Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders
- 569 Downloads
Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases.
We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats.
Rats received vehicle or iron at postnatal days 12–14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training.
A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.
The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.
KeywordsCannabidiol Memory Neurodegenerative disorders Neuroprotection Iron
This research was supported by the National Council for Scientific and Technological Development (CNPq; grant number 305905/2009-0 to N.S.), and the National Institute for Translational Medicine (INCT-TM). JASC, JECH, AWZ, and NS are recipients of the CNPq fellowship research awards. TB is a recipient of the FAPERGS fellowship.
- Cassol-Jr OJ, Comim CM, Silva BR, Hermani FV, Constantino LS, Felisberto F, Petronilho F, Hallak JE, De Martinis BS, Zuardi AW, Crippa JA, Quevedo J, Dal-Pizzol F (2010) Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture. Brain Res 1348:128–138PubMedCrossRefGoogle Scholar
- El-Remessy AB, Khalil IE, Matragoon S, Abou-Mohamed G, Tsai NJ, Roon P, Caldwell RB, Caldwell RW, Green K, Liou GI (2003) Neuroprotective effect of (−)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-d-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol 163:1997–2008PubMedCrossRefGoogle Scholar
- García-Arencibia M, González S, de Lago E, Ramos JA, Mechoulam R, Fernández-Ruiz J (2007) Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res 1134:162–170PubMedCrossRefGoogle Scholar
- Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L (2009) Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci Ther 15:65–75Google Scholar
- Kell DB (2010) Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 84:825–889PubMedCrossRefGoogle Scholar
- Krishnan S, Cairns R, Howard R (2009) Cannabidiol for the treatment of dementia. Cochrane Database Syst Rev 2:CD007204Google Scholar