ArticleAutophagy2016
Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Cannabinoid tolerance relies on CBProceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Development and characterization of endolysosomal trafficking targeting chimera degraders of αJournal of advanced research · 2026Article
- Anticancer drug development against ribosome synthesis and the nucleolus.Biochemical Society transactions · 2025Article
- Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer.Oncology research · 2025Article
- Exercise-activated hepatic autophagy via the FN1-α5β1 integrin pathway drives metabolic benefits of exercise.Cell metabolism · 2023Article
- Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running.International journal of molecular sciences · 2023Article
- Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases.Frontiers in cell and developmental biology · 2022Review
- Renal Cellular Autophagy in Obesity: Boon or Bane?Seminars in nephrology · 2021Review
- Article
- An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system.Science advances · 2021Article
- A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease.PLoS genetics · 2017Article
- Regulation of Exercise-Induced Autophagy in Skeletal Muscle.Current pathobiology reports · 2017Article
- Activating Autophagy by Aerobic Exercise in Mice.Journal of visualized experiments : JoVE · 2017Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases. The pathogenic mechanisms of cannabinoid tolerance are not fully understood, and little is known about its prevention. Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids. To target BECN2 therapeutically, we established a competitive recruitment model of BECN2 and identified novel synthetic, natural or physiological stimuli of autophagy that sequester BECN2 from its binding with GPRASP1, a receptor protein for CNR1 degradation. Co-administration of these autophagy inducers effectively restores the level and signaling of brain CNR1 and protects mice from developing tolerance to repeated cannabinoid usage. Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.