Genetic analysis identified the PDE4B gene and the enzyme hyaluronidase as promising drug repurposing targets for cannabis use disorder.
Pharmacogenomics researchers, addiction medicine specialists, and drug development scientists.
1 in 5 cannabis usersmay develop cannabis use disorder, yet no effective pharmacological treatments currently exist
What the researchers found
The phosphodiesterase gene PDE4B emerged as a prioritized target for drug repurposing in CUD, with credible causal variants also associated with inflammatory and other substance use phenotypes.
Why it matters
Cannabis use disorder affects up to one in five adult cannabis users and has no effective pharmacological treatments. Repurposing existing drugs could accelerate treatment availability.
The numbers in context
CUD affects up to 1 in 5 adults who use cannabis. PDE4B identified through gene-level aggregation. NPTX1 identified as a novel CUD-associated gene in blood. Genetic overlap found with lymphocyte count and serum triglycerides.
How the study worked
Genomic analysis combining gene-level variant aggregation, probabilistic fine-mapping, transcriptomic/proteomic integration with GWAS data, and genetic correlation with biochemical traits.
Who was studied
Genome-wide association study data from cannabis use disorder cases and controls (population not specified in detail in abstract).
What this study cannot tell us
Genetic associations do not guarantee that drug targeting will be effective clinically. Population studied may not represent all ancestries. Drug repurposing candidates require clinical validation.
How to read the evidence
Genomic analysis provides hypothesis-generating evidence; identified targets require preclinical and clinical validation.
When this study was published
Recent genomic study leveraging current GWAS data and bioinformatics approaches.
The bigger picture
This precision medicine approach demonstrates how existing genetic data can be leveraged to identify new treatment strategies, connecting CUD to immune system pathways and potentially shared biology with other substance use disorders.
Replication
Genomic findings are hypothesis-generating; clinical trials needed to validate drug targets.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Could PDE4B inhibitors already in development for other conditions be tested for CUD?
- What role does neuroinflammation play in the development and maintenance of cannabis use disorder?
Read the original research
Exploring opportunities for drug repurposing and precision medicine in cannabis use disorder using genetics.
Addiction biology, 28(8), e13313
Citation
Greco, Laura A; Reay, William R; Dayas, Christopher V; Cairns, Murray J. (2023). Exploring opportunities for drug repurposing and precision medicine in cannabis use disorder using genetics.. Addiction biology, 28(8), e13313. https://doi.org/10.1111/adb.13313