Final Activity Report Summary - NMARIE-ERG-2004 (Characterisation and role of interactions between opioid and cannabinoid systems)
The molecular mechanisms underlying drug addiction processes are poorly understood. However, their understanding is essential both at the fundamental level (study of the functioning of the CNS (Central Nervous System) and the interconnections of neuronal networks) and at the level of public health (addictions being considered as chronic and recurrent diseases). Epidemiological data show that polyconsumption is the most habitual mode of misuse of psychoactive substances and association of different drugs may influence the establishment of an addicted state as well as the neurotoxic effects. In the understanding of addictive processes, cannabinoid and opioid system are of particular importance as they are the targets of two major drugs (cannabis and heroine respectively) and they play a major role in establishment and maintenance of addiction to other drugs (alcohol, cocaine...).
So, we initiated a study on interactions between the opioid and cannabinoid systems. We defined them in two types: direct (oligomerisation of opioid and cannabinoid receptors) or indirect (interactions between the signal transduction pathways).
Concerning the indirect interactions, we are currently characterising a cell model to study how cannabinoid receptor could induce enkephalins (endogenous ligand of opioid receptor involved in addiction processes) release. Using behavioural experiments, we found that the potentiating effect of delta-9-THC (psychoactive compound of cannabis) on opioid-mediated analgesia could involve a third partner: the cholecystokinin system underlying the complexity of addiction processes.
Considering the data we obtained, we plan to continue the characterisation of our cell model and decipher the interrelation we pointed out between cannabinoid, opioid and cholecystokinin system.
So, we initiated a study on interactions between the opioid and cannabinoid systems. We defined them in two types: direct (oligomerisation of opioid and cannabinoid receptors) or indirect (interactions between the signal transduction pathways).
Concerning the indirect interactions, we are currently characterising a cell model to study how cannabinoid receptor could induce enkephalins (endogenous ligand of opioid receptor involved in addiction processes) release. Using behavioural experiments, we found that the potentiating effect of delta-9-THC (psychoactive compound of cannabis) on opioid-mediated analgesia could involve a third partner: the cholecystokinin system underlying the complexity of addiction processes.
Considering the data we obtained, we plan to continue the characterisation of our cell model and decipher the interrelation we pointed out between cannabinoid, opioid and cholecystokinin system.