IACM-Bulletin of November 9, 2003

Science — Cannabis reduces symptoms of multiple sclerosis, large British study shows

The biggest study of the use of cannabis and THC (dronabinol) to relieve symptoms of multiple sclerosis produced mixed results but doctors said there is enough evidence to warrant licensing the treatment for the illness.

Although there was no objective evidence that cannabis relieved spasticity, or muscle stiffness, caused by the disease, patients reported improvements in pain relief and rigidity. Mobility was improved as well.

657 patients with stable MS and muscle spasticity received either a capsulated cannabis extract, THC or a placebo. Cannabis capsules contained 2.5 mg THC and 1.25 mg cannabidiol (CBD). The trial lasted 15 weeks. It started with a 5-week dose titration phase: During this period, patients were asked to increase their dose by one capsule twice daily at weekly intervals up to a maximum daily dose of 10-25 mg THC (depending on body weight). If side effects developed, patients were advised not to increase the dose.

The medication was generally well tolerated. There was no objective evidence, that spasticity measured by the spasticity scale according to Ashworth was improved. However, there was a trend towards a small improvement with cannabis and THC, with a mean reduction in total Ashworth score for cannabis of 0.32 and for THC of 0.42 compared to placebo. There was evidence of a treatment effect on some subjective symptoms. 61 and 60 percent, respectively, of patients receiving cannabis extract or THC reported an improvement in spasticity, compared to only 46 percent with placebo. Corresponding figures for pain were 42, 35 and 26 percent respectively. There was also evidence of an improvement of walking ability with cannabis and THC for mobile patients.

“There is a range of positives and a range of negatives. Overall, I think there is enough evidence to take this forward with the licensing and regulatory authorities,” Dr. John Zajicek, who headed the study, told Reuters. He said the research raises questions about what's more important: a doctor's measurements or the patient's perspective.

"I think if there's a conflict, it's what the patient feels which is important, so I think it's quite encouraging," Dr. Roger Pertwee, a professor of neuropharmacology at University of Aberdeen, who was not connected with the study, told Associated Press.

One explanation for the mixed results could be the muscle test, called the Ashworth scale, is not sensitive enough to detect changes that are meaningful to patients. "It is very far removed from everyday life. Moving someone's leg up and down when he is lying flat on a table doesn't necessarily translate very well into what happens when they get up and try to walk around or do the housework or whatever," Dr. Alan Thompson, professor of neurology from London, said.

(Sources: Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A, on behalf of the UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 2003; 362(9385): 1517-1526. Reuters of 7 November 2003, Associated Press of 6 November 2003)

USA — For doctors it remains a difficulty to recommend cannabis to patients

For doctors who want to discuss using medical marijuana with their patients, the line between advice and advocacy remains almost as blurred as it was before a recent court decision guaranteed a physician's right to address the issue openly.

Many doctors are relieved that the United States Supreme Court let stand a lower-court decision on 14 October that barred the federal government from punishing doctors who advised patients that marijuana might ease some symptoms. But the decision essentially affirms the federal government's right to hold physicians accountable if they actually take steps to help patients obtain marijuana. In this case the court left open the possibility that doctors could be charged under federal drug statutes.

"This decision says that it's fine and appropriate to talk with patients about medical marijuana, and I can even say, `I think you can benefit from it,' " said Dr. Steve O'Brien, of an AIDS Centre in Oakland, California. "But does that mean I can now sign a form from a medical pot club or write, `I recommend marijuana,' on a prescription pad?"

(Source: New York Times of 28 October 2003)

News in brief

USA — California

Governor Gray Davis has signed a controversial medical-marijuana bill which will take effect on 1 January 2004. The new law offers confidential photo identification cards, on a voluntary basis, to document patients who are registered and protected. But although California has vowed to protect the identity of medical-marijuana ID card holders, many patients worry that federal drug agents will seize any list that they can get their hands on and use it as a hit list for arrests. (Source: Los Angeles Daily Journal of 6 November 2003)

Science — Anxiety

Pharmacological blockade of the enzyme FAAH that is responsible for the degradation of the endocannabinoid anandamide produces anxiolytic-like effects. FAAH blockade results in an increased anandamide concentration. These findings suggest that anandamide contributes to the regulation of emotion and anxiety, and that FAAH (fatty acid amide hydrolase) might be the target for a novel class of anxiolytic drugs. (Source: Gaetani S, et al. Trends Mol Med 2003;9(11):474-8)

Science — Pain

THC in a dose of 5 mg was not effective in reducing postoperative pain. 40 women who had undergone surgery received either 5 mg THC or placebo, if patients requested further analgesia on the second postoperative day. There were no significant differences between the two substances. As demonstrated in earlier studies 5 mg THC is usually an ineffective dose for the treatment of pain. (Source: Buggy DJ, et al. Pain 2003;106(1-2):169-72)

Canada — GW and Bayer

GW Pharmaceuticals und Bayer HealthCare of Canada announce a marketing agreement to bring Sativex, GW's cannabis-extract to the Canadian market. (Source: Canada NewsWire of 6 November 2003)

Science — Schizophrenia

Public health researchers in the Netherlands now believe that there is "converging evidence" to show that using cannabis is a risk factor for schizophrenia. Researchers from the Netherlands Institute of Mental Health and Addiction warn that cannabis approximately doubles the risk of schizophrenia. The researchers draw their conclusions from a review of five longitudinal studies recently published in four medical journals. They accept that epidemiological cohort studies do not offer complete proof, as there may be other underlying social or biological factors for this increased risk. (Source: Sheldon T. BMJ 2003;327(7423):1070)

Science — Glaucoma

In glaucoma, the increased release of glutamate is the major cause of retinal nerve cell death. In this study it was shown that glutamate causes apoptosis (programmed cell death) of retina nerves via the excessive formation of peroxynitrite, and that the neuroprotective effect of THC and of cannabidiol (CBD) is via the attenuation of peroxynitrite formation. (Source: El-Remessy AB, et al. Am J Pathol 2003;163(5):1997-2008)