Eight-Factor Analysis of Kratom: 2022 School of Pharmacy, Concordia University Wisconsin
Final Report from PHAR 537 – Medicinal Natural Products
Claudia Betancourt-Perez, Mackenzie E. Burns, Mitchell J. Glodoski, Timothy H. Vogt Uvidelio Castillo (Course Coordinator), Terry-Elinor R. Reid, Christopher W. Cunningham
Abstract. As a semester-long course project, the third-year pharmacy students of PHAR 537 (Medicinal Natural Products) completed an “eight-factor analysis” of Mitragyna speciosa (“kratom”). The eight factors are considered as part of a process by which legislatures determine whether a product should be regulated as a controlled substance. We evaluated the literature concerning the pharmacokinetic and pharmacodynamic (PK/PD) properties of M. speciosa, and its impact on public health to the United States at large and Wisconsin specifically. Based on our review of the available literature, we conclude that regulation of M. speciosa in Wisconsin as a schedule-I substance is not justified at this time. We base this conclusion, in part, on the scientific evidence demonstrating that M. speciosa and its chemical constituents have lower potential for overdose and abuse relative to other agents that are not scheduled in this way. We believe that controlling M. speciosa and its chemical constituents under schedule-I harms public health and stifles much-needed research into its therapeutic and toxic properties.
I. Introduction
Per Wisconsin statute 961 (Uniform Controlled Substances Act), the state legislature has the authority to regulate the “manufacture, distribution, delivery, possession, and use of controlled substances for other than legitimate purposes” [1]. The authority to determine whether a substance shall be scheduled is given to the Controlled Substances Board (CSB) [2], and the CSB shall consider the following factors, generally known as the “eight factors” [3]:
(a) The actual or relative potential for abuse;
(b) The scientific evidence of its pharmacological effect, if known;
(c) The state of current scientific knowledge regarding the substance; (d) The history and current pattern of abuse;
(e) The scope, duration and significance of abuse;
(f) The risk to the public health;
(g) The potential of the substance to produce psychological or physical dependence liability; and
(h) Whether the substance is an immediate precursor of a substance already controlled under this chapter.
Further, the CSB “shall add a substance to schedule I upon finding that the substance:
(a) Has high potential for abuse;
(b) Has no currently accepted medical use in treatment in the United States;
(c) Lacks the accepted safety for use in treatment under medical supervision.” [4]
Alternately, the CSB could schedule a substance to schedule I if it is controlled in this way under 21 USC 812 (c) [5].
Controlling a substance under schedule I has broad consequences. First, there are legal consequences to individuals who are caught with a compound that is controlled under schedule-I, as the penalties for possessing schedule-I compounds are generally harsher than those for compounds that are regulated under higher schedules [6]. Patients that experience legitimate therapeutic value from products that are regulated under schedule-I would also be harmed, as scheduling substances in this way effectively prevents them from accessing the therapeutic agent. The process of controlling substances also has consequences for research and innovation. In terms of research, schedule-I substances are subject to stricter control and regulation, which adversely impacts the ability of faculty at smaller schools to engage in scholarship related to these substances [7]. Such scheduling also adversely impacts innovation: businesses seeking to develop medicinal products would be disincentivized from working with partners in states that label products as schedule-I substances [7].
Recognizing the significance that scheduling a substance has on patient health and beyond, our class took on the challenge of conducting an “eight-factor analysis” of Mitragyna speciosa, also known as “kratom.” Two constituents of M. speciosa, termed mitragynine (MG) and 7-hydroxy-mitragynine (7-OH-MG), are explicitly listed under schedule-I in the state of Wisconsin [8]. This project was conducted as a part of a 3rd year elective course for Pharm.D. graduate students at Concordia University Wisconsin called Medicinal Natural Products (PHAR 537). What follows is the result of our independent review of the available literature surrounding this medicinal plant. In the next section, we will summarize our findings in the context of the “eight factors” outlined above. Of note, none of the students of PHAR 537, nor the instructional faculty, have conducted research using M. speciosa, its constituents, or their derivatives, nor do any of the co-authors of this document have plans to do so in the immediate future. This project is an exercise in state and federal pharmacy law, and we intend for this analysis to be potentially of value to the Wisconsin CSB as they consider whether schedule-I is the appropriate place for the constituents of kratom.
II. Results and Discussion
Aiding our research were two recent reviews that were written by experts in the field of substance use disorders [9][10]. These two articles provided helpful content and context as we conducted this analysis. Since the second article was written in 2021, we also sought to find newer articles that were published in 2022 that could further aid the discussion. Our analysis can be considered complementary to these articles previously published; we agree with their assessment that kratom should not be considered a controlled substance at this time.
a. Factor 1: The actual or relative potential for abuse.
