Impairment of Synaptic Plasticity by Cannabis, Δ9-THC, and Synthetic Cannabinoids.
Alexander F. Hoffman, Eun-Kyung Hwang, Carl R. Lupica
Cold Spring Harbor perspectives in medicine May 3, 2021 preprint DOI: 10.1101/cshperspect.a039743 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review |
|---|---|
| Interventions | Δ9-THC synthetic cannabinoids |
| Topics | Cannabis Neuroplasticity |
| Key findings | The authors argue that Δ9-THC and synthetic cannabinoids impair synaptic plasticity across multiple neuronal circuits by disrupting endogenous cannabinoid signaling, and that this impairment contributes to their documented ability to disrupt cognition and behavior. |
Abstract
The ability of neurons to dynamically and flexibly encode synaptic inputs via short- and long-term plasticity is critical to an organism's ability to learn and adapt to the environment. Whereas synaptic plasticity may be encoded by pre- or postsynaptic mechanisms, current evidence suggests that optimization of learning requires both forms of plasticity. Endogenous cannabinoids (eCBs) play critical roles in modulating synaptic transmission via activation of cannabinoid CB1 receptors (CB1Rs) in many central nervous system (CNS) regions, and the eCB system has been implicated, either directly or indirectly, in several forms of synaptic plasticity. Because of this, perturbations within the eCB signaling system can lead to impairments in a variety of learned behaviors. One agent of altered eCB signaling is exposure to "exogenous cannabinoids" such as the primary psychoactive constituent of cannabis, Δ9-THC, or illicit synthetic cannabinoids that in many cases have higher potency and efficacy than Δ9-THC. Thus, by targeting the eCB system, these agonists can produce widespread impairment of synaptic plasticity by disrupting ongoing eCB function. Here, we review studies in which Δ9-THC and synthetic cannabinoids impair synaptic plasticity in a variety of neuronal circuits and examine evidence that this contributes to their well-documented ability to disrupt cognition and behavior.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 5
- Longer chronic cannabis use in humans is associated with impaired implicit motor learning and supranormal resting state cortical activity bioRxiv (Cold Spring Harbor Laboratory) April 21, 2025
- Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia Current Addiction Reports February 27, 2026
- Effects of cannabis use on antidepressant treatment response to repetitive transcranial magnetic stimulation and ketamine medRxiv Preprint Server June 28, 2023
- Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration. Neuroscience May 25, 2026
- Three-day delta-9-tetrahydrocannabinol (THC) exposure eliminates long-term depression in ventral tegmental area of young, but not adult mice. Journal of Cannabis Research May 31, 2025
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and 19 more in the library