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Opiates and cannaboids the fight against pain


Opiates and cannaboids, apart from being drugs, have curative properties. Thus, opiates (morphine, methadone, etc.) have been used for some time as a pain-reducer and many cannaboids have also analgesic properties.

Regarding their curative aspects, it is very important to know the effects produced after a prolonged period of treatment. Carrying out this analysis with opiates and cannabinoids, two important problems arise: given that they are drugs, they create psychological dependency and, in the long term, physical dependency and tolerance appears.

Psychological dependency involves the need to consume the drug while physical tolerance, on the other hand, means a cellular adaptation. Apart from the two dependencies, however, the tolerance effect is of great importance, for example in the case of pain. Tolerance appears when the drug loses its effect, i.e., when the body gets used to the medication, and then the pain-killing process begins to disappear. Thus, in order to achieve the same effect, to eliminate pain, the dose to be supplied to the patient has to be greater.

The hypothesis of a solution

According to a research team at the Pharmacy Faculty at the Basque University at Leioa (Bizkaia) Campus, one of the keys to the problem presented by opiates and cannabinoids could lie in nitric oxide. Nitric oxide is a neurotransmisor found in the brain in gaseous form. According to the hypothesis, if nitric oxide inhibitors are supplied together with the opiates and cannabinoids, the therapeutic effect is maintained and, moreover, the dependence on and tolerance to the narcotic can be avoided.

A number of results have confirmed this hypothesis; but the conclusions are not so clear-cut. For example, nitric oxide inhibitors have been shown to partially minimise tolerance but, at the same time, they increase blood pressure, because the inhibitors do not act only on the brain and so they have side reactions. This is why researchers are currently trying to find inhibitors which are specific for the brain.

Opiates have been around for some time, but cannabinoids when?

The research being carried out at Leioa is, in many aspects, innovative. Given that, although opiates have been used and studied for a long time, its mechanism of operation is still unresolved; with cannabinoids, very few studies have been carried out.

This is why the Leioa group will also carry out the greatest part of their research on the opiates, more specifically on morphine. They will analyse the effects of nitric oxide inhibitors on neuronal activity and its effect on pain. To this end, they will analyse neuronal activity at different parts (locus coeruleus and spinal medula) and, by measuring brain reflexes, they will find out if pain is felt more acutely or less so. Moreover, the reserve of receptors will be measured and their pharmacodynamic characteristics will be evaluated.

The final tests will be carried out with the cannabinoids. Their effect on the locus coeruleus will be assessed so that a subsequent measurement of the tolerance to this effect can be made.


Main researcher: Joseba Pineda Ortiz
Research-team: Mª I. Ulibarri, M. Torrecilla, M. Santamarta, A. Mendiguren, J. Llorente
Department: Pharmacology
Faculty: Medicine and Odontology Faculty (Leioa)

Garazi Andonegi | Basque research
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