Functional effects of cannabinoids during dopaminergic specification of human neural precursors derived from induced pluripotent stem cells.
Nancy Stanslowsky, Kirsten Jahn, Anna Venneri, Maximilian Naujock, Alexandra Haase, Ulrich Martin, Helge Frieling, Florian Wegner
Addiction Biology September 2017 DOI: 10.1111/adb.12394 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Human cord blood-derived induced pluripotent stem cell (hCBiPSC)-derived small molecule neural precursor cells (smNPCs) |
| Interventions | Anandamide (AEA) THC |
| Dose | 1 µM and 10 µM AEA; 1 µM and 10 µM THC |
| Topics | Neuroplasticity |
| Keywords | Cannabinoids Dopaminergic differentiation Epigenetic Patch clamp |
| Key findings | Cannabinoid effects on maturing human neurons depended on concentration: 10 µM AEA or THC reduced ion currents and synaptic activity, while 1 µM THC had no marked effect and 1 µM AEA increased synaptic activity frequency. No significant DNA methylation changes were found, suggesting a non-epigenetic mechanism. The authors conclude 10 µM AEA and THC have neurotoxic, dysfunctional effects during human neurogenesis in vitro. |
Abstract
Among adolescents cannabis is one of the most widely used illicit drugs. In adolescence brain development continues, characterized by neuronal maturation and synaptic plasticity. The endocannabinoid system plays an important role during brain development by modulating neuronal function and neurogenesis. Changes in endocannabinoid signaling by Δ9 -tetrahydrocannabinol (THC), the psychoactive component of cannabis, might therefore lead to neurobiological changes influencing brain function and behavior. We investigated the functional maturation and dopaminergic specification of human cord blood-derived induced pluripotent stem cell (hCBiPSC)-derived small molecule neural precursor cells (smNPCs) after cultivation with the endogenous cannabinoid anandamide (AEA) and the exogenous THC, both potent agonists at the cannabinoid 1 receptor (CB1 R). Higher dosages of 10-μM AEA or THC significantly decreased functionality of neurons, indicated by reduced ion currents and synaptic activity. A lower concentration of 1-μM THC had no marked effect on neuronal and dopaminergic maturation, while 1-μM AEA significantly enhanced the frequency of synaptic activity. As there were no significant effects on DNA methylation in promotor regions of genes important for neuronal function, these cannabinoid actions seem to be mediated by another than this epigenetic mechanism. Our data suggest that there are concentration-dependent actions of cannabinoids on neuronal function in vitro indicating neurotoxic, dysfunctional effects of 10-μM AEA and THC during human neurogenesis.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 2
Cites 3
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- Association Between Cannabis and Psychosis: Epidemiologic Evidence. Biological Psychiatry April 1, 2016
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology January 2008