Anti-obesity therapy with peripheral CB1 blockers: from promise to safe(?) practice.

1. Int J Obes (Lond). 2020 Nov;44(11):2179-2193. doi: 10.1038/s41366-020-0577-8.
Epub 2020 Apr 21.

Anti-obesity therapy with peripheral CB1 blockers: from promise to safe(?)
practice.

Quarta C(#)(1)(2), Cota D(#)(3)(4).

Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U1215, F-33000, Bordeaux, France. .
(2)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, U1215, F-33000, Bordeaux, France.
.
(3)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U1215, F-33000, Bordeaux, France. .
(4)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, U1215, F-33000, Bordeaux, France. .
(#)Contributed equally

Pharmacological blockers of the cannabinoid receptor type-1 (CB1) have been
considered for a long time as the holy grail of obesity pharmacotherapy. These
agents were hastily released in the clinical setting, due to their clear-cut
therapeutic efficacy. However, the first generation of these drugs, which were
able to target both the brain and peripheral tissues, had serious
neuropsychiatric effects, leading authorities to ban their clinical use. New
peripherally restricted CB1 blockers, characterized by low brain penetrance,
have been developed over the past 10 years. In preclinical studies, these
molecules seem to overcome the neuropsychiatric negative effects previously
observed with brain-penetrant CB1 inhibitors, while retaining or even
outperforming their efficacy. The mechanisms of action of these peripherally
restricted compounds are only beginning to emerge, and a balanced discussion of
the risk/benefits ratio associated to their possible clinical use is urgently
needed, in order to avoid repeating past mistakes. Here, we will critically
discuss the advantages and the possible hidden threats associated with the use
of peripheral CB1 blockers for the pharmacotherapy of obesity and its associated
metabolic complications. We will address whether this novel pharmacological
approach might ‘compete’ with current pharmacotherapies for obesity and
diabetes, while also conceptualizing future CB1-based pharmacological trends
that may significantly lower the risk/benefits ratio associated with the use of
these drugs.

DOI: 10.1038/s41366-020-0577-8
PMID: 32317751 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus