Cannabis has a long history of use as medicine, with historical evidence dating back more than 4000 years. The potential therapeutic benefits of cannabinoid compounds are huge, but this substance can also have negative effects. A recent paper by Andrés Ozaita and colleagues at the Neurophar laboratory of Rafael Maldonado (CEXS-UPF) has given new insights into the molecular mechanisms that underlie cannabinoid-mediated effects.
Using mice as a model system, the authors had previously shown that blocking the mTOR pathway prevented the amnesic-like effects of THC (a synthetic form of cannabinoid). In the present study, published in the journal Neuropsychopharmacology, they have gone further, proving that the inhibition of the mTOR pathway by the rapamycin derivative temsirolimus, prevents both the anxiogenic- and the amnesic-like effects produced by acute THC, but has no effect on THC-induced anxiolysis, hypothermia, hypolocomotion, and antinociception (lack of pain perception).
Therefore, treatment with temsirolimus could segregate the potentially beneficial effects of cannabinoid agonists, such as the decrease of pain and anxiety, from the negative effects, such as amnesia and an increase of anxiety. As the authors say, these results could help targeting the endocannabinoid system in order to prevent possible side effects.
Puighermanal E, Busquets-Garcia A, Gomis-González M, Marsicano G, Maldonado R, Ozaita A. Dissociation of the Pharmacological Effects of THC by mTOR Blockade. Neuropsychopharmacology. 2013 Jan 28;
Drug abuse and emotional disorders, such as anxiety and depression, are generating a serious social problem. This is why Rafael Maldonado’s neuropharmacology group at the CEXS-UPF studies the common biological mechanisms involved in these two phenomena. They focus particularly in nicotine, cannabis, cocaine and ecstasy, and in the possible mechanisms underlying the abusive consume of these substances.
Maldonado explains there are three factors to understand why some people become addictive and others don’t: drug consume (the quantity, the frequency, the mode); social and environmental factors; and individual vulnerability, which includes genetic factors. A classical example of the effect of the environment is how the American marines that were heroin addicts in Vietnam quitted easily once back at home.
In order to understand addiction and emotional disorders, the group, formed by 29 people, uses different techniques: classical pharmacological strategies, using compounds that act on the nervous system receptors; ‘knock-out’ mice in which a specific gene has been deleted in order to understand its function; and animal models for behaviour studies which, according to Maldonado, are very complex but once they are established they allow a good prediction of what can happen in humans.
Maldonado highlights the discovery that specific components of the endogenous opioid system are a common substrate for different addictive behaviours as a major contribution of his group. His dream: that this knowledge gives rise to effective treatments for the addicts, who are people with a chronic disease, emphasizes the researcher.
This article was published in the El·lipse publication of the PRBB.
Effects of cannabis at the hippocampus
In this image provided by Emma Puighermanal (Neuropharmacology lab, UPF) and obtained by Xavier Sanjuan, from the microscopy service of the UPF, shows a cut of the hippocampus of a mouse. It has been labelled against the kinase p-p70S6K (red), the dendritic marker MAP2 (blue) and the cannabinoide receptor CB1 (green). After administering Δ9-tetrahidrocannabinol (THC), the main psychoactive component of marijuana, the signalling pathway for mTOR/ p70S6K is activated in the hippocampus. This pathway is responsible for the amnesic effects of cannabis.