Importance: As cannabinoids are becoming legal in more states, their use has increased.  The overall effects of cannabinoids on the hippocampus, and thereby learning and memory, need to be determined.  This will allow the population to understand the risks associated with cannabinoid use and researchers to determine a possible therapeutic option.

Objective: The cause, mechanism of action, prevention, and potential therapies will be discussed.  Analysis methods, results, and trial results will be compared.

Data Sources: Cannabinoid effect on the hippocampus searched for general information.  Trials searched for in-vivo/human studies.  Meta-analysis searched for additional study information regarding cannabinoids and hippocampus changes.  Studies/Trials were limited to the past 10 years (2011 – present). 

Study Selection: Trials reviewed were limited to randomized, controlled trials.  Areas tested were limited to behavioral testing (learning and memory) and hippocampal regions.  No exclusion factors for methods used or tested therapeutics. 

Data Extraction and Synthesis:  PRISMA guidelines used for assessing quality data and validity.  Individual extraction by primary author.  PRISMA guidelines were used for abstracting data and assessing data quality and validity.  Data was pooled using a fixed-effect model (2-way linear fixed effects regression – 2FE).

Main Outcome(s) and Measure(s): With cannabinoid use, the expected outcomes of this Kelli McDonald, Miranda Reed, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran  Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, AL study were that proteins (receptors), neurotransmitter levels, as well neurotransmission would be effected in the hippocampus.  We expected to see deficits in memory and learning behavioral tests.  Initial hypothesis was that there would be learning and memory deficits observed with cannabinoids use, due to changes in the hippocampus. 

Results: Electronic database searches of PubMed, ScienceDirect, and PsycINFO identified 897 papers. 546 papers were found to be duplicates. Of the remaining papers, screening of title and abstracts resulted in 468 being discarded for not meeting the main eligibility criteria. The full text of the remaining 78 papers was further assessed, resulting in the identification of 28 empirical studies. Further cross-referencing identified an additional 6 studies.   Overall, the studies’ selection led to the identification of 24 studies that were used in the meta-analysis.

Conclusions and Relevance:  Studies have shown that there is localized deflation of the hippocampus in chronic cannabis users.  These results have shown a change to the size (volume) and shape of the hippocampus.  Glutamatergic transmission, specifically glutamate release has been shown to be decreased in animals that were gestationally and postnatally exposed to cannabinoids.