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Elisaldo Carlini

Elisaldo Carlini: The medicinal use of marijuana

Specialist in psychopharmacology says that the medical qualities of the drug in Brazil should have been recognized a long time ago

Eduardo CesarDoctor Elisaldo Carlini, a specialist in psychopharmacology, an area he helped disseminate in Brazil in the 1960’s after he had spent four years in the United States, three of them at Yale University, seems to have an obsession. The focus of his work is to try to understand how Cannabis sativa – marijuana – acts on the human organism, his research target for 50 years. He inherited this interest from José Ribeiro do Valle, his pharmacology professor at the Paulista Medical School in the 1950’s. Since then he has worked to try to expose the lie underlying the concept that marijuana is a useless and evil drug.

In the 1970’s and 1980’s in Brazil, he led a research group that published more than 40 pieces of work in international scientific journals. These results, along with the investigations of other international groups, made it possible to develop abroad drugs based on Cannabis sativa, which is currently used in several countries around the world for treating the nausea and vomiting caused by cancer chemotherapy, to improve the cachexia caused by those suffering from HIV and cancer and to relieve some types of pain. For Carlini, the time is long overdue to recognize the medicinal use of marijuana in Brazil.

In May this year, there will be an international symposium in São Paulo to deal with this issue. Carlini sees a lot of prejudice against marijuana, but is betting that if researchers insist on going in the right direction, with the support of science, this approval will be eventually obtained. One should stress that this 79-year-old physician is against the recreational use of this or of any other drugs.

Carlini acts socially, which sometimes hides the scientist he is. He is the founder of the Brazilian Information Center for Psychotropic Drugs (Cebrid) – an important supplier of information for the formulation of educational policies – and of the Brazilian Society of Drug Surveillance (Sobravime), in 1990. Between 1995 and 1997 he headed up the National Health Surveillance Department, the predecessor of the current Anvisa, where he faced the thorny mission of fighting corruption in the sector; successfully, it has to be said. Currently, he is in his seventh term as a member of the World Health Organization’s Expert Advisory Panel on Drug Dependence and Alcohol Problems. He has six children and five grandchildren. In December, between one meeting and another, Carlini gave the following interview.

What proposal is going to be put forward at the international symposium on marijuana that is to take place in São Paulo in May?
– We’re going to propose that marijuana is accepted for medical use in Brazil. My grandfather became a doctor at the end of the nineteenth century and at that time, he was already using a book written in 1888, which I still have, with a marijuana prescription for various problems. At the time, it was a therapeutic treatment around the world, including  Brazil. The international symposium will be entitled “A Brazilian agency for medicinal Cannabis?”. The United Nations Organization (UNO) recognizes that marijuana may be used as medication – despite the prohibition of the 1961 Single Convention on Narcotic Drugs – provided that countries set up an official special agency for Cannabis and its derivatives within their health ministries. There are already some 10 countries doing this: the United States, Canada, the United Kingdom, Italy, France, Germany, Spain, Switzerland and others.

When and how did you decide to choose marijuana as the object of study?
-When I entered the Paulista Medical School [EPM, today the São Paulo Federal University – Unifesp] in 1952. As a second-year student, I began to get interested in pharmacology and did a training course with Professor José Ribeiro do Valle. He was the first person who really did any scientific work on Cannabis sativa on laboratory animals in Brazil.

What experiments?
– He tried to find out the types of reaction [behavioral] that animals had when submitted to the effects of marijuana and he wanted to quantify the power of  different types of this plant. At the time, experimental psychology was not very developed in Brazil. In 1960, I went to the United States with the mission of studying more modern neurochemistry and experimental psychology techniques in order to introduce them here. That’s what I did when I got back in 1964.

Did you go right after graduating?
– No. I graduated in 1957 and worked as a voluntary assistant in pharmacology until 1960 on a grant from the Rockefeller Foundation. That was when I received another grant to go to the United States. I stayed there four years and did my Master’s at Yale University. When I got back I managed to get a place at EPM, despite the efforts of Ribeiro do Valle. I went to the Medical School of Santa Casa de Misericórdia that had just started functioning.

Why weren’t you hired by the EPM?
– There weren’t any vacancies. In 1964, I was married and had three children. I stayed for two months at the EPM and went to Santa Casa, which I left in 1970. That was when I really started studying marijuana, with behavioral tests.

How did you return to the EPM?
– When they told me that they didn’t want any more research at the Santa Casa. As I didn’t want just to teach I went to EPM and I talked to the director, Professor Horácio Kneese de Mello. I asked him if he’d accept me going there and giving a course that didn’t exist at the time, in psychopharmacology, alongside the pharmacology course of Ribeiro do Valle. He agreed and promised that as soon as the first vacancy arose I’d be hired fulltime. Two years later, that happened. I started as an assistant professor and then became a full professor.

Did you continue with your studies into marijuana there?
– I continued working on the subject. When we study the history of marijuana it’s easy to see that there’s nothing scientific in prohibiting it being used medically; it’s ideological. Until the beginning of the twentieth century, marijuana was considered an excellent drug. It was imported from France in the form of cigarettes that were called Grimaldi. Then from the 1930’s onwards, marijuana became an evil drug. The Egyptian government even said at one point that it was a totally destructive drug that deserved the hatred of civilized people. Brazil played a part in the criminalization of marijuana via a lie told by the Brazilian representative to the League of Nations, the predecessor of the UN. In 1925, the League of Nations held its second international conference about opium, with 44 countries present, including Brazil. It was to discuss how to control opium, but Egypt brought up the topic of marijuana and the Brazilian representative, Pedro Pernambuco Filho, said that it was more dangerous than opium in Brazil. Naturally, this was not right. First, because marijuana is much less dangerous than opium and second because opium was never a problem here. The result of all this was that the League of Nations condemned marijuana. After the UN was created, there was the first Single Convention on Narcotic Drugs in 1961, signed by more than 200 countries and placing Cannabis on a list along with heroin, as a particularly dangerous drug. It’s something that’s not scientifically correct, nowadays.

In any event, there’s no debate about the fact that marijuana has a toxic effect.
– Of course it does, like all drugs. There’s no medicine where the directions for use leaflet says: “Does not cause any type of problem”. That goes for plants, too. We’re developing the Planfavi (Plant and Pharmaco-surveillance) Program and we also warn people about the danger of natural products.

EDUARDO CÉSARCompared with a nicotine cigarette, is a marijuana cigarette better or worse?
– It’s difficult for me to give you a definite reply. There’s no doubt that a normal cigarette is carcinogenic. We know that marijuana also contains carcinogenic substances. The marijuana leaf is covered with a layer of wax that contains naphthalene, anthracene… If we rub marijuana tar deposits on the skin of rats, in those that are born without hair, the animal develops cancer 50 weeks later. It just so happens that marijuana is not used in the same way that cigarettes are − with the same intensity and frequency. Another difference is that cigarettes have a very serious effect on the heart, while marijuana doesn’t have this problem. With regard to clinical aspects it has be shown by various authors, but it needs to be confirmed, that the use of marijuana may facilitate the development of cancer in certain people if used excessively. We’ve not yet managed to do a sufficiently large epidemiological study, like those done with cigarettes, in which hundreds of thousands of people were interviewed. To do this you would need to monitor a lot of people who continuously use marijuana and are susceptible to its effects.

Do you favor the use of marijuana recreationally?
– No, I don’t. I don’t favor the use of any drug for “getting stoned”, which alters the mind without the real need for it. However, I’m heavily in favor of the use of morphine, for example, as a painkiller. It would be totally absurd to prohibit the use of morphine or opium because they’re highly addictive. What I can’t do is publicize the recreational use of morphine, but I must publicize, and well, the use of morphine as an extremely powerful agent for giving quality of life to those final moments of someone with cancer who dies howling in pain, for example. In the case of marijuana, there are scientific reports saying that the drug is a first rate substance for treating certain types of pain. Not common pains, like a headache, toothache or colic, but myopathic and neuropathic pains that involve muscles and nerves. Multiple sclerosis, for example, causes this type of pain. And marijuana has a very good effect when it comes to alleviating these pains. However, here in Brazil this resource cannot be used. In other countries this use is fairly widespread.

Even in the United States, which is coming out of a very conservative period?
– There, at least one drug already exists. They synthesize delta-9-tetrahydrocannabinol (THC), which is the active substance in marijuana, and they sell the compound all over the world: Marinol is its trade name. It was initially advertised for reducing the nausea and vomiting caused by cancer chemotherapy. It was approved by the FDA [USA Food and Drug Administration] under controlled use, as it should be.

And is it possible to import the drug into Brazil?
– It’s prohibited to import it and use it. The interesting thing is that the anti-nausea therapeutic use was accidentally discovered by young people from California who had leukemia, cancer of the blood. They were having chemotherapy and on Saturdays, they used to go out to have fun and they used to smoke marijuana. They started telling their doctors that they didn’t feel nauseous, nor did they vomit when they were under the effect of the drug. The specialists started to investigate; they did some work on it and showed clearly that there was an anti-nausea effect. They later studied another consequence of the use of marijuana, popularly called larica, the extreme hunger individuals feel after smoking. This time they also proved the effects and patented the drug, Marinol, for cachexia, the heightened weight loss that occurs with cancer and AIDS.

Is it possible to make tea from it instead of smoking it?
– No, because the compounds that are in the leaves are not soluble. Delta-9-THC is sold in gelatinous capsules, given their lipid-like nature. There’s also a synthetic cannabinoid, called Nabilone, which is used in Canada. And a mixture of two marijuana strains has just been launched, also in Canada, and in England. Both come from Cannabis sativa. One of them produces cannabidiol, which is the forerunner of delta-9-THC. The other has a high concentration of delta-9-THC. The English company, GW Pharmaceuticals, makes two extracts from these plants. The strategy is to mix the two in such a way as to have a suitable quantity of cannabidiol and delta-9-THC. This mixture was launched under the commercial name of Sativex, in a little inhaler such as those used for asthma, directly into the mouth. Each dose releases 5mg. of delta-9-THC.

What is it recommended for?
– Neuropathic pain, nausea and vomiting caused by cancer chemotherapy, cachexia and multiple sclerosis. What’s interesting is that the person who first showed that mixing cannabidiol and delta-9-THC in certain concentrations better modulates the effect of marijuana was our own Department of Psycho-pharmacology at Unifesp. The work done in England originated here. That’s internationally recognized. Cannabidiol modulates the effect of delta-9-THC, in such a way that delta-9-THC in the presence of cannabidiol, generates less anxiety and works longer.

When did you show this?
– These studies date from the 1970’s and 1980’s, with work that was published in the British Journal of Pharmacology, the Journal of Pharmacy and Pharmacology and the European Journal of Pharmacology, high level journals. However we never managed to take anything positive from this work here in Brazil in order to create a product. It’s not a priority in this country.

So this work was only useful for other people?
– Just abroad. It was the same thing with Maytenus ilicifolia, or “espinheira santa“. We did a huge amount of work on it. We showed in laboratory animals and in humans that it has the effect of protecting the stomach. We published a lot here and abroad, but we were unable to register a patent. Japan asked for it and succeeded. What frustrates me is that the Japanese patent says more or less the following: “… Maytenus ilicifolia belongs to the Celastraceae family and is used in Brazilian folk medicine for treating ulcers.”

History repeated itself.
– That’s common. Official attempts at making medicine in Brazil accept marijuana as a drug have been going on since before the 1990’s. In 1995, as national secretary of Health Surveillance I coordinated the country’s drug register. I talked to the Minister of Health, Adib Jatene, who wanted to organize a meeting within the Health Surveillance agency to discuss if delta-9-THC could be licensed as a drug against nausea and vomiting in cancer chemotherapy. He agreed and I spoke to the president of the National Narcotics Council, Luiz Mathias Flack, who also accepted it. The two of them opened the meeting. However we didn’t manage to do anything; the doctors didn’t accept it.?

EDUARDO CÉSARWhat’s the reason for this resistance? Is it the fact that marijuana is known as something that opens the door to other drugs?
– But we were talking about it as a drug, not as recreation. We organized other meetings, including one here at Unifesp in 2004, with specialists from abroad. This gave the first positive result. General Paulo Yog de Miranda Uchôa, from Senad [National Department for Drug Policies], was present and he accepted that the Brazilian government should ask the UN, via Itamaraty, for marijuana to be removed from the list of evil drugs, considering it was the Brazilian government itself that had put marijuana in this situation. This request is being sent to the UNO.

You’re not in favor of the general legalization of marijuana?
– I’m against legalization because I think that human beings don’t need to use drugs that just pollute the body and mind for recreational purposes. I’m in favor of marijuana as a drug used in a controlled way. Decriminalization already exists in Brazil. No one goes to prison any longer; they don’t even write out a police incident today if someone’s caught with just a few grams − unless the policeman wants to do so.

Do you smoke?
– Not marijuana. I smoked ordinary cigarettes for a long time. I stopped more than 20 years ago for a curious reason, when there was still no clear proof that smoking was harmful. I was at Cumbica Airport in Guarulhos, which had recently been opened. Everything was all very new; the carpet, the chairs, everything. I went to get a cup of coffee and I left my cigarette in the ashtray. When I got back, it had fallen and burned a hole in the new carpet. I was so ashamed that I stopped smoking and I don’t miss it.

You mentioned morphine as a drug that is also feared by doctors.
– In my time in the National Department of Health Surveillance it was believed that just 5% of the patients with severe pain who needed morphine to ease their suffering – people with terminal cancer, severe burns, polytraumatized – received the drug. There are lots of reasons for this and they occur all over the world. There’s a concept called opiophobia. Doctors don’t prescribe opiates, of which morphine is an example, for fear of causing dependence. It’s obvious that dependence is horrible, but not for a terminally ill person or for someone who’s polytraumatized. It’s very difficult to get over the phobia of the doctors.

We’re talking about drugs and we’ve still not mentioned alcohol.
– Alcohol is a psychotropic drug. It produces an effect on the central nervous system and creates dependence. A psychoactive drug is one that acts on the nervous system, but doesn’t generate dependence because it has no reinforcing properties. On the other hand, psychotropic drugs act on the brain and produce its effect – analgesia, sleepiness, euphoria, happiness, relaxation – while also reinforcing these sensations in the individual. He experiences well-being or pleasure, which is very important for him. The person easily becomes dependent. As far as I’m concerned, alcohol is the most terrible drug that exists in the world. In the Household Census of 2005, carried out by Cebrid, a test was applied in the 108 largest cities in Brazil to check for alcohol dependence. It showed that 12.3% of the population interviewed runs this risk. That’s too many people; that corresponds to more than 20 million Brazilians. At the moment we’re doing some work that’s being supported by FAPESP to try and improve treatment levels for alcoholics.

What’s this project about?
– We start by talking to the patient and trying to understand them. Then we explain four therapeutic actions to them, including an illustrative film. We let them go home with an explanatory leaflet, think what they’re going to do, discuss it with their family and finally tell us what the best treatment would be. They’re the ones who are going to choose the technique they consider most convenient. Since they’re the master of the situation involving them we expect sick people to adhere better to the treatment. That’s the current line we’re taking. The project is long and it’s likely to be a long time before we get measurable results. At the moment, we’re recruiting alcoholic patients to take part in the research. [They can join by calling (11) 5084-1084; speak to Valéria.]

How do you see damage-reduction policies, such as the distribution of syringes to addicts?
– I think it’s very good. It’s something that society resists because it doesn’t recognize that dependence is a disease. For some people, the people who have to get syringes are diabetics, not “addicts”. What is not known is that the degree of dependence and suffering of that person is enormous. They have to be treated as a sick person.

Can we say that the work of the 1960’s on sleep deprivation and aggressiveness in rats resulted in the research lines about sleep in the Sleep Institute itself, led by Professor Sérgio Tufik?
– Sérgio was my student in the Santa Casa Medical School and for his PhD. We did the first work on paradoxical sleep deprivation and marijuana together. There’s no doubt that it came from here. He’s an uncommonly intelligent person and fits that rare profile of a scientist who sees what everybody sees and thinks what no one else has ever thought.

How did Cebrid come about?
– I really wanted to find out about the drug situation in Brazil as soon as I got back from the United States, but I was unable to. I’d already started an outline of Cebrid in the Santa Casa and I saw that I’d have to produce the information because there was very little reliable data. The only way was to begin collecting data to become available in an archive. We began looking for work on drug abuse in all the libraries here in São Paulo. Right at the outset of the work, we came to Unifesp and put together a database of the work of Brazilian researchers who’d written about this. Today there are almost 4000 pieces of work available for anyone who wants to do research with them. A good part of the work was old and we thought we’d have to produce other, more current studies. We collected the first information from students in Brazilian state capitals and from boys who lived on the streets in 1987. We repeated it in 1989, 1993, 1997 and 2004 and we should do it again this year. These data is used in Brazil as a source of information for preparing public educational policies.

There’s a lot of interest in the possible results of studies on medicinal plants, especially because of the enormous Brazilian biodiversity. However, it seems to be very hard to turn the expectation of finding molecules or active principles that can become drugs into a reality. Why is that?
– It really is difficult to go just down this path. If we analyze the imported drugs that reach Brazil currently, theres a large number that are no longer made from the active principle but from the dried extract of the plant. I believe we committed a tactical procedural error. We always chase after the plant’s active principle, but there are dozens, perhaps hundreds of substances and we have to research each one of them to find out which one is responsible for the effect we want. When an extract is used and it produces the desired effect, that’s great; it’s no longer necessary to research substance by substance. There’s also another advantage: these extracts usually come from plants that have been popularly used for centuries and probably they’re not very toxic. Perhaps, in fact, it’s not the best strategy to use an isolated and single active principle. Research with some plants is showing that the interaction between components is responsible for the desired effect. Our problem is that there’s no priority for this type of research in Brazil. Beginning with government organs themselves, which don’t believe in this and create limitations, such as these imposed by the CGEN [Council for the Management of Genetic Wealth], of the Ministry of the Environment. CGEN undoubtedly has good intentions and, like us, aims to protect our genetic wealth so that it doesn’t fall into the hands of others and also, like us, it intends granting rights to those that are in fact the owners of popular knowledge. However, in practice it established such hare-brained rules that it ended up preventing Brazilian scientists from working with plants. And there’s another problem: working with plants creates little impact, which generates little interest from other researchers and from the support agencies.

Pesquisa FAPESP nº 70, from 2001, published a report on the work of biologist, Eliana Rodrigues, whom you tutored, and who had identified 164 plant species used by the Krahô Indians for medicinal purposes. The Indians were demanding R$ 25 million in compensation from Unifesp. How was that situation resolved?
– It wasn’t. The situation is still complicated today. We’re accused of stealing Brazilian biodiversity. Recently, we received a letter from the Public Prosecutor wanting proof that we haven’t published this work in any foreign journal. At the same time, hundreds of pieces of work by Brazilians were published by different Brazilian universities abroad in association with foreign industries, and what’s more, there are four studies with exclusive plants from Brazil that were done by universities overseas. And we were the ones chosen to account for our actions and we don’t know why. To be able to do research on a Brazilian plant we, as pharmacologists, have to prove that we’re doing bioprospecting. By definition, bioprospecting is anything in the science field that might in the future generate commercial interest. Now, pharmacology is the study of drugs, something that can always generate a commercial product, even if the researcher doesn’t want it to. It might be a medicine, a cosmetic or some type of paint.

Are you being sued by the Indians?
– No, they’re on our side. They came here and we spent three days with the public authorities. One of the leaders who speaks Portuguese the best said to us, “that it’s quite clear, if the research doesn’t work out it’s the fault of you white people, because we want it to”. We’re in this squabble. It’s the government against the government, because after all, Unifesp is a federal university. Our project had already been approved by FAPESP. I insisted on one point: I wanted the Indians to have the right to a patent. As Indians come under the protection of the State and can’t sign anything I tried to interest Funai, but at the time, they changed three or four Justice ministers and the respective presidents of Funai. The solution was to enter in to an “ethical” contract between the university and the Indians in such a way that they were guaranteed the rights to the royalties by the university itself. Everything was signed – and then it all died a complete death.

What was it like working with the National Department of Health Surveillance, now known as Anvisa?
– The Health Surveillance Department had a fearful reputation for corruption, which was known nationwide. When I accepted the invitation from Minister Adib Jatene, the mission was to moralize and modernize it. I asked the employees for their collaboration in order to change the reputation of the place and I think they listened to me. I used to receive a lot of presents, such as watches, Mont Blanc pens, household appliances and I decided to return them in order not to create any more bad feeling. I thanked the people and told my secretary to put them on a specific set of shelves. There were dozens and dozens of presents. After, I used to take the people who had given me the presents to see what the set of shelves was like. At the end of the year, I called in all the Anvisa employees and held a big raffle with these presents. I also removed 15 employees and “closed” from 100 to 150 ghost laboratories, all with normal registers and several of them taking part in public bids. This gives you an idea of the level of the nonsense that was going on at the time. I also cancelled more than 300 registers of pharmacies that used to make the celebrated slimming formulas themselves. However, it didn’t do a lot of good. With Jatene out and with me leaving the Health Surveillance Agency everything went back to where it was before. Fortunately, soon after another Minister of Health took over, Anvisa was created and nowadays I believe that that black phase will never again return. The interesting thing is that after so much of a struggle I earned a lot of respect from people in the industry and from the Health Surveillance Agency itself.