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IACM-Bulletin of 16 June 2013

USA: An increasing number of people use cannabis to treat medical conditions of animals

The Associated Press published an article on the medical use of cannabis products in dogs and other animals. Leading the charge is Los Angeles veterinarian Doug Kramer. "I grew tired of euthanizing pets when I wasn't doing everything I could to make their lives better," he said. "I felt like I was letting them down." Some other vets contacted said they share Kramer's view on cannabis, but they wouldn't talk on the record for fear of arrest or other problems.

Dr Duncan Lascelles, a professor of surgery and pain management at North Carolina State University College of Veterinary Medicine, thought about studying cannabis a decade ago. He didn't, not for lack of interest, but because the timing was wrong. "I have been considering looking at that field again because I think it does have a lot of potential," he said. The article cites several examples including that of Jessica LeRoux in Denver, who used cannabis that helped extend the life of her dog named Thor. "I got the 15th year out of that relationship because of the product I made for him," she said. Old or ailing pets who take cannabis usually experience an immediate boost in appetite and relief from pain. That lets them get around, relieve themselves without help, sleep better and enjoy their families until age or disease catches up, LeRoux said.

Associated Press of 5 June 2013.

Science/Human: Moderate interaction of THC with other medicinal drugs influenced by the same enzymes in the liver

Cannabis-based medicines can be administered safely together with other medicinal drugs that induce or inhibit enzymes in the liver responsible for the degradation of cannabinoids. This is the result of research conducted by GW Pharmaceuticals with their cannabis extract Sativex containing THC and CBD in combination with other drugs in 36 healthy subjects. THC and other cannabinoids are degraded by so-called cytochrome P450 (CYP450) enzymes. Sativex was combined with rifampicin (an antibiotic), which increases CYP450 enzymes, and the inhibitors of CYP450 ketoconazole (an antifungal medication) and omeprazole, which reduces the production of gastric acid.

A single dose of four sprays of THC/CBD (10.8/10 mg) following repeated doses of rifampicin reduced the maximum blood concentrations of THC and CBD. Ketoconazole co-administration with THC/CBD spray had the opposite effect, increasing the maximum blood concentrations of cannabinoids. No significant deviations were observed when THC/CBD spray was co-administered with omeprazole. However, the interactions were relatively low. Authors concluded that “on the basis of our findings, there is likely to be little impact on other drugs metabolized by CYP enzymes on the PK parameters of THC/CBD spray, but potential effects should be taken into consideration when co-administering THC/CBD spray with compounds which share the CYP3A4 pathway such as rifampicin or ketoconazole.”

Stott C, White L, Wright S, Wilbraham D, Guy G. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. Springerplus 2013;2(1):236.

News in brief

Science/Human: Cannabis extract moderately effective in chemotherapy-induced neuropathic pain
There was no significant difference between a treatment with the cannabis extract Sativex and a placebo in a small study with 16 patients suffering from chemotherapy-induced neuropathic pain.
All participants received both the extract and the placebo at different times (crossover study). Five patients tended to respond to a treatment with cannabis. Authors noted that there were five “responders”, which “supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.”
Pain Management Unit, Dalhousie University, Halifax, Canada.
Lynch ME, et al. J Pain Symptom Manage. 2013 Jun 4. [in press]

France: The government considers making the cannabis extract Sativex available in France
A decree of 7 June by the government allows the approval of cannabis-based medicines in France. This is the first step to make Sativex available, which is considered by the health authorities.
Le Nouvel Observateur of 7 June 2013

Spain: Court rules against the plans of a small town to grow cannabis
A court rejected a plan by a small town in north-eastern Catalonia to ease its municipal debt and help lift itself out of the financial crisis by growing cannabis. When the seven-member town council of Rasquera - population 960 - voted in favour of cultivating cannabis just over a year ago in order to create jobs and shore up its finances, the news flashed around the world.
Associated Press of 31 May 2013

Science/Human: Oral THC is associated with great variation in bioavailability
The pharmacological effects and pharmacokinetic of large oral doses of THC were investigated in 7 cannabis users. Doses were administered in ascending order in 15 mg increments across separate sessions; up to a maximum of 90 mg. Low cannabinoid concentrations were associated with significant effects, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in maximum blood concentration and time until maximum blood concentration was observed. Authors concluded that “individualized dose adjustment is needed to avoid side effects and maximize therapeutic response.”
Department of Behavioural Science, University of Kentucky College of Medicine, Lexington, USA.
Lile JA, et al. J Clin Pharmacol. 2013 Jun 10. [in press]

Science/Human: CB1 receptor variations associated with age at onset in Huntington disease
Variations in the genes, which encode the CB1 receptor, were associated with the age of onset in 473 patients with Huntington disease. Authors concluded that “these findings support the idea that CNR1 variation may have modifying effects” on Huntington disease.
Department of Human Genetics, Ruhr-University Bochum, Germany.
Kloster E, et al. EUR J Med Genet. 2013 Jun 6. [in press]

Science/Animal: Permeability of THC through the cornea of the eye was increased by surfactants
Solubility in water and permeability of THC through the cornea of the eye was enhanced significantly in the presence of surfactants. However, THC levels in many other parts of the eye were not significantly increased. Researchers concluded that “although delivery of THC to the anterior chamber ocular tissues could be significantly increased (...), further studies are needed to increase penetration to the back-of-the eye.”
Department of Pharmaceutics, The University of Mississippi, Mississippi, USA.
Hingorani T, et al. Pharm Res. 2013 Jun 5. [in press]

Science/Animal: Blockade of cannabinoid receptors reduced inflammation
Blockade of the CB1 and the CB2 receptor by two specific cannabinoid receptor antagonists reduced inflammation caused by the implantation of polyester-polyurethane sponges into mice. There was a reduction in pro-inflammatory cytokines, accumulation of white blood cells and production of new blood vessels.
Departamento de Bioquímica e Imunologia-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Guabiraba R, et al. Inflamm Res. 2013 May 31. [in press]

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