1st Conference on Therapeutic use of cannabis in Figueres (Part 2 of 4)

Transcript of Dr. José Carlos Bouso's speech :

Oscar Parés

José Carlos, when you want...

Dr. José Carlos Bouso

Thanks Oscar, and thanks also to David and Ramon from Alchimia Foundation.

Since some years ago, the relationship has been fantastic, since thanks to them we at ICEERS Foundation could start the first study being conducted today in Spain in regard with what happens to people or patients who use cannabis.

Most studies are clinic trials, in laboratories, under very artificial conditions and we want to conduct a more naturalistic study as we say in science, more focused on reality, on the reality of patients, on their quality of life. That is some of the things that interests me most.

In medicine, many times we're worried about sthe ympthoms or the disease, but a very important aspect of the disease is the quality of life of patients. In that sense I think cannabis does lots of interesting things, but from my point of view, the most interesting one is improving the patient's quality of life.

Well, thanks to the Alchimia Foundation we could start this study, then we also got funds from the Canna Foundation and some collectives, but thanks to them we could take the first step, also other initiatives that we've proposed them, which they've always kindly accepted.

So...I'm also feeling at home...I know Oscar since many years ago. Before we worked together, and Joan collaborates with us at the Spanish Observatory of Medicinal Cannabis (OECM), so I can say they're part of my catalan family, despite they have failed to make me speak catalan in my talks...but I'll work on that and perhaps I can do something in the next one.

It is impossible to replace Dr. Mariano García de Palau, I believe his knowledge is unrivalled, it is not that we know nothing, but he knows so much! Anyway, Joan and myself will try to do our best, I'm pretty sure we'll do it with dignity...

Oscar pointed me to some subjects, and each of them could take us some seminars, so I'll try to synthesize and explain the most important among these subjects.

Starting with the current knowledge we have. What do scientific publications say about medical cannabis. Depending on who's talking, we can hear from almost miraculous virtues of cannabis to almost demonic properties. In medicine, none of these ends exist and cannabis, as any other medicine, is usually between them.

Cannabis starts from a premise, it is not a panacea, it does not work for everybody, it does not work for all diseases. It cures few of them but reduces the symptoms of many, and that is a first knowledge that will be furtherly explained by Joan.

It is not a substance to cure everything, but it does work for some things. And we certainly have many scientific studies, despite some times we hear that we don't have enough studies to start and promote initiatives towards its prescription or sale at pharmacies.

Actually, well... in most presentations the slides are in English language, but you just ignore them, they're a guide for my talk. A first review of all studies conducted between 2005 and 2009 listed 37 clinical trials. Trials conducted in hospitals with different groups of diseases: neuropathic pain, experimental pain, multiple sclerosis, AIDS and HIV, glaucoma... and we have 32 studies from 2010 to 2014. So, more than 5.000 patients have been somehow involved in clinical trials conducted around the world in the last 10 years.

We then have sufficient evidence to take decisions on the benefits of cannabis. Most studies have showed positive results. For example, in spasticity, we have two studies in which some patients have been treated and only 3 out of 12 patients experienced negative effects. In nausea, which is the most studied subject, and as consequence of certain anti-cancer medicines, a clinical trial obtained positive results in 40 patients and negative in just one.

We could continue disease after disease, I just wanted to mention some examples to transmit that the evidence found with regard to cannabis derivatives shows that they're more efficient than other medicines.

Here I have a website, for anyone interested in accessing all the studies published up to date, in which they'll found more than 100. When these studies have been observed as a whole and processed with sophisticated statistical analysis, it has been observed a moderated quality of evidence. I mean, it is not solid enough, it's a moderated evidence, which supports the use of medical cannabis for chronic pain and spasticity, and a lesser degree of evidence for other types of symptoms like nausea or vomiting caused by chemotherapy, weight loss or sleeping disorders.

This is speaking in merely statistical terms. When this review has been performed from the clinic point of view, not only taking numbers into account, but also the actual improvement on patients health, what we find is that this evidence becomes much stronger. Why do I say this? Because many times it is said that the evidence degree is not strong enough, as I mentioned before, and that is partly true , but it's also true that when speaking about efficiency degrees in clinical trials we're talking about cannabinoids, why? Because most clinical trials don't use the plant. They're conducted with isolated products which, as we'll explain later, do not work as well as the whole plant does, for the plant has different cannabinoids which cooperate with each other
to produce a more beneficial effect and also to reduce side effects.

In any case, as I was saying, it's much more interesting the level of efficiency in relation to the patients quality of life than in relation to symptoms.

Another fact that clinical trials don't show, which we've already found in our current study and has also been found in international studies, is that while perhaps they (cannabinoids) don't have the level of efficiency required for medicines, they do reduce the side effects of other medicines, and that is, from my point of view, another major beneficial property of cannabis.

Actually, many patients using medical marijuana may not find the complete relief that they seek, but are taking much less medicines with important side effects than people who don't use it. With regard to side effects, there is also concern about the possible long-term effects of cannabis in patients who use it for medicinal purposes.

Well, here I have a recently published study conducted not with medical patients but with recreational users, adult users, in which the only difference found between long-term users (20 years) and non-users are some oral problems...probably as a consequence of smoking, which could be easily avoided by vaping or using another route of administration.

As I say, most side effects observed in these trials with cannabinoids are caused by this fact, by using cannabinoids instead of the whole plant. Isolated cannabinoids, like pure THC or synthetic analogs of THC, have their tolerability profile, are worse tolerated than the plant.

For the reason that I explained before, it is something weird also in herbal therapies. Normally, plants contain a series of therapeutic active principles, but also some active principles which aren't therapeutic and which can produce some type of side effect.

That's why generally doctors prefer isolated products, pure products, efficient to reach their objectives. In the case of using the whole plant this rule is somehow broken, but as I'll explain later the cannabis plant breaks many rules.

And the rule broke is that the present compounds actually cooperate to obtain a more efficient therapeutic effect while reducing negative side effects. Of course, we still have few studies on side effects of long-term use, the more consistent ones made with Sativex, which is the only cannabinoid-based pharmaceutical product available today and is only used, as Oscar mentioned, in very specific conditions, especially multiple sclerosis and in some other diseases as compassionate use.

The current data from the United Kingdom, Germany and Spain shows that these medicines are well tolerated in the long term, so if Sativex is correctly tolerated there is no reason to think that the whole plant will not.

Well, I assume most of you already know this but, for those who don't, the cannabis plant contains different compounds. It is actually said that cannabis is a true factory of chemical compounds. It produces more than 800 different compounds, 100 or 105 of which (new ones are discovered every day) being cannabinoids. And today, in humans, only THC and CBD have been relatively well characterized...

Ok, for those who know a bit more about pharmacology, and this is one of the peculiarities of cannabis, cannabis must be accurately adjusted to the patient's needs, because the same dosage does not always produce the same effect...this is a graph of, for example, THC level in blood at different dosages, and what we pharmacologists love is to find what we call a dependant dose-response, so the increase in the dosage is proportional to the physiological response.

Cannabis breaks this rule somehow, that's why dosages must be very accurate. For example in tasks involving psychomotor performance, tasks dealing with, let's say, driving a car or performing certain complete activities, the curve is not proportional according to the effect. Even at average dosages the psychomotor performance is improved instead of being worse, and only with high dosages it is seriously reduced.  And at very high dosages it is also reduced... For example, in other effects like being thirsty, the feeling of being high is one of the graphs shown here, the curve is not linear and upwards, it looks like a roller coaster. This means that according to dosages we'll obtain one response or another, even the feeling of being high. Dosages here of 60ml have milder psychoactive effect than 15 or 18ml dosages.

These are aspects that must be taken into account and that patients should know about, and which doctors should know when practicing personalized medicine. Because if there is a medicine that requires personalized medicine is cannabis... Perhaps in relation to arterial pressure is where we find the most consistent dose response curve.

Another interesting thing recently published is that cannabis is more viable when not exposed to heat than when exposed. That means that more THC is absorbed, so the therapeutic effect is more efficient if cannabis is not heated. Thus, as we'll see in a moment, the performance of cannabis will be higher if it is vaped rather than smoked. For example, in this graph we compare a vaping device with different temperatures with smoking a cigarette or joint, and we see that despite smoking extracts higher amounts of all the products contained in the smoke, vaping extracts more cannabinoids and less products which are not cannabinoids and don't influence in the therapeutic effect, so that's one of the reasons why patients and those who use and smoke cannabis should think about start vaping it.

First, because you avoid all the risks derived from combustion and second, because you get the most out of your plant material.

I've also brought some...as well as curious effects, from studies conducted many years ago...because despite being a pharmacologist I come from the psychology field, and I can't resist to talk about some of these interesting psychological effects. For example, if you give people some marijuana to smoke and let them speak out in a group, the amount of discourse decreases as the dosage is increased. In other words, people become more quiet in conversations or social situations as the dosage is increased...and there is also an important difference between men and women. We can't see it here, I had to scan this article and it didn't work properly, but in the second part of the graph for example when men and women smoke in social context, women show what we call positive reinforcement. They are more prone to conversation than men and rely less on body language than men under the effects of cannabis.

Also, another curious effect from another study...I'll explain why it happens later... in studies in which people are given marijuana in social contexts, if - when they're high - the researcher tells them that there is an emergency and their help is needed, all of a sudden is like if the high disappeared and they can concentrate on the task. These psychological effects may seem of low importance...I'll explain their importance and how they can be translated into clinical practice.

Well... Mariano had to talk a little bit more about CBD... I've brought some last-minute slides to help us approach this issue. First of all, THC and CBD act on different parts of the brain which indicates us that they have different effects, both at psychological and therapeutic level.

I'm not excessively enthusiastic about the CBD issue, which is the trend today. CBD is one of the medicinal compounds of cannabis, but to this day THC is the main medicinal compound.

What is interesting about CBD is that it allows us to counteract the psychological effects of THC, and those who don't tolerate THC, who can't cope with being intoxicated or high, or can't be as efficient as they would in their normal life, see the feeling of being high reduced. In my opinion, CBD has 4 major applications. The first of them is in the treatment of psychosis. Psychosis is a chronic mental disease very difficult to treat, and we have seen in the studies conducted that CBD acts as efficiently as last-generation anti-psychotic medications and without the side effects observed in the latter.
What does it all mean? That people with psychosis problems will probably hold on their treatment, that is to say, we'll have less cases of people giving up on treatment than with traditional treatments.

Another psychological property is that is acts as excellent anxiolytic. We're claiming that anxiety is at the basis of all diseases...all. Both mental and medical. In the sense that anyone suffering from any medical condition is exposed to anxiety simply because they're suffering from a disease. The possibility of getting a highly efficient medicine with almost no side effects
means that we can use this medication to treat a vast number of conditions, either medical or psychological... and in one of these studies CBD has been observed to be particularly efficient in generalized anxiety disorder.

I'm rushing now because my time is almost over and I´m still halfway through my talk. But well, it always happens the same...

These are...in the studies conducted where isolated CBD and THC and placebo have been used, it is clear that the feeling of being high is much stronger with THC and there is hardly any difference between CBD and placebo.

This means that the intoxicating level of CBD does not produce psychological effects.

Also, as I said before and in regard to anxiety, while THC can be quite anxiogenic CBD is quite anxiolytic, and the same happens with mental decline...one of the interesting things I wanted to tell you: CBD is also becoming popular for its counteracting effect on THC. I've also said this before, but this depends on when it is administered.

Only if you take CBD before taking THC is it capable of counteracting this psychological effect, so the feeling of being high will be present if they're administered at the same time.

About myths...there are countless graphs on the internet where they tell you the diseases that can be treated with cannabinoids...well, to this day, this is a chimera, it is more based on laboratory research and cell culture than on clinical trials. What we can state is that marijuana has a level of efficiency to treat the aforementioned diseases, but in no way it is as versatile as it may seem...

And it also has some side effects. As physical side effects we have tiredness,  dizziness, tachicardia, hypotension,  dry mouth... It also develops tolerance to many side effects, which means that side effects disappear  with constant use.

And that is also interesting: it does not develop tolerance to medicinal effects. Tolerance is the need to raise the dosage to get the same effect... what happens? Many times, when speaking about non-regulated medicines like cannabis, patients tend to identify the beneficial therapeutic effect for their condition with the psychological effect that they're feeling.

But cannabis doesn't need...many times the psychological effect is not needed to get medicinal effect. What does it mean? That we often overdose thinking that we need the high to get some beneficial effect. But there's no need...to raise the dosage in many diseases even if we have to raise the it to get psychological effect, it's not the same with medicinal effect.

Finally, at international level, which was the last point of my speech...how is regulation? In Spain cannabis is only allowed for therapeutic , educational and scientific purposes and international laws are allowing to conduct medical cannabis programmes.

The United Nations, which is the institution regulating these issues, has set the stage, the rules which should be followed by countries implementing these programmes.

Spanish laws also allow it, because one of the requirements for starting these programmes is that the plant must have a traditional medical use in the territory, and we know that back in the 40s and 50s we had tens, hundreds of different products available at pharmacies.

Thus, cannabis has been proved to be a useful plant, traditionally used in Spain, which is proven by its sale at pharmacies.

With regard to the international reality, and although in Spain we dn't have any of this medical programmes yet, in the USA we already have 25 states with these programmes, with more than 1 million people  registered. We have around 25.000 in Israel, 45.000 in Canada...

Other countries have also started medical cannabis programmes, like Chile, Colombia, Macedonia, Uruguay or Canada, and some others are starting theirs now, so it's only a matter of political will before we also have these programmes in Spain.

Furthermore, these programmes are not only necessary bacause cannabis is a medicine that could help many people, but also baacause it has been proved that when these programmes exist, patients use cannabis more responsibly than when there is no regulation. Actually, the average consumption in the Netherlands, which was the first country to implement these programmes, is around 0,68 grams, it doesn't even reach 1 gram per person and day, while in the rest of Europe the average is around 3 grams.

That's not explained by major levels of stoicism from Dutch patients, that's related to how it is regulated, since patients use it more rationally if they have proper information and the use is legit.

Finally, we still have so much to say, I invite you on the 16th and 17th December to a congress at our Foundation, also sponsored by Alchimia Foundation. It's exclusive for cannabis users, so we can have a dialogue between medical patients and health professionals, we don't want this congress to be a place where experts talk unidirectionally to non-experts, but a place of coexistence.

I'm done now. I'm sorry if I extended myself too much, I'll give the floor to...