cannabis health

Dr. Bonni Goldstein: Cannabis Therapeutics

Dr. Bonnie Goldstein speaking on cannabis and epilepsy
By on February 02, 2016

Dr. Bonni Goldstein discusses using cannabis medicine in her practice for patients with intractable epilepsy, cancer, autism, and mental health conditions.

Transcript

Project CBD: I’m here with Dr. Bonni Goldstein from Los Angeles. Please introduce yourself, Bonni.

Dr. Goldstein: My name is Bonnie Goldstein. I’m a physician and I am the medical director at Canna-Centers, a group of medical practices throughout California that educate patients on the use of cannabis therapy. And I also do some medical consulting for Ghost Group, the parent company that owns Weedmaps.

Project CBD: So we have heard a lot over the years, in terms of the “reefer madness” context, about marijuana being the “assassin of youth.” But in your practice, as a pediatrician, you’ve seen different results. Maybe you can tell us about that.

Dr. Goldstein: That’s true, Martin. So, remember, healthy kids are not coming to a doctor for help with cannabis. It’s the children that are sick. And, in my practice I’m seeing the sickest of the sick. I’m seeing children who have intractable epilepsy, that means they’re not responding to any treatment that’s available. And there’s some aggressive treatments – brain surgery, special diets that are very difficult to keep, lots of different medications that have toxic side effects. I’m also seeing children with autism. And we know, really there is no medicine for autism. There’s therapy, which can be very helpful, but there’s only two approved medications, and both of them are anti-psychotics, not great for children (many bad side effects). As well as children with cancer. And also I’m seeing some children with severe psychiatric disease where current conventional medication hasn’t helped.

What we have to remember is that the endocannabinoid system, the part of the brain that’s required for many physiologic processes throughout the body, this system helps with homeostasis. It keeps the brain in balance. And, in certain patients – people with illness – that system is the core of the problem. In most healthy children, their endocannabinoid system is functioning and actually adding cannabis to that endocannibinoid system may actually interfere with developing brains. So I don’t encourage teenagers – and I’m the mom of a teenage boy – to use cannabis until their endocannabinoid system is “finished developing the brain.” But in children who are sick, these are special cases. These are children who sometimes are not finding the answers. Years go by, and when you lose years of a child’s life, you’re losing development, quality of life – the burden of illness is tremendous, not only for the child but for the whole family.

Project CBD: So what have you seen in terms of your practice that has surprised you?

Dr. Goldstein: Well, with the group of patients with intractable epilepsy, the average number of medications that the children who come to me – by the time they get to me – they have usually tried 12 medications that have failed them. They often have developmental delay. They often have significant other problems, pulmonary problems, GI problems, immune function problems, which all can be interrelated with the endocannabinoid system. They also aren’t living what I would call a “normal” life. They’re not going to school. They’re not able to go to school. The school doesn’t want to have them there if they are having lots of seizures and so on. So, what I’m seeing is, when we add CBD-rich medicine – so basically an oil that the children take under the tongue or they swallow it or it goes through a G-tube – what we’re seeing is that number of seizures is reduced. Many parents report frequency down, severity down, duration down. And interestingly, they say, where my child had a seizure before and it would take all day to recover, my child just bounces back. And then we can get up and go do things. So that was very interesting to see that the positive response, not only in less seizures and so on, but even when they still continue to have seizures they’re not as disruptive. So that was an interesting thing to see.

Project CBD: When you talk about the CBD oil, what are you actually referring to?

Dr. Goldstein: So I’m talking about oils that come from a plant that has the genetics to grow high CBD and low THC. And what we’re talking about is a ratio. Some of my patients respond to a ratio that’s 25 parts CBD to 1 part THC. Some of my patients respond to a 10:1. Every individual responds differently to medicines, as we know from all medicines, but especially with cannabis medicines. CBD oils, remember, contain not only CBD but whole plant, and so there’s THC, there’s other cannabinoids, there’s also terpenoids which are the essential oils – all of these interplay to give the beneficial effects. You know, we talk about CBD only in dosing CBD, but really it’s the whole plant that’s very important because it’s all of these compounds that work synergistically to give the effects.

There’s one particular compound called beta-caryophyllene which is a terpenoid, which has been shown to be anti-inflammatory. And I really believe that that’s one of the compounds that’s very important for a child who has seizures. One of the interesting things that I’ve seen is that neuro-inflammation is documented in a lot of research in a brain that has active seizures going on, yet most of my patients come in and nobody’s doing anything to treat the inflammation. And I really believe that the reason – one of the reasons that CBD is so helpful, not only because CBD, cannabidiol the compound, itself actually works to help balance some of the messages being transmitted in the brain and lessen the firing that causes the seizures, but also the anti-inflammatory effect. One of the other parts is the neuroprotective effect of cannabidiol. And remember, in a developing brain seizures are damaging. And so, having that neuroprotective property is extraordinarily important.

Project CBD: What would be some of the cases that you’ve dealt with that have had the kind of outcome you had hoped for when using the CBD-rich oil? What would be an example?

Dr. Goldstein: Well, I have this beautiful little girl that comes to see me. She was adopted by this fantastic mom and dad, and it appears that there was some event while she was still in the womb that they’re likening to a stroke. And so when she was born there was a lot of complications. And she started having seizures right away. And, it appears that as she developed through the first year of life a portion of her brain didn’t develop properly. You can see it on a scanning test. So, she had a lot of seizures. She’s small for her age. And, she wasn’t responding to any medications. And her parents came to see me and they had heard about CBD on TV, and then they did their research and they came to see me. So we started her on CBD oil, and my protocol is to start low dose based on weight and to titrate up which is very typical in the pediatric population.

And, I’ll never forget this, because I was on vacation when the mom texted me, but prior to this particular text, pretty much every week they checked in with me as I had asked them to. And so, the next week we go up on the dose, and the week later we go up on the dose – no negative side effects, but they haven’t really seen any reduction of seizures. And this is a little girl that’s having about 40 seizures a day. One particular week I get the text on Friday morning, and the text says: Well we went up on the dose on Friday a week ago, and on Monday we only had 20 seizures instead of 40. On Tuesday, we had only 13 seizures instead of 40. And on Wednesday, we only had nine. And yesterday, we had four. And so far today, nothing. That child is currently seizure free on CBD oil. She’s been weaned off her anti-seizure medications. And she’s making some developmental progression, doing things that nobody thought that she could do. She’s a happy child. And the parents are thrilled.

Project CBD: And what other kinds of cases, in terms of the pediatric patients you’ve been dealing with? You talk about seizures, epilepsy, the autism spectrum which could include seizures as a symptom, what other kinds of cases have you been dealing with?

Dr. Goldstein: So, I’ve seen a fair amount of teenagers who are struggling with various psychiatric disease, things like bipolar disease, severe anxiety, depression. Most of them who come to me have tried pharmaceuticals and have not done well on them. Not to say that you can’t do well them, it’s just that’s the population I see. Many of them are teenagers, so they tried cannabis with their buddies and then came home and said, either the parents noticed, my child’s not anxious today, my child’s being pleasant today. And then the parent confronts and says what’s going on? And the child will often say, well you know, mom guess what I did with my friends. Or the parents read about it and they say maybe this is an answer to our problem that we have.

So again, going back to the developing brain, in those patients you know they may have found, you know that kind of smoking pot with their buddies really helped, but we have to remember too that that may be the answer but again, in a developing brain, I think combining CBD with THC is probably the better bet. The combination is probably going to be something that will benefit them more and hopefully they can find a balance. I’ve had very good success. I had one young man who’s 15 years old, who struggled with severe anxiety to the point where, before they came to see me, the patient’s father said maybe you could make a list of what bothers you and we can bring it to Dr. Goldstein’s office. It was three pages long. He worried about everything at school, everything with sports, everything with girls, everything with everything. This poor kid had so much on his mind that he couldn’t function. It really, you know, just overwhelming anxiety including social anxiety. I taught the family about CBD oil. They were interested in trying a high-CBD to THC ratio. And two weeks after starting the oil, I got a text from the dad and he said that he had received a text from his son, which is very unusual, and his son said: I’m having a good day, I’m really happy, dad. And, I had talked to the father maybe a week later, and he was in tears. He was just blown away by the fact that there was a solution and they didn’t have to take all the various drugs that they didn’t really want their son to be on.

Project CBD: So when you’re dealing with a patient like this, how do you determine dosage and ratio? Are there criteria you go by? Is it a case-by-case thing? It’s just on the basis on your experience you’re drawing from? Is there a lot of experimentation typically that’s involved?

Dr. Goldstein: Well, the interesting thing with cannabis – and I find this easy because I tell all my patients this – you start low and you titrate up to effect. If I guess a dose, I could be way off. I really can’t guess that you’re going to get 50 mg and this guy over here gets 10. There is a clinical sense that when you start taking care of a lot of people doing this, you get a sense of where they may end up. But since everybody’s endocannabinoid system is different and different sensitivities, and remember there’s other factors involved – what’s their metabolism, does it last longer in their body, right, meaning because some people metabolize very quickly and some people metabolize very slowly. I’ve had patients who tell me that they will get a full day’s effect from one morning dose. I have other patients that have to dose multiple times during the day, maybe a lower dose multiple times. So, some of it’s the clinical experience. Some of it’s learning from my colleagues, what they’re doing as well.

But in general, starting low and titrating up. With children who are non-verbal, we pretty much, you just have to observe and you have to trust the parents to observe. I have yet to meet a family or a parent who doesn’t want the best for their child. They’re in my office because they’re seeking a solution. When it doesn’t work, I know about it. I trust the parents to tell me. They may have missed two seizures because they ran off to the bathroom or they’re cooking dinner, but in general, when your child is doing things that they have never done before – when they’re smiling, when they’re learning – I currently have a little girl who is doing very well on cannabis oil and the mom just sent me a video of her first time she ever said “mama.” And she’s around 9-years-old. So, we know her brain is doing well on this oil. We can tell. She hasn’t been able to do that before. And that’s probably because she’s on much less medication and she’s not having seizures all the time that are interfering with development.

So the dosing is really, you know it’s a little bit of a – it’s not like dosing that we know with pharmaceuticals. It’s different. Cannabis is a different compound. Remember it’s not one molecule; it’s a whole bunch of different molecules. Really, I think one of the very important things is that we really can’t harm people with cannabis. Of course, someone who uses a dose of THC that alters them and they shouldn’t be driving, sure they can get hurt. But that’s not what I’m doing in my practice. We’re giving measured doses of CBD oil to children, again starting based on weight, low dose, titrating up, looking for that child’s – what I call the sweet spot. And sometimes less is better than more. Sometimes we hit a point, we say, ‘Oh no we did much better at a lower dose,’ and we back down. And so there’s a lot of dose management going on, but because the tolerance is so good there’s no negative side effects really. I’ve even had the experience of three particular patients over the last few years that measured wrong on the syringe and overdosed their children. The child had a very nice nap! Slept all night, and really there was no negative – other than the parents worrying – there was no downside.

Project CBD: That’s important information for parents to hear, particularly for parents who may not be able to get a consultation with you directly. Let’s face it, there’s not many physicians that are doing this kind of work. I can probably count them on one hand really, who are doing this kind of cutting-edge work with oils, cannabis oils. And yet, there are so many families that are in need of this kind of therapeutic information. What could you tell a family or parents of a child who can’t get into see you – you have a waiting list or they’re in another part of the country. Can you give advice that’s more than just, ‘Okay this won’t hurt if you overdose’? What can you tell people in this situation, because there are so many people in this situation?

Dr. Goldstein: Well, it is hard, because you want to have the whole picture beforehand. I was trained very well as a doctor. I feel that my training was excellent. And I think the nuances of somebody’s illness is important to kind of gather up before you proceed forward. I have had a few patients that came in who were actually doing well without side effects on a medication. The parents came for my opinion. And at the time, I made the decision to hold off on treatment just to see where we end up. Because, you know, sometimes with children with seizures, they do stop. And they may not have another seizure, ever. It’s a very strange phenomenon but it happens. And so, if you’re four months away from being taken off your medication, I don’t want to rock the boat and cause a seizure because of the drug interactions.

So sometimes getting the whole story is really needed beforehand, it’s hard to just throw doses out there. For any physician – you know, I don’t want to be irresponsible and say, ‘Oh do this and do that.’ But, I think gathering as much research as you can gather, talking with people about – you know people who are in the business of either making the oils or who are helping patients with the oils – there’s a lot of people out there who know a lot. I think one of the big things is that my colleagues in the medical community need to start seeing this as an option, and they need to learn about it, and have it in their amamentarium of medicine. It is a medicine.

Lee: Why isn’t that happening more with doctors? Why aren’t there more doctors jumping on board? Because certainly there’s a buzz about medical marijuana in the culture, and there’s a general respect that something’s going on here among the population. Where are the physicians in all of this?

Dr. Goldstein: Right. Well it’s interesting and I think there’s lots of answers to that, so bear with me here. The first thing is, when you’re in medical school you’re taught that cannabis is a drug of abuse. When we’re children we’re taught that cannabis is a drug of abuse. And then it’s reinforced when you go to medical school. There’s a billing diagnosis for cannabis abuse. And there are some people who do abuse it, usually they are not the very sick, it’s usually someone who may be self-medicating but you know I have found in my practice that somebody comes in sometimes and says I think I have a problem with it. We talk about it. I educate them about their receptors and how by overdoing it the receptor number goes down and then you don’t get a good response – so sometimes an educational intervention, because it’s not so highly addictive, does the trick. So, one, is the cannabis is a drug of abuse. Any drug can be a drug of abuse. And we’ve seen that of course with the opiate, prescription opiate death increase in this country.

I think the second thing is that when California passed – when we as voters passed the law here in California [in 1996] – the medical board and the environment was negative toward doctors who recommended this, and some doctors actually were brought up on charges with the medical board and had to defend themselves. That’s scary. If your livelihood is based on the fact that you have a medical license, you really don’t want to risk all those years of practice and your livelihood to step out on a limb in that kind of environment. The people who did that were very special pioneers. There’s no question. They’re the ones who we can thank now in 2015 that were able to do this.

And then I think, in general, it’s that the lack of education about the endocannabinoid system, the lack of understanding about cannabidiol. I still, to this day, get people who come to see me, parents of children who say when I told my doctor we were going to look for medical cannabis treatment, they asked me if I was going to blow smoke in the child’s face. And that’s, you know to me, is one of the most ignorant statements because I just feel that if you’re a physician you need to look at the science, you need to look – just the same way you would learn the preparations of a medications that came out on the market that was, that you thought was beneficial – you need to take the time and learn.

Project CBD: People hear about medical cannabis, and then they hear about this “CBD,” and it’s almost like a fairy tale. You know, they hear these miraculous outcomes of children who are seizing 100 times a day, and then they stop seizing. Give us a perspective here. Is this a magic bullet? Is it, you know, once in a million that you get this kind of response? Based on your practice – and I understand you’re dealing with really tough cases, people come to you when nothing else has worked, and people come with a sense of hope, and that’s important, that’s therapeutic in and of itself that they can be hopeful. But give us a perspective. You don’t want to raise false hopes either in talking about these things. Give us a realistic sense of what the potentials are here.

Dr. Goldstein: Sure. So realistically, there’s a lot of variables to get to the point where “somebody’s a success story.” There are children who respond immediately and beautifully and do well – and that is not the usual case, but I have seen it, where literally within two days of starting CBD oil, life as they knew it is not the new normal. So that happens. But for most cases, it’s over time because remember inflammation doesn’t go down overnight; getting off other medications is not something that you do overnight. I have patients who’ve been weaning medications for two years.

If you remember in the CNN documentary showing little Charlotte, there’s the video of her laying on the floor having seizures, but then it cuts to her riding a bike. And I think that it’s a nice side-by-side comparison, but that didn’t happen overnight for Charlotte. It took time for her to get there. And so, I tell my patients that you know it’s not magic fairy dust. It is medicine and you have to take it, and we have to find the dose, and we may have to wean other medications, but that if you’re willing to give it a shot you kind of have to be on board for at least three to six months if not longer, if we’re seeing good results. I have had some patients who, you know, tried numerous different CBD preparations and it took them until the third one to actually see a result. And if you talk to adult patients who are using cannabis for other treatments, they’ll tell you oh that strain works for migraines, but this strain doesn’t. Well, the same may be true – and I see it – with children who are sick. One strain may work better than the other and there are a few different CBD strains that patients can try. Finding something affordable – because remember, it’s out of pocket. Finding something consistent that you can get over and over again, something tested, that’s a lot of the difficulty. So, you know it’s not an easy answer. It’s not a miracle. But when you look back at what some of these families have been through with 10 years and 15 different medications, that’s what they’ve been doing all along.

Project CBD: Well it is not only important that people can access the good medicine, but they also need good health counseling. And we’re very, very fortunate Dr. Bonni Goldstein that you are part of this community and have really been leading the way with cutting edge clinical input. Thank you very much.

Dr. Goldstein: Thank you, Martin.

Copyright, Project CBD. May not be reprinted without permission.

Audio-visual category: 

Get High and Lose Weight?

Marijuana for weight loss
By on November 23, 2015

Marijuana Use Associated with Decreased Chance of Developing Metabolic Syndrome

First the bad news: The United States is facing epidemic levels of obesity, diabetes, and cardiovascular disease.

Now the good news if you are a cannabis consumer: According to a recent study published in the American Journal of Medicine, marijuana users are much less likely than non-users to develop metabolic syndrome, which is a significant risk factor for obesity, type II diabetes, and heart disease.

Conducted by scientists at the University of Miami in Florida, this study examined the relationship between cannabis consumption and the individual components of metabolic syndrome, such as high blood pressure, increased abdominal fat, elevated blood sugar, and unhealthy cholesterol levels. 

Nearly 8,500 people from age 20 to 59 provided survey data for the study. Participants were separated into three categories—current marijuana users, past users, and those who had never smoked the herb. Whereas metabolic syndrome afflicts 22 percent of the U.S. adult population, less than 14 percent of current cannabis-using adults in this study had metabolic syndrome.

Among young adults, cannabis consumers are 54 percent less likely than non-consumers to present with metabolic syndrome. Past marijuana use is associated with lower odds of metabolic syndrome among middle-aged adults. And seniors who medicate with cannabis tend to be slimmer and less insulin-resistant than seniors who just say no.

The Munchies Receptor

The results of the study, entitled “Metabolic Syndrome among Marijuana Users in the United States,” may seem counterintuitive given marijuana’s notorious appetite-stimulating effects, jocularly known as “the munchies.” Under the influence of marijuana, flavors seem to jump right out of food. That’s because tetrahydrocannabinol (THC) activates CB1 cannabinoid receptors in the brain that rouse one’s appetite and heighten one’s sense of smell.

The munchies are a scientifically proven phenomenon. THC is a CB1 “agonist” that turns on the appetite receptor and causes it to signal. An “antagonist” will block the receptor and prevent it from signaling. Tetrahydrocannabivarin (THCV), a minor but medically significant component of the cannabis plant, is a neutral CB1 receptor antagonist.

Scientists have also synthesized “inverse agonists” that can activate a cannabinoid receptor and cause it to signal in the opposite manner from how it functions naturally. A CB1 inverse agonist will curb appetite and reduce food intake by binding to CB1 receptors, whereas THC boosts appetite and food intake by binding to CB1.

One could reasonably assume, given what we know about the munchies, that increased use of marijuana will result in greater caloric consumption with consequent adverse metabolic outcomes, including obesity. However, the results of this study and other reports indicate that such is not the case. Indeed, the opposite appears to be true.

In addition to underscoring potential health benefits of herbal cannabis, these findings highlight the discrepancy between human research that links marijuana use to lower rates of obesity compared to preclinical studies involving synthetic isolates in which CB1 antagonism (blocking the munchies receptor) and CB1 inverse agonism (flipping the anti-munchies switch) are shown to prevent obesity.

How is it possible that marijuana consumption, which activates CB1, is associated with preventing obesity in humans, while blocking or reversing the CB1 receptor via a synthetic, single-molecule compound results in weight-loss in animal models and human trials? What can explain this apparent contradiction? It may have something to do with the complementary, yet opposing functions of two different sets of cannabinoid receptors.

CB2 Receptor Activation

Australian scientists recently examined the role of the cannabinoid CB2 receptor “in modulating energy homeostasis and obesity-associated metabolic pathologies.” The CB2 receptors are concentrated in the peripheral nervous system, immune cells, and in metabolically active tissue. The Australian researchers found that CB2 receptor activation by JWH-015, a “selective CB2 receptor agonist,” reduces food intake in mice and prevents the build-up of body fat.

THC, a non-selective, plant-derived agonist, binds to both the CB1 receptor and the CB2 receptor. The fact that THC and other cannabis components (including the aforementioned THCV) activate CB2 receptor signaling may explain why marijuana users are less likely to develop metabolic syndrome than marijuana abstainers. Metabolic syndrome is a generalized, low-grade inflammatory condition, and the THC-sensitive CB2 receptor regulates immune function and inflammation.

CB2 receptor activation—through healthy diet and cannabis-enabled stress reduction—may prove to be a better strategy for preventing and treating metabolic syndrome than the misguided attempt by French pharmaceutical giant Sanofi-Aventis to market Rimonabant, a synthetic CB1 inverse agonist as an appetite suppressant. Promoted as a blockbuster diet drug in 2006, Rimonabant was soon recalled in Europe because of severe side effects, including neurological deficits, depression, and suicide. The anti-munchies pill was never approved for sale in the United States.

Sorry Big Pharma, but when it comes to preventing or mitigating metabolic dysfunction, synthetic isolates are much less effective than whole plant cannabis with its synergistic treasure trove of natural medicinal components that enhance and balance each other’s effects.

Martin A. Lee is the director of Project CBD and the author of Smoke Signals: A Social History of MarijuanaMedical, Recreational and Scientific.

Copyright, Project CBD. May not be reprinted without permission.

Sources:

  • Englund A, et al. “The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.” Journal of Psychopharmacology. 2015 Nov 17.
  • Karlsson C et al, “Baseline anandamide levels and body weight impact the weight loss effect of CB1 receptor antagonism in male rats,” Endocrinology, 2015 April.
  • Verty, AN, et al. “Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice. PLoS One. 2015 Nov 20.
  • Vidot DC, Prad G, Hlaing WM, Arheart KL, Messiah SE. “Metabolic Syndrome among Marijuana Users in the United States: An Analysis of National Health and Nutrition Examination Survey Data.” American Journal of Medicine. 2015.
  • Yale University press release, “Mulling the marijuana munchies: How the brain flips the hunger switch,” 18-Feb-2015.

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