This study was designed to test our hypothesis that an ultra-low dose of delta-9 tetrahydrocannabinol (THC) reverses age-dependent cognitive impairments in old mice and to examine the possible biological mechanisms that underlie this behavioral effect. Old female mice aged 24 months that had been injected once with 0.002 mg/kg THC (3–4 orders of magnitudes lower than doses that induce the conventional cannabinoid effects in mice) performed significantly better than vehicle-treated old mice and performed similarly to naive young mice aged 2 months, in 6 different behavioral assays that measured various aspects of memory and learning. The beneficial effect of THC lasted for at least 7 weeks. The single injection of THC increased the level of Sirtuin1, an enzyme that has been previously shown to be involved in neuroprotection and neuroplasticity, in the hippocampus and in the frontal cortex of old mice, for at least 7 weeks. Magnetic resonance imaging demonstrated a larger volume and higher tissue density in various regions of the brain of THC-treated old mice. These findings suggest that extremely low doses of THC that are devoid of any psychotropic effect and do not induce desensitization may provide a safe and effective treatment for cognitive decline in aging humans.
|Number of pages||10|
|Journal||Neurobiology of Aging|
|State||Published - Jan 2018|
Bibliographical noteFunding Information:
The authors thank Prof. Raphael Mechoulam of the Hebrew University of Jerusalem for his generous donation of tetrahydrocannabinol. This study was supported by The Mauerberger Foundation , South Africa and by Therapix Biosciences , Israel.
- Aging brain
- Cognitive deficits
- Magnetic resonance imaging (MRI)