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IACM-Bulletin of November 18, 2012

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USA — Massachusetts becomes the 18th state to legalize the medical use of cannabis

On 6 November Massachusetts voters have overwhelmingly approved a bill to legalize the medical use of cannabis. The law allows the use of cannabis by people with cancer, chronic pain, AIDS, multiple sclerosis and other conditions determined by a doctor. It will create non-profit treatment centres to grow and provide cannabis to patients or their caregivers. Now 18 states and the District of Columbia allow the medical use of cannabis: Alaska, Arizona, California, Colorado, Connecticut, Delaware, Hawaii, Maine, Massachusetts, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, and Washington.

The law, which will take effect on 1 January 2013, calls for the Department of Public Health to issue a set of regulations within 120 days after that. The Department must decide what amount of cannabis constitutes the 60-day supply patients can get for their personal use, register patients and caregivers, register treatment centres that will distribute the cannabis, and register the treatment centre’s personnel. The law limits the number of centres to no more than 35 in 2013, but says the Department of Public Health could allow more after that.

CBS News of 7 November 2012

Science/Human — Sativex is well tolerated long-term with maintenance of therapeutic effects in cancer patients with chronic pain

In an open study with 43 patients with cancer-related pain the long-term use of the cannabis extract Sativex was generally well tolerated, with no evidence of a loss of effect for pain relief. The study was headed by Dr. Jeremy Johnson, Medical Director of the Severn Hospice in Bicton Heath, UK. Patients had participated in a previous three-arm controlled trial, where they received either Sativex containing THC and CBD, a THC spray or a placebo. Participants in the open follow-up study self-titrated Sativex (39 patients) or THC spray (4 patients) to symptom relief or maximum dose.

Mean pain severity and worst pain decreased compared to baseline. Quality of life increased according to a questionnaire in the domains insomnia, pain and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from the study. Patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, “suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit,” researchers wrote in their article.

Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics. J Pain Symptom Manage. 2012 Nov 7. [in press]

USA — Colorado and Washington are the first states to legalize cannabis

Colorado and Washington became the first U.S. states to legalize the possession and sale of cannabis for recreational use on 6 November in defiance of federal law. Under the recreational cannabis measures in Colorado and Washington, personal possession of up to an ounce (28.5 grams) of cannabis would be legal for anyone at least 21 years of age. They also will permit cannabis to be legally sold and taxed at state-licensed stores in a system modelled after a regime many states have in place for alcohol sales.

The outcomes in Colorado and Washington, which already have laws legalizing the medical use of cannabis, put both states in further conflict with the federal government, which classifies cannabis as an illegal narcotic. The U.S. Department of Justice reacted to the measure's passage in Colorado by saying its enforcement policies remain unchanged, adding: "We are reviewing the ballot initiative and have no additional comment at this time."

Reuters of 7 November 2012

News in brief

Israel — The number of medicinal cannabis users surpasses 10,000

More than 10,000 patients now have official government permission to consume cannabis in Israel, a number that has strongly increased in recent years. Unlike in the United States and Europe, the issue inspires almost no controversy among the government and the country's leadership. Even influential senior rabbis do not voice any opposition to the spread of the medical use of cannabis. Now, Israel's Health Ministry is considering the distribution of medical cannabis through pharmacies.

Associated Press of 2 November 2012

Science/Animal — Cannabidiolic acid prevents nausea and vomiting

In a study with rats and shrews cannabidiolic acid (CBDA) reduced nausea and vomiting by enhancing 5-HT1A receptor activation. CBDA is the precursor of CBD (cannabidiol) present in high concentrations in fibre hemp. CBDA is transformed to CBD by heating. Authors wrote that “CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.”

Institute of Medical Sciences, University of Aberdeen, UK.

Bolognini D, et al. Br J Pharmacol. 2012 Nov 2. [in press]

Science/Animal — The endocannabinoid system is activated after spinal cord injury

Blockade of the CB1 and CB2 receptors reduced spontaneous recovery of motor function after spinal cord injury (SCI) in rats. Authors suggested that “the endocannabinoids acting through CB1 and CB2 receptors are part of an early neuroprotective response triggered after SCI that is involved in the spontaneous recovery after an incomplete lesion.”

Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain.

Arevalo-Martin A, et al. PLoS One 2012;7(11):e49057.

Science/Animal — Lipoxin A(4) changes the state of the CB1 receptor so that it is activated easier by endocannabinoids

The anti-inflammatory lipid lipoxin A(4) is an enhancer of the CB1 cannabinoid receptor, by “allosteric” modulation. It binds to the CB1 receptor and by this it increases the affinity of the endocannabinoid anandamide to the receptor. Authors noted that this offers new therapeutic possibilities.

Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.

Pamplona FA, et al. Proc Natl Acad Sci U S A. 2012 Nov 12. [in press]

Science/Human — Feeling anxious and feeling bored are frequent withdrawal symptoms

In a study with 120 schizophrenic patients, who stopped using cannabis the most frequently reported withdrawal symptoms were craving for cannabis (59.2%), feeling anxious (52.57%), feeling bored (47.5%), feeling sad or depressed (45.8%), feeling irritable or jumpy (45.0%), feeling restless (43.3%), and trouble failing asleep (33.3%).

Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.

Boggs DL, et al. J Psychiatr Res. 2012 Nov 9. [in press]

Science/Animal — The activation of the CB2 receptor reduces inflammation in pancreatitis

The activation of the CB2 receptor by a synthetic cannabinoid (HU210) reduced inflammation in a mouse model of acute pancreatitis.

Institute of Virology of the Technical University Munich, Germany.

Michler T, et al. Am J Physiol Gastrointest Liver Physiol. 2012 Nov 8. [in press]

Science/Animal — Beta-caryophyllene reduces pain by activating the CB2 receptor

The injection of the essential oil beta-caryophyllene into the feet of mice reduced pain caused by a chemical (capsaicin) and this effect was mediated by activation of CB2 receptors, which stimulated the local release of an endogenous opioid (beta-endorphin). Beta-caryophyllene is present in many plants, including cannabis.

Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.

Katsuyama S, et al. Eur J Pain. 2012 Nov 9. [in press]

Science/Animal — Endocannabinoids reduce pain, which is caused as a side effect of a chemotherapeutic agent

Cisplatin, which is used in cancer therapy, produces painful nerve damage. An animal study demonstrates that cisplatin alters endocannabinoid tone and that inhibition of endocannabinoid degradation alleviates chemotherapy-induced pain, which was mediated by CB1 and CB2 cannabinoid receptors. These therapeutic effects were similar or superior to the efficacy of anti-neuropathic pain medications used clinically, such as morphine.

Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.

Guindon J, et al. Pharmacol Res. 2012 Nov 2. [in press]