Israel’s Medical Marijuana Program
Paradoxically, at time of writing, while the U.S Federal Government is denouncing medical marijuana, America’s closest ally, Israel, quietly set up a state/government legalized medical marijuana program in August of 2011. Not surprisingly, Israel’s medical marijuana program has received virtually no press in the U.S. or elsewhere. Israel currently has about 7,000 medical marijuana patients, but the program is so popular that there are estimates that number could increase to 40,000 by 2016.
As a result, some of the world’s foremost research into the medical benefits of cannabis is being conducted in Israel.
Israel’s inroads into legalizing cannabis for pain relief and managing terminal illness rest on the ground breaking research of Prof. Raphael Mechoulam, an expert in medicinal chemistry, of the Hebrew University in Jerusalem’s Center for Research on Pain.
In 1964, working from bags of hashish seized by the local police, Mechoulam isolated the active compound of cannabis, Δ9-tetrahydrocannabinol. As a result he became recognized as a world leading authority on cannabis and the medicinal benefits of cannaboids.
Mechoulam was recently (2012) awarded the Rothschild Prize in physical and chemical sciences in recognition of his contributions to science. With Mechoulam acting as an advisor Israel started to implement policies so that medical marijuana could be legally accessed by those who needed it most.
At present there are five categories that are officially recognized in Israel as being helped by medical marijuana.
One is cancer or patients with malignant tumors who are in one of two stages — either during chemo to ease nausea and promote appetite, or those with a final-stage tumor, terminal patients who have a prognosis for living for no longer than six months.
Other categories are HIV patients who attend one of the country’s eight HIV centers; chronic pain patients being treated at pain clinics or by a certified pain physician; patients with Crohn’s disease or ulcerative colitis being treated by gastroenterologists; and MS patients, specifically for their spasticity symptoms, upon recommendation from an MS treatment center or a neurological specialist.
Research is also being conducted with patients who suffer from Post Traumatic Stress Syndrome.
Patients of all ages may apply for approval through their doctor and must pass a rigorous screening process. Those eligible include cancer patients undergoing chemotherapy; cancer patients with final-stage tumors; patients enrolled in an Israeli HIV center; and people under treatment for chronic pain, Crohn’s or ulcerative colitis, MS and post-traumatic stress disorder.
Israeli Scientists Develop Cannabis Without the High
In May of 2012, according to the Maariv daily, medical cannabis growing center Tikun Olam has developed a high CBD (cannabidiol), extremely low THC strain of cannabis for medical purposes. The aim of the new cannabis strain is to provide the medical benefits associated with marijuana without the high linked to THC which many medical marijuana users find inhibits their ability to function normally.
“It has the same smell, the same look and taste as the original plant — it is all the same, but without the feeling of numbness that users are used to… Not only does it leave users stone-cold sober, it also doesn’t induce the munchies, the hunger pangs that the drug’s smokers generally suffer.”
Researchers at the growing center, located in the northern Galilee region, reduced the amount of THC in the plant and increased the presence of CBD, another chemical that previous research has shown could be effective against diabetes and various psychological disorders, and possibly prevent the spread of cancer.
In actual fact, this was nothing new. U.S. and other Medical Marijuana researchers have long recognized the value of high CBD, low THC cannabis for use in stopping the spread of breast cancer and for treatment of other diseases. For some time research has been conducted using high CBD, low THC strains and, if anything, the Israeli’s are simply the first to breed a very specific strain for given medical purposes.
Animal and human studies have shown CBD to possess anti-convulsant properties, particularly in the treatment of epilepsy. CBD, when administered in combination with THC, significantly reduces pain, spasticity and other symptoms in multiple sclerosis (MS) patients.
Additionally, clinical studies show CBD to be neuroprotective against strokes and cerebral infarction (cell death in the brain). Clinical trials have also shown CBD to possess anti-tumoral properties, inhibiting the growth of glioma (brain tumor) cells in a dose dependent manner and selectively inducing cell death in malignant cells.
A 2011 study by Mateus M Bergamaschi et al showed that symptoms of Social Anxiety Disorder can be reduced by treatment with CBD. The paper by Crippa et al, “Neural basis of anxiolytic effects of cannabidiol in generalized social anxiety disorder: a preliminary report,” was published online Sept. 9 in the Journal of Psychopharmacology. Ten men with severe Social Anxiety Disorder (SAD), ages 20 to 33, participated in the study, which was conducted at the University of Sao Paulo. Prior to undergoing a neuroimaging procedure to measure blood flow in the brain, the test subjects were given either 400 mg of CBD dissolved in corn oil and packed in a gel cap, or a placebo gel cap. A week later they were given the alternative treatment. The investigators assumed that the neuroimaging —Single Photon Emission Computed Tomography (SPECT), which involves insertion of an intravenous tube and observation by a technician deploying a high-tech apparatus— was in itself an anxiety-producing event. Subjects recorded their anxiety levels before, during, and after the neuroimaging by means of a “Visual Analogue Mood Scale (VAMS).” The researchers were able to correlate these subjective reports with blood-flow activity measured in the brain. “CBD was associated with significantly decreased anxiety,” the research concluded. 1
McAllister et al (2007) discovered that CBD (Cannabidiol) is a very potent inhibitor of breast cancer. The research concluding “CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.”2
A follow up study by McAllister et al in 2011 took an in-depth look at how CBD kills breast cancer cells in an animal model. It turned out that CBD affects a protein called ID-1, which appears to be a major conductor of cancer cells. When cancer spreads it can eat through tissue (the process is called “metastasis”). CBD appears to inhibit the cells’ aggressive behavior. The research demonstrated that treatment with CBD significantly reduced primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis, concluding that the data demonstrated the, “efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression. “ 3 Download paper on U.S. based high CBD, low THC research (PDF)
High-CBD strains might enable patients who need large doses of cannabis to ingest pharmacologic doses of these strains while remaining functional. According to Jeffrey Hergenrather, MD, “Patients with cannabis-sensitive cancers, seizure disorders, and inflammatory bowel disease, to name a few, could all benefit with a higher blood level of cannabinoids than is convenient with our high-THC strains. For them, availability of a high-CBD strain could be life saving.”
For this reason, at least this author sees the development of high CBD, low THC cannabis strains as a progressive move forward in medical marijuana breeding, with just one proviso.
- Mateus M Bergamaschi, Regina Helena Costa Queiroz, Marcos Hortes Nisihara Chagas, Danielle Chaves Gomes de Oliveira1,3, Bruno Spinosa De Martinis3,4, Fla´vio Kapczinski3,5, Joa˜o Quevedo3,6, Rafael Roesler3,7, Nadja Schro¨der3,8, Antonio E Nardi3,9, Rocio Martı´n-Santos3,10, Jaime Eduardo Cecı´lio Hallak1,3, Antonio Waldo Zuardi1,3 and Jose´ Alexandre S Crippa*,1,3 (2011) Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naı¨ve Social Phobia Patients
- Sean D. McAllister, Rigel T. Christian, Maxx P. Horowitz, Amaia Garcia and Pierre-Yves Desprez (2007) Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells
- Sean D. McAllister, Ryuichi Murase, Rigel T. Christian, Darryl Lau, Anne J. Zielinski, Juanita Allison, Carolina Almanza, Arash Pakdel, Jasmine Lee and Chandani Limbad, et al (2011) Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis
The Proviso – Taking the Munchies out of Med
The Maariv daily article notes:
Not only does it leave users stone-cold sober, it also doesn’t induce the munchies, the hunger pangs that the drug’s smokers generally suffer.
Suffer? I don’t know about that! (I’m quite partial to the munchies myself).
There is a very obvious problem here where is comes to wasting (appetite loss) experienced by AIDS and cancer patients – the very reason that medical marijuana was identified as a positive treatment for cancer and AIDS related Anorexia. In simple terms, where THC increases the appetite, CBD doesn’t. This probably renders Israel’s THC free cannabis ineffective as a treatment for AIDS and cancer related wasting. For instance, research by Celia JA Morgan et al (2010) demonstrates that CBD-rich Cannabis works as an appetite suppressant. The study conducted at the University College London, tested 94 subjects on two occasions. The subjects smoked their own Cannabis and “while acutely under the influence” were offered more Cannabis, other drugs, and food. Morgan et al measured the eagerness with which the subjects responded to the offerings, and found that it correlated inversely with the CBD-to-THC ratio of the Cannabis the subjects were smoking. In other words, the higher the proportion of CBD they had ingested, the less desirous they became for food. 1
On the other hand, Israel’s Raphael Mechoulam notes this re THC:
One of the symptoms of AIDS is weight loss. Many patients smoke marijuana because it is an appetite stimulant. This has been supported by clinical studies. In one such study, the effects of THC (also known as dronabinol) (2.5 mg bid) on appetite, weight and nausea were examined in 39 patients with AIDS over a six-week period. After four weeks, the patients’ weights were stable in the treated patients but lower in the placebo recipients. The data indicated that drabinol caused increased appetite in about one-third of patients. The author of this study concluded that:
Dronabinol is a safe and effective treatment for anorexia in patients with weight loss due to AIDS. By improving appetite and mood, decreasing nausea, and stabilizing weight, dronabinol may significantly improve the quality of life of patients infected with HIV.2
Dronabinol is a synthetic THC and has been approved by the Food and Drug Administration (FDA) for the control of nausea and vomiting associated with chemotherapy and more recently for appetite stimulation of AIDS patients suffering from wasting syndrome. Synthetic dronabinol is supplied as MARINOL in the U.S. and consists of approximately 98% THC.
According to case reports of the Centre for Palliative Medicine and Paediatric Pain Therapy of the University of the Saarland (Germany) dronabinol is an effective and well-tolerated medicinal drug in the treatment of different severe illnesses in children. A scientist of a university reported of experiences from the treatment of 13 children with severe disabilities and spasticity aged 7 months to 17 years as well as of about 50 cancer patients aged three months and older.
All children in the trial received a slowly increased dose. In all children a reduction in pain, which was considerable in some of them, was observed within 48 hours after start of treatment. Efficacy with regard to spasticity set in within one to two weeks. In some patients opioid treatment could be reduced. Most cancer patients profited from an increase in appetite and weight, reduction of nausea and vomiting, as well as improved sleep and reduced anxiety. Even with long-term treatment no relevant side-effects were noted.3
A pilot study to determine if delta-9-tetrahydrocannabinol (THC) can improve taste and smell (chemosensory) perception as well as appetite, caloric intake, and quality of life for cancer patients with chemosensory alterations was undertaken by Brisbois TD et al (2011). In the study, adult advanced cancer patients, with poor appetite and chemosensory alterations, were recruited from two sites and randomized in a double-blinded manner to receive either THC (2.5 mg, Marinol(®); Solvay Pharma Inc., n = 24) or placebo oral capsules (n = 22) twice daily for 18 days. Twenty-one patients completed the trial. THC-treated patients reported improved and enhanced chemosensory perception and food ‘tasted better’. Premeal appetite and proportion of calories consumed as protein increased compared with placebo. Additionally, THC-treated patients reported increased quality of sleep and relaxation.4
Marinol’s patent states:
Among the many problems endured by patients suffering from symptomatic HIV infection, which includes inter alia AIDS (Acquired Immune Deficiency Syndrome) and ARC (AIDS Related Complex), are loss of appetite with consequent loss of weight. This loss of appetite and loss of weight further debilitates the patients and increases the many problems associated with the HIV infection.
The compound delta-9-tetrahydrocannabinol, which is the active ingredient in marijuana and which was produced chemically as described in U.S. Pat. No. 3,668,224, has been used as an antiemetic to relieve nausea and vomiting in patients receiving cancer chemotherapy.
A number of cancer investigators have used delta-9-tetrahydrocannabinol to attempt to increase appetite and modify weight loss in cancer patients. For example, in a randomized double-blind crossover study employing oral delta-9-tetrahydrocannabinol and prochlorperazine, 50% of the subjects on delta-9-tetrahydrocannabinol reported an increased food intake while only 29% had a similar response on the prochlorperazine..sup.1 In another study of similar design and using the same medications, patients on delta-9-tetrahydrocannabinol reported feeling more hungry than patients on prochlorperazine..sup.2 Results suggestive of an appetite stimulating effect were also noted by Ekert, et al..sup.3 in groups of children and adolescents 6-19 years of age administered delta-9-tetrahydrocannabinol, prochlorperazine or metaclopramide in crossover design studies.
In a double blind study, Regelson, et al..sup.4 observed that advanced cancer patients on chemotherapy receiving delta-9-tetrahydrocannabinol maintained their weight better than those not receiving the delta-9-tetrahydrocannabinol.
In an open study, Wadleigh, et al..sup.5 observed appetite increases and a lessening of the rate of weight loss in cancer patients.
In addition, The first cannabinoid agonist, nabilone (Cesamet), which is a synthetic analogue of Δ9- THC was specifically licensed for the suppression of nausea and vomiting produced by chemotherapy. The synthetic Δ9- THC, dronabinol (Marinol) entered clinical treatment in1985 as an anti-emetic (preventing vomiting) and in 1992 as an appetite stimulant (Pertwee, 2009). In early studies, several clinical trials compared the effectiveness of Δ9- THC with placebo or other anti-emetic drugs. Comparisons of oral Δ9- THC with existing anti-emetic agents generally indicated that Δ9- THC was at least as effective as the dopamine antagonists, such as prochlorperazine (Carey et al., 1983; Crawford & Buckman, 1986; Cunningham et al., 1988; Layeeque et al., 2006; Ungerleider et al., 1984; Tramer et al., 2001).
Prochlorperazine, a non-cannaboid drug, belongs to a group of medications called phenothiazines. It is typically used as an antipsychotic medication for schizophrenia; however, it also commonly prescribed for nausea related illnesses including pregnancy (morning sickness). What’s most concerning about the latter is there is evidence to indicate that exposure to Prochlorperazine during pregnancy may have a teratogenic effect on the fetus. A teratogen is a substance that can cause birth defects. Additionally, it is not entirely known exactly how Prochlorperazine works. However, it is known that the drug blocks or lessens the effects of dopamine, a chemical in the brain. Since dopamine can activate the part of the brain that controls nausea and vomiting, prochlorperazine can treat severe nausea and vomiting.
Common side effects of prochlorperazine include, drowsiness, dizziness, unusual body movements, shakes or twitches, blurred vision, sexual problems and a dry mouth.
While more severe side effects are listed as:
“Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest or throat; swelling of the mouth, face, lips, or tongue; unusual hoarseness; wheezing); chest pain; confusion; decreased coordination; drooling; fainting; fast, slow, or irregular heartbeat; mask-like face; muscle spasms of the face, neck, or back; muscle weakness; new or worsening mental or mood problems; numbness of an arm or leg; prolonged or painful erection; restlessness; seizures; severe or persistent constipation; severe or persistent dizziness, drowsiness, or headache; shuffling walk; sleeplessness; stiff or rigid muscles; sudden shortness of breath or vomiting; swelling of the hands, ankles, or feet; symptoms of infection (eg, fever, chills, persistent sore throat); symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; severe or persistent nausea, stomach pain, or loss of appetite); tremor; trouble urinating; twisting or twitching movements; uncontrolled muscle movements (eg, twitching of the face or tongue; loss of balance; uncontrolled movements of arms or legs; trouble speaking, breathing, or swallowing); unusual bruising or bleeding; unusual eye movements or inability to move eyes; unusual or excessive sweating; unusual tiredness or weakness; unusually pale skin; vision changes (eg. blurred vision).”3
Sounds like great stuff! I.e. comparing cannabis to prochlorperazine is like comparing shit to shinola! And yet one is legal and the other is not. Go figure!
- Celia JA Morgan1, Tom P Freeman,, Gráinne L Schaferand H Valerie Curran (2010) Cannabidiol Attenuates the Appetitive Effects of Δ9-Tetrahydrocannabinol in Humans Smoking Their Chosen Cannabis http://www.nature.com/npp/journal/v35/n9/abs/npp201058a.html
- R Mechoulam, L Hanus (2001) The cannaboids: An overview. Therapeutic implications in vomiting and nausea after cancer chemotheraphy, in appetite promotion, in multiple sclerosis and in neuroprotection
- Gottschling S (2011) [Cannabinoids in children] [Article in German] Cannabinoide bei Kindern.
- Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, Macdonald N, Baracos VE, Wismer WV (2011) Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial.