IACM-Bulletin of July 23, 2000

Science USA — Short-term use of marijuana and THC safe in AIDS patients taking protease inhibitors

The first U.S. study using marijuana for people with HIV has found that smoking the plant does not disrupt the effect of antiretroviral drugs that keep the virus in check.

The results were presented on 13 July at the 13th International AIDS Conference in Durban/South Africa. Professor Donald Abrams and colleagues of San Francisco General Hospital were restricted to focusing on marijuana's safety rather than its effectiveness. The 67 people who participated in the study were kept in the hospital during the 21-day study period.

Researchers were especially interested to study people on drug regimes that contain protease inhibitors, because THC is metabolised by the same system in the liver as those drugs. The participants were divided into three groups, with one set smoking marijuana (3.95% THC), another taking oral dronabinol capsules (3x2.5 mg daily), and a third taking oral placebo capsules.

In all groups the level of virus in the blood dropped or remained undetectable by current tests. There was no statistically significant difference among the three groups, those taking THC or marijuana having slightly lower levels. Furthermore, researchers found that those using dronabinol (THC) or marijuana experienced significant increases in caloric intake and gained an average of 3.5 kg (marijuana group) and 3.2 (THC group) compared to 1.3 kg in the placebo group. There was no significant difference between marijuana and THC with regard to side effects and benefits.

"Now that we've demonstrated the safety in a population as vulnerable as people with HIV, I think it paves the way for doing studies of efficacy," Abrams said. Indeed he hopes to soon begin studying the use of smoked marijuana for cancer patients to see if it can control nausea and pain.

(Sources: San Francisco Examiner of 13 July 2000, File of the Poster presented at the Durban conference provided by D. Abrams)

Science — News at the meeting of the ICRS (II)

Below are some additional interesting new research results presented at the annual meeting of the International Cannabinoid Research Society (ICRS) from 22 to 24 June in the USA (see the last Bulletin of 9 July at http://www.acmed.org/).

(1) A research group at the University of Massachusetts/USA investigated the anti-proliferative and anti-tumour effects of ajulemic acid (CT3). Ajulemic acid is a derivative of the non-psychotropic THC metabolite THC-COOH. At higher doses it causes reduction of proliferation in several cell lines. Preliminary findings in tumour models with C6 glioma cells in mice demonstrated prolongation of survival time after administration of this acid. The feasibility of ajulemic acid in the treatment of certain cancers is under investigation. (Source: Abstract by Sumner Burstein, et al)

(2) A British research team analysed the effects of cannabinoids in experimental multiple sclerosis. Experimental multiple sclerosis was induced in mice. They developed tremor and spasticity. Reduction of symptoms was observed following the administration of CB1 receptors agonists (THC, WIN55,212, methanandamide), the administration of a CB2 agonist (JWH-133), and the administration of substances that increase endocannabinoid levels (AM 404, AM 374). In contrast, CB1 and CB2 receptor antagonists worsened tremor and spasticity. It can be concluded that the cannabinoid system controls tremor and spasticity associated with nerve damage. This may be used therapeutically. (Source: Abstract by David Baker, et al)

(3) Italian researchers investigated the association of activity of the enzyme anandamide hydrolase (fatty acid amide hydrolase = FAAH) and spontaneous abortion. 120 pregnant women were divided into two groups, one with low and one with high FAAH levels, measured between week 7 and 8 of pregnancy in lymphocytes of the blood. During the follow-up 15 subjects out of 15 in the low FAAH group compared to only 1 subject out of 105 in the high FAAH group aborted. Excessive levels of the endocannabinoid anandamide in the uterus might be responsible for pregnancy failure and high FAAH seems to prevent this. FAAH activity and expression might be a useful marker of spontaneous abortion. (Source: Abstract by Mauro Maccarrone, et al)

(4) An Israelian group investigated metabolites of CBD (cannabidiol) with regard to possible therapeutic effects. The results showed that the natural metabolites and their dimethylheptyl analogues are anti-inflammatory, the acids more than the hydroxy metabolites. (Source: Abstract by Susanna Tchilibon, et al)

(Source: Book of abstracts of the 2000 ICRS meeting)

Germany — Rejection of applications for the medical use of cannabis by the Federal Institute for Pharmaceuticals and Medical Products

The Federal Institute for Pharmaceuticals and Medical Products in Bonn, a subordinate Board of the Health Ministry, last week rejected applications of several applicants for approvals to use cannabis products therapeutically. In the next days rejections of all other applications are to be expected.

The applications followed a decision of the Constitutional Court (Bundesverfassungsgericht) of 20 January. The highest German Court had argued: "The medical supply of the population is a public purpose that may justify an approval in individual cases." Thus, a corresponding application would "not be hopeless from the start".

Dr. Franjo Grotenhermen of the IACM: "Despite the overall positive political signs and efforts of the last months it seems to be desirable that some applicants oppose to this rejection before administrative courts. Beyond all regulations relating to pharmaceuticals the general denial of a medical use of cannabis products by seriously ill persons seems to be disproportional. It is very welcome, that this opinion is increasingly adopted by politicians. Examples from other countries show that court procedures can play a speeding role in the finding of adequate political decisions."

(Source: Letters of the Federal Institute for Pharmaceuticals and Medical Products to some applicants, personal communications)

News in brief

USA

A federal judge has cleared the way for an Oakland club (California) to distribute marijuana for medicinal purposes, saying the government hasn't proven why seriously ill patients should be denied the drug. The groundbreaking decision of 17 July will allow the Oakland Cannabis Buyers' Cooperative to provide cannabis to members who face imminent harm from a serious medical condition and have found that legal alternatives to marijuana don't work or cause intolerable side effects. U.S. District Judge Charles R. Breyer modified an injunction he issued in 1998, noting that the U.S. 9th District Court of Appeal ordered him to consider an exemption for patients who face imminent harm and have no effective legal alternative to marijuana. (Source: AP of 17 July 2000, Reuters of 17 July 2000)

Germany

THC Pharm got the approval to provide German pharmacies with dronabinol (THC), allowing them to prepare medicaments (capsules, tinktures) from it. Dronabinol of THC Pharm costs 1,200 German Marks per gram. Until now only Marinol imported from the USA and dronabinol preparations from a pharmacy in Frankfurt have been available. German pharmacies that are interested to get dronabinol and would like to know the conditions for the storage of dronabinol are asked to contact the fabricator. E-Mail: info@thc-pharm.de. (Source: THC-Pharm)

USA

A district attorney of San Francisco (California) announced on 14 July that local sick people with 25 dollars and a doctor's note can get an official city ID card entitling them to use marijuana. Under the program, a doctor must sign a form agreeing to monitor the patient's medical condition. The cards are good for up to two years. (Source: XINHUA of 14 July 2000)