IACM-Bulletin of August 4, 2002

Science — Endocannabinoids extinguish bad memories in the brain

Researchers at the Max Planck Institute of Psychiatry in Munich (Germany) have shown that the endogenous cannabinoid system plays a central role in the extinction of aversive memories.

Transgenic mice without the brain cannabinoid receptor (CB1) and mice treated with a CB1 receptor antagonist showed strongly impaired extinction of fear in experiments. The animals that were conditioned to associate a musical tone with an electric shock, produced a fear reaction, and continued to react even when the tone was not followed by a shock. Normal mice quickly stopped reacting to the tone once it was not associated with a shock, but the treated mice needed much more time to forget their fear.

Dr. Beat Lutz and his team found out that the amygdala, an area of the brain central to storing memory and fear, was flooded with endocannabinoids, when the mice were gradually forgetting the learned response to the shock. The use of cannabis would not produce the same effect in humans, Lutz said, because it overflows the whole brain and is not specific enough.

Dr. Pankaj Sah, a neuroscientist at the Australian National University in Canberra said in a comment the latest findings may explain why some people with psychiatric problems try to find relief with marijuana. He suggested that people with certain psychiatric problems perhaps are self-medicating in an attempt to help their brains extinguish some painful or traumatic memory or thought.

(Sources: Marsicano G, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002 Aug 1;418(6897):530-4; Sah P. Neurobiology: Never fear, cannabinoids are here. Nature 2002 Aug 1;418(6897):488-9; Reuters of 31 July 2002; Seattle Times of 1 August 2002; Abstract of Giovanni Marsicano et al. at the 2002 ICRS Meeting)

Science — News at the 2002 meeting of the ICRS (I)

Below are some research results presented at the 12th Annual Symposium on the Cannabinoids of the International Cannabinoid Research Society (ICRS) from 10 to 14 July in the USA (California). (See also the next IACM-Bulletin.)

(1) Effects of cannabinoids on autoimmune diseases of the central nervous system were investigated in animal models. Autoimmune diseases of the brain and spinal chord (EAE) and of the eye (EAU) were induced in normal mice and in transgenic mice devoid of CB1 receptors. Disease progression was much faster in transgenic mice than in normal mice. Exogenous cannabinoids (THC and WIN 55,212-2) produced a significant degree of preservation of the retina in EAU. This suggests that cannabinoids may have some neuroprotective effects during multiple sclerosis. (Abstract by Gareth Pryce et al.)

(2) The possible role of endocannabinoids in the inhibition of colon cancer growth was examined in healthy and cancer tissue obtained by means of biopsy from humans. Both healthy and cancer colon tissue expressed CB1 and CB2 receptors. Anandamide and 2-AG levels in colon cancer tissues were about twice as high as in healthy colon tissue. Moreover, anandamide dose-dependently inhibited the growth of colon cancer cells, which was blocked by a CB1 receptor antagonist. (Abstract by Vinzenzo di Marzo et al.)

(3) The non-psychotropic phytocannabinoid cannabidiol (CBD) reduced inflammation and hyperalgesia in a rat model of acute inflammation. Furthermore, animals that had received CBD showed lower biochemical parameters of inflammation, a lower level in prostaglandins E2 (PGE2) in plasma, a lower activity of cyclooxygenase (COX) in the inflamed paw, and a lower content of nitric oxide and free radicals in the paw. (Abstract by Barbara Costa et al.)

(4) The daily simultaneous application of low doses of THC and morphine prevented the development of tolerance to morphine as observed with daily high doses of morphine, but yielded similar analgesic effects in mice. (Abstract by Diana C. Cichewicz and Sandra P. Welch)

(5) In glaucoma cell death in the retina may occur due to toxicity of the increasingly produced neurotransmitter NMDA. The effect of cannabinoids (CB1 agonists) on NMDA induced retinal nerve cell death in mice were investigated. Eyes treated with both the cannabinoid and NMDA retained two times the retinal nerve cells as the eyes exposed only to NMDA, demonstrating a protective effect of the cannabinoid. (Abstract by G. Ayoub et al.)

(Source: Reader of the 2002 ICRS meeting. The 182 page reader with all abstracts is available for download at

www.cannabinoidsociety.org.)

News in brief

Science — THC aerosol

An aerosol of THC was administered to mice with a metered dose inhaler (MDI) to test its physiochemical and pharmacological properties. Results showed that further development of a THC metered dose inhaler could provide an appropriate delivery device for the therapeutic use of cannabinoids. (Source: Wilson DM, et al. Drug Alcohol Depend 2002 Aug 1;67(3):259-67)

A free sample copy of the Journal of Cannabis Therapeutics and the new Journal of Industrial Hemp is available from:

Sample Copy Dept

The Haworth Press, Inc.

10 Alice Street

Binghamton, NY 13904

USA

USA — Press conference at Capitol

On 24 July members of the House of Representatives Barney Frank (Democrat), Ron Paul (Republican), Dana Rohrabacher (Republican) and Janice Schakowsky (Democrats) joined former Ronald Reagan presidential aide Lyn Nofziger and several patients in a press conference at the Capitol Hill in Washington to call on Congress to allow states to allow the medical use of cannabis. Their bill has little chance of passing Congress this year. (Source: AP of 24 July 2002)

USA — San Francisco

Frustrated by the federal government's determination to shut down medical marijuana clubs, the city of San Francisco is thinking about growing its own cannabis. A measure will be put on the November ballot that would have city officials explore the possibility of growing marijuana on publicly owned lots and distributing it to ill patients. (Sources: Associated Press of 23 July 2002, New York Times of 24 July 2002)

Science — Lung function

The effects of cannabis and tobacco use on the lung function of 900 young adults from New Zealand who were examined at the age of 18, 21 and 26 years were investigated. The effect of cumulative cannabis use on the ratio of the forced expiratory volume in one second (FEV1) and the vital capacity was marginally significant (p<0.09), while cigarette smoking (p<0.05), age (p<0.001) and weight (p<0.001) were significant predictors of lung function. (Source: Taylor DR, et al. Addiction 2002 Aug;97(8):1055-61)

Science — Apoptosis I

Ceramide was used to induce apoptosis (programmed cell death) in astrocytes (certain cells in the brain that are not nerve cells). Cannabinoids were shown to rescue astrocytes from ceramide-induced apoptosis in a dose- and time-dependent manner. (Source: Taylor DR, et al. et al. J Biol Chem 2002 Jul 19)

Science — Apoptosis II

Experiments with cell cultures and mice showed that the immunosuppressive effects of THC might in part be caused by the induction of apoptosis in immune cells. (Source: McKallip RJ, et al. J Pharmacol Exp Ther 2002 Aug;302(2):451-65)

Canada — Asylum seekers from the US

Cannabis-smoking political asylum seekers from the United States are unlikely to receive refugee status in Canada, immigration experts said on 23 July. At least three Americans (Steve Kubby, Ken Hayes and Renee Boje) living in Canada are arguing that they have been persecuted in their homeland because of their attempts to grow, cultivate, or use marijuana for medical purposes. (Source: Globe and Mail of 24 July 2002)

Science — Dexanabinol

On 24 July Pharmos Corporation received approval from the Israelian Health Ministry to clinically test dexanabinol as a preventive agent against the mild cognitive impairment that can follow heart surgery. Dexanabinol is a non-psychotropic THC derivative. Cognitive loss following heart surgery was not considered a major problem until two years ago, when a study showed that the impairment caused by a blockage of blood flow to the brain that followed the surgery was long term. (Source: Jerusalem Post of 25 July 2002)