Long-term behavioral and biochemical effects of an ultra-low dose of Δ9-tetrahydrocannabinol (THC): neuroprotection and ERK signaling.
Miriam Fishbein, Sahar Gov, Fadi Assaf, Mikhal Gafni, Ora Keren, Yosef Sarne
Experimental Brain Research September 2012 DOI: 10.1007/s00221-012-3186-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Dose | 0.002 mg/kg |
| Duration | Protection assessed at least 7 weeks after treatment |
| Topics | Cannabis |
| Key findings | A single ultra-low dose of THC (0.002 mg/kg) protected mice from cognitive deficits induced by pentobarbital anesthesia, repeated MDMA treatment, and carbon monoxide exposure, with protection lasting at least seven weeks. The authors report that this dose also produced long-lasting changes in ERK activity and related signaling molecules (MEK, MKP-1, pCREB, BDNF) in several brain regions, suggesting THC can modify brain plasticity. |
Abstract
We have previously reported that a single injection of an ultra-low dose of delta-9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) protected the brain from pentylenentetrazole (PTZ)-induced cognitive deficits when applied 1-7 days before or 1-3 days after the insult. In the present study we expanded the protective profile of THC by showing that it protected mice from cognitive deficits that were induced by a variety of other neuronal insults, including pentobarbital-induced deep anesthesia, repeated treatment with 3,4 methylenedioxymethamphetamine (MDMA; "ecstasy") and exposure to carbon monoxide. The protective effect of THC lasted for at least 7 weeks. The same ultra-low dose of THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that produce the known acute effects of the drug in mice) induced long-lasting (7 weeks) modifications of extracellular signal-regulated kinase (ERK) activity in the hippocampus, frontal cortex and cerebellum of the mice. The alterations in ERK activity paralleled changes in its activating enzyme MEK and its inactivating enzyme MKP-1. Furthermore, a single treatment with the low dose of THC elevated the level of pCREB (phosphorylated cAMP response element-binding protein) in the hippocampus and the level of BDNF (brain-derived neurotrophic factor) in the frontal cortex. These long-lasting effects indicate that a single treatment with an ultra-low dose of THC can modify brain plasticity and induce long-term behavioral and developmental effects in the brain.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice. Frontiers in Neuroscience July 18, 2023
- Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol. ACS Chemical Neuroscience May 15, 2019
- Delta-9-tetrahydrocannabinol disrupts hippocampal neuroplasticity and neurogenesis in trained, but not untrained adolescent Sprague-Dawley rats. Brain Research February 22, 2014
Cites 8
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and 3 more in the library