By Mariano Garcia de Palau
Born in Barcelona, 17 February 1956. Graduated in medicine and surgery from the University of Barcelona in 1979. For 38 years has worked as an emergency physician in the area of occupational medicine. He became interested in cannabis by chance, and for the last 15 years has studied its therapeutic uses.
Currently he continues to advise on cannabinoid treatments and performs clinical work with patients, collaborates with various organizations and associations, serves as Senior Consultant for Grupo Curativa Colombia and is a spokesperson for the Spanish Medical Cannabis Observatory.
This series of chronicles describes the personal experience of a Medical Doctor who prescribes medical cannabis in his/her country. Each article is narrated in the first person and reports the subjective experience of each expert.
Cannabis use in Spain in recent years
My first contact with cannabis was when I was 23 years old, in my last year of medical school; I remember a joint of hashish shared among several classmates after an afternoon of group study. At the time, I would never have guessed that I would end up devoting myself to the study of the Endocannabinoid System (ECS) and the cannabis plant; much less that I would end up treating patients with phytocannabinoids.
About 20 years ago, I started reading and studying the articles that were published on the ECS, and the use of phytocannabinoids for therapeutic purposes. I have to say that there were not too many publications then, and the sources of knowledge on the subject were limited: not a single clinical trial or study in humans, so just anecdotal data and animal studies, basically mice. I still think that these do not provide clinicians with important data, such as dosages, since the results in animals cannot really be extrapolated; they also use isolated molecules, when the secret of the cannabis plant is how it works on several molecules and several targets. Clearly, research on the molecular pathways of action is critical to understanding how the ECS is modulated by phytocannabinoids. The cannabinoid-based products developed by the pharmaceutical industry have never worked better than products formulated from whole plant extracts; there is no epidemiological data that provides us with information on toxicities, or adverse or side effects, of treatments with non-pharmaceutical products, and there are many users in the world of these "full plant" formulated oils. And cost multiplies exponentially when using products such as Sativex or Epidiolex, derivatives created by the pharmaceutical industry.
In 2010, I founded THCterapeutico.org, a website that aimed to provide guidance on the therapeutic use of cannabis to users in general, and to put some order on the ideas that were circulating about cannabis – adult use, essentially –in those years. Cannabis consumers really knew very little about the plant, and when they intended to use it for medicinal purposes, there was no basic knowledge of the doses or, of course, of the cannabinoids or terpenes contained in the different varieties of cannabis at the time, and very little data on the composition or chemotype of the different varieties.
On this website, in addition to answering questions from users, including patients, who sent us their questions about the use of cannabis, we periodically published articles and studies on cannabinoids so that the general public could access them, with the intention of making therapeutic use more effective with more knowledge about the plant, its characteristics, and its components.
The website really began to have quite an impact since it was free, as was our intention from the beginning, and we began to think that the use of cannabis for therapeutic purposes was going to have a future.
The THCterapeutico website lasted almost 3 years, during which time we published answers to patients' questions, as well as scientific information on the therapeutic use of cannabis. We gathered a good amount of information that, unfortunately, was not collected or materialized even in an observational study, due to various circumstances.
I also remember the Spannabis Fair (a fair dedicated exclusively to the world of cannabis held in Barcelona) in 2013 as my first live public intervention in the world of cannabis. At that time, I was obsessing over the studies of Professor Mechoulam's group, and of our researchers, Manuel Guzman, Cristina Sánchez and Guillermo Velasco, and again, I would never have thought to end up sitting with them in the meetings of the OECM (Spanish Observatory of Medicinal Cannabis) and enjoying the privilege of their friendship. If they participated in any fair, without fail they were a reference for me. In my first talk, Spannabis 2013, my intention was to explain the basics of the Endocannabinoid System as we knew it in those years: it's incredible how much things have changed since then. Now, if we search PubMed for published studies on cannabis, we find 28,000 published studies, many of them probably within the last 5-6 years.
The Kalapa-Clinic project
A year later – I remember it well; it was during working hours – I received a call in which they asked me if I wanted to professionally dedicate myself full time to therapeutic cannabis. Apparently there was a group of investors who were interested in a therapeutic cannabis project, and I did not think much about it: interrupting 38 years of work as an emergency physician and surgeon, working in very advantageous working and economic conditions, to go to work in, at best, a legal grey area: remember that, in the "kingdom of Spain", the therapeutic use of cannabis is still unregulated. Everyone around me thought that I was going from job security to a very unsafe situation, but at the time it seemed like a decision I had to make, if I was being honest with myself. I had already been studying for some time, and I was convinced that it was feasible to start working with patients, if we also had the right products; a laboratory to prepare extracts and finally oils for patients, which were always chromatographed, was also part of the project, and we had the data to dose accurately and to control the main components of the extracts. In those years, here in Spain, it was a novelty to work with these products: it was the first year in which CBD began to have a lot of prominence. Recall Charlotte Fidji's case in 2013, and how the treatment of her refractory epilepsy with a CBD-rich cannabis strain drastically reduced her daily seizures and brought her quality of life, until she passed away from COVID barely 1 year ago.
2014 was also the year in which we started treating paediatric patients, basically refractory epilepsies, in many cases associated with many orphan diseases, or specifically with ASD (autism spectrum disorder): a series of events related to autistic patients occurred, which convinced me that treatment with CBD, and also THC in certain proportions and doses, generated a very positive effect at a cognitive and psychomotor level in these children: physical contact and gaze tracking are initiated, and parents told me that their children were more connected and calmer. 8 years later, I am still treating these patients and obtaining very interesting results, if we compare them with their prospects with pharmacological treatments in terms of side effects and toxicity in the short, medium, and long term. But a treatment is never based only on cannabis: it is necessary to control more parameters such as food and microbiota, physical activity, recreation, and other complementary therapies, such as cannabis, so that autistic patients improve their quality of life.
In those years, and until the commercialization of "legal" CBD with less than 0.2% THC, we worked with some very interesting and illegal products, obviously, because of the percentage of THC. Patients had access to these products that came from industrial hemp extracts, which contained the original percentage of THC. Brands of CBD with THC below the legal limit, or even without THC, began to be marketed, using pharmaceutical grade CBD, and patients could easily access CBD online, by contacting one of the laboratories that marketed it, at that time as a food supplement: this was the marketing niche that was found to introduce CBD in the "legal" market. Currently in Europe, you cannot sell CBD as a food supplement, and we are awaiting a law on "new food", which would regulate the situation of CBD.
In Spain, although the therapeutic or adult use of cannabis is not regulated, there are cannabis clubs or associations, which allow members access to herbal products, or in some associations, to handmade oils or creams. In order for patients to have access to controlled oils in this case, an association was founded and registered that allowed patients who required THC oils, to have access to the products in the most "legal" way possible, after signing up as members, and above all, with the assurance that only patients who had undergone a medical consultation had access to these products.
The first thing we did was to look for a place where we could start the activity, but since it was cannabis, everything was a problem in terms of someone trusting in the intention of our work. During the years that I have been working in Kalapa-Clinic, we have gone through multiple locations to have face-to-face consultations with patients, since we do not have the permission of the competent authority for this clinical activity, although I have to admit that I have never felt monitored or controlled – on the contrary; otherwise, we would not have been able to continue working with so many patients.
The first year of work we did not really have much clinical activity, but the number of patients consulting has been increasing during these years, and to our astonishment, they consult from many different countries, even from countries like the USA, in states where therapeutic cannabis had already been regulated (??)
There were really not many of us who worked with patients in those years, but this situation has changed with the passage of time, although there is still much to do in Spain, where the stigma of cannabis use persists, and the majority of the population, among which I include many medical colleagues, does not know why it was outlawed, and only accepts official information about the lack of evidence, ignoring the ECS, which is actually the protagonist of this story: there are many drugs that exert their effects by modulating it, such as paracetamol or ibuprofen, for example. We also modulate it using phytocannabinoids, but with the advantage of being able to work with almost no side effects, which are predictable and easily solvable. This makes the treatments safe: although there are doubts about the safety of polymolecular treatments, clinical experience with their use confirms these data.
There has never been a death from acute THC intoxication, although THC is commonly referred to as an intoxicant. Well, if we refer to the definition of intoxicant, any substance can be intoxicating, depending on the dose.
This past year, 2021, the Nobel Prize in medicine went to physiologists David Julius and Ardem Patapoutian for their work on the TRPV1 receptor in relation to pain perception, having also identified the TRPM8 and Piezo receptors. Well, these TRPV1 and TRPM8 receptors can be modulated with CBD, THC and THCV. And I personally believe that they are also involved in the regulation of epilepsy and in oncological processes. It is the first Nobel Prize awarded for the study of the ECS, and it certainly won't be the only one.
In 2016, the Spanish Observatory of Medicinal Cannabis (OECM) was created around its sponsor and current president, Carola Perez. Without her work and her leadership it would not have been possible to gather and encourage the group of people who formed the OECM in 2016. It was presented in Madrid, with the sponsorship and financial support of the CANNA Foundation, and was attended by Professor Mechoulam, to whom we were very grateful, given his age and his work, for his recognition of the group of researchers that made up the OECM.
On a personal note, I think Prof. Mechoulam should have been awarded a Nobel Prize for his discovery of the classic ECS in the 1990s, but so far is it not even mentioned in universities, much less studied with a certain level of knowledge, and I think it is the most important regulatory system we possess, and really essential to maintain the balance of the organism. Even more so in situations like the current one, in which we try to survive in a hostile environment, especially in cities, and in situations in which the environment makes it difficult to be healthy and not suffer from any disease: it is clear that overcrowding has been crucial in the COVID 19 case, since we start from a situation in which environmental and noise pollution will most likely generate pathologies, without being able to prevent them in an acceptable way.
I worked alone for a few years, but there came a time when I could no longer reasonably manage the workload and we felt it was time to expand Kalapa's staff. Different doctors have passed through our centre, and I currently work with Dr. Mery Peña and Dr. Robert Ulhembrock, who have been with us for 3 years. The team makes it possible for us to work and treat patients in an orderly manner, in addition to contributing to our projects, and all this despite the legal situation, which puts added pressure on the work.
The years have gone by and, during this time, we have worked with many patients, with the desire to first improve their quality of life, whatever their condition. The results were generally good, with over 65% efficacy, although not always with the same degree of improvement. We are talking about very diverse illnesses, but if we value the improvement in quality of life, this would be the percentage of success, although, as always, there were patients who did not tolerate the treatment well, or could not afford the treatment financially when we reached certain doses: this was relatively frequent, and, especially if the treatment was working, the feeling was one of impotence. How many drugs are financed by public health without being as safe or as effective, not to mention being toxic, compared to phytocannabinoids!
We collaborated closely with Grupo Curativa Colombia, with my great friend Dr. Paola Pineda and her team, for 7 years, developing lines of work, studying formulations and chemotypes, elaborating water-soluble products through macroemulsions from plant extracts, and, above all, sharing concerns and knowledge.
We have tried to be in contact with the different working groups in different countries: Colombia, Peru, Chile, Mexico, Uruguay and the USA, sharing information and generating knowledge from the different perspectives of the countries that have already regulated the use of cannabis, although as it was outlawed, it would be better to say "normalization" of its use, since its use was common until 1937, when we had products in all pharmacies in Europe and America.
Until the arrival of COVID 19. Here there is an important turning point, which is still generating many health problems, not only physical but also mental, with an increase in the number of patients who have been consulting with us for the last 2 years, basically due to stress management problems added to their underlying disease, which leads to a fairly incompetent immune system, and in a situation like the present one, we close the circle of stress - immunosuppression - COVID19. In Spain, the saturation of emergency services and the collapse of primary care has led many patients with chronic or even acute pathologies, as is the case of oncology patients, to come to our office, as they feel that they are, and really have been, without health coverage, or have seen their tests or even surgical interventions delayed.
With confinement we were physically cut off, but in our case we were already teleworking with many patients, and the number of in-person consultations decreased a lot.
And this is where the webinar activity began, as it was not possible to travel. Different working groups and actors in the field of cannabis proposed various webinars, that were intended to replace the congresses or symposiums that are held periodically in different countries.
It must be admitted that, without this possibility of connection, we would have been really isolated, and if it were not for the Internet, it would not have been possible to hold these events, which now, I believe, have become normal in every sector. I would never have thought I would treat a patient through the screen, but if it's this or nothing, or if the patient resides far away from your practice, I think it is a very interesting technology, and in the case of prescribing cannabis, it is very useful.
To finish this story, I would like to say that I have retired and cannabis is still not regulated in Spain, and that not only it should be allowed for therapeutic use, but also for adult or recreational use, of course. We have regulated alcohol and tobacco, for their great contributions to humanity, and this political hypocrisy is based on the economic benefits that derive from them, and on the pressure of the tobacco industry. It is evident that our health does not concern our leaders in the least and that economic decisions prevail over health decisions; we are seeing the same with the management of this pandemic, and I ask myself, if it is a global problem, as its name indicates, why are we acting locally?
We are really perplexed that Spain, which has always had a cannabis tradition and culture, in spite of everything, is still in this situation regarding cannabis.
Our politicians continue to talk about evidence, when there are already many models of therapeutic cannabis to evaluate and it would be enough to just arrive at the model that is most interesting for us, and for our patients, who are the objective of our work. Again, misinformation and the foolishness of our politicians is what is delaying regulation in Spain, but for me it is clear that regulators and legislators do not know what they are regulating. Their ignorance of the subject is evident; in most countries, the economic context comes before the interests of the patient.
The crime against public health, in my view, is to prohibit access to cannabis to patients who could benefit from a safe treatment with very low toxicity. As physicians, we have to seek safe solutions for patients, regardless of their legal status: it's the ethics of illegality.