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IACM-Bulletin of 12 April 2009

Science: THC induces autophagy in human brain cancer cells

Spanish researchers were able to demonstrate that the cannabis compound THC (dronabinol) induces death of human brain cancer cells through stimulation of autophagy. They also showed that autophagy happens before apoptosis, a form of programmed cell death, in dronabinol-induced cancer cell death and that this cell reaction was necessary for the anti-tumour action of cannabinoids in animals. "Our findings support that safe, therapeutically efficacious doses of THC may be reached in cancer patients," Guillermo Velasco of Complutense University in Madrid and colleagues reported in their article for a scientific journal.

The term "autophagy" from Greek means literally "self-eating". Autophagy can promote cell death, but the exact mechanisms underlying its role in cancer remains unclear. It involves the degradation of a cell's own components and plays a normal role in cell growth and development, helping to maintain a balance between synthesis and degradation of cellular products. The most well-known mechanism of autophagy involves the formation of a membrane around a region of the cell, separating the contents from the rest of the cell content, which is then degraded. Autophagy may play a role in the battle against cancer and in the defence of infections.

(Source: Salazar M, Carracedo A, Salanueva IJ, Hernández-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, Nowak J, Fimia GM, Piacentini M, Cecconi F, Pandolfi PP, González-Feria L, Iovanna JL, Guzmán M, Boya P, Velasco G. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009 Apr 1. [Electronic publication ahead of print])

News in brief

USA: Michigan
On 6 April the state of Michigan started to accept applications for its medical cannabis program. Medical conditions that qualify for the new program include cancer, glaucoma, HIV/AIDS, Hepatitis C, Crohn's disease, severe and chronic pain or nausea, seizures and spasticity. The state issues identification cards for these patients. In November 2008 voters decided Michigan should join twelve other states to allow the medical use of cannabis. (Source: Detroit News of 7 April 2009)

Spain: Mallorca
Doctors on Mallorca should be able to prescribe to their patients cannabis for therapeutic purposes. On 7 April the parliament of the Baleares voted in favour of this issue with a large majority. It is intended first to evaluate results of pilot projects in other regions of Spain. The decision of the regional parliament of the Baleares is possible because the responsibility for the health system has been passed on to the regional government by the central government. (Source: mallorazeitung.es of 9 April 2009)

Science: New cannabinoids
Nine new cannabinoids were detected in a cannabis variety with a high dronabinol content by researchers of the University of Mississippi, USA. Two of them belong to the cannabichromene type (CBC), one to the cannabigerol type (CBG) and two to the cannabinol type (CBN) of cannabinoids. One of the new CBN type cannabinoids (8-hydroxycannabinol) and another cannabinoid displayed significant antibacterial activities. The number of cannabinoids ever detected in cannabis now increases to about 80. (Source: Radwan MM, et al. J Nat Prod. 2009 Apr 3. [Electronic publication ahead of print])

Science: Systemic sclerosis
According to research at the University of Erlangen, Germany, a synthetic CB2 receptor agonist reduced dermal thickening and fibrosis, which was induced by a chemical (bleomycin). Researchers noted that "CB2 might be an interesting molecular target for the treatment of early inflammatory stages of systemic sclerosis." (Source: Akhmetshina A, et al. Arthritis Rheum 2009;60(4):1129-36.)

Science: Stroke
In an animal model of stroke a CB2 receptor agonist reduced the consequences of reduced blood supply to the brain. Neurological function was improved compared to a control group. This protective effect was attributed to the attenuation of dysfunction of the smallest brain arteries. (Source: Zhang M, et al. Microvasc Res. 2009 Mar 27. [Electronic publication ahead of print])

Science: Diabetes
South African researchers investigated the effects of a cannabis extract on insulin sensitivity in insulin resistant fat cells. Insulin-resistance, i.e. failure of cells to uptake glucose (sugar) despite the presence of insulin, was induced using TNF-alpha. Insulin-induced glucose uptake was increased in these cells after exposure to the extract, which suggests an anti-diabetic effect of the cannabis extract. (Source: Gallant M, et al. Phytomedicine. 2009 Apr 1. [Electronic publication ahead of print])

Science: Positive affective memory
According to research at the University of Oxford, UK, a single dose of the CB1 receptor antagonist rimonabant did not alter subjective mood in 30 study participants. However, rimonabant selectively reduced recall of positive self-relevant information, an effect contrary to that seen following the administration of antidepressants. Researchers concluded that "these results suggest that a single dose of rimonabant decreases positive emotional memory." (Source: Horder J, et al. Psychopharmacology (Berl). 2009 Apr 1. [Electronic publication ahead of print])

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