“This polypharmacology renders kratom unique from other opioids and to label kratom an opioid is scientifically and factually incorrect.”
Biography
Dr. McCurdy is a Professor in the Department of Medicinal Chemistry with a courtesy appointment in the Department of Pharmaceutics and The Frank A. Duckworth Eminent Scholar Chair in Drug Research and Development. He is also the Director of the UF Translational Drug Development Core. Dr. McCurdy completed his PhD in medicinal chemistry from the University of Georgia and a postdoctoral fellowship in the Department of Medicinal Chemistry at the University of Minnesota College of Pharmacy.
Dr. McCurdy is a broadly trained pharmaceutical scientist, and pharmacist whose research focuses on the design, synthesis, and development of drugs to treat pain, anxiety, and substance abuse. For over 25 years, much of his research has focused on opioid, neuropeptide FF, and sigma receptor ligand/probe design, synthesis, pharmacological evaluation, and development. He is an internationally recognized expert on kratom (Mitragyna speciosa), which is under investigation for opioid withdrawal syndrome, opioid use disorder, and treating pain. A significant portion of his career has been dedicated to the development of novel sigma receptor ligands, in collaboration with interdisciplinary groups, to generate and optimize selective ligands that could serve as critical experimental tools. More recently, he has worked to develop these as potential medication development leads to attenuate the effects of cocaine, methamphetamine, and pain.
Most notably, Dr. McCurdy has developed a PET/MR imaging diagnostic agent for visualizing the origins of chronic neuropathic pain by interacting with sigma receptors at the site of nerve damage. The Phase 1 and 2 human clinical trials are currently being conducted at Stanford University. He has published more than 150 manuscripts and holds 6 patents. He is currently funded by multiple NIH grants and the Florida Department of Health. In addition, Dr. McCurdy previously served as President of the American Association of Pharmaceutical Scientists and also serves as a consultant to the US Food and Drug Administration’s Drug Safety and Risk Management Advisory Committee.
Kratom (Mitragyna speciosa): Recent advances in understanding the chemistry, pharmacology, and human uses.
“The historical use of kratom to prevent withdrawal and ween users from opioids is of great relevance to the current global opioid crisis.”
Transcript Abstract
Mitragyna speciosa Korth (Rubiaceae) is a tree that was first identified in Southeast Asia where the borders of Thailand and Malaysia meet. The leaves are the origin of the ethnopharmacological preparation “kratom”. Traditional use involves decoction of the leaves and has paradoxical effects that include a coca-like stimulant as well opium-like depressant actions. Traditionally, the plant extract has been used as an opium substitute, and it has been clinically used in Thailand to wean addicts off opiates. Much attention has been drawn to this recently due to the exponential increases of users in the Western world where some harm has been reported. For centuries kratom has been used to increase mood, stamina, energy, and decrease anxiety and pain. The historical use of kratom to prevent withdrawal and ween users from opioids is of great relevance to the current global opioid crisis. As kratom use has steadily increased in the United States (US), reports of adverse events have risen. It is estimated that >15 million US individuals consume kratom products. Poison control center calls mentioning kratom totaled 682 in 2017. This number of kratom incidents is small when put in context with other analgesics, sedatives, and antidepressants which resulted in 334,729 calls in 2019. Nonetheless, there has been increased scrutiny around the opioid nature of kratom.
From our conducted studies, supported by two (2) large grants from the National Institute on Drug Abuse (totaling $11,535,437), we conclude that kratom has low abuse liability when it is utilized in its pure leaf/plant material form. We believe issues arise from concentrated extracts and other formulations that utilize dried or cured leaf materials. The abuse liability in these products is most likely due to the varying concentrations of one alkaloid, 7-hydroxymitragynine (7OHMG). We have not detected this alkaloid in freshly harvested leaf material or freshly prepared traditional teas in SE Asia. As part of our research, we monitor products in the US marketplace and over the past decade, the presence of 7OHMG has been decreasing to low or non-detectable levels in many products. This is a result of the published science around 7OHMG from our team as well as other kratom researchers. 7OHMG is a potent mu opioid receptor agonist with abuse potential. It is a metabolite or decomposition product of the major alkaloid, mitragynine (MG). We, and others, have shown that MG has no abuse potential and has a unique pharmacology involving several neurotransmitter systems. In fact, alkaloids in kratom interact with the adrenergic and serotonergic systems to a greater extent than opioid systems. This polypharmacology renders kratom unique from other opioids and to label kratom an opioid is scientifically and factually incorrect. MG and lyophilized kratom tea can reduce opioid withdrawal symptoms in opioid dependent subjects. Two reports in the literature demonstrate the ability of MG to block self-administration of opioids in animals. We have reconfirmed through a more extensive study that is not yet published. In 2016, the US determined further research was needed before a ban. That research has exponentially increased to the point of FDA sanctioned human clinical trials where results are pending. In October 2021, the 44th Expert Committee (ECDD) on Drug Dependency of the World Health Organization convened to determine if kratom should undergo ‘critical review’ for an International ban. The ECDD determined that there was inadequate evidence to recommend a critical review and kratom will be kept under surveillance.