Excessive activation of the cannabinoid type-1 receptor (CB1) in the brain by synthetic, endogenous or plant-derived
(cannabis sativa) cannabinoids can lead to pathological states, which could be ameliorated by blocking receptor signalling.
However, due to the large number of functions involving the CB1 receptor, direct CB1 antagonist drugs induce side effects
limiting their therapeutic use. During the ERC-StG funded project, we found that a particular endogenous and labile lipid
compound, pregnenolone, acts as an allosteric and signal-specific inhibitor of CB1 receptors in the brain. Thus, stable
pregnenolone-derivative drugs have been produced to exploit the therapeutic potential of allosteric inhibition of CB1 receptor
signalling, which can be used to decrease pathological over-activation of CB1 receptors. One clear pathological state where
over-activation of CB1 receptors plays a key role is schizophrenia and psychotic syndromes. Indeed, cannabis and synthetic
cannabinoids can induce psychotic states and excessive CB1 receptor signalling has been proposed to participate in the
etiopathogenesis of human schizophrenia. Thus, the present project aims at establishing the innovative and commercial
potential of this new class of drugs, stable derivatives of pregnenolone, as allosteric inhibitors of the CB1 receptor for the
treatment of psychotic syndromes.
The following issues will be addressed:
1. Technical activities will identify the compounds with the best therapeutic potential.
2. Market studies will determine the potential competitiveness of these compounds.
3. Additional industry partnerships will be sought for later stages of commercial development.
By covering these essential steps bridging a scientific idea from basic research to therapeutic applications, the present
project is fully integrated in the spirit of the ERC PoC program and, if successful, will provide key medical, economical and
societal benefits to Europe.
Field of science
- /social sciences/economics and business/business and management/commerce
- /medical and health sciences/clinical medicine/psychiatry/schizophrenia
Call for proposal
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