The grass is green

Doctor, this one is positive for weed, what should we do? says my sister Mare discreetly in my ear.

Over the past ten years, this question has been asked so often that we have begun to wonder whether people need to be tested for marijuana at all. Of course, the procedure requires a discussion with the patient, but even here a new pattern has emerged – more and more young people see marijuana not as something harmful, but as something normal. The fact is that smoking weed has become almost a generational social behaviour. They don’t make a difference between alcohol, cigarettes and weed, and there are also interesting answers like: “Well, it’s medicine, doctor – you prescribe it, where’s the problem, I won’t smoke on board.

Hmm, there is something to that. Drug testing is a dubious procedure with many dilemmas anyway, and now portals and newspapers are full of articles about how to get “weed oil” with a prescription. And how to explain to the young man that this could cost him his job and, in some countries, his head. At first glance, it’s clear why drug abuse is a problem on board. Here are some random quotes from the literature to back this up. For example: drug users are 1.7 times more likely to be involved in an accident at work (Crouch 1989); absenteeism is higher among drug users (Normand 1989); cadets in the US who use marijuana are more likely to be discharged from the Navy (Blank 1989); injury and illness rates are 55-145% higher among marijuana and cocaine users (Zwerling 1990); in Rijeka in 1970-1978, of 44 registered drug addicts, 25% were sailors (A Haasz 1980). If, in a study of 2400 seafarers, 13% were positive, this means that every commander with a crew of 18 can expect to have 2 seafarers using drugs (J Van Damme 1996). Such information is not surprising when we know that the ILO has presented data according to which 60% of drug users are actively employed. And this data is deliberately twenty years old, when marijuana was not yet a “medicine”.

There is no doubt that a person under the influence of drugs is unfit to work and there is no skipper who would under any circumstances accept the responsibility of sailing with such a person on board. The ability to sail, in addition to the specific knowledge acquired through years of training, also includes the complete integrity of all psychophysical functions, expressed in the ability to carry out work tasks on board in the field of navigation. These include cognitive abilities expressed as intelligence, good sensory abilities such as vision and hearing, psychomotor abilities such as coordination, muscular strength, precision of movement, speed and accuracy of complex reactions. There is also general endurance and the ability to withstand stress during various manoeuvres, constant noise, vibration and physical environmental conditions, as well as continuous communication. Any change in the integrity of these skills will jeopardise navigation and safety at sea. These changes in the integrity of psychophysiological functions occur under the influence of various factors, such as fatigue, de-synchronisation of biological rhythms during shift work, or emotional stress, which are an integral part of working on board a ship, so it is already a difficult state and it is unthinkable to endanger it by the use of psychoactive substances. Even if addiction does not develop, any state of drug dependency significantly reduces a person’s ability to sail for a few hours, just as the withdrawal syndrome (abstinence syndrome) will reduce it if, by some miracle, he passes the test and remains drug-free at sea.

It is also a fact that the deterioration of all these psycho-physiological functions occurs most rapidly under the influence of psycho-active substances, but this is where the first doubts arise. It is interesting to note that most maritime states do not require routine drug testing in their legislation, but prevent seafarers with clinical addiction or declared drug abuse from working. Such “flags” leave the option of testing to companies that develop their own anti-drug policies on board. In general, employers seek to reduce the short-term risk and take no responsibility for the long-term health of seafarers, in this case addiction treatment. With short-term contracts, it is more important for the employer to be legally “covered” in the event of an accident than to worry about the long-term health of the seafarer, especially when there is a lot of competition among seafarers. Many employers prescribe very dubious and, one might say, medically unfounded rules of the game, which puts the doctors assessing work capacity in an ethically dubious position. For example, some shipping companies consider a positive pre-employment drug test to be grounds for automatic disqualification, which is contrary to good, medically acceptable drug testing practice. It is a basic rule stated in all relevant international documents (ILO/WHO) that “no result may be interpreted as positive without the necessary measures being taken to obtain a possible explanation of such results from the subject” Good practice is that drug testing is carried out by preliminary immunological tests and, if the result is positive, by mass spectrometry or other proven scientific methods. The procedure must be agreed in advance and all participants in the procedure must be informed about it. The doctor responsible for interpreting the results must have the right, on the basis of his knowledge (statement by the seafarer, observed error in the procedure), to downgrade the result to a positive result.

But what happens to the person who tests positive, because there is no systematic monitoring of “positive” tests? The seafarer, after a short period of abstinence (until he is “clean”), simply goes to the testing service in another office or even in another country. For all drugs except cannabis, the tests only show whether someone has used the drug in the last two or three days, not whether they are addicted – which would actually be a medically justified disqualification for the job. In addition, some drugs leave traces for days after use, although they no longer have any effect on cognitive, psychomotor and other functions. Is such a seafarer also unfit to work on a ship? Is the person from the beginning of the text who celebrated his birthday three days ago with “grass” able to work or not? The problem of occasional drug use during seafarer examinations is a real one. What to do with a sailor who has taken drugs during his leave, we have found traces and now there is no sign of any influence on psychomotor skills. The safety of the ship is certainly a priority and, should he be allowed on board at all, or perhaps just increased surveillance or automatic exclusion? The fact is that a positive test on entry to a profession, and according to our law we only test for drugs on first entry, simply does not indicate a risk for later behaviour. Do we have the right to deny such a man the right to work?

In addition to these basic problems, the characteristics of the tests themselves do not guarantee accuracy, especially if the procedure is not followed and other tests using a more accurate method are not carried out. For example, immunological tests such as those used in most practices may show that someone has taken benzodiapines, but they do not detect lorazepam. So someone taking apaurine will fail the test and someone taking lorsilan, which has virtually the same effect, will pass. Some painkillers available without a prescription may contain substances on the banned list (codeine). Tests for opiates are designed for morphine and can give false positives for codeine, analgesics, morphine antagonists or agonists and even poppy seeds. In all these cases, without confirmatory testing, for example by chromatography, we simply cannot say what the seafarer has taken. On the other hand, some combinations of psychoactive substances (alcohol, drugs, medicines) may have a significant effect on cognitive, psychomotor and other functions due to synergistic effects, even when used in small quantities that result in a negative drug test. The fact that the drug test is negative can also mean that, for example, an addict has abstained for a few days, the test is negative, but the abstinence syndrome significantly reduces his psychomotor abilities, so that he enters the ship with reduced ability to work. There is also the problem of determining the cut-off value of the tests, which can significantly affect whether someone tests positive or negative. Limit value in itself is not an analytical term, but it has a medico-legal meaning.

There is also no clear correlation between the lower sensitivity limit of the method and the degree of disability of the seafarer. Tests with a limit of 300 ng/ml are used for opiate testing in addiction centres, and for seafarers the limit should be 2000 ng/ml – this would reduce false positives. The new generation of THC tests has a limit of 20 ng/ml, but other metabolites react to it in addition to the target substance, so there is a risk of “passive smokers” being declared positive on a drug test. It is recommended that this limit be set at 50 ng/ml, but the question is how many doctors testing seafarers even consider this limit of the sensitivity of the test, and whether any seafarer has thought to ask.

Nobody should be declared an addict and unfit to work on a ship ONLY because of a positive drug test, so we had to talk to this guy from the beginning of the article, but I’m pretty sure we didn’t convince him that “weed” is a drug and not a medicine.

The use of Indian hemp (cannabis) for therapeutic purposes is a fascinating and ubiquitous topic today. Over the last decade, the use of cannabis for medical purposes has increased, although data on effectiveness and safety are still rather scarce. Of course, the media is very positive about the medical use of cannabis, because who would read a text saying that “weed” is harmful? Nobody cares about that. After all, we read the texts in the “black chronicle” when they seize a larger quantity. Of course, patients, especially the heavier ones, are a special story. They are ready to accept anything that is offered to make them feel better and they believe that it is a natural medicine and therefore without significant side effects compared to the synthetic medicines that we offer them. Cannabis has become something like a universal medicine that cures almost everything, and the “evil” pharmaceutical industry is blocking it because they want to market their chemicals and poison us with them.

It never occurs to anyone that if it’s such an effective drug, why doesn’t some pharmaceutical company put it in a pill and sell it that way? And then, as the icing on the cake, the politicians got in on the act. Of course, they jump into the game as soon as they see that an issue is of interest to the public, and they immediately assess how their electorate will react to it. It doesn’t matter whether it’s same-sex marriage, abortion or marijuana. The story of cannabis as an ‘easy drug’ is very popular with them because, unlike other more serious issues, it is used by their PR teams as proof of their conservatism or liberalism. And the fact is that everything works together, because in Croatia we have the law legalising cannabis for medical purposes, which has some medical reasons. However, since in most “Western” countries the affirmation of the health benefits of marijuana was only the first step towards its legalisation for “recreational purposes”, it will be interesting to observe how long it will take Croatia to follow this trend and for “weed” to become a “recreational drug” in Croatia. Um, recreational, I’m not sure you’d be happy if your child was “recreating” in that way, or if you had a helmsman on board who was regularly “recreating”. As usual, neither this decision nor future ones seem to be based on an overall understanding of the problem, and least of all on listening to the profession, which is nothing new for us in the creation of public health policies. In the case of liberalisation and decriminalisation, we must certainly expect spill-over effects that may occur in various areas, for example, that a greater number of users of other psychoactive substances will be recruited from the increased pool of marijuana users. Or, if we go all the way, will the trade unions, under such influence, ask to allow the “recreational” use of marijuana on ships?

I am afraid that this will not be decided by doctors, but by those who weigh up the tax advantages for the state, for a manufacturer or a pharmaceutical company. We’re not even going to talk about hypocrisy here, and the guy at the beginning of the text tried to corner me by saying: well, doctor, do you drink, of course you do, and do you smoke – don’t smoke, that’s fine, I smoke, and those are even more dangerous drugs and I can get on the boat with them. 

And neither is alcohol, nobody sells tobacco as medicine! Is it hypocritical to defend marijuana while allowing alcohol, cigarettes and sugar to be advertised? Who decides what is most harmful to us, scientific research or powerful lobbies? There are also arguments for legalising the “recreational” use of marijuana, which should lead to a reduction in marijuana-related crime; the so-called harm reduction principle, price reduction, better control of the “market”, the claim that prohibition has no effect, and the like. More and more often, there are calls for the complete legalisation of the cultivation of cannabis for medical purposes, so that people suffering from various illnesses can cultivate this plant themselves for personal use, which is allowed in some countries. Cannabis has become a real “socio-political drug”. In fact, the World Health Organisation (WHO) has stated that the benefits of cannabis have been confirmed in controlled studies for the treatment of asthma, glaucoma, depression, and for achieving antiemetic, anticonvulsant and antispasmodic effects. WHO encourages basic and clinical research to further elucidate the role of these preparations and their possible beneficial effects. It is important to emphasise that the WHO does not make recommendations, but only lists conditions for which studies have shown improvement (without commenting on the quality of the studies). Unfortunately, systematic scientific reviews give a different picture.

And on 13 February, the European Parliament adopted a resolution on the use of cannabis for medical purposes. With this document, MEPs called for a distinction to be made between medical and other types of cannabis use, for innovation and research in the field of medical cannabis to be encouraged, and for effective cannabis-based medicines to be covered by health insurance. And then, of course, we reacted (Hungary did not). After evaluating the scientific evidence, in 2015 our committee gave the green light for the use of cannabis only for the following indications: symptomatic treatment of spasticity in patients with multiple sclerosis in whom these symptoms cannot be adequately controlled by conventional therapy, treatment of moderate to moderately severe pain in patients with advanced malignancy, relief of nausea and vomiting in malignancy patients receiving emetogenic therapy, and treatment of cachexia and anorexia in AIDS patients. The committee also made recommendations on the dosage of THC and CBD. At the same time, it is made clear that this is only about so-called add-on therapy, i.e. the use of THC and CBD at the same time as the patient is taking medications with proven efficacy. It was also clearly emphasised that there is no evidence that cannabis prevents the progression of malignant diseases or multiple sclerosis. Nevertheless, the Commission’s decision was often perceived by the public as proof that cancer or multiple sclerosis could be causally treated with cannabis, especially its oil.

After all, is the use of marijuana primarily a political issue or a medical one? Well, here I will try to show you how things really are with the medical use of marijuana:

The term “cannabis” includes preparations derived from the Indian hemp plant (Cannabis sativa L.). It contains over 500 compounds, 104 of which are cannabinoids. Cannabinoids are substances that bind to cannabinoid receptors in the human body, and in addition to phytocannabinoids, there are endogenous and synthetic cannabinoids. Pharmacologically, the most important cannabinoids are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). The primary psychoactive cannabinoid is Δ9-THC, which is also responsible for the majority of adverse effects, and the potency of a particular cannabis preparation is defined by its Δ9-THC content. . On the other hand, CBD has no psychoactive effect, it can antagonise some of the harmful effects of THC, and it also has certain specific effects such as anti-inflammatory and anticonvulsant. In general, our endocannabinoid system is very complex and cannabinoid receptors mediate effects on a number of organ systems. Preparations containing a precise dose of THC and/or CBD, such as oils or soft capsules, are used for medical purposes. In 2018, the US Food and Drug Administration approved Epidiolex”, a plant extract containing only cannabidiol (CBD), for the treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in children over the age of two. Abiximols (Sativex”), an oromucosal spray, is registered as a medicine through national procedures in 18 EU countries and contains 2.7 mg Δ9-THC and 2.5 mg CBD. It is prescribed for the symptomatic treatment of spasticity caused by multiple sclerosis in adults who have not responded to other conventional medicines. “Dronabinol” is a synthetic form of Δ9-THC. It is approved in the US for the treatment of anorexia associated with weight loss in AIDS patients and for the treatment of chemotherapy-induced nausea and vomiting (when there is no response to conventional antiemetics). Nabilone is a synthetic analogue of Δ9-THC and is approved in the United States and Canada for the treatment of chemotherapy-induced nausea and vomiting.

So what evidence do we have? Despite the increasing number of articles on cannabis and cannabinoids in the medical literature, there are very few randomised controlled clinical trials and meta-analyses. Most of the evidence is of poor quality, and different studies have used different preparations of cannabis and cannabinoids, with different methods of administration and in different doses. With such heterogeneous data, it is difficult to draw clear and unambiguous conclusions, which is the conclusion of many systematic reviews. Of course, it is much easier for portals and journalists to reach a conclusion that costs them nothing, regardless of the consequences.

After numerous systematic reviews, including those from the Cochrane Library, the European Monitoring Centre for Drugs and Drug Addictions (EMCDDA) has published on its website a list of conditions for which there is evidence that cannabinoids have some efficacy , which is briefly described below (edited text published in our medical journal):

Use of cannabis and cannabinoids in malignant diseases. To date, there is no scientific evidence that any preparation that acts on cannabinoid receptors affects the progression of malignant disease. Some cannabis preparations can alleviate some of the symptoms of malignant diseases, such as pain or nausea and vomiting caused by chemotherapy. There is a phase I pilot study in 9 patients with recurrent glioblastoma multiforme in which Δ99-THC was injected directly into the tumour, reducing tumour cell proliferation. Despite many media reports that the National Cancer Institute (NCI) has actually admitted that there is evidence that cannabis can cure cancer, the fact is that the NCI only cites certain experimental and non-clinical evidence of its effect on cancer cells. However, we know how long it takes to move from laboratory indicators of some effect to clear and credible evidence of effectiveness and harmlessness in clinical trials, i.e. drug approval. Scientifically sound and credible clinical trials are needed. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board regularly updates the NCI on all laboratory, non-clinical, and clinical data on the potential effects of cannabis and cannabinoids on cancer. A study in mice and rats showed the possible effect of cannabinoids in preventing the formation of some types of tumours, such as liver adenomas and hepatocellular carcinomas (the animals were given various doses of THC in the food). In another study, delta-9-THC, delta-8-THC and cannabinol inhibited the growth of lung adenocarcinoma cells in vitro and in vivo. In some other tumours, cannabinoids have been shown to inhibit their growth. 

These in vitro anti-tumour effects are mediated by apoptosis, inhibition of cell growth and inhibition of angiogenesis. In its conclusions, “PDQ” states that in oncology there is some evidence that cannabinoids can alleviate certain symptoms of malignant diseases, such as nausea and vomiting (it is also emphasised that the evidence is stronger in this sense for dronabilone and nabinol, because there are controlled clinical trials and a meta-analysis), while for the use of inhaled cannabis there is no clear evidence that it could alleviate some symptoms of cancer or the side effects of cancer treatment; further studies are recommended in this sense. Regarding the effect on nausea and vomiting, a 2015 review by Whiting et al concluded that most of the 28 clinical studies evaluated showed a better effect of cannabinoids than the active comparator or placebo, although this was not statistically significant in all studies. The limitation of this evidence is that chemotherapy is less emetogenic today than when most of these studies were conducted.

Comparators are also a problem, because most of the studies used the now-rare drug prochlorperazine (which belongs mainly to the group of typical antipsychotics), whereas modern antiemetics are more effective than prochlorperazine in treating and preventing nausea and vomiting. For all these reasons, the 2015 Cochrane review concluded that the quality of the evidence for this indication is low. A 2018 systematic review by Mucke et al. on cannabinoids in palliative care for cancer patients included 9 clinical trials. Compared to a placebo, there was no statistically significant effect on caloric intake, nausea or vomiting, pain, or sleep. There was also no evidence that cannabinoids affected cachexia in cancer patients. It was concluded that better-designed clinical trials with larger numbers of participants are needed to assess the effect in palliative care. So far, there are only a few good-quality studies with a small number of participants, which makes it difficult to draw clear conclusions about effectiveness.

Treatment of cachexia in AIDS patients. The synthetic THC Dronabinol is approved for this indication in the USA on the basis of a few studies with a small number of subjects, and the strength of the evidence for this indication is therefore low (as concluded in several systematic reviews). In developed countries, the use of highly active antiretroviral drugs makes AIDS patients less likely to develop cachexia.

Treatment of spasticity caused by multiple sclerosis. Most systematic reviews consider the quality of evidence for this indication to be moderate. Most clinical trials in this indication have used nabiximolsone, a standardised cannabis extract with approximately equal amounts of THC and CBD. In randomised trials of both nabiximolsorn and dronabilone, patients had statistically significantly less muscle spasticity, although objective clinician assessment of spasticity reduction was less convincing. Unfortunately, there is no evidence that cannabis affects the progression of multiple sclerosis.

Treatment of chronic non-malignant pain. In a 2018 Cochrane review article, Mucke et al analysed the effect of phyto and synthetic cannabinoids on the treatment of chronic neuropathic pain. With cannabinoids, the percentage of patients who experienced a 50% reduction in pain was 21%, compared to 17% with placebo. As patients on cannabinoids were twice as likely to drop out of the trial as those on placebo (10 vs 5%), the authors conclude that the side effects of cannabis probably outweigh its positive effects. Most of these trials are of low quality because they have too few participants and do not include people with significant comorbidities. Similar findings were reported in another systematic review (Stockings et al). It was concluded that the percentage of respondents who had a 30% reduction in pain with cannabis was statistically significant, but side effects were also more common. The authors conclude that the evidence for the effect of cannabinoids in chronic non-cancer pain is limited.

Severe forms of epilepsy. A systematic review of clinical trials showed that adding cannabidiol (CBD) to conventional antiepileptic drugs significantly reduced seizure frequency in children with Dravet syndrome and Lennox-Gastautovirus syndrome. As previously reported, the US Food and Drug Administration (FDA) has approved a CBD-only formulation (Epidiolex) for this indication.

And that’s about it. Doctors prescribe or advise such things when they have no other options, but even there the idea of a “herbal medicine that can’t hurt” has crept in. However, there are also very significant consequences of using cannabis. The effects of short-term cannabis use include impairment of short-term memory (difficulties in learning and retaining information), impairment of motor coordination (which affects driving ability and risk of injury), altered reasoning ability, and, in high doses, paranoia and psychosis. The effects of long-term cannabis use are: addiction (9% overall, 17% among those who start using in adolescence, 25-50% among those who use daily), changes in brain development (especially among those who start using in early adolescence), poorer performance at school or university, cognitive impairment (lower IQ among those who used cannabis frequently in early adolescence), symptoms of chronic bronchitis, higher risk of developing chronic psychosis, including schizophrenia among those with a predisposition. Several studies have shown the link between cannabis use and the development of psychosis. A study that included patients with a first episode of psychosis in 11 research centres showed that daily cannabis use increased the risk of psychosis compared with subjects who had never used cannabis, and the risk was even higher in those who used high-potency cannabis with a THC content > 10% (OR 4.8, 2.5-6.3). In connection with the possible harmful effects of cannabis and interactions with other drugs, a group of authors from Israel published earlier this year the results of a retrospective study of 140 subjects who received immunotherapy with nivoluranab (indications were advanced melanoma, light-paused kidney cancer and non-small cell lung cancer). Of these 140 people, 89 received nivolumab alone and 51 received nivolumab and cannabis. In the group that received cannabis in combination with immunotherapy, there was a significantly lower tumour response rate (37.5 vs. 15.9%). There was no statistically significant effect of cannabis on progression-free survival or overall survival. These results indicate the need for further research into possible interactions between immunotherapy and cannabis/cannabinoids. It is known that cannabidiol has (still poorly understood) effects on the immune system through cannabinoid receptors, so there may be a pathophysiological basis for these interactions.

For some other conditions, such as depression, anxiety, sleep disorders and inflammatory bowel disease, there are no clinical trials to prove effectiveness.

And what should I and my colleagues do now, and it is a cure and it is not. In any case, as usual, nobody asks you anything, the law is the law, and the boss is the boss.

Your Maritime Doc’

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