Cannabis cultivation: Methodological issues for obtaining medical-grade product Suman Chandra a , Hemant Lata a , Mahmoud A. ElSohly a,b , Larry A. Walker a,c , David Potter d,* a National Center for Natural Product Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, MS 38677, USA b Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, P.O. Box 1848, MS 38677, USA c Department of Biomolecular Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, MS 38677, USA d GW Pharmaceuticals plc, Sovereign House, Vision Park, Histon, Cambridge, CB24 9BZ, United Kingdom abstract article info Article history: Received 19 October 2016 Revised 21 November 2016 Accepted 21 November 2016 Available online xxxx As studies continue to reveal favorable findings for the use of cannabidiol in the management of childhood epilepsy syndromes and other disorders, best practices for the large-scale production of Cannabis are needed for timely prod- uct development and research purposes. The processes of two institutions with extensive experience in producing large-scale cannabidiol chemotype Cannabis crops—GW Pharmaceuticals and the University of Mississippi—are de- scribed, including breeding, indoor and outdoor growing, harvesting, and extraction methods. Such practices have yielded desirable outcomes in Cannabis breeding and production: GW Pharmaceuticals has a collection of chemotypes dominant in any one of eight cannabinoids, two of which—cannabidiol and cannabidivarin—are supporting epilepsy clinical trial research, whereas in addition to a germplasm bank of high-THC, high-CBD, and in- termediate type cannabis varieties, the team at University of Mississippi has established an in vitro propagation pro- tocol for cannabis with no detectable variations in morphologic, physiologic, biochemical, and genetic profiles as compared to the mother plants. Improvements in phytocannabinoid yields and growing efficiency are expected as research continues at these institutions. This article is part of a Special Issue entitled “Cannabinoids and Epilepsy”. © 2016 Published by Elsevier Inc. Keywords: Cannabidiol Cannabidivarin Chemotype Phytocannabinoid Pharmacognosy Organogenesis 1. Introduction Plant-based drugs present unusual challenges in the pharmaceutical world with respect to large-scale cultivation, processing, quality, and consistency. In the case of Cannabis sativa L., considerable additional complexity derives from regulatory concerns, depending on the coun- tries of production and marketing. In recent years, the production of cannabidiol (CBD)-based medicinal materials for research as potential therapeutics in childhood epilepsy syndromes and other disorders has come into greater focus. This article will describe the botany and phar- macognosy of Cannabis sativa L. and approaches employed in the United States and the United Kingdom (UK) for biomass selection, cultivation, and harvest/processing biomass to ensure quality supplies for medical research and for pharmaceutical product development. 2. Historical background in the United States and United Kingdom In the United States, cannabis was common in patent medicines in the late 1800s and was listed in the US Pharmacopeia from the 1850s up until 1942, prescribed for various pain conditions and nausea. In 1899, cannabis was listed in the first edition of Merck's Manual [1] and recommended for the management of several conditions including epi- lepsy. It also had some history of use as an intoxicant, but, in 1937, the Marihuana Tax Act made it illegal except for medical use, which was taxed. Those who produced, prescribed, or dispensed marijuana were required to buy a stamp and pay the tax. This requirement greatly re- stricted legal use of marijuana, and, gradually, in the mid-20th century, when the use of most crude botanical drugs in US medicine declined, cannabis medical use plummeted as well. Of course, illicit use contin- ued, but no “dealers” for this purpose would buy the stamp and pay the tax, because doing so would incriminate themselves. This practice was a major basis on which the Marihuana Tax Act was ruled unconsti- tutional in 1969. In 1970, congress passed legislation that included mar- ijuana on the “Schedule I” list with many other controlled substances, and it remains so to this date. Epilepsy & Behavior xxx (2016) xxx–xxx ⁎ Corresponding author. E-mail addresses: melsohly@olemiss.edu (M.A. ElSohly), djp@gwpharm.com (D. Potter). YEBEH-05123; No of Pages 11 http://dx.doi.org/10.1016/j.yebeh.2016.11.029 1525-5050/© 2016 Published by Elsevier Inc. Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh Please cite this article as: Chandra S, et al, Cannabis cultivation: Methodological issues for obtaining medical-grade product, Epilepsy Behav (2016), http://dx.doi.org/10.1016/j.yebeh.2016.11.029