Defense Date


Document Type


Degree Name

Master of Public Health


Preventive Medicine & Community Health


Purpose: Marijuana is the most widely used illicit drug in the United States. However, marijuana and cannabinoid derivatives have potential therapeutic uses. Studies in cannabis users have yielded contradictory results with regard to long-term effects on cognitive functions. There is no prospective study assessing this issue, and such studies may raise ethical issues in humans, whereas mice have been shown to exhibit similar cannabinoid-mediated behaviors as humans. The purpose of this study was to assess the consequences of chronic administration of Δ9-THC, the major psychoactive component of marijuana, in a mouse memory model. Methods: In Experiment 1, the dose-response relationship of Δ9-THC was assessed in the object recognition task, a well-documented rodent memory model. In Experiment 2, mice were treated repeatedly with either escalating doses of Δ9-THC or vehicle for one week, and then challenged with the drug to assess whether tolerance had developed. Results: Acute Δ9-THC dose-dependently interfered with memory as assessed in the object recognition task (ED50 95% C.I. = 0.5 (0.1 to1.7) mg/kg). No tolerance to the memory disruptive effects of 1 mg/kg Δ9-THC was evident after chronic treatment. Conclusions: Considerably low doses of Δ9-THC impaired memory. The failure of chronic Δ9-THC to produce tolerance in this model was surprising considering that a similar dosing regimen has been reported to produce tolerance in non-mnemonic behaviors. The results suggest that memory is particularly sensitive to the disruptive effects of Δ9-THC and chronic cannabis use is likely to elicit persistent impairment of cognitive function. Caution should be applied in advocating chronic use of medicinal cannabinoids. Potential solutions lie in reinforcing education on the harm caused by cannabis use and availability of alternative solution to cannabis users, especially among youth that have shown to be more vulnerable to this drug.


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Date of Submission

June 2008