think it was worth it! We even managed not to displease the several English, French, German, Italian and Spanish soccer fans by letting Greece win the European Soccer championship (I have the feeling that the two Greek participants whom we had the pleasure to meet for the first time this year will not agree with this statement).

Anyway, it is just as well that Guy Cabral and Robyn Puffenbarger did such a good job at summarizing the scientific outcome of the conference in the last Newsletter, since I must confess that, unfortunately, this year I could only attend perhaps half of the oral and poster presentations. Yet, I have a few additional comments:

First, just some “numbers”. This year we had 92 oral communications and 150 poster presentations. Both represent an unprecedented record. This should not be surprising since the Society is rapidly growing

Headlines:

Letter from the President 1-2 Awards: Mechoulam Award 3 Student / Young

Investigator Awards 4-5 2004 Symposium: Paestum Sanofi- Aventis Banquet 6

and encompasses now many new groups that are being attracted by exciting research on the endocannabinoid system. The oral program was maybe a bit too tight, and it is possible we may have to limit the number of oral presentations. However, it must be taken into account that the ratio of oral presentations to total participants this year was lower than in previous years. In other words, if we want to have more and more participants we can’t help allowing more oral communications to be presented!

Also impressive was the number of: a) company representatives, and b) participants from countries that are “new” to the ICRS community. We had, possibly for the very first time, delegates from Turkey and South Korea (thank you very much for attending!). These two observations underlie the ever-growing interest in cannabinoid research from the

fff ooo uuu nnn ddd eee ddd iii nnn 111 999 999 111

ICRS President: Vincenzo Di Marzo

President-Elect:

Daniela Parolaro

Past President: Guy Cabral

Secretary:

Patricia Reggio

Treasurer: Jenny Wiley

International Secretary:

Roger Pertwee

Executive Director: Richard Musty

L e t t e r f r o m t h e P r e s i d e n t

Continued on p.2

Newsletter of the

International Cannabinoid

Research Society

W i n t e r 2 0 0 4

Dear ICRS Members,

I am very happy to be able to address you all finally, only now due to a small delay in our Newsletter publication schedule. First, just a few personal comments on the past ICRS meeting in Paestum, in addition to the nice and exact account of our Past President, Guy Cabral, in the last newsletter. It was for me a breathtaking, exhausting and, eventually, extremely gratifying experience. We had never had such a huge and international attendance at any of the previous meetings. Neither I, nor Diane Mahadeen or Rik Musty or the other members of the local organizing committee, could have foreseen that over 450 people including delegates and accompanying persons, would have attended. Nor could we predict how much work all this would have taken (quite naively I thought that most of the work was done once we got to the day before the beginning of the meeting). But, I must tell you, that, judging from your enthusiasm, your clear enjoyment of both the scientificand social programs, and what we could see later of your overall final impression of the four days, we all

V i n c e n z o D i M a r z o

V o l u m e 1 4 , N u m b e r 2

pharmaceutical industry, and the ever-growing international character of the Society, once comprised of mostly US members. Both of these aspects are extremely important, not only because it will likely result in the possibility of having well sponsored conferences all over the world, but also because they indicate that our field, although still strongly linked with many different others - the opiate, nicotine, alcohol, bioactive lipid and vanilloid receptor fields, just to name a few - is finally entering an exponential growth phase. With the first cannabinoid receptor-based pharmaceuticals expected to appear soon on the market, we can foresee these developments for many years to come. This will also allow the Society to gain position similar to that of other important Societies, with even more scientific independence but without forgetting our origins.

As a consequence of the above points, this year we had many more topics than usual to discuss. The ”historical” themes very well represented, with important news regarding, for example, the possible therapeutic exploitation of cannabinoid receptor agonists, antagonists and inhibitors of endocannabinoid degradation, in particular in cancer therapy and neurodegenerative disorders. More avant-garde communications dealt with the possible targeting of osteoporosis and liver cystic fibrosis. Finally, there were a surprisingly large number of studies examining non-psychotropic cannabinoids. Cannabidiol, above all, received much attention, thus indicating that our scientific community is not going to overlook any possibility to devise new therapeutic drugs from the cannabinoids and their endogenous counterparts. Basically, all aspects were covered to some extent - including evolution!

Finally, we had, for the first time, the “Controversial Issue” poster sessions. This was the result of a specific request from the Students’ Committee, to whom I think we should all be very grateful for this innovative idea. The two sessions were a great success, and, for these, we have to

thank all the poster presenters who actively participated. I strongly believe that this “experiment” should be repeated during the forthcoming meetings, possibly by allowing more time (perhaps a full hour instead of half an hour) but keeping the same format, which, and this is just my personal opinion, results in more “heated” discussions and more participation from the audience than a traditional session with oral communications.

In my opinion, the Conference was scientifically up to our standards, maybe not the most exciting ever (too many distractions from…the location of the venue?), but still full of very promising “novelties”. Let me mention just a few. On the “signaling” side, the work of Kearn et al. (p.16 on the abstract book) on the ever growing complexity of the CB1 receptor four-dimensional structure, or the findings by Niehaus et al. (p.18) and Elphick et al. (p.19) and Breivogel (p.21), who described proteins associating with cannabinoid receptors, as well as the differences between humans and rodents. On the subject of “endocannabinoid metabolism”, it seemed quite interesting to me the new findings on the biosynthesizing enzymes by Okamoto et al. (p.9) and Bisogno et al. (p.10). Perhaps I am not being very objective when I point out the interactions between vanilloids and cannabinoids, as described in the abstracts by Sala et al., Costa et al. and van der Stelt et al. (pgs.24-26). And, speaking of interactions, what about CB2 receptors in the skin, whose activation, as described by Malan et al. (p.52), reduces nociception by stimulating the release of endorphins? Finally, I was impressed by the osteoporosis studies presented by Bab et al. (p.74) and Karsak et al. (p.75), and by the suggestion that both CB2 agonists and CB1 antagonists may be able in the future to ameliorate chronic liver disorders (Grenard et al., p.60; Julien et al., p.220); by the possible neuro-protective role of CB2 agonists in a model ofHuntington’s disease (Sagredo et al., p.171); by new data pointing to a cross-talk between CRH and CB1 (Hermann et al., p.166); by the effect of cannabidiol on

Continued from p.1

2

beta-amyloid-induced neurotoxicity (Esposito et al., p.46), or by the involvement of the endocannabinoid system in HIV-1-induced neuronal apoptosis (Bari et al. p.172); and by many, many other innovative ideas andconcepts that have emerged from this meeting, and which cannot be all mentioned here.

Finally, on different note, Daniela Parolaro - another Italian scientist and early ICRS member - was elected to become President starting from the endof next year’s conference (“another Italian?” some will say). Let me reassure you that it is not our intention to start an “Italian Connection,” to quote an old mob movie. And also for this reason, we are holding the XV annual meeting in Clearwater, Florida. The meeting will take place from the 24th to the 27th of June, 2005. We now have the difficult job to contribute of making it a success at least as big as the latest conference. The first challenge will be to keep the high number of new members that we were fortunate to have in 2004, and the second will be to attract to beautiful and sunny Florida all of you and, why not, possibly even new members. We shall not be able to succeed without your continuing support and enthusiastic participation, for both of which I am very grateful. The last challenge will beto have food as good as in Paestum (which, if I may remind you, has nothing to do with the world famous “Pesto” sauce). However, I am sure that even the local organizers will agree that we do not have much hope of succeeding in such a task. It will not matter too much, since the outstanding science of our members is able to compensate even for the loss of Italian food.

I wish all of you a peaceful and cheerful Holiday season, and hope to

see you in Clearwater!

V i n c e n z o

cannabinoid antagonist SR141716, the structure of which was first disclosed at the 1994 ICRS Meeting in L'Esterel, Canada. This compound was largely distributed in the cannabinoid research community and proved to be a valuable tool for biochemists and pharmacologists trying to understand the physiological role of the endocannabinoid system.

Pharmacological studies later showed that the compound selectively decreased the intake of sweet and fat food in several animal species and decreased body weight in pharmacological models of obesity in rodents. Under the name rimonabant, SR141716 was engaged in several clinical trials for the treatment of obesity and for smoking cessation. The first results of the Phase III trials were published earlier this year,a and appear to be very encouraging. encouraging.

In 1997, Murielle and a Francis discovered another p pyrazole derivative, 1 SR144528, which was r the first CB2 selective n cannabinoid receptor t antagonist. SR144528 was no notably used to elucidate th the role of the CB2 e receptors in immune f d function and peripheral a pain mechanisms. Since 9 1992 they have published ab about 10 papers in the field of cannabinoids and have filed nearly 20 patentapplications disclosing structurally novel CB1 and CB2 antagonists and agonists.

Within the newly created group Sanofi-Aventis, they both continue their research in the cannabinoids in the search for new drugs based on the modulation of the cannabinoid system. Long-time members of the ICRS, Murielle and Francis co-chaired the Organizational Committee for the widely attended 1998 Symposium in La Grande Motte, France.

Paestum, Italy — The fifth annual Mechoulam Award for outstanding contributions to the cannabinoid field by senior scientists was given to Murielle Rinaldi-Carmona and Francis Barth by Raphael Mechoulam at a special roundtable session entitled: CB1 Receptor Agonists as New Therapeutic Drugs.

Murielle was trained as a Biochemist at the University of Montpellier, France, where she received her Ph.D. in 1981, working on the modulation of cardiac slow calcium channel. She then joined Sanofi Recherche, working successively in the cardiovascular and exploratory research departments. In charge of the 5HT2 receptor program for several years, she initiated the cannabinoid program in 1990.

Francis was trained as an Organic Chemist at the University Louis Pasteur in Strasbourg, France. He received his Ph.D. in 1988, working on the synthesis of terpenoid like compounds. He then spent two years at Syntex Research in Palo Alto, California as a post-doctoral fellow, working on radical chemistry and the synthesis of new fluorinated carbocycles. He joined Sanofi Recherche in Montpellier in 1991, where he started the cannabinoid program together with Murielle.

Using both in vitro binding screening techniques and chemical lead optimization, they developed the first selective CB1

Sanofi Scientists Win Mechoulam Award

Murielle Rinaldi-Carmona Francis Barth Raphael Mechoulam

Executive Newsletter Editor: Brian Thomas

Newsletter Editor: Diane Mahadeen

Layout and Design Editor: Jason Schechter

Editorial Assistants: Richard Musty Roger Pertwee

Nicole Schechter Jason Schechter

Photographers: Lou Deutsch Fred Gardner

Deborah Lewis

Home Web Site: http://cannabinoidsociety.org

Webmaster: Jason Schechter

Office eMail: ICRS@cannabinoidsociety.org

Office Telephone: 802.656.4189

Office FAX: 802.656.8783

Office Mailing Address: ICRS, Diane Mahadeen

55 Elsom Pky. So. Burlington, VT 05403

USA

ICRS Corporate Address: Department of Psychology

John Dewey Hall University of Vermont Burlington, VT 05405

USA

Corporate Office Contact: Diana St. Louis

Office Phone: 802.656.2670 Office Fax: 802.656.8783

eMail: Diana.St.Louis@uvm.edu

U.S. Federal ID Number 03-0345758

3

By Diane Mahadeen

SR141716

Darren Fegley (not pictured) is a predoctoral student from the University of California, Irvine, working on endocannabinoid degradation. His poster presentation was titled “Anandamide transport is independent of FAAH activity and is blocked by the hydrolysis resistant inhibitor AM1172.” Darren plans to finish his Ph.D. in the Spring of 2005. Natalia Battista, a predoctoral student from University of Rome "Tor Vergata," is working on the interactions of the endocannabinoid and dopaminergic systems in the central nervous system. Her poster presentation was titled “Interactions between dopamine D2 receptors and endocannabinoids mediate the effects of cocaine in the striatum.” Natalia plans to finish her Ph.D. this year.

Guadalupe Soria Rodriguez, a predoctoral student from Universidad Pompeu Fabra, Barcelona, is working on the relationship of the endocannabinoid system with addiction to drugs of abuse. Her poster presentation was titled “Lack of CB1 cannabinoid receptor impairs cocaine-seeking behavior.” Guadalupe plans to finish her Ph.D. in 2005.

Paestum, Italy — Five postdoctoral students and 10 predoctoral students were given $200 awards in recognition for ScientificAchievement at this year’s meeting. A Judging Committee comprised of Chair Cecilia Hillard, Tiziana Bisogno, Chris Fowler, Michelle Glass, George Kunos, Mauro Maccarrone, Brian Thomas and Michael Walker rated presentations on scientific merit, originality, quality of Power Point slides or posters, as well as a student’s ability to field questions from the audience.

15 Students Receive Scientific Achievement Awards

•

•

•

Jason Niehaus, a predoctoral student in the lab of Deborah Lewis at the Medical College of Georgia, was recognized for his oral presentation, "CRIP1a and CRIP1b: Novel CB1 Cannabinoid Receptor Inter- acting Proteins." He plans to apply for a post-doctoral position upon completion of his graduate training.

Silvia Ortega-Gutiérrez’s oral presentation was titled “Anandamide uptake inhibition as therapeutic approach in a a murine model of multiple sclerosis.” She obtained her Ph.D. degree under the guidance of Prof. María L. López- Rodríguez in Universidad Complutense de Madrid. Her work has been focused on the synthesis of anandamide uptake inhibitors as a possible therapeutic strategy for the treatment of neurodegenerative diseases such as multiple sclerosis. She plans to apply for a postdoctoral position in the U.S. next year.

Erica Carrier is a predoctoral student working under the guidance of Dr. Cecilia Hillard at the Medical College of Wisconsin. She was recognized for her oral presentation, "Inhibition of microglial proliferation by the plant-derived cannabinoids THC and CBD."

• •

•

•

• •

4

Christopher Kearn is currently a Senior Fellow in the Department of Anesthesiology at the University of Washington. Some of his investigations involve the signal transduction of cannabinoid receptors, which resulted in his oral presentation “Physical Interactions of CB1 Cannabinoid and D2 Dopamine Receptors.” Chris will continue his work in the cannabinoid field as a Research Assistant Professor in his department.

Isabel Matias, a postdoctoral student from the Endocannabinoid Research Group, Istituto di Chimica Biomoleculare, Pozzuoli, Italy, was recognized for her oral presentation, “Occurence and Biological Role of the Endocannabinoid System in Ciona intestinalis.” She plans to continue her post doctorate with the same group.

Yehoshua Maor, a predoctoral student at the Hebrew University, Jerusalem, works on the vascular activity of novel cannabinoids in the laboratory of Professor Raphael Mechoulam. His oral presentation was titled “Atypical cannabinoids and their role as blood pressure regulators.” Yehoshua plans to finish his Ph.D. in December of 2005 and then apply for a post-doctorate position in the U.S.

Alessia Ligresti, a pre-doctoral student from University of Naples, is working on the involvement of cannabinoids in cancer therapy. Her oral presentation was titled “Effect of plant Cannabinoids on cancer cell proliferation.” She is completing her doctorate working at Istituto di Chimica Biomolecolare in the lab of Dr. Vincenzo Di Marzo and plans to remain in the cannabinoid field.

Marta Valenti from Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, C.N.R., Pozzuoli, Italy, won her

15 Students Receive Scientific Achievement Awards

Pascale Grenard, postdoctoral fellow at INSERM U581, Créteil, France, is a newcomer in the cannabinoid field. She is working on the role of the endocannabinoid system in liver fibrosis. Her oral presentation was titled ”Reduced liver fibrosis in mice invalidated for CB1 receptor.”

Monica Bari, a postdoctoral student from the University of Rome "Tor Vergata," is examining the role of the endocannabinoid system in HIV induced apoptosis in the central nervous system. Her poster presentation was titled “Involvement of the endocannabinoid system in neuronal apoptosis induced by HIV-1 coat glycoprotein gp120.” Monica plans to continue her work with the endocanna-binoid system in Rome.

Wing-Sze Vanessa Ho was recognized for her poster presentation, “The Effect of CB1 Receptor Activation on Hyperemic Response Induced by Whisker Stimulation.” Vanessa is a post-doctoral student working in the lab of Dr. Cecilia Hillard at Medical College of Wisconsin and plans to remain in the field of cannabinoid and cardiovascular pharmacology.

Natalya Kogan is a Ph.D. student from the Hebrew University, Jerusalem, under the supervision of Prof. Raphael Mechoulam. She is working on novel anticancer activities of cannabinoids. Her poster presentation was titled “Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.” Natalya plans to finish her Ph.D. in 2006 and apply for post doctorate positions in the U.S. or Europe.

•

•

•

award for the presentation of “Endocannabinoids control feeding in carassius auratus.”

•

•

•

•

•

•

•

•

•

• •

5

•

Paestum, Italy — Thanks to the generosity of Sanofi-Aventis, the 14th Annual Symposium on the Cannabinoids culminated in a spectacular gala banquet on the beautiful garden lawns of the Hotel Meridiana. Over 400 attendees and social registrants were treated to a five-course feast of local specialties, wines, and of course, Limoncello, for which the region is known. A fabulous dance band played well into the night. We owe a debt of gratitude to Gérard Le Fur, as well as to Banquet Organizer Nathalie Aru, for a most memorable evening. Luciano De Petrocellis Adriana Oliviero-Di Marzo Dan Malone Leonora Long Vincenzo Di Marzo Nathalie Aru Diane Mahadeen Robyn Puffenbarger

Maurizio and Magda Bifulco

6

2005 ICRS Symposium June 24 – 27, 2005 Hilton Clearwater Beach Clearwater, Florida USA

•

•

Sponsors Banquet Dinner

Marco Landi Barbara Costa Fabio Guagnini

Luciano De Petrocellis Adriana Oliviero-Di Marzo Vincenzo Di Marzo Nathalie Aru Diane Mahadeen

Magali Gary-bobo Gérard Le Fur Nathalie Aru