live in the PAG, they live in lots of other brain areas and in the brainstem, and inside the viscera, inside your internal organ cavity. And CB1 cannabinoid receptors are also everywhere else. But what’s really fascinating is that somehow, by activating the CB1 receptor with Delta nine THC, yes, you still get some activation of the reward pathway just like the opioids, you have this. That’s what causes mirth and euphoria. That’s what is rewarding and reinforcing about cannabis. It’s Delta nine THC binding to CB1 receptors in the brain’s reward pathway. However, the difference is that it doesn’t hijack the brain’s reward pathway in the way that opioids do. It doesn’t prioritize cannabis, or THC, over everything else in life. It also doesn’t bind to those receptors in the brainstem, which control respiration. That’s why you can’t have a lethal overdose from, or respiratory depression from, THC, is because that’s just not how it works. It doesn’t have anything to do with respiration. So yeah, the mechanisms fundamentally are identical to how opioids work in terms of turning off the pain signal at the level of the PAG, the brain’s pain headquarters, but the differences lie in everything else.

What is the CB1 receptor?

The other really interesting thing about the CB1 receptor in particular is that it is the most ubiquitously expressed G protein in the entire brain. What I mean by that is, if you were to die all of these receptors green and then zoom in and try and find where they are, they look like stars in the sky, they’re literally everywhere, it’s almost impossible to find a brain tissue that doesn’t have some level of expression of the CB one receptor. And that says less about what the brain is doing in response to THC, but it says more about how important the CB1 receptor is in evolution. How if it’s on every single neuron in our brain, pretty much, what is it doing there? Why is it there? And so the role that that receptor plays in our everyday function is huge. We have endogenous cannabinoids like 2AG and anandamide, and a whole set of cousins that are similar. And those little molecules have very important jobs in regulating our brain activity, which regulates all of our homeostatic processes, all of the processes that keep us alive, our metabolism, our circadian rhythm, our responses to stress, our ability to relieve our own pain. The CB1 receptor has an incredibly important role in all of those homeostatic processes. For whatever reason, evolution has set it up to where if you stimulate them, your opioid receptor, you end up with some pretty gnarly consequences. And if you stimulate the CB1 receptor, you end up with kind of a balance of what could potentially be some risky things, but mostly innocuous things like relieving pain and experiencing mirth and euphoria.

Well, first of all, it’s so nice to hear somebody actually use the word mirth. I haven’t heard that word in a long time. I probably only read it, so I like that. So it’s remarkable how many of the same plays. I’ll say, that delta nine THC has in common with the opioids. And somehow, it’s also equally as messy and not as targeted. But it’s the fact that when delta nine THC is being messy, it’s not causing all these other frickin problems that opioids do. And so it’s more, it’s more benignly messy.

THC, CBD and Terpenes work together – the entourage effect

Yeah. And you know, what’s even crazier about that, Shingo, is it gets even messier. And because it gets even Messier, it becomes even safer. What I mean by that is we are capable of ingesting delta nine THC by itself. And that ends up not to be a very enjoyable process, unless you’re like a daily diver, and that’s your thing. Great. But that’s very few people who really enjoy totally overloading their brains solely with Delta nine THC for most human beings. If they consume THC, by itself, it ends up you know, especially once you get up and over a certain dose, it ends up not being super fun. And so, part of the safety and part of the tolerability of cannabis is that delta nine THC isn’t acting alone, it’s being consumed with scores of other biologically active molecules, like canabidol CBD, and all of the terpenes. And all these flavonoids and alcohol are sorry, aldehydes, esters, all of these other molecules that are all working together to make a really messy thing that because you have all these molecules, which are competing for binding sites, some of them are activating processes, while others are simultaneously turning things down, what you end up with is a really buffered effect. So, if you could imagine I love music, and I think about the world from the perspective of audition, mostly. And if you think about if you have a tone, a pure tone, when you imagine like B, that gets really old really fast, it’s not particularly pleasant. And that’s like, literally a one trick pony. Right? It has one job, it does one thing, and that’s what an opioid does, or that’s what Delta nine THC does. By itself is just one note. But then if you start adding in all these other tones and layering it with all these other things, what you end up with is white noise, which is what we use to put babies to sleep. Right. So that buffered effect, when you have that principal component in there doing its job, very important job relieving pain, activating CB one receptors in the PAG, but you add in all these other molecules, which are also promiscuous, then you end up with this really buffered effect. And the sum total of all of those different molecules doing their jobs at the same time, is that you have a very tolerable experience.

Ethan Russ very frequently has championed the idea of the entourage effect or the ensemble effect, which is that these molecules work better together than they do in isolation. And from my perspective, the principal component driving the entourage effect is just tolerability, you’re able to reap the medical benefits of cannabis, because it is simply more tolerable, not necessarily that it’s more effective, but that it is more tolerable, and that that tolerability comes from this buffered effect of all these molecules acting at once. That’s great. All right.

Let’s circle around and go back to the top of the slide again. You just took us on this explanatory trip of delta nine THC, and how it works on pain. But as I often tell patients, we have to start over now and talk about cannabidiol because it’s not just that cannabis helps pain, it’s that cannabis helps pain in multiple different ways. And we really have to treat them independently. Let’s go back to the top of the slide and would you go through the same process with cannabidiol CBD?

How does CBD act against pain?

CBD is a lot more complicated. There are at least 14 plus known mechanisms of action of CBD in the central nervous system. Delta nine THC, it’s pretty straightforward. It is a partial agonist at the CB one receptor, and that’s largely it. But cannabidiol at a range of doses does lots of different things. It’s actually a partial allosteric modulator, a PAM, at both the Mu and delta opioid receptors. What that does is it puts the receptor in a position where it is more receptive to the endogenous opioids that are there. So just like our body produces anandamide into AG, our body also produces endorphins, enkephalins, and lots of other peptides that naturally act at our body’s opioid receptors. So cannabidiol, binds to the mu opioid receptor, the primary pain relieving target in the brain to make it more receptive and activatable by its endogenous peptides, like the endogenous opioids, so that’s at least one mechanism of action that CBD could potentially be having in the central nervous system.

CBD is a profoundly anti-inflammatory agent

However, I think that the more profound and direct effect that CBD is having is it is a profoundly anti-inflammatory agent, as is THC, as are lots of the other molecules that are found in the cannabis plant. This is especially why when we have patients who are suffering from some kind of inflammatory condition, cannabidiol alone or in combination, especially in combination with these other molecules from the plant, it’s profoundly effective because it is directly acting at those anti-inflammatory pathways.

I myself have seen the knuckles of patients with rheumatoid arthritis, and literally, their only thing that they engage in is putting a topical on their knuckles every couple of hours every single day. And you don’t want to have to be a rheumatologist to look at someone’s hands and go, Oh, wow, yeah, you look better. I think that especially for patients who have an inflammatory component to their pain, and we talked earlier about how even in neuropathic patients people with neuropathic pain, often there is an inflammatory component to neuropathic pain. So wherever you have any kind of inflammatory thing going on cannabidiol is going to be an outline, especially if you’re consuming it in a whole plant preparation. I tend to refer to type three and hemp cannabis as nature’s multi vitamin for inflammation. It truly is. It is so much better to take 12 active ingredients that are fighting inflammation from 12 different pathways than just one ibuprofen that does anti-inflammation from one pathway alone, because just in inflammation, there are lots of different kinds of processes and lots of different kinds of molecules involved. If you imagine a construction site, you have all of these people who are buzzing around and from a 30,000 foot view, you have a bunch of construction workers, but when you really dive down in there, you’ve got the welding guy, you’ve got the plumber, you’ve got the electrician, you’ve got the concrete person, you have the engineer and so all of these people, they have different roles, but they’re all contributing to this main effect. It’s the same thing with inflammation. The main effect is inflammation. But there are all these different molecules involved in that process. If you’re able to knock out every one of those roles that’s contributing to inflammation then you’re clearly going to have a better outcome than if you’re only going after the electrician.

Talking about the effects of CBD

Alright, let’s talk about a minute about how fastest CBD works because there are two different ways of thinking about CBD helping pain. The first is that I’ve got whole plant CBD tincture in front of me and I take it. What will the cannabinoids do for me right now in this moment and lasting for the next three hours, shall we say, which is usual efficacy for CBD or any cannabinoid, but then there’s this second mode, which is people are taking CBD to simply supplement their endocannabinoid system and strengthen it because a properly functioning endocannabinoid system itself turns down the volume of pain and helps with the homeostasis of all these different key body functions, that when they come back into balance, our experience and likelihood of pain is decreased. But that’s something, the building up of an endocannabinoid system is something where you need to be taking whole plant CBD for a few weeks before it’s really starting to work on the endocannabinoid system as a whole. So would you tease out the differences in the patient experience of taking CBD about whether or not the patient can take whole plant CBD now and get benefits now, versus taking CBD now, but we’re taking it every day for the benefit of my endocannabinoid system in the future to decrease my pain.

Man Shango, we’re gonna need another 90 minutes.

What does CBD do?

First of all, I want to say that I really like to have evidence-based conversations. And frankly, there’s very little evidence that CBD does anything acutely, especially at the common doses that people typically take. They’re like, Oh, I have my five milligrams in my soda in the morning, every day. That probably does nothing except make someone feel better via the placebo effect or the expectation that it’s going to do something, which I am not at all knocking. I love a drug that does absolutely nothing except make you feel better. So, there’s that component. We are taking this thing, empowering ourselves, taking our health into our own hands, expecting it to help us, expecting it to make us feel better. And lo and behold, it does. That’s because our brain is profoundly powerful at creating that experience for ourselves. I think that probably the most immediate benefit that someone could get acutely from taking any dose of cannabidiol is the knowing that they’re taking care of themselves, and you know, there could be some underlying pharmacology that is actually doing that, especially in a within a certain dose range or after taking it via a certain inhalation route, particularly. But the reality is that we don’t have the clinical studies to tell us what are the acute pain relieving or any other the medical benefits of cannabidiol.

Cannabinoids are stored in fat cells

We definitely have evidence to suggest that over time, there is some bio accumulation of CBD in the in the brain and then the body. Cannabinoids are very lipophilic, they’re stored in the tissue and our fat tissue really well. And it does after a certain level of accumulation, it ends up with like the slow release. We see this with Dravet patients. Epidiolex is CBD. And with the FDA clinical trials, we see that there is a profound benefit, medical benefit, of daily consumption of pretty high doses of CBD. You know, the doses that are given to these kids are pretty whopping, and it would be quite expensive to try and recapitulate that on your own. And there are definitely more efficient and cost effective ways to go about it. But yes, I think that that latter part of your hypothesis that maintaining a healthy endocannabinoid system is by far the best way to set yourself up for success for any health condition, pain included. The other thing that we didn’t mention was, again, going back to this affective component of pain.

Is CBD psychoactive?

CBD is psychoactive. You hear all the time that CBD is not psychoactive. Anything that changes the brain chemistry and the physiology of the brain is psychoactive. So we know that CBD is psychoactive because it shuts off seizures. It acts in the brain to change the physiology of the brain to create a beneficial effect. CBD is psychoactive in that aspect.

CBD Relieves Anxiety

One of CBD’s other psychoactive properties is that again, under certain conditions at certain doses, it relieves anxiety. It provides positive affective, positive emotional support. We also see this in the opioid world because there’s a researcher at Mount Sinai in New York Yasmin Hurd who has been studying CBD for a very long time. Her work demonstrates that in people CBD profoundly reduces anxiety, and that that reduction in anxiety is also associated with a reduction in craving for opioids.

CBD for Addiction

In addiction, one of the one of the primary drivers for drug-seeking-behavior when someone is in recovery, when they have been physically dependent on a substance and they’re trying to come out of it, one of the primary drug seeking craving triggers is negative emotions. You feel crappy. That feeling is a trigger for seeking drugs. The aspect of emotional support that comes from chronically ingesting CBD, I don’t think we can underestimate. I think it’s going to be very difficult to measure. But given what we know from these little bits and pieces from the literature that we do have, I think that it is wise to say that having a rich endocannabinoid system, a supplemented endocannabinoid system, if that’s what you need, that will provide both that bodily sensation support that you need, as well as the affective support that you need.

That’s great. I think it’s important to hit this one more time because I really was caught off guard and pleased that you said that taking CBD now does not have an acute effect, meaning it will help you now, and actually your example of taking five milligrams of CBD in your morning soda cracked me up, because I’m often telling people you know, you got to be really careful about how you’re taking your cannabinoids because you know, your CBD gummies filled with crap sugar and artificial coloring is probably doing worse for you than the CBD that you’re trying to get through it. But I think that it’s important for us to understand that taking cannabidiol is a long-term commitment. And that if you want to get relief from it, you’ve got to, you know, you can’t just take it when you’re feeling bad. It’s important to take it every day on a on a regular schedule. And heck, if you can take it every day, small doses two or three times a day, that’s even better because you will metabolize more of it.

Remember to Change Your Lifestyle

But the overall idea that, yes, take cannabidiol to help your endocannabinoid system. But also don’t forget that you should be doing the lifestyle changes that are necessary so that you ease off the trauma that you’re giving your endocannabinoid system so that you don’t have to take CBD forever. A lot of people start taking CBD, and they get these great effects. And then they’re like, Oh, I’m feeling so much better. And then they get off of it. And then they feel like crap again, and they’re like, Oh, my God, am I gonna have to take CBD the rest of my life. And I said, and I say, you don’t necessarily have to, but you’re probably gonna have to start exercising and getting proper sleep and not drinking coffee. And then and then they’re all like, screw that I’ll buy CBD, you know?

CBD is Similar to Omega 3

You’re absolutely right, in that CBD is far more like a micronutrient than it is a drug. So, you know, we think of taking a drug, I’m going to take this and I’m going to feel better, right? And especially in America, that is our expectation. That is why we have a healthcare system built around commerce. Give me the thing, make me feel better now. That is that is our culture of medicine. And that is not how CBD works. CBD works more like omega 3. And it’s actually not that dissimilar from omega 3 is structurally. We don’t take fish oil when we have a headache. We’re not expecting fish oil to miraculously make us feel better in 30 to 90 minutes. It’s a nutrient, and it’s a part of our lifestyle, where if we’re deficient in some way, if we don’t have the diet, or we don’t have the lifestyle to provide us that kind of nutrient by some other means, we have to supplement it by taking fish oil.

It’s the exact same thing with cannabidiol. If you’re not stimulating your own endogenous cannabinoid system through like you said, exercise, sleep, a balanced diet, acupuncture, all these other things that mimic the endocannabinoid system, support the endocannabinoid system, without the plant derived cannabinoids. If you’re not doing those things, then clearly, yeah, you’ve got to make up for it by taking CBD as a micronutrient on a very regular basis. And if you’re going to be taking it on a regular basis, it’s going to be expensive. So, you might as well find out how to take it in a way that’s economical. There’s tons of products out there that are orally ingested, like you can eat something or drink something that has cannabidiol in it. And the sad fact is that only about 5% of what you swallow ends up making it into your bloodstream.

CBD has terrible oral bioavailability

CBD has terrible oral bioavailability. That means if you put it in your mouth and you swallow it, hardly any of it is getting to your brain and the rest of your body. Something like the lungs, you’ve got about 50% bioavailability. If you look at how much does it cost you to vaporize a kilo of hemp flower, versus how much does it cost you to ingest 300 milligrams, or rather 300 grams of CBD, if we’re talking like 30% cannabinoid content. That’s a lot of oil. That’s really expensive. Thinking about more efficient ways to utilize that micronutrient to support your endocannabinoid system is a good thing, unless you are also using it in combination with all these lifestyle factors. And then like you said, you won’t need to use it forever.

Let’s tease out one bit about using CBD orally because I agree with you up to a point. And the point is a lot of these oral solutions, and we’ll talk more about this during the third set, but a lot of these oral solutions like capsules and various edibles that have got CBD added to them, you eat them. And for that CBD to become accessible to the human, they have to go through your gut and eventually through your liver and it takes time. Plus you’re getting all the other random sugars along the way. It’s a long road to go. In contrast, I find that patients get good results with a whole plant ethanol extracted tincture, because when they are putting it in their mouth, whether sublingually or not, the ethanol acts as such an effective carrier for cannabinoids. The CBD is actually making the jump through the mucosal membranes and the tongue and the cheek and the esophagus. And by the time any remaining fluid of the tincture gets down to the small intestine. It’s already been soaked in other places. What do you think about that delineation?

How do I use cannabis oil?

Shango. Thank you. Thank you, thank you so much, because there’s so many products out there that are labeled as a tincture, which are you know, it is a cannabinoid, which is an oil in an oil. And that’s not the same thing as a cannabinoid suspended in a solvent like ethanol. And you’re absolutely right. If you have some kind of oil, if you have two bottles of tincture, let’s say one of them is oil, and one of them is ethanol, either way, your best bet at getting those cannabinoids into your blood is right in your mouth. And so, if you’re going to use an oil-based tincture, then you have to use cannabis oil more like a topical, you have to put it under your tongue, and you have to use your tongue to rub it in, you have to rub it in under your gums into your cheeks, you have to actually it really is more of a topical than it is a you know, orally ingested product. And you’re right that with the ethanol, there might be some chance of enhanced permeability right there in the mucal tissue, the tissue on the side of your cheek, right in the sublingual tissue, you’ve got a ton of blood vessels in there. Wouldn’t it be great if you could just take the cannabinoids and shove them right into all those blood vessels inside your mouth? Yeah, that’s the idea. So oral bioavailability typically refers to when a drug is swallowed. That’s clinically what we talk about. When we’re looking at an oral preparation, that’s a preparation that’s swallowed, which is kind of different than a preparation that is absorbed in the mouth, which is you know, a far more efficient way to take cannabidiol.

Fantastic. Alright. So, we will pick up that topic again in the third set when we start talking about dosing and methods. But there’s one more thing I want to hit on before we go to our second commercial break. And I know that you are very evidence based and so you may not have a lot to say about cannabigerol but I do want to talk about CBG because I was lucky enough to get my hands on a high CBG no THC plant material about a year and a half ago. That was part of a R&D seed grow in Oregon. And that set sets type for Nick Crawford. Yeah.

We might as well. I wasn’t gonna out him. But this is the stuff developed by Seth and Eric Crawford at Oregon CBD. They’re in Oregon. And it’s fantastic stuff. I was able to get some of this, because they know that I work a lot with patients and that I run a lot of dosing trials, because I think that one of the biggest challenges with patients using cannabinoids is that everyone’s using totally uncontrolled dosing. They’re just taking some. And one of the things that is important about any kind of medicine is repeatable results. Anyway, what I got this material, and I did ethanol extractions, and we made a bunch of tinctures and I’ll say RSO (Rick Simpson Oil), so people know what I’m talking about. But really, we’re talking about full extract cannabis oil. And so we did a bunch of dosing trials here on vashon Island, with pain patients. And because it was said in some casual, early CBG studies. that it was really great for neuromuscular pain, and I’m like, Alright, well, CBG is going to be the hot novel cannabinoid, let’s find out how to actually take this stuff. So that when I talk to people, I actually have my own first hand knowledge. Great. So we make this questionnaire and I take the tinctures and RSO and we cap a bunch of it up, and we give it to a lot of patients.

CBG is good for pain

And absolutely, we got a positive response from people regarding their pain. And it tends to act like a non intoxicating Delta nine THC as far as the patient experience. But where I’m going with it is this next part, the part that was really startling was that everyone said that it put them in a better mood. And so I teased that out with folks. And it was decreasing people’s anxiety about having pain at all. And when you tease that out more, this is how I explained it now to folks, is that people turn to cannabis for anxiety and pain but THC tends to slather you. I understand that, that generally we’re looking for doses of THC that you don’t actually feel right? That don’t cause intoxication. But at this point, few people take it that way. But most people think if you’re not a little high it doesn’t work. So, based on people’s actual experiences, delta nine THC slathers a little bit of intoxication over your anxiety and pain and you know, does decrease your pain and acts as a distraction. But involve some intoxication, and then the CBD, it doesn’t work for today, but it’s gonna work for next month, if you take it everyday for the next month.

CBG is a different category, it actually makes the patients feel like they are capable of handling their day or their pain, with the resources and abilities they have in front of them. And the patient said like my pain is the same as yesterday, but I feel like I can just frickin handle it more, because of the change in attitude. And so, they’re all like, I think that I’m having some pain relief. But I can tell you one thing, I can cope with my pain a lot better. And I love CBG for pain relief. And then with that, we kind of did a secondary trial with people who had extreme daily background anxiety and performance anxiety. And they took to it like a duck to water. They’re like, Oh my gosh, this stops my ruminating and fear of social situations. And these things. This is all a big setup to ask you: As somebody who studies the pharmacological aspect of these cannabinoids, have you seen any either legitimate peer reviewed evidence for what I’m describing, or even some significant anecdotal or heck, since you know how these mechanisms work? I could imagine you might go, oh, there aren’t any studies. But from what you described, I bet you ABC is happening. So, I’m just gonna hand that whole explanation to you on a big platter and say, what do you think?

Yeah, so we’ll start with the evidence that we do have which is preclinical, so in petri dishes and animals and CBG is kind of like cannabidiol. It is non-intoxicating, and it is psychoactive. It is very similar to CBD. It is not nearly as deeply studied as cannabidiol. We don’t know exactly all the mechanisms of action, which proteins it’s interacting with. But in general, it is anti-oxidative and anti-inflammatory. It looks like it’s doing good things and not bad things to the brain. At a very fundamental molecular level, there does seem to be some kind of basis that this could be a profoundly therapeutic molecule because it looks like it does a lot of good things without causing impairment.

You know, with that said, the anecdote that you just told me is the deepest and most wide anecdote that I have ever heard about CBG. Because to date, it has been nigh impossible to get enough of it to actually give to a human being at a dose that would do something. This is changing now. Because I think that now we have this year will be really the first time that we have large commercial operations which are growing type four CBG dominant cultivars, and we’ll have the opportunity to do this sort of real-world scientific experiment of putting this stuff in our bodies and watching what happens.

I do think that there is some fundamental basis for it to be a profoundly therapeutic molecule. But we also again, don’t have any evidence to look at either the acute or the chronic effects for either an effect of support or pain relief. The other thing I will say, and I always lean on this, because it’s so true, and I don’t lean on it in a negative way to downplay the power of pharmacology. I clearly am a cannabis pharmacologist, I believe in these tools. But I also equally believe in the power of the brain and what we know about all drugs, any drug, the newer it is, the more profound the placebo effect is. So, the small test cases that you do with your patients on vashaun…. Do they know what they’re getting? Do they know that it contains CBG?

Well, they knew at the beginning of the study that it was a new novel cannabinoid called CBG. But they did not know what the effects were supposed to be. I searched, and I certainly didn’t prime them for this anxiety stuff, which I wasn’t even looking for myself. But I also think about like, what ails people generally, and if you’re a chronic pain patient, it’s both about that bodily sensation of pain as well. We talked about earlier that effect of component of pain which is inseparable from the bodily suffering. So I approach this from like you said, I really appreciate the evidence, And wouldn’t it be lovely if we could do double-blind placebo-controlled crossover clinical trials with this stuff? Yeah, that’d be great.

As a matter, as a matter of fact, Dr. Ethan Russo happens to live on the same island that I do. And I actually told him what I was doing, and I described it to him. And he kind of raised his eyebrow, because he’s like, well, that he says, you’re using this term study, he says, this isn’t really a study. You’re just kind of giving it to people and asking them questions. And I’m like, Yeah, a study. And so you know, this. Yeah, there was no double-blinded in this or peer review madness to this, right? But I totally understand dosing protocols. I want to recommend it to people now, which was the actual point, for sure. And I also want to say that everything we know about cannabis started from anecdotes. You know, 20 years ago, patients were coming into their doctor’s offices and saying, Hey, Doc, when I smoke a joint before bed, I don’t need to use my dilaudid. Or like, I’ve noticed that since I started smoking cannabis, I use half as many opioids, and those anecdotes all collected into community-defined evidence. And that community-defined evidence grew to a point where we were able to do more closely controlled experimental trials. And so, all of this stuff has value heuristic value, if nothing else, in that it allows us to go down a line of questioning. Isn’t that interesting that these chronic pain patients who experience anxiety, have this, what looks to be a very profound therapeutic effect, why don’t we dig into that a little deeper?
I think there’s a ton of value in this both from a cellular molecular level, there’s rationale there. And there’s definitely rationale to listen to the people when what they’re saying is real. And it’s worth looking into.

Citizen Science about cannabis oil

A lot of my scientist friends, when I talk with them, say we’re at Emerald cup or something which pulls cannabis researchers and scientists, doctors from all over the world get together. A lot of them talk a lot of trash about citizen scientists, right, essentially what I’m doing, and they’re like, yeah, we understand what you’re doing, but there doesn’t have a lot of value to it.

I’m actually a big proponent for citizen science that that like let’s all work at home on our own. And especially since cannabis is federally illegal and getting the research approved is so difficult. Let’s start doing this research on our own. And then, as it becomes more commonplace in the population when legitimate research scientists go to divine their studies, they’ll be like, Well I’ve heard this thing, anecdotally, let’s go ahead up and fire up the funding machine and get the university to do this study. But that wouldn’t have necessarily been indicated. Without regular nobody’s doing it on their own first, for sure. And the other component to that is that when we do clinical trials, we have a very long list of exclusion criteria. You have to be pretty neurotypical, and you have to have a pretty narrow range of conditions, and you can’t have abused drugs in the past, and you can’t have this and you have to be this and you have to be a certain age. So, we have a very lengthy list of exclusion criteria, which means that we’re self selecting, that drug might work in this population that you have developed a rigorous exclusion criteria for and it only works for them. But what about everybody else? What about all these other people who lie all over the place on the neurotypical spectrum and who have all these other comorbidities, and who have all these traumatic childhoods? So that’s also a really great thing about a large but messy data set is that if you do have an effect, which is profound, you’re gonna detect it in both populations. If a drug really works, it should work for everybody, no matter what their you know, neuro type, or, or background or underlying conditions. Rather than some drug that only works for this very, very narrowly defined population of people. I want to hit on one other thing about you mentioned that last summer was the first summer that Cannabigerol was in commercial, acres and acres of it were grown with those Oregon, CBD seeds all over the country. And I was very excited, because while I got my sample for these tests, almost two years ago, now, I was like, Alright, great, I’ll do this stuff now. And then at the end of the summer, 2019, there’ll be all these whole plant oils coming to market and I can send people to purchase them, and it will be like this new arrow in the quiver. And I’ll be damned, I was very disappointed to see that the vast majority of the people who grew CBG, they ended up making single molecule isolate out of it, and using it to spike edibles and things like that. And as you’ve mentioned several times, during this episode, so far these cannabinoids, especially the novel ones are, they work their best in the presence of other cannabinoids. And so I feel like, you know, CBG grown in volume at acres was extracted in the isolate for the monetary value and ease of integrating into products. And yet again, patients lose out because what they really needed to do was turn all that stuff into a whole plant, full extract oil, put it in capsules, and give it to people so that it was actually effective. Yeah, I mean, like, you’re right.

But you’re also like fighting economic, you’re fighting commercial this, this is not new for me or this show.

You know, like commerce is and commerce does, and like, what is best for the patients is not necessarily the same.

I am encouraged, because this is one more frontier that we get to go down. What happens when we have that full cannabis extract, what happens when we have it in large doses in capsules, what happens if we can somehow vaporize that flower?

I don’t know a lot about the phenotype of that flower, I’ve never had a chance to encounter it myself, or even look at a certificate of analysis. But I could imagine how it could potentially be, at least right now. And in this stage, a relatively low yielding plant in terms of you know, what is the cannabinoid per gram, but I don’t know. So maybe that’s the thing too, we maybe we need to get it hybridized into these like really oil rich rather than just biomass producing plants, these oil producing plants, maybe that’ll help popularize it. I’m excited because I do think that this is a really interesting molecule and we have a long way to go with it.

Very good. So last thing before we go to commercial Are there any other cannabinoids or constituents of cannabis that you see coming down the line that we should look out for for dealing with pain? I mean there’s a slew of cannabinoids but there’s almost no research on the vast majority of them. But what do you… anything you want to flag for us to make sure that we keep an eye out for the future?

Beta-caryophyllene for inflamation

Yeah, I think there are two big ones. And you know, if you are a nerd for the literature like I am, they’ve been there all along. And it shouldn’t be a huge surprise. But the evidence is profound like Beta-caryophyllene is a full agonist at the CB two receptor so it’s not a cannabinoid per se, but it is a cannabinoid in that it is a full agonist at a cannabinoid receptor.

So Beta-caryophyllene is profoundly anti-inflammatory. It has tons of therapeutic potential, and it’s abundant. I think that this one in particular could be playing a really important role in pain relief, especially because of the mechanisms of pain and inflammation in particular. So at basil conditions when you have a normal healthy organism, the CBT receptor’s pretty silent, there’s not much of it around. So much that for a long time, even at the International Cannabinoid Research Society ICRS, that’s the main professional scientific society in the cannabis and cannabinoid sphere. ICRS, you know, still to this day, there’s a little bit of debate about is the CB2 receptor even present in the brain? And that’s because under normal conditions, no, it’s not, it’s, there’s no need for it. But when you have chronic drug exposure, chronic stress, chronic inflammation any kind of insult to the organism, these things bloom like crazy. Expression of the CBT receptor goes up under any kind of insult or injury. And so particularly in those conditions, if you have all those receptors sitting around waiting further little key to come float in and activate it, maybe beta caryophyllene could be a good component to introduce.

So, it’s not a particularly sexy one because it’s everywhere, but it is it is it has a lot of promise.

Tetrahydrocannabivarin THCV

The other one that there’s some preclinical evidence for is tetrahydrocannabivarin THCV. So that one especially in combination with other cannabinoids does look like there’s a large amount of promise. I think it’s a few years behind cannabigerol. And I definitely don’t know anyone who’s trying to cultivate THCV dominant plants, but certainly there’s some semi synthetic folks out there working with yeast who are trying to produce this at scale.

And I think THCV has a lot of promise as well. I also think, and again, this one’s not super sexy, because it’s so obvious, THCA. The acid form, the non decarboxylated version of THC, this thing’s proudly anti inflammatory.
But again, it goes back to that sort of micronutrient territory where if you have low but consistent ingestion, or somehow putting the non intoxicating THC into your body and supporting the endocannabinoid system that way as from a micronutrient perspective, that also has a lot of promise. There are tons of patient stories out there of people who have been preparing their own non intoxicating sort of cannabinoid rich hemp seed elixirs for many years. And it seems to be, at least anecdotally, that has worked for them to manage chronic diseases. So those are some of the big ones. The acid form of THC, the non-decarboxylated form, beta caryophyllene and thcv. Fantastic, thank you Adie. We’re gonna go ahead and take that last short break and be right back you are listening to shaping fire and my guest today is cannabis pharmacologist Adie Rae.

Cannabis oil dosing

Our guest this week is cannabis pharmacologist Adie Rae. So here we are in the third set. And we want to go through dosing and methods of taking in your cannabinoids. Because now that you perhaps have these ideas that you might want to replace your opiates with cannabis, one of the hardest things is figuring out what the hell to do next. We’re gonna go through a couple of the different common methods for ingesting or taking in cannabinoids, and we’ll kind of riff on each of those so that we can all kind of learn together.

Adie, I know from watching your other presentations that you are not particularly a fan of smoking. And I mean for medicinal, right? We all love to smoke some smoke. But actually, as far as it being medicinally effective, would you explain why that’s what you teach?

Is smoking cannabis medicinal?

Yeah. The basis for that is purely from poly aromatic hydrocarbons, from things that are potential carcinogens. You know, putting burnt plant material inside of your body is less healthy than not putting burned plant material inside your body. However, that being said, I’ve always been a firm believer that the best kind of medicine is the one you will take. So, if smoking cannabis feels like medicine to you, and it is the path of least resistance to getting medicine into your body, then you’re better off with the medicine than without it. For a lot of people, smoking simply doesn’t feel like medicine. It was never part of their culture, it was always frowned upon. There’s some fear and shame and there’s a lot of war on drugs stuff happening there. And smoking simply is not going to work for them. The benefits of smoking are really the benefits of inhalation, which is an immediate onset. Here you have an activated molecule, and delta nine THC in particular has to be decarboxylated. It has to be converted from its acid inactive form to its decarboxylated active form. So THCA has to be converted into THC. To do that, you have to apply heat. And the easiest way for 1000s of years to apply heat to the cannabis plant is just set it on fire. The benefit of smoking is that you have an activated THC, which goes directly into your freshly oxygenated blood supply, which goes directly up to your brain, which is exactly why it has an immediate effect. And for someone who is experiencing, for instance, breakthrough cancer pain, nothing is going to help better than to have an immediate relief of that pain. So anything that can literally instantaneously shut off the pain, that’s amazing. And so if smoking does that for you, great. There are other ways of inhaling the cannabinoids that don’t involve the burnt plant material that can potentially cause other health effects. And when I say other health effects, there are known side effects of smoking cannabis. Although we have yet to see any sort of cancer or lung cancer come out of chronically smoking cannabis like we see with chronic tobacco smoking clearly causes cancer, that’s gnarly. But what we do see are COPD, chronic inflammatory respiratory issues. We see coughing. We see phlegm production. It’s not to say that smoking is totally unsafe, but it’s also not totally safe. There’s still other ways of reaping the benefits of inhaled cannabinoids without exposing yourselves to all of those, that the toxins and the irritants that lead to all of those other you know, inflammatory conditions.

I’ll go ahead and add to that for a lot of people. Your example of cancer related pain and the immediate succession of pain is spot on. And yet, there are a lot of patients who are taking either THC for other types of pain or maybe they’re looking for CBD. Where smoking it has that very fat fast effect, It fills your lungs, it’s instantly in your brain and you go up fast. That’s not necessarily what everybody who is fighting, say for example, inflammatory pain, is looking for. Taking a say a tincture or something, or a topical where the cannabinoids enter the body at a slower rate. So instead going up and getting this peak and then slowly coming down, you instead have this slow pathway up, and then the slow pathway down. It’ll tend to last for longer, and allow you to be more productive because so many pain patients, they still got to go to work. And, it’s hard to titrate or control your dosage when you’re smoking and so people are like, Oh, I’m gonna smoke, and then they’re like, shit, now I can’t go to work. I’m frickin baked, you know. And so, for those folks, they should definitely be aware that in addition to not scorching your lungs, some of these other options that we’re going to talk about may be better for you because they are going to be less intoxicating. Right. I think that for all of these methods of administration, there are really three major components that we can talk about. Where you’re managing impairment, you’re also talking about the onset of the effect, how quickly it works, as well as the duration of the effect, how long it works.

Cannabis oil is better than smoking cannabis for sleeping

One other element of pain relief is a lot of chronic pain patients have a lot of trouble sleeping. They have a difficulty falling asleep, because they’re in pain, they have difficulty staying asleep, because their pain wakes them up in the middle of the night. And so just from a sleep management perspective, smoking is probably not the best idea because the peak, the onset might be almost immediate, but the duration of that effect is really not very much. Two to three hours if you’re lucky. So you really do for something like you know, where you need a long term effect something that’s going to get you through a good six hours, smoking isn’t going to be the best for you, because you need something with a longer duration. Just as a little side note, one of these days somebody is going to figure out a good way to do time released whole plant capsules, and they’re just going to crush the market. Because, I mean, some people use it in Terek capsules, which help a little bit. But most of the time to make something time-released, you have to over process to the point that it’s not whole plant anymore.

But your description is right on point, because so many pain patients, they will take whatever cannabis they’re going to take in the evening. And then by 2:30 in the morning, their pain is waking them back up again. And so they have to have strategies to have a second dose on their nightstand, which then occasionally in some people with some cultivars, make them feel a little groggy in the morning. But at some point or worse, it can cause tachycardia. Right. So what I mean by that is a racing heart. So ironically, you’re trying to go to sleep, and yet you inadvertently consume a little bit too much THC causes this like sympathetic nervous system reaction where your brain interprets a fast-paced heartbeat as paranoia and anxiety.

Yeah, I hate that. And also, I guess it’s worthwhile to point out, at least my understanding is that the tachycardia is actually most likely attributed to a particular terpene in the plant and not THC directly. And so, if you use cannabis, and you do get the racing heart, which is something that I hate, you need to try to find out what the terpene is for you in those plants, and then avoid those plants.

And I would say that this is kind of the cutting edge of understanding using whole flower and there’s not a lot of research on it. But, I think there will be soon. I think you’re right, too. But, I do think that the patients who use Durabinol, which is the synthetic form of THC, they also experienced this. So, I think that there probably is some interaction between all of our cannabinoids and terpenes. There’s clearly something going on there.

Where you’ve got to for any product that you’re using and ingesting it, by any means, you’ve got to find that personal therapeutic window, right? You’ve got to take enough of the stuff to get your good effect without taking so much that you get a bad effect. Yeah, I totally agree with you.

Cannabis Oil Tincture

Alright, so that’s smoking. Let’s talk. Well, we’ve already talked quite a bit about tincture, but let’s talk about tincture. A lot of people like tinctures because they feel much more in control with smoking. I know it’s really hard to control how much you’re actually going to take and with things like capsules, you’re kind of beholden to whatever they put in the capsule, but with tinctures This is very much individualized medicine. You’re able to say, okay, you know this this lab tested tincture, I know the potency of it. And so, I’m going to slowly increase my dosage over the next few days. And then I’m going to find my sweet spot. And then I know it’s going to be X amount of a dropper, X amount of drops themselves so that you can get repeatable results. And for me, that’s why I generally recommend tinctures for people because of the patient control.

I love tinctures for several reasons. One of them is that like you said, it does feel like medicine to people. You know, like for a lot of people my grandparents age, I’m lucky enough that my grandmother is still alive. And you know, there’s absolutely no way she would even use something that looked like an inhaler to inhale cannabinoids. But a tincture, that feels like medicine to her, so she’ll actually use it. You can’t benefit from a medicine that you are opposed to using. So, there’s that component. It’s easily titratable easily digestible, reliable results, those are all amazing. The other thing that I like about some of these tinctures is that depending on the formulation, it can act as somewhat of a hybrid between a product that’s available both immediately in your mouth, and if you swallow some of it, and it does get all the way through the liver, then you have you know, like a two for one where you have the immediate onset from some of the THC to produce some sedation, whereas you have that sort of slow release effect from the from the liver, and converting Delta nine into other metabolites.

That gives you this more prolonged slow-release effect. You have both immediate onset and a long duration, which is really not achievable through any other product. One of the things that I find very liberating about tinctures is that even though there are certainly artisan and craft ways to make a good ethanol tincture, that is going to be potentially better than a novice tincture maker.

I like the fact that it is a process that’s available to everyone. Anybody can grow their own cannabis plants in their yard. They can take the flower, and they can pour everclear ethanol over the top shake it for 90 seconds, strain it through a coffee filter, and guess what? You just made your own tincture. And, sure there are fancier ways to go about it, by freezing everything first and all that kind of stuff. But essentially, if you just pour ethanol over your flower, and strain it, you have made tincture. And, depending on what state you live in, many, many state cannabis labs will allow patients to get things tested. And so you can find out how strong what you made is as well. And I think that kind of, I don’t know, I guess I’ll call it egalitarian pharmacology is something that’s very attractive to me because I do not support the ivory tower medicine idea. I guess we already established that with the whole citizen scientist thing.

Tinctures are great because you can have control of your own health by growing your own plant making your own tincture and now you are self-sufficient. It’s wildly less expensive than purchasing it either licensed or unlicensed.

Pharmaceutical Egalitarianism

Absolutely. The word that I use for this is empowerment. And I think that it’s beyond just not being reliant upon someone else. When you see a project through from beginning to end, and I see this with my trainees and my students all the time, you have an investment in it. When you pop that seed, when you drop that clone in the soil when you are attending to that plant, when you are looking for signs of maturity, when you are harvesting it with your own hands you have a lot invested in yourself. And that whole process is supportive of your health. That is you taking your own health into your hands. We see this all the time in the pain clinic. Those people who are able to take control of their own lives and decide, I am going to do this for myself, those aren’t the people we see in the pain clinic because they don’t have any pain because they have figured it out for themselves. This being invested in it has sort of a holistic support from a human level in addition to you, also as a byproduct, are not reliant upon some commerce or pharmaceutical company or something. So, yeah, I love that idea of this pharmaceutical egalitarianism.

Cannabis oil edibles for pain

Okay, let’s talk about edibles because a lot of people use edibles, and swear by them for their pain, and pretty much will express that they can’t live without them. But edibles are a complex medicine and they’ve got pros and cons. So, let’s start there. What are your general impressions of the efficacy of edibles and when you do recommend edibles? What do you recommend people try?

Yeah, so let’s start with the pros. So clearly, we have something that’s really easily dosable, just like we have with tinctures. It’s pretty easy. Even if you have something that is more than the dose that you would prefer, it can often be really easy to divide that dose. I am not a five milligram gummy person, like two and a half is just fine, thank you. That’s the benefit, is that you have something that is easily digestible, which means that a patient knows what to expect and there’s some consistency in that effect, which is huge. What I love that about edibles is that it’s easy to dose and easy to divide doses. The other thing that I really like is the duration, because we’re putting the cannabinoids through the liver and you are recruiting the liver to prolong the effects of the medicine. And often, that can be extremely therapeutic. If you’ve got to get all the way through workday, if you’ve got to get all the way through a night of sleep, you need a slow release formula, something that wears off in two to three hours is not going to work for you. So, I like it for the ability to dose and the ability to last for a long time. I could see why patients would totally swear by that, because those are really important components of medicine.

And also we talked about earlier about the smoking. While certainly the the power of edibles is not to be scoffed at. It’s nice because you don’t go up so as fast as you do with smoking. If you’re looking for pain relief and anti-inflammation without the stony aspect of it, edibles can often be a good choice. They can, as long as you stay within your own therapeutic window. We talked briefly about that before, how you’ve got to take enough of it to feel something but you can’t take so much that you start to experience negative effects. And unfortunately, with edibles, the likelihood of experiencing a negative effect, it can be pretty high.

Cannabis oil dosage explained

If we look at the data that came out of Colorado, when legalization first came around, we saw that the vast majority of people who came into the emergency departments after ingesting cannabis were having an acute psychotic episodes, or they thought they’re going to die. If there’s some kind of THC overdose, the vast majority of those cases are edibles. Part of the reason for that is that in when you ingest cannabis, delta nine THC is converted into 11 hydroxy THC, which is far more potent, and lasts for a very long time. Inhaling five milligrams of THC is not at all the same thing as swallowing five milligrams of THC because your liver converts it into something that’s more powerful and lasts longer.

The other thing about the liver is that everyone’s liver is different. The different effects of edibles say far more about the differences in our livers than they do about the difference in manufacturing processes or the differences in the products themselves. The enzymes within our liver that metabolize drugs and dump things into our bloodstream and protect us from toxins, all of those enzymes are our proteins and those proteins are encoded by our DNA and our DNA is different. Drug metabolism is affected by other drugs that you’re taking, other medications that you’re taking, it’s affected by your diet, it’s affected by your exercise and your other lifestyle components. For all of those reasons, the effects of an edible are not only variable between people, but also variable within one person. Although, yes, it might be really easily to dose and it might last a long time, there’s also some degree of risk there. Because you’re allowing your liver to produce a very potent molecule. And you could experience different effects from day to day because of the other you know, sort of lifestyle factors.

This is such a challenge for pain patients who are new to cannabis. Because what we’re kind of teasing apart is actually a really complex situation, where the patient wants the cannabinoids. And so they take an edible because they’re approachable and they’re pretty easy to get, in legal states anyway. But then, if you take it, and you take too much, we’ll call it, over medicate itself. Not only is it way more intense, because it’s become 11 hydroxy, but because your body is processing it more slowly, your bad experience lasts longer too. If you smoke too much pot, it’s like, Oh, all right, well I’m going to go and sit in nature and I’ll be pretty good in about 45 minutes, I know it’s going to go away. And while it’s going to go away with an edible, that could easily be two and a half hours. That will often scare people away from cannabis medicine, when it really had nothing to do with the inherent value of cannabis medicine. It had to do with, using edibles properly for pain takes some pre-education, and then an awareness to start at a low amount.

Absolutely. And this adage, the start low and go slow applies absolutely to any product that is ingested or swallowed. It is incredibly important to start really, really low. And when we’re working with our chronic pain patients in Philadelphia, I have a collaboration with Thomas Jefferson University and the Rothman Orthopaedic Institute. When we’re working with our chronic pain patients we’re advising them if they’re going to use an edible product, to start at one milligram of THC. Because there really are some individuals out there who are hypersensitive to THC. There’s a lot of variability. Some people can tolerate an entire 100 milligram edible to themselves and other people’s spin out into total paranoia and psychosis at one milligram. So, it’s far more conservative, and it’s better to not take enough than it is to take too much, because you can always take more, but you can never take less, especially with an edible.

And while we’re talking about liberation medicine, let’s talk about ego and being cool. I want to make sure I point out to patients that there’s a certain vibe within the cannabis scene that taking more THC is cool. And if you take less, you are somehow less than, or have got baby lungs. There’s a lot of different ways that people with high tolerances can kind of disrespect people who take a small amount. But I want to encourage folks. If taking 2.5 milligrams of THC, which most people don’t feel it at 2.5 milligrams, it’s a nice, steady, three times a day, anti-inflammatory dose, but you don’t get intoxicated. And I’ll mention sometimes, oh 2.5 milligrams, and someone in the group I’m talking with will totally scoff. And they’re like, Nah, I take 25 milligrams six times a day. And I’m like, I’m glad that you found something that worked for you. But there are a lot of people, myself included, if I took 25 milligrams, like, I’m going to have a bad day. Like, I’m going to, I don’t know if I can call it subpar psychosis, but I need to go lay down, and I’m going to be scared for a few hours, and I hate it.
Individualized medicine is very modern. And it’s important for pain patients to remember that you need to start low and you need to increase it slowly. And comparing your dosage to anybody else should not matter at all. You’ve got a different number of candidate cannabinoid receptors in your body. Your body is going to process it at a different rate. There really is not any kind of hard and fast comparisons patients to patients. You might be able to get guidance from other patients, but understand that guidance and then start at one milligram.

So I love that you’re bringing this up, and I don’t know, at least for my patients that I’m working with, we are seeing a whole lot of people that are entirely cannabis naive. Luckily they’re not bringing that kind of thinking, more that kind of, for lack of a better word, machismo, to the table. It’s entirely novel for them, and they’re just looking to their doctors for help. Fortunately, we can start working with people with all of those factors that you mentioned in your individual experience. And the beautiful thing about this plant is that it is dynamic enough that there is something for pretty much everyone. And I love the idea of, we’re all unified in our process, but not necessarily in our dose, or our amount. So, our process is always the same, we start somewhere, and we either have a good time, and we can keep going, or we have a bad time, and we have to back off. And the magnitude at which we increase or the magnitude at which we decrease our consumption or our frequency may vary. But that’s the process. And this is something that we don’t talk about, in all of the rest of allopathic medicine very much, that this is true for lots of other drugs that people go to their doctors for. Some people go for anxiety medication, or a tricyclic antidepressant and the doctor tries you on one thing, and it didn’t work. So, you just switch to a different drug, and then you have to up the dose, and then it was too much. So then you back down the dose. But the difference between allopathic pharmaceuticals and cannabis is that instead of your doctor telling you you’re having a bad time, let’s do something different. You have to pay attention to yourself and look at your journal and say, that didn’t work for me, I need to do something different, which for some people can be incredibly empowering. And it can make all the difference in the world in their health. But for other people who are really accustomed to having their hands truly held by a healthcare professional, and putting all of their trust and getting all 100% of their guidance about their health from you know, a person in a white coat, that can be really intimidating to have to say like, Oh, geez, I have to like figure out all of this stuff by myself. This is really overwhelming. And I feel for that person. It is absolutely true. It is work to try and find a place to start. And then fine tune your own process in accordance to your own body and your own lifestyle needs. It can be a process, but it can also be an incredibly rewarding process, and trully for anybody in the audience who’s new to cannabis who’s trying to you know, transition from opioids to cannabis, who is saying, Okay, I need to get a good education first, right? Because it’s sad, how much of the licensed market cannabis packaging and marketing is intended to confuse the buyer of what it actually is, maybe trying to sound like a product of higher quality than it is, or making claims that are untrue. And so when you when you take your health into your own hands, and you do your research in advance, you are really doing yourself a service,

For sure. And that can be really hard. It’s very difficult to know who to trust. This is on the label that it relieves pain, and then it improves cognition, or whatever it is. Whatever it is on the label. Oh, it was formulated by a PhD, therefore, it’s a good product. All of those things can be kind of deceiving. I do feel for people who are just embarking on this journey, because it is a lot of homework and it is a lot of time that not a lot of people have the luxury of navigating.

Sciencewashing and Greenwashing

I’ve heard you use the term sciencewashing before and I got a chuckle out of that. And you’re comparing it to greenwashing. Things that are faking being environmental. That there are so much many cannabis products that are faking having a scientific basis to them. Not cannabis itself, which has a scientific basis, but that particular method may not be in line with the science.

Exactly like if you have a vaporizer pen that has sleep in its branding or its effects, I think that your listeners would benefit from applying some scientific thinking to that. How do you know that it’s good for sleep? Where did you get your information? How many people tried it? For how many people did it work? Where did the formula come from? I love the idea of everyone being a little bit more skeptical, especially when it comes to this kind of stuff, we have been relying on the pharmaceutical industry. We trusted them to provide us with safe medicine for a long time. And it didn’t happen. We were extremely misled by the pharmaceutical industry when it came to the opioids. And I think it would behoove all of us to think a little bit more critically and skeptically about any kind of claim that appears on some packaging.

I realized we’ve kind of set ourselves up. We’ve just spent this show recommending that people try cannabis instead of opioids. And now we just said there’s the market is full of lies, and you can’t trust what’s on the shelves, and the damn thing is that they’re both true. And the best thing that I recommend to people is do your research on the dosing protocol that you want to do for yourself, and then do some research beyond just talking to a bud tender on the product that you’re going to buy. But then also humans have been using cannabis and smoking it and making cannabis tinctures, for 1000s, and 1000s of years. The new cool hot fancy thing is not necessarily better. And if you’re just starting out, and you don’t have a very good bullshit detector, when it comes to cannabis products, I would always recommend to start with something that is more simple than more fancy. Everybody was all excited when water soluble CBD became available. And they’re like, Oh, we can put in all these beverages. And I’m like, What use do water soluble isolate have because I don’t think it’s healthy to take isolate. And you have to over-process it even more to make it water soluble. And so, maybe that makes me less cool. It certainly got rid of any soda advertisers I would have gotten on the show. But I think that sometimes it’s better if you stick with the basics.

Cannabis oil is safe and effective for most people with chronic pain

Yeah. And I many times before I have said that we did phase one clinical trials on cannabis 5000 years ago in China. It’s safe for most people, and now the question is, is it effective? I do think that we have a lot of evidence to demonstrate that cannabis oil is both a safe and effective pain reliever for most people with chronic pain. We can’t say that about opioids, we do know that it does work for some people ,a very small proportion of people, it works over the long term. There are people who have been on opioids for decades, and it’s effective for them. But the risk of physical dependence and the risk of overdose and the risk of constipation, cognitive impairment and all these other things. it’s greater than the pain relief that results from engaging with opioids.
Where these two start to interact is largely at a point where patients often get to a point where their opioids are becoming more difficult to obtain. And when you have a person who’s physically dependent upon an opioid, they’re kind of stuck. They need something to be introduced into their body to feel normal. And so a lot of people have been using cannabis in combination with their opioids, especially initially. And you know, my work in academia has been supporting this approach for a very long time, because we know at a very fundamental mammalian level, when you have these compounds in your body at the same time, they produce synergistic pain relief. That means a greater than additive effect. It’s not two plus two equals four, or two plus two equals one. So when you have something like that, when you have a seven instead of a four, then you can back off on the doses of each of those components, so that you can achieve the same level of pain relief you had before at a much smaller dose. Anything we can do to reduce the dose of an opioid required to elicit pain relief, that is a really good thing. Nothing, no other no single other drug, no other law, no prescription drug monitoring program, no abuse deterrent formulation of a pharmaceutical, no other intervention has reduced the number of opioid overdose deaths as much as legalizing cannabis has reduced opioid deaths.

Transitioning from opioids to cannabis oil for pain relief

We’re about to go into the how-to of actually doing the transition because I know you’ve given this a lot of thought. But before we go there, there’s one more thing I want to hit on the on the edibles tip. And that is, you. I mentioned in passing that, that many folks, they just stop at 2.5 milligrams, because that takes care of their pain. Maybe if they want to feel like a little jocular with it, they’ll go up to five milligrams, and so they’re getting some of the other attributes of pain relief as well. But then you’ve got these people who have got long term chronic pain, and they’re taking 100 milligram brownies. And they’re both pain patients. I know there’s several different variables at play. So I’ll just toss it to you like that and say, What’s up with that?

Well, one of the fundamental things there is tolerance, which is both a tool and a hindrance. In order to reap the benefits of THC in cannabis, you do have to have some degree of tolerance so that you can widen your own personal therapeutic window, you can widen the dose range at which you feel something, but you can still fall below the threshold of feeling bad things. Staying in that therapeutic window is easier if you have some tolerance to THC. If it’s more tolerable you have a wider window of good effects. The problem comes in and this is something that you know, we would be wise not to repeat with opioids, right it with opioids. No doctor ever told their patient, hey, this stuff can produce physical dependence. To manage your physical dependence, you should monitor your tolerance. If you find yourself taking more or more frequently, take a break, switch to something else for a couple of days, allow your body to reset and come back to it. That could have saved 1000s of people’s lives. But we never had that conversation with our opioid consuming patients. This is one thing that we have the opportunity to do right with cannabis. We can have that exact conversation. This is a substance that you can develop physical dependence. It is rewarding, you could develop some kind of cannabis use disorder or hyperemesis or some other dysregulation in your endocannabinoid system. It’s prudent to take a break from time to time, not only to allow your body to re-sensitize, but if you are able to take those periodic tolerance breaks, you’re able to re-sensitize to a point where you don’t need 100 milligrams in order to feel that effect that you felt on Friday night. It is a far more economical approach to take tolerance breaks, reduce the amount that is required to elicit that same effect.

For pain patients who have pain every day, then who have transitioned to cannabis, what do you tell them to do on those tolerance break days? Because, so many of the pain patients I talked to, the idea of taking a tolerance break and experiencing 48 hours of their pain straight just makes them cry. And they want to avoid that at all costs.

To be quite frank, I don’t tell them anything, because people are very resourceful at figuring out what’s gonna work best for them. A lot of people turned to other kinds of pain therapies, anti-inflammatories the non-steroidal ones. Some of them might take an opioid for a couple of days. The risk with opioids is over the long term. Where they increase risk, and where they lose their efficacy is when you take them chronically. But if you’re only taking opioids for two days, that’s exactly what they were designed for. Short term use. Some of them switch back to opioids, some of them just rely on meditation and cognitive sort of techniques. There are, in fact, digital health technologies and apps that people can download, to sort of go through practices daily to cognitively manage their pain. Fortunately, I don’t need to have those conversations, frankly, at all because people are very resourceful in figuring out how can I just get through a couple of days and it’s different for everyone.

It just makes me sad when they don’t want to go back to the opiate because maybe they had a challenge with it before. And then they are on cannabis and they know they need to take the break. So, either a they resist taking a tolerance break, because they are afraid of those days off or as I see so common, they just turn to alcohol. And so, they’re sloshed for two days and then they come back and I just wish there were more options.
I do too. And you know, I feel like this is going to be, I would hope that as this chronic pain management with cannabis becomes more mainstream that we will have more of our best and brightest minds in clinical practice, and in scientific development, that we will have some answers for people.

All right, so let’s get down to the brass tacks of actually transitioning. Going cold turkey on opioids can be not only difficult, but dangerous. And there are definitely advantages of doing kind of like a measured transition. But I know you’ve developed this out in detail, why don’t you tell us your recommendations for transit for the actual transition time, the process.

This is very different for every patient. Just because you’re on an opioid doesn’t mean that you’re on the same opioid as anyone else who is going to the same pain clinic. There are short-acting opioid drugs and longer-acting opioid drugs, which all have their different profiles in terms of how rapidly you can taper off of them. So again, this is where the personalized component is critical. We’ve been attempting to develop a formal opioid tapering protocol for a number of years, and we make some observations, one of which is if we tell a patient absolutely nothing, by the three-month mark, they have just sort of figured out how to take half as many opioids or get off of them entirely on their own. So again, this kind of comes back to the self-empowering component where you know, people are perfectly capable of figuring things out for themselves. If you need some strategies specifically for doing that, what we found is that a lot of patients just start by eliminating one of their daily doses. A really common one that people eliminate is the one right before bed. If they switch to some kind of ingested or swallowed preparation of cannabis right before bed, they no longer need their overnight dose of their opioids. So that’s probably the most common one, to skip the dose of the opioid that’s taken right before bed. And then often a lot of patients wake up feeling refreshed, having slept through the whole night without having that heavy sort of sedation, and the hangover from the heavier narcotics. And just that cognitive state alone is able to get them through the day, so that they’re able to walk beside their pain, and live in the presence of the pain rather than trying to totally numb it with their next dose of their opioid.

So those are my practical ones. And then I would also advocate for the personalized component, which is to do what is right for you. A lot of patients will do just fine on one or two doses of their opioids every day. A lot of people can decide that they don’t want to be reliant on this anymore, and they’re willing to have a little bit because the thing about cannabis is that it doesn’t profoundly eliminate the pain the way that an opioid does. But it certainly profoundly improves the quality of life. For some people, the physical sensation of the pain is so intense that they just can’t ever get away from it, then they’re always going to be consuming opioids, and that’s fine. If that’s what your body needs, in order for you to have a high quality of life, then shoot for that. But really what it boils down to is figuring out what your own personal priorities are, and utilizing cannabis in combination with and eventually for some people potentially, in substitution for the opioids.

I think that patients who are going through that transition, really should, or I’m doing great, and should I. These are not good words. It is described to me often by patients that they think it’s going to be worse than it is, and that the transition becomes easier for even very simple things. Part of taking Delta nine THC is it can cause a little bit of cascading forgetfulness, the kind of thing where we joke as cannabis people… Oh, I forgot where my car keys were. Just basic stuff like that. And so many patients, they’re so used to taking their opioids on a schedule, and that if they aren’t on their schedule, they’re afraid that their pain will flare-up. But then they start incorporating cannabis alongside the opioids, and a little bit of the pain relief kicks in that’s natural, but also a little bit of that that forgetfulness comes involved as well, and they actually forget that they’re in pain, or they forget to take their dose. And they realized, oh my gosh I’ve naturally started replacing the opioids just because of the nature of cannabis.

Yeah, that’s absolutely true. I think that that’s been reflected in some of the anecdotes that we hear in the clinic. To each their own. For a lot of our patients, more than half of our patients don’t experience any impairment whatsoever. And for those that do experience some impairment, this either doesn’t affect their day, or they’re more willing to deal with the impairment than they are to deal with their opioid side effects.
Well, this is all fantastic. Adie, thank you so much for taking your time to, actually a lot more time than we had planned on, we actually got on a roll. This is a lot of really great information. Thank you so much for sharing the caring that you have for patients and your in-depth scientific research. I think that there’s so much in our scene which is anecdotal evidence, and people sharing only what worked for them. And then a whole bunch of kind of like, myth and taboo leftover from the Reefer Madness days. And I think that people like you doing the real research and then interacting with patients, and then coming out and sharing the reality of what they can do to save themselves is really important.

Shango, it’s an honor and a privilege to do this work. And I feel very strongly about sharing the work as widely as possible. Thank you so much for the opportunity to share it with your audience. Wonderful.

So if you want to find out more about Adie, there are a couple of different ways to do it. First of all, I recommend that if you like the kind of information we talked about today, and you would like to hear it with pictures, I recommend that you go to the YouTube channel for cultivation classic. It’s a fantastic event in the Portland area. And on the cultivation classic YouTube channel, there is a recording of Adie’s 2017 presentation on beyond opioids. And so you’ll hear a lot of the stuff that you learn today over again, but there’s also a bunch of stuff she covered there that we did not cover, and it’s got pictures, so that’s great. Also, she did a great talk at the Cato Institute on harm reduction for opioids. And you can find that on the Cato Institute website at cato.org. That’s cato.org. And then finally, if you want to reach out to Addie Raw herself, or find out more about her work in her company, you can go to smartcannabis.life. So that would be www.smartcannabis.life. And you can reach out if you want to or just learn more. Find more episodes of the Shaping Fire Podcast and subscribe to the show at shapingfire.com and on Apple iTunes, Stitcher, and Google Play. If you enjoyed the show, we’d really appreciate it if you’d leave a positive review of the podcast wherever you download it. Your review will help others find the show so they can enjoy it too on the shaping fire website. You can also subscribe to the weekly newsletter for insights into the latest cannabis news and product reviews on the shaping fire website. You will also find transcripts of today’s podcast as well. For information on me and where I will be speaking, you can check out shangolos.com. Does your company want to reach our national audience of cannabis enthusiasts email hotspot at shaping fire calm to find out how. Thanks for listening to shaping fire. I’ve been your host Shango Los.