After all the pain elicited by the crisis at the Hadassah University Medical Center’s pediatric hemato-oncology department in the past eight months, it was perhaps apt that the conference organized by the Hadassah Medical Organization earlier this month focused on medical cannabis used to relieve human suffering.
Half of the all-day 11th annual Israel Medical Conference held at the Jerusalem International Convention Center was dedicated to the utilitarian green weed, with the rest of the time divided up among inequality in medical care between the center and the periphery, new medical technologies and Israeli clinical trials.
Although pretentiously called the Israel Medical Conference, the free event was sponsored by only three hospitals – Hadassah, its Jerusalem competitor Shaare Zedek Medical Center and Haifa’s Bnai Zion Medical Center plus various companies and organizations. The 1,400 people in the hall were members of the general public, many of them pensioners with time on their hands (some of whom were attracted by food and a stand-up comedian) rather than working physicians and researchers.
The choosing of medical cannabis, however, was opportune, because Health Minister Ya’acov Litzman, who remained only for a short time, declared that he opposed in principle the export of marijuana because it’s a drug like any other.
“Make no mistake about it.
It should not be taken by people who are not patients and not by all patients,” Litzman said. But if the government approved the move, he added, he would demand that some of the profits go to the health system.
Last Sunday, Litzman and Finance Minister Moshe Kahlon accepted and approved the recommendations of a committee headed by their directors-general to allow such exports, given Israeli agricultural expertise in growing and processing medical cannabis, the suitable climate in the Arava and innovative medical technologies for using it.
The state will earn NIS 1 billion to NIS 4 billion annually from such foreign sales of medical cannabis, the committee estimated.
The overall global price for cannabis in the world is about $10 per gram. The price of medical cannabis is growing significantly. In 2000, global production stood at 1.3 tons and in 2014 production rose to 57.3 tons. Litzman, who has gradually expanded the number of individual licenses for using medical cannabis to 30,000 patients, conceded that the process involves a “deplorable, absurd amount of red tape” in his ministry, and that the approval of 100 more physicians who have been trained for prescribing it to patients should help relieve the queues for medical cannabis.
Meretz MK Tamar Zandberg, chairman of the Knesset’s Special Committee on Drug and Alcohol Abuse, told the audience: “Wow! I can hardly believe that cannabis is being discussed at such a conference.
“The Health Ministry has gone far in approving it for patients. But there is a lot of bureaucracy in getting it. A few years ago, I met for two hours with patients who cried about their pain and their diseases such as Crohn’s, fibromyalgia and others that could have been helped by the drug. They were angry and impatient, and they suffered from the stereotypes that worked against approval of it,” said the MK.
“There is addiction of opiate drugs, which are used legally, but not marijuana. I am for full legalization and decriminalization of marijuana. There are dangers of addiction and abuse, but there are also many benefits. I am for evidence-based use of medical cannabis.”
PROF. RAPHAEL Mechoulam, the 87-year-old world pioneer in cannabis research at the Hebrew University of Jerusalem Faculty of Medicine’s department for medicinal chemistry and natural products was lauded by the speakers and applauded by the audience for his foresight in studying the plant when no one else thought of it.
A former rector of the university and a member of the Israel Academy of Sciences, Mechoulam’s main contributions are in the field of the constituents of cannabis and the endogenous cannabinoids found in the brain and their pharmacological activities.
He noted that when he began his studies of cannabis more than 40 years ago, “nobody was interested in it. But recently, Nature Neuroscience put the subject on its cover. There is huge interest in the medicinal and social aspects of it. The article stated that modulating endo-cannabinoid activity may have therapeutic potential in almost all diseases affecting humans – from obesity, metabolic syndrome, diabetes and complications to neurodegenerative, inflammatory, cardiovascular, gastroenterological, dermatological, psychiatric and oncological diseases and pain.”
Marijuana, in the form of hemp, is a very old plant and was used by the Assyrians, who called it “ganzigunnu” and “azallu.”
But when morphine was isolated from opium, which can be highly addictive, and due to various legal reasons, research into cannabis significantly declined. Yet, HU set up a special center with 20 research groups that are studying cannabinoids.
Today, there is research into phytocannabinoids, endocannabinoids, anandamide and 2AG, all derived from cannabis, which have different chemical structures than THC.
Although Mechoulam identified the main psychoactive constituent in cannabis, tetrahydrocannabinol (THC), the plant is known to contain some 500 compounds, among them at least 113 cannabinoids.
Besides THC, he said, some strains of cannabis produce cannabidiol (CBD), which is not psychoactive or toxic and does not cause side effects but has been shown to block the effect of THC in the nervous system.
There is also synthetic THC, which does not contain cannabinoids.
Mechoulam, impressive with his erect posture and clear mind, said that pure THC does not cure disease but reduces pain and the unpleasant side effects of chemotherapy in cancer patients.
“Four decades ago, we did research on cannabidiol on mice; it stopped their epileptic attacks and also was shown to be effective in humans.
Neurologists were not interested in it, but we know that it can be used to treat children with epilepsy. But giving too much of it can actually cause an epileptic attack. I don’t know why it took so long to give it to them.”
The chemical was also given to mice with type 1 (autoimmune) diabetes whose pancreatic cells were under attack. There has not been a single clinical study on the substance or type 1 diabetics. I can’t explain why.”
It can also be effective against graft vs. host disease, a complication after bone-marrow transplants.
“But because cannabis cannot be patented, companies are not very interested in producing products.
Schizophrenia patients can benefit from CBD, but not from THC. There are many brain regions in which cannabinoid receptors are abundant.”
Cannabis derivatives can be used to improve osteoporosis in menopausal women, reduce withdrawal symptoms from opiates and have been shown even to block nicotine addiction in mice and possibly in humans addicted to tobacco, Mechoulam said.
“Medical cannabis should not be given to all,” he concluded, “but for specific things. One needs knowledge and experience. Every company markets different things and even single companies don’t sell uniform products.”
PROF. ZVI Bentwich, an AIDS expert at the Health Sciences Faculty of Ben-Gurion University of the Negev in Beersheba who is also chief scientist of medical marijuana research and supply company Tikun Olam (one of eight legal growers), said his was the first Israeli patient to get medical cannabis legally. “He had AIDS,” he said, giving “much credit” to Mechoulam for his “pathfinding research.”
In general, he said, cannabis is not addictive, and cannabinoids are not psychotropic. There are different strains of the plant, and different amounts of components are given for various conditions. Cannabis comes in various forms, not only smoking it – which is absorbed the fastest – in capsules, as drops of oil under the tongue and as food products.”
There have been 600 clinical and other studies on medical cannabis, but in Israel, there have been very few; those that exist have not yet been concluded. There is proof that it relieves pain, nausea and spasticity.”
Research into cannabis should be more common here, said Bentwich, because there is less restrictive legislation, and “we have the knowhow.” Asia, specifically the Himalayas, and for 6,000 years was exported to Japan, said Dr. Hinanit Koltai, a senior research scientist at the Agricultural Research Organization-Volcani Center in Rishon Lezion.
“There are three subspecies, but cannabis sativa is the most common.
It has been used and cultivated for difference uses. We know its genome.”
Hemp, she said, “was cultivated in ancient times for fiber, ropes and sails. There was widespread crossing of male and female plants and there are many kinds.”
The Agriculture Ministry even set up a comprehensive genetic database for cannabis research and development.
“We can give a chemical fingerprint to each kind. But we need to set the levels of active ingredients that are safe and effective. There are hundreds of them, and we understand only some of them. We need evidence-based research on them.”
THE 1899 Merck Manual of Diagnosis and Therapy, whose current edition is today’s foremost medical textbook, listed cannabis among the numerous pharmaceuticals that were commonly used, said Prof.
Arnon Afek, associate director-general of Sheba Medical Center at Tel Hashomer. “It was suggested for many uses.”
The Health Ministry set up a medical cannabis unit (called YAKAR) a few years ago for medicalization, preventing misuse and ensuring public safety.
“It’s a very emotional issue, as it is used also for recreational use and involves smoking. It’s important that medical cannabis be standardized so that they can be prescribed in a uniform manner,” said Afek, who previously was associate director- general and director-general of the ministry.
“We established a committee to determine medical indications for prescribing it, and we trained medical practitioners to treat patients with it. We allowed some 140 studies on it. Companies even make products under Good Manufacturing Practices (GMP) approval.”
Dr. Tamir Gedo, CEO of BOL (Breath of Life) Pharma, one of the pioneers in Israel’s medical cannabis industry, also spoke. A marketing and business strategy expert who has served in academia, government and industry, Gedo said that the Health Ministry and YAKAR “have created a revolution. We are impatient. In the early 1990s, doctors claimed that ulcers came from tension and stress. Now we know it is caused by helicobacter bacteria.
Old ideas that are long accepted can fall and be replaced by new ones. We want standardization, with GMP approval, on all available cannabis products.”
Dr. Adi Aran, director of the neuro- pediatric unit at Shaare Zedek Medical Center, described his work on understanding the therapeutic effects of CBD-based medical cannabis in neurocognitive disorders, including autistic spectrum disorders (ASD).
“The dramatic clinical effect seen in some cases has led me to further explore the potential benefits, and possible risks, of cannabinoids, particularly in children. I have initiated studies exploring the effects of medical cannabis in epilepsy and ASD.”
Aran is a consultant to the Health Ministry on medical cannabis, indications and use in children and spend much time educating physicians and lay audiences on this topic. His study on autistic children and medical cannabis was “small but promising” and should be followed up, he said.
An amazing new technology involving the delivery of cannabis compounds was presented by Perry Davidson, founder and CEO of Syqe Medical in Tel Aviv. The company, which last year assigned a cooperation and distribution agreement with the now financially ailing Teva Pharmaceutical Industries, developed for the first time an inhaler that enables the precise delivery of cannabis at the level of safety and precision of conventional drugs, similar to inhalers used for asthma. The hi-tech device, which contains an internal cartridge with 45 compartments, each containing a specific dose raw cannabis, has been used on certain patients with Health Ministry approval for about two years at Haifa’s Rambam Medical Center. The device changes the physical structure of cannabis leaves, preserving all its characteristics and enabling safe, precise and measurable dosing and delivery by inhalation, the company official said.
Other forms of medical cannabis can take hours to reach the bloodstream, said Davidson, but inhalation is the fastest. Patients who need the drug but cannot or don’t want to smoke it would benefit from the delivery system.
Given the severe financial battering suffered by Teva in recent weeks and the mounting international interest in medical cannabis, its agreement with Syqe could offer significant help in resuscitating the shrunken pharmaceutical company.