Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.
Wen Jiang, Yun Zhang, Lan Xiao, Jamie van Cleemput, Shao-Ping Ji, Guang Bai, Xia Zhang
Journal of Clinical Investigation November 1, 2005 DOI: 10.1172/jci25509 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study (in vitro cell culture and in vivo rat experiments) Peer reviewed |
|---|---|
| Population | Embryonic and adult rat hippocampal neural stem/progenitor cells and adult rats |
| Intervention | HU210 |
| Duration | Chronic treatment (duration not specified); acute treatment also tested |
| Topics | Neuroplasticity |
| Key findings | HU210 promoted proliferation but not differentiation of cultured embryonic hippocampal neural stem/progenitor cells, likely via CB1 receptor, G(i/o) protein, and ERK signaling. Chronic, but not acute, HU210 treatment increased neurogenesis in the adult rat dentate gyrus and produced anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both effects, suggesting the behavioral effects depend on hippocampal neurogenesis. |
Abstract
The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G(i/o) proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
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|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 31
- Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex Journal of Neuroscience October 24, 2007
- Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders Frontiers in Pharmacology May 23, 2017
- Legal highs: staying on top of the flood of novel psychoactive substances Therapeutic Advances in Psychopharmacology January 26, 2015
- The cannabinoid CB 1 receptor and the endocannabinoid anandamide: possible antidepressant targets Expert Opinion on Therapeutic Targets October 14, 2008
- Pathways from Cannabis to Psychosis: A Review of the Evidence Frontiers in Psychiatry 2013
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