Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage.
Fadi Assaf, Miriam Fishbein, Mikhal Gafni, Ora Keren, Yosef Sarne
Behavioural Brain Research June 20, 2011 DOI: 10.1016/j.bbr.2011.02.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal (mouse) experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Δ9-tetrahydrocannabinol (THC) Pentylenetetrazole (PTZ) |
| Dose | THC 0.002 mg/kg; PTZ 60 mg/kg |
| Duration | THC given 1–7 days before or 1–3 days after PTZ; outcomes assessed 3–7 weeks later |
| Topics | Cannabis |
| Key findings | A single 0.002 mg/kg dose of THC, given 1–7 days before or 1–3 days after PTZ (60 mg/kg), abolished PTZ-induced long-lasting cognitive deficits measured 3–7 weeks later. Cerebellar phosphorylated ERK was reduced seven weeks after THC. The authors suggest extremely low-dose THC pre- or post-conditioning may provide long-term neuroprotection. |
Abstract
Preconditioning, a phenomenon where a minor noxious stimulus protects from a subsequent more severe insult, and post-conditioning, where the protective intervention is applied following the insult, offer new insight into the neuronal mechanism(s) of neuroprotection and may provide new strategies for the prevention and treatment of brain damage. We have previously reported that a single administration of an extremely low dose of Δ(9)-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to mice induced minor long-lasting cognitive deficits. In the present study we examined the possibility that such a low dose of THC will protect the mice from more severe cognitive deficits induced by the epileptogenic drug pentylenetetrazole (PTZ). THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that induce the conventional effects of THC) was administered 1-7 days before, or 1-3 days after the injection of PTZ (60 mg/kg). The consequences of this treatment were studied 3-7 weeks later by various behavioral tests that evaluated different aspects of memory and learning. We found that a single administration of THC either before or after PTZ abolished the PTZ-induced long-lasting cognitive deficits. Biochemical studies indicated a concomitant reduction in phosphorylated-ERK (extracellular signal-regulated kinase) in the cerebella of mice 7 weeks following the injection of THC. Our results suggest that a pre- or post-conditioning treatment with extremely low doses of THC, several days before or after brain injury, may provide safe and effective long-term neuroprotection.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice. Journal of Molecular Neuroscience December 1, 2014
- Acute Ultra Low Dose THC Attenuates Anxiety-Like Behavior in a Mouse Model for Major-Depressive Disorder Journal of Molecular Neuroscience October 12, 2026
- Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice. Frontiers in Neuroscience July 18, 2023
- Biphasic effects of THC in memory and cognition. European journal of clinical investigation May 2018
- Long-term behavioral and biochemical effects of an ultra-low dose of Δ9-tetrahydrocannabinol (THC): neuroprotection and ERK signaling. Experimental Brain Research September 2012
Cites 2
- Long-term consequences of a single treatment of mice with an ultra-low dose of Delta9-tetrahydrocannabinol (THC). Behavioural Brain Research January 20, 2010
- Modulation of extracellular signal-regulated kinases cascade by chronic delta 9-tetrahydrocannabinol treatment. Molecular and cellular neurosciences March 2004