In order to define the finest cultivation practices for two of the most commercial hemp cultivars (‘Fedora 23’ and ‘Futura 75’) under the Mediterranean climate, the treatment of topping was applied in hemp crop in Central Greece. The object of the study was to assess if topping can increase the cannabidiol (CBD) production. In addition, the growth of the two cultivars was also investigated. Our results showed that the treatment of topping and cultivar affected the CBD content. The inflorescence compactness index and the number of nodes were affected by cultivar and topping. The number of inflorescences on secondary shoots was affected only by topping. The leaf area was affected by the interaction of cultivar and topping. The maximum height was recorded in un-topped Futura 75 plants, while the highest fresh and dry weight were found in topped Futura 75 plants. The total inflorescence dry matter was higher in topped plants.