Abstract
Alcohol use disorder (AUD) is a public health issue that affects millions of people worldwide leading to physical, mental and socio-economic consequences. While current treatments for AUD have provided relief to individuals, their effectiveness on the long term is often limited, leaving a number of affected individuals without sustainable solutions. In this review, we aim to explore two emerging approaches for AUD: psychedelics and epigenetic drugs (i.e., epidrugs). By examining preclinical studies, different animal species and procedures, we delve into the potential benefits of each of these treatments in terms of addictive behaviors (alcohol drinking and seeking, motivation to drink alcohol and prevention of relapse). Because psychedelics and epidrugs may share common and complementary mechanisms of action, there is an exciting opportunity for exploring synergies between these approaches and their parallel effectiveness in treating AUD and the diverse associated psychiatric conditions.
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Abbreviations
- 18-MC:
-
18-Methoxycoronaridine (a potential treatment for opioid addiction)
- 4-phosphoryloxy-N,N-dimethyltryptamine:
-
This is the chemical structure or full name for DMT
- 5-HT:
-
5-Hydroxytryptamine (serotonin)
- 5-HT2a:
-
5-Hydroxytryptamine 2A (a subtype of serotonin receptor)
- 5-HT2aR:
-
5-Hydroxytryptamine 2A Receptor
- ADP:
-
Adenosine diphosphate
- AMPA:
-
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- B-caapi:
-
Banisteriopsis Caapi (a plant used in ayahuasca preparation)
- BDNF:
-
Brain-derived neurotrophic factor
- BLA:
-
Basolateral amygdala
- CA1:
-
Cornu ammonis 1 (a region of the hippocampus)
- CBP:
-
CREB-binding protein
- CeA:
-
Central amygdala
- CNS:
-
Central nervous system
- cFos:
-
Cellular oncogene Fos
- CREB:
-
CAMP response element-binding protein
- CpGs:
-
Cytosine-phosphate-Guanine sites (DNA methylation)
- DBS:
-
Deep brain stimulation
- DMT:
-
Dimethyltryptamine
- dmPFC:
-
Dorsal medial prefrontal cortex
- DOI:
-
2,5-Dimethoxy-4-iodoamphetamine
- DNA:
-
Deoxyribonucleic acid
- DNMT:
-
DNA methyltransferase
- DOM:
-
2,5-Dimethoxy-4-methylamphetamine
- DOI:
-
2,5-Dimethoxy-4-iodoamphetamine
- Egr2:
-
Early growth response 2
- EMA:
-
European Medicines Agency
- Epidrugs:
-
Epigenetic drugs (drugs that target epigenetic modifications)
- ERK:
-
Extracellular signal-regulated kinase
- FDA:
-
U.S. Food and Drug Administration
- GABA:
-
Gamma-aminobutyric acid
- GABRA1:
-
Gamma-aminobutyric acid type A receptor subunit alpha 1
- GDNF:
-
Glial cell-derived neurotrophic factor
- GRIK3:
-
Glutamate ionotropic receptor kainate type subunit 3
- GRIN2C:
-
Glutamate ionotropic receptor NMDA type subunit 2C
- Grm2:
-
Metabotropic glutamate receptor 2
- HAT:
-
Histone acetyltransferase
- HDAC:
-
Histone deacetylase
- I.V.:
-
Intravenous
- KO-R:
-
Kappa opioid receptor
- LSD:
-
Lysergic acid diethylamide
- LTD:
-
Long-term depression
- LTP:
-
Long-term potentiation
- MDMA:
-
3,4-Methylenedioxymethamphetamine (commonly known as ecstasy or molly)
- MeA:
-
Medial amygdala
- mGluR2:
-
Metabotropic glutamate receptor 2
- mGluR3:
-
Metabotropic glutamate receptor 3
- mRNA:
-
Messenger RNA
- NaB:
-
Sodium butyrate (a histone deacetylase inhibitor)
- NAC:
-
Nucleus accumbens
- NMDAR:
-
N-methyl-d-aspartate receptor
- Npy:
-
Neuropeptide Y
- NP-rats:
-
Non-preferring rats (rats that do not prefer alcohol)
- P-rats:
-
Preferring rats (rats that prefer alcohol)
- PCP:
-
Phencyclidine (also known as angel dust)
- PFC:
-
Prefrontal cortex
- PPM1G:
-
3′-Protein-phosphatase-1G
- PTMs:
-
Post-translational modifications
- rTMS:
-
Repetitive transcranial magnetic stimulation
- SAHA:
-
Suberoylanilide hydroxamic acid
- SUD:
-
Substance use disorder
- tDCS:
-
Transcranial direct current stimulation
- TBG:
-
Thyroxine-binding globulin
- TSA:
-
Trichostatin A (an HDAC inhibitor)
- VPA:
-
Valproic acid or valproate (an HDAC inhibitor)
- VTA:
-
Ventral tegmental area
- WHO:
-
World Health Organization
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Funding
The present work was supported by the national research Agency (ANR; project ANR-23-CE17-0034-03, PAPAUD), the IReSP-INCa (IRESP-AAPSPA2021-V1-04, ADELY), the IReSP-INCa (SPAV1-22-019, RAPSICO). FH is supported by a PhD fellowship from INSERM. SBH is supported by the STaRS grant from the regional council of Hauts-de-France.
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Hilal, F.F., Jeanblanc, J., Deschamps, C. et al. Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies. J Neural Transm 131, 525–561 (2024). https://doi.org/10.1007/s00702-024-02757-3
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DOI: https://doi.org/10.1007/s00702-024-02757-3