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Dr. Ethan Russo: Cannabinoids as Medicine


Dr. Ethan Russo is a well-known name in cannabis research. He has been studying the plant since around 1996 and coined the tern “Endocannabinoid Deficiency”. We covered a TON in this episode, Some topics include:

  • What is the Endocannabinoid System
  • What is Endocannabinoid Deficiency
  • How to Use Cannabis to Solve Endocannabinoid Deficiency
  • Cannabis and The Opioid Epidemic
  • Cannabis for Cancer, Alzheimer’s, and other Diseases
  • Topicals, do They Work?
  • Industry Predictions

Listen or Read below!


Dr. Ethan Tell Us About Yourself?

I am a board-certified pediatric and adult neurologist. Somewhere around 1990, I developed an interest in medicinal plants that led me eventually to become embroiled in the cannabis controversy as I like to call it, circa 1996. 

That was the same year that prop 215 developed in California, which provided medical access to cannabis. I really see that as the catalyst for everything that’s happened in the ensuing 23 years. 

Ethan Russo

I tried to get formal permission from the federal government to do research on migraines and cannabis but was stonewalled. But all that time I was learning a great deal about cannabis and the endocannabinoid system and I became very enamored of the subject. 

Eventually, it became a full-time career. 1998 was the year that GW pharmaceuticals began, I was a scientific advisor and was asked to come on with them full time in 2003 where I was involved in a variety of endeavors, including being the medical monitor and study physician for about 20 phase1-3 clinical trials and also serving as a liaison to clinicians and basic scientists in the cannabinoid realm.

Endocannabinoid System

You Are One of the World’s Experts On The Endocannabinoid System –  Could You Explain That System to us?

First, we have to define physiology. Physiology is the science of how things work in the body. As it turns out, the endocannabinoid system is innately involved in keeping our physiology and balance no matter what aspect it pertains to. 


To explain, endocannabinoids are endogenous cannabinoids. They are natural chemicals in our body, specifically Anandamide and 2-arachidonoylglycerol (2-AG) that closely parallel what THC does in the body. Beyond that, the reason this works is we have receptors in our body for these endocannabinoids in the same places that THC lodges in the brain and other organs. 


The third part of the system are the enzymes that make the endocannabinoids and break them down. The endocannabinoid system is involved in regulating how things work in the body, specifically in the brain. It regulates how much neurotransmitter release there is.


If there’s an excess of activity in a system, the endocannabinoid system will act to bring it back in balance. If it’s too low, it will bring it back up into the normal range. If the activity is too high, it’ll bring in back down into the normal range. Additionally, the endocannabinoid system is not just working the brain on things like whether someone will have seizures or not, vomit or not, and regulation of emotions. Out in the body, it works on digestion has effects in the liver muscles and any Oregon you can imagine.

Endocannabinoid Deficinecy

What Happens When Parts of the Endocannabinoid System Aren’t Working –  Endocannabinoid Deficiency?

When things get out of balance, it can have bad consequences. but when there’s a deficiency of Endocannabinoid function, there are a large number of things that can go wrong. Most prominently, the development of pain even where there isn’t an obvious explanation for it. There also can be the development of nausea, inability to sleep, and the list just goes on and on from there. Digestive upset, diarrhea, gut pain, it’s an extensive set of circumstances. 


Additionally, people might develop a tendency towards seizures or epilepsy that wasn’t otherwise evident. So patients could become anxious, suicidal, paranoid, all of these things.


If You Develop a Deficiency How do you fix it? How do you Know That it’s an Endocannabinoid Deficiency?

It’s a bit of a tough one. Clinical endocannabinoid deficiency has been implicated in a number of very common conditions including migraine, fibromyalgia, and irritable bowel syndrome. This is a theory, but it’s been largely born out by experimental evidence. 


One example, there was a study done in Italy circa 2007 in which they took samples of cerebral spinal fluid using a spinal tap or a lumbar puncture and we’re able to show deficiencies marked reduction in anandamide levels as compared to the fluid from people who didn’t have a migraine. This was strong corroboratory evidence of an endocannabinoid deficiency at the root of migraines. 

But this isn’t an easy thing to measure. We’re not advocating that people get a spinal tap to try and ascertain their endocannabinoid levels. Eventually, we hope that there will be simple blood tests. Right now the blood tests are tough because this material is very unstable and has to be frozen under liquid nitrogen and sent for analysis.


Additionally, it is not always the case that the levels in the endocannabinoids in the serum will exactly parallel the levels in the brain. Although we’d like to have it, we don’t yet have scans of the brain that would show on the degrees of endocannabinoid function. So it is what we call a clinical diagnosis based on patterns of disease. 


The next thing is what do you do about it if you have one of these conditions? That’s part of the problem. When we’re talking about migraines, irritable bowel, and fibromyalgia, it really is the case that current standard medical treatments really don’t help the majority of people in all instances. 


There would be two approaches to helping ones endocannabinoid system get back into balance. One would be non drug approaches. These would include lifestyle factors, that would include things like aerobic exercise, dietary changes, and anti-inflammatory diets, particularly ones that would, influence good bacteria in the gut (what’s called the microbiome) and that could be done with prebiotics and probiotics. 


Beyond that, one can certainly boost a cannabinoid function through the use of cannabis-based medicines.


If you’re looking to use actual cannabinoids to balance your system where should you start?

The most immediate approach would be to use something that mirrors endocannabinoid function. So that would be THC. As you’re aware, that’s sort of a double edge sword in that a little bit helps stimulate the CB1 receptor and is good, but too much can be counterproductive in terms of side effects. 


So a little bit of THC could help a great deal with pain control, slowing down the gut, and reducing anxiety, but too much will aggravate anxiety. So there has to be a fine balance there.


 The point of treatment with any cannabis-based medicine is to reduce symptoms with the least side effects. A key question that has been answered already is yes, it is possible to treat symptoms of disease with an inappropriate dose of cannabis-based medicine in a way that does relieve those symptoms without producing an undue burden of side effects.


In treatment, one way to do that is when we have a mixed preparation that includes components of THC and cannabidiol (CBD). CBD has a really interesting role. It doesn’t work directly on the cannabinoid receptors but works indirectly. It reduces the side effect profile of THC and making it a more acceptable medicine increasing in what’s called a therapeutic index.


That is better tolerated. Additionally, in longterm news, it seems that CBD can work indirectly to boost endocannabinoid levels and certainly the combination has proven very useful in treating a wide variety of conditions.

Hemp Seed Oil

If you’re thinking about using CBD with a little bit of THC, but not enough to aggravate anything, Let’s talk about the different options?

This is very much dependent on where a person lives. We can divide the country up into areas where there are lots of choices such as the West Coast and places where there are fewer to none, in terms of what’s available in a given state. 


Someone in Idaho is going to have a hard time, but I would almost always advocate the CBD on its own works a great deal better with at least a small component of THC. We know this from studies that have demonstrated that doses of CBD required to effectively treat certain types of epilepsy may be as much as five times higher as compared to a mixed preparation – a full spectrum extract and doesn’t exclude other components. 


It’s really tough for the consumer out there because they may not live in the right place where there’s the availability of these types of medicines. 


Number two, there isn’t a lot of truth in advertising. We have very poor labeling in most places. My personal bias is that every sale of a cannabis-based product, whether for adult use or for medical, should be accompanied by a certificate of analysis on the current material. That way the patient will know not only what the cannabinoid profile is, but also the profile of terpenoids that contribute additionally to the medical benefits of cannabis through what’s called the entourage effect.

If you’re trying to pick a tincture, what are the biggest warning signs to look out for?

I wish I could offer a simple solution. With all the different options there are on the market for CBD and other various tinctures, what are some of the biggest red flags that people should be looking for?


It’s not always easy for the consumer to know this, but if you have a label that doesn’t specify the amount of material (mgs of CBD)., One thing we see a lot is they’ll say there is a certain amount of hemp oil. Well, that’s meaningless on its face (see video: the difference between Hemp Oil and Extract). You want to know the exact concentration of material per unit. 


In other words, how many milligrams of CBD are there per milliliter? I can’t endorse a single product. I would emphasize that some of these cannabidiol products are extracted from hemp refuse. We don’t know how it was grown, how it might be contaminated, whether there is any accuracy to the label. 


In areas where there is availability, a full-spectrum product accompanied by an analysis, it’s going to be the best way for the potential consumer to go.

Cannabis and the opioid epidemic and how cannabis might be able to help us?

It’s a very complex topic, but first, let’s lay the groundwork. In 2017, there were 72,000 Americans that died in overdoses. Unfortunately, my niece was one of them. 


This is a situation where we have a great deal of evidence both from animal work and in humans of an opioid-sparing effect of when cannabis is available as medicine. What that means is that people can lower their dose and often get off of chronic opioids when they substitute a cannabis-based medicine.


There’ve also been various public health studies that show reductions in opioid prescriptions and total usage of opioids in places where cannabis is available medicinally. It’s not clear in all instances whether that’s a cause and effect relationship, but those of us that are working in this space have no doubts that cannabis is part of an exit strategy from excess opioid use. 


Among the findings are that we know that opioid doses are reduced particularly in painful conditions when cannabis is aboard and that it reduces withdrawal symptoms – or makes it a great deal easier for people to escape that trap.


If you are trying to help somebody reduce their opioid use what path would you suggest going down?

Well, obviously our recommendation is that this is done under the supervision of a physician who has experience in the area. But that’s a big ask. The odd thing is that many patients find them tapering the opioids on their own when using cannabis.


They may notice that their pain’s a lot reduced, doesn’t get any worse if they reduce the dose of the opioid, or they may have taken more notice of opioid side effects. Patients tend to taper on their own even without instruction. That’s not something we’d recommend. This is something that a patient should pursue very slowly in a stepwise fashion. But in talking to my colleagues, they find repeatedly that patients often manage a taper and even discontinuation of opioid medications. Quite amazing,

Other conditions that cannabis seems to have a lot of potential for like Alzheimer’s, Parkinson’s, Brain tumors?

There’s an expression in neurology that there’s no such thing as a benign brain tumor. That may seem surprising, but a relatively common type of tumor is a meningioma. It’s benign tissue, but it’s not benign because of the location. if it reaches any size, it’s encroaching on the brain and causes big problems. But most commonly we’re talking about malignant brain tumors or cancers, especially the most severe one. 


Glioblastoma multiforme that Senator McCain and Senator Kennedy both had and in both instances led to their deaths. Currently, this is considered an incurable condition. There is a very low five-year survival with this diagnosis. The treatment often includes surgery, attempts at chemotherapy, and radiation, but almost inevitably people succumb to this. Over the course of the last 20 years, both in laboratory studies and now with the initial studies in humans, it seems that this terrible tumor is particularly sensitive to treatment with cannabis-based medicines.


That offers many advantages over the standard approaches. Normally we want to combine with standard approaches because that is where the best results are obtained. But for instance, there was a study that’s been reported online, not yet published, and I’ll give the reason why in a moment. 


Sativex, a cannabis-based medicine that’s approved in 30 countries but not the US, is a combination of a high THC extract and a high CBD extract. They use 12 sprays a day of this, which is about 32.4 milligrams of THC and 30 milligrams of CBD in conjunction with a chemotherapy drug called temozolomide. Patients that used Sativex had a much longer survival rate than the people that got didn’t.


The reason this hasn’t been reported on in a journal yet is because there’s continued survival over that normally expected.


In other words, statistics are improving every day. The patients survived. This is a very promising approach and it’s also one that many thousands of people across the country are using on their own outside of formal clinical trials. Those of us in this space are well acquainted with situations where people were told that there was nothing more than medicine could offer, but who have had prolonged survival because of cannabis-based medicine. 


I would emphasize, however, though that our best evidence is that cannabis-based medicine should be combined with standard treatment approaches. And our best evidence is also that they need to be continued indefinitely to enjoy hopefully prolonged remission.


My best advice to people is to with an oncologist who will be open-minded to the combination – but they shouldn’t avoid standard approaches and think that they’re going to get a cure from cannabis alone.

Fresh Grown Cannabis

What Do We Know About Alzheimer’s?

People are probably aware that there’s an increased incidence of Alzheimer’s disease in this country and in Western industrialized countries, and it’s been attributed by most people to advancing age, but that really isn’t the story. 


There seem to be many other factors and including dietary ones. This is a complex disorder. We know that there can be genetic predispositions to it, but most cases are not familial. 


This is a degenerative disorder of the brain, impairing memory and other cognitive thinking functions that eventually leads to deterioration and death from other causes typically from pneumonia or something else. 


But standard approaches have been extremely disappointing in treating this. We have a few drugs that might temporarily improve memory function, but nothing that arrests the inexorable progression of the disease. However, there is hope, in that it has been demonstrating that both THC and CBD can interfere with the production of abnormal proteins  in their accumulation in the brain.


 We also know from anecdotal evidence on that cannabis-based treatments are excellent in reducing anxiety and agitation in patients who are institutionalized, allowing them to rest, get sleep, and in some instances improve their functional abilities. So it’s a very promising area that really needs formal randomized controlled trials.


Can Cannabis Be Used preventatively?

If we look at the demographics of cannabis use, the rises of use are most apparent in the over 50 years of the age demographic. So a lot of people are discovering an enhancement of their functioning. It may be that they’re treating a specific condition, could be as simple as arthritis or insomnia. 


But we do hear a lot about people using cannabis in the same way that they would use another health supplement to enhance some aspect of their health or wellbeing. I’m not going to stand here and say that this is for everyone, they have to be cognizant of the risks and benefits also the legal situation where they live. But as we’ve already discussed, there are many ways in which cannabis-based medicine can enhance health and help treat disease.

I’m always curious about topicals and how effective they might be. Do you have any comment on that?

This is one of the most common misconceptions. Cannabis is great for treating skin conditions such as acne and inflammatory conditions. However, our best evidence is that it just isn’t absorbed well. 


We hear lots of stories of people rubbing Cannabis Salve on their joints and feeling like they have instant relief of the pain. If so, that’s great, but it’s unclear how it’s working. It may be acting on pain receptors in the skin above the joint rather than in the joint itself. 


We know very well at this point that the levels in the blood of the cannabinoids [when used on the skin] are inadequate to treat an internal condition. There was a study done with a topical trying to treat epilepsy and it was a failure, which I think any scientists would have predicted


Do you have any specific resources that you would recommend people to look into for some of these things?

I’ve written extensively about cannabis in various conditions. Some of that material is available online. Probably the easiest thing is  a website called semanticscholar.org. Or if they input my name Ethan Russo and cannabis on google there’ll be a large list of studies with some with available free PDF access. 


That would be the simplest way. Additionally, although the also contains a lot of contrary material, a great source is the pubmed, a website that’s the national library of medicine. People can input any search terms there and they would get a listing of articles and abstracts that are peer-reviewed scientific publications.

Trichomes up close

One, five and 10 year industry predictions?

It’s always a tough one. It really is more of a political question. I think that we could have a situation in 10 years in which we have good access to a large number of cannabis-based materials with excellent evidence behind them and excellent quality control. 


But it totally depends on what happens with federal law. I expect that we’re always going to have a mix of three different things. Those will be pharmaceutical forms of cannabinoids that have been through the food and drug administration approval process. We also may have supplements that have some body of evidence behind them and we’ll have garden variety cannabis that people use perhaps through their own cultivation or  through legal channels. 


A problem we are seeing is that one another of these aspects of the industry may harbor the illusion that they can eliminate the other two. I just don’t see that happening nor do I think that it should happen.


Is there anything that maybe I wouldn’t be informed enough to ask you about or anything we missed that you’d like to add?

I would just make a statement that for people who haven’t really considered this topic before, that they are open-minded about the therapeutic possibilities of cannabis and if they have the time and resources to delve into the topic and learn more about it. It is likely that they or someone in their immediate family is going to need it at some point. And that’s an unfortunate fact, but a better to be educated in advance.


It’s not a wonder drug but has a lot of potential and some that we don’t even know about yet and some that maybe we’ve inflated.

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