About

Christopher R. McCurdy, Ph.D., FAAPS, is a broadly trained medicinal chemist, behavioral pharmacologist, and pharmacist whose research focuses on the design, synthesis, and development of drugs to treat pain and drug abuse. Over more than 20 years, his work has concentrated on opioid, Neuropeptide FF, and sigma receptor ligand/probe design, synthesis, pharmacological evaluation, and development. He has successfully discovered unique and selective tools for sigma receptors, NPFF receptors, and opioid receptors, and is recognized as an international expert on Kratom (Mitragyna speciosa), which is under investigation for opioid withdrawal syndrome. A significant part of his career has been dedicated to developing novel sigma receptor ligands, collaborating with interdisciplinary groups to generate and optimize selective ligands that serve as experimental tools and potential medication development leads to attenuate the effects of cocaine, methamphetamine, and pain. Notably, he developed a PET/MR imaging diagnostic agent for visualizing the origins of chronic, neuropathic pain by interacting with sigma receptors at nerve damage sites, with first-in-human studies currently underway in a Phase 0 trial. Dr. McCurdy also serves as the director of the UF Translational Drug Development Core and has held leadership roles such as President of the American Association of Pharmaceutical Scientists and Co-Chair of the FIP's Special Interest Group on Drug Design and Discovery. His collaborative work has led to the development of patented highly selective sigma receptor ligands, including CM304/FTC146, which is advancing into human clinical trials for chronic pain diagnosis. His research also includes generating non-peptide small molecules for studying Neuropeptide FF receptors, funded by the National Institute on Drug Abuse, and exploring the therapeutic potential of kratom in opioid dependence and withdrawal. Overall, he leads a multidisciplinary drug discovery and development team focused on finding alternative treatments for pain and addiction, with over 100 peer-reviewed publications, multiple book chapters, and numerous invited talks at international meetings.

Research topics

• Chemistry
• Biochemistry
• Pharmacology
• Biology
• Stereochemistry
• Medicine
• Anesthesia
• Internal medicine
• Biophysics
• Agronomy
• Botany
• Horticulture
• Psychology

Selected publications

• Physiologically Based Pharmacokinetic Model for Clinical Translation and Prediction of Drug Interaction of the Major Kratom Alkaloid, Mitragynine

  ACS Pharmacology & Translational Science · 2026-01-13

  articleOpen access

  The opioid crisis presents a significant public health issue and underscores the urgency of developing effective treatments for opioid use disorder (OUD). Mitragynine (MTG), the major active alkaloid found in kratom (Mitragyna speciosa), presents as a potential OUD therapy. A physiologically based pharmacokinetic (PBPK) model has been established to support first-in-human (FIH) dose selection and assess potential drug–drug interactions (DDIs). Extensive physicochemical and in vitro studies were performed to define MTG’s pharmacokinetic properties for the model. The model was validated through in vivo pharmacokinetic studies (intravenous and oral) in both male and female Sprague–Dawley rats, revealing sex-related pharmacokinetic differences. Further validation in nonrodent models included pharmacokinetic studies in female beagle dogs. Utilizing this model, single and multiple-dose simulations of MTG (either as the pure compound or as the major alkaloid present in kratom) administration in humans were conducted, predicting the plasma concentration–time profiles of MTG and its active metabolite, 7-hydroxymitragynine (7-HMG) to facilitate dose selection. The model also evaluates MTG’s potential as both a victim and perpetrator in drug interactions, considering its effects with CYP3A4 and CYP2D6 inhibitors and substrates. Simulation results indicate that potent CYP3A4 and CYP2D6 inhibitors have minimal impact on MTG exposure. However, coadministration with CYP3A4 inhibitors leads to a reduction in 7-HMG formation. As a perpetrator, MTG has negligible effects on CYP2D6 substrates but increases midazolam exposure by 2.2 to 2.7-fold. This comprehensive model supports the therapeutic development of MTG.

  PublisherOA PDFDOI

• A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom

  Journal of Clinical Psychopharmacology · 2026-03-16

  article

  BACKGROUND: Kratom (Mitragyna speciosa) is a plant indigenous to Southeast Asia. This pilot study evaluated the pharmacodynamic (PD) effects, safety, and pharmacokinetics (PK) of kratom and several of its alkaloids. METHODS: Recreational polydrug users (8 participants/cohort; 6 active: 2 placebo, N=40) completed the study. Participants had experience with opioids but were otherwise healthy. This study utilized a double-blind, between-subjects design where participants randomly received a single dose of placebo or kratom. The kratom used in the study had alkaloid levels representative of botanical kratom products (i.e., leaf) previously characterized in the literature and contained trace levels of 7-hydroxymitragynine (7-OH). The starting dose was 1 g and doses of 3, 8, 10, and 12 g were administered after safety reviews after each dose. After dosing, pupillometry and assessments of subjective effects were performed, and blood samples were collected. Safety assessments included adverse events (AE) monitoring, laboratory tests, vital signs, ECG assessments, physical examination findings, and assessment of suicidality. RESULTS: No deaths or serious adverse events (SAEs) occurred. Somnolence, vomiting, and nausea were the most common AEs reported. Kratom alkaloid concentrations showed generally orderly, dose-related effects. At doses ≥3 g, kratom produced pupillary constriction. Few dose-related effects were observed, although the 12 g dose of kratom produced increases on several subjective measures including ratings of "drug liking." CONCLUSIONS: This study investigated the safety of single-sourced botanical kratom; the results may not be representative of other kratom-containing products. Kratom produced some opioid-like effects including pupillary constriction, and the 12 g dose produced effects commonly associated with drugs of abuse such as visual analog scale (VAS) ratings of drug liking, good effects, and high.

  PublisherDOI

• The Sigma1 receptor antagonist CM304 potentiates the antinociceptive effects of the cannabinoid receptor agonist delta9-tetrahydrocannabinol in rats and mice

  Pharmacological Reports · 2026-02-09 · 1 citations

  articleSenior author
  PublisherDOI

• Comparative analysis of monoterpene indole alkaloid composition and genotypic variation in Thai Mitragyna speciosa

  Frontiers in Plant Science · 2026-05-04

  articleOpen access

  Mitragyna speciosa (commonly known as kratom) is a tropical tree native to Southeast Asia, ethnobotanically used for pain relief and fatigue management. Kratom has gained popularity in Western countries for its dose-dependent stimulant and opioid-like effects, and its reported use in the self-treatment of opioid withdrawal. Kratom leaves accumulate over 50 monoterpene indole alkaloids (MIAs) and oxindole alkaloids that have pharmaceutical significance, to which many of these effects are attributed. In this study, we characterized eight kratom accessions originating from Central and Southern Thailand which exhibited phenotypic variation in leaf morphology, including differences in shape, margins, and vein coloration. To authenticate and evaluate genotypic variation among these accessions, we employed DNA barcoding using four loci: the nuclear ITS , and three plastid barcodes including rbcL, MatK , and trnH-psbA. No polymorphisms were detected using ITS and rbcL barcodes. However, sequence analyses revealed insertion-deletion polymorphisms in trnH-psbA , and single nucleotide polymorphisms in both MatK and trnH-psbA , resolving intraspecific variation and separating the accessions into two distinct haplotypes. Targeted metabolite profiling was conducted using UPLC-MS to quantify 17 MIAs and oxindole alkaloids from both young and mature leaves across all kratom accessions. Mitragynine was the most predominant alkaloid in mature leaves, reaching up to 1.19% w/w of leaf dry mass, whereas juvenile leaves accumulated speciociliatine as the major alkaloid, at levels up to 1.14% w/w. Notably, strictosidine, the central precursor of MIA biosynthesis, was detected exclusively in juvenile leaves, which also exhibited significantly higher levels of upstream intermediates including corynantheidine, and iso-corynantheidine compared with mature leaves. In addition, juvenile leaves were dominated by 3 R MIAs, whereas mature leaves accumulated higher levels of 3 S MIAs. However, the relative distribution of 3 S and 3 R stereoisomers remained consistent across accessions. Under the conditions examined, leaf developmental stage exerted a greater influence on alkaloid composition than accession or haplotype variation. Despite visible distinction in leaf vein coloration, alkaloid profiles at maturity remained largely consistent across all accessions. The developmental chemotype patterns presented in this study provide a valuable framework for targeted breeding, metabolic engineering, and controlled cultivation strategies aimed at optimizing specific MIA profiles, particularly those of pharmacological interest.

  PublisherOA PDFDOI

• Identification of peripheral pain generators with sigma-1 receptor Positron Emission Tomography/Magnetic Resonance Imaging in complex regional pain syndrome: initial study in a prospective trial

  Pain · 2026-01-15 · 1 citations

  articleOpen access

  ABSTRACT: Complex regional pain syndrome (CRPS) is a poorly understood chronic pain condition of the extremities presenting severe pain disproportionate to the causative injury. Owing to its heterogeneous clinical presentation and the lack of specific diagnostic tests, CRPS is often a diagnostic and therapeutic challenge. Early diagnosis and treatment of CRPS improve quality of life and delay disease progression. Identification of focal peripheral pain generators would provide an opportunity for targeted treatments with more limited side effects. A highly selective sigma-1 receptor positron emission tomography (PET) radioligand, [18F]FTC-146, has been developed and has shown promise in identifying inflammatory or nociceptive processes. Our aim was to investigate the utility of [18F]FTC-146 PET/MRI for identifying peripheral pain generators and assessing its impact on subsequent clinical management of patients with CRPS. This single-center study enrolled 15 subjects with a clinical diagnosis of CRPS to undergo [18F]FTC-146 PET/MRI. PET/MRI findings were reviewed and discussed with referring pain specialists. Pain scores and subsequent changes in pain management for each patient were prospectively noted. Potential pain generators were observed in 9 of 15 subjects. Subsequent pain treatments guided by abnormally increased foci of uptake on [18F]FTC-146 PET/MRI resulted in an average 5-point improvement in pain score in 80% (7/9) of subjects. Overall, [18F]FTC-146 PET/MRI was able to identify potential peripheral pain generators in the affected limbs of subjects with CRPS and subsequently guided targeted treatments that resulted in varying degrees of improvement in subjective pain scores.

  PublisherOA PDFDOI

• Preclinical assessment of mitragynine as a treatment for methamphetamine use disorder 

  Research Square · 2026-02-16

  preprintOpen access
  PublisherOA PDFDOI

• From Kratom to Semi‐Synthetic Opioids: The Rise and Risks of MGM‐15

  Drug Testing and Analysis · 2025-09-11 · 3 citations

  articleCorresponding

  Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has long been used for its stimulant and analgesic properties. 7-Hydroxymitragynine (7-HMG) is a potent and selective opioid agonist in vitro and demonstrates a potent opioid effect in living subjects, reversible by naloxone. It has been semi-synthesized into products that are readily available in retail and virtual shops. It is known that 7-HMG has earned the nickname "legal morphine," and has gained popularity among users seeking pain relief and/or a "high" comparable with prescription opioids. Medicinal chemistry efforts have led to synthetic 7-HMG derivatives such as MGM-15, where stereospecific saturation of the imine N(1)-C(2) double bond increases opioid receptor affinity and activity. Despite its higher in vitro opioid potency, MGM-15 is currently sold in the US for human consumption as a "research chemical" in tablet form, even though there is an absence of this being studied in humans and obviously no FDA approval. In this study, we analyzed commercially available MGM-labeled tablets using UPLC-MS/MS and subsequently evaluated the binding affinities of purified MGM-15 across multiple opioid receptors. Tablets contained an average of 10.9 ± 0.2 mg (10.7 to 11.2 mg) of MGM-15, with no naturally occurring kratom alkaloids or illicit substances detected. MGM-15 shows greater hMOR and hDOR binding affinities than 7-HMG, indicating the potential for higher opioid effects and risks, emphasizing the urgent need for more research to advise regulation and hopefully prevent misuse and harm.

  PublisherDOI

• List of contributors

  Elsevier eBooks · 2025-09-27

  book-chapter
  PublisherDOI

• In Vitro Pharmacology of Mitragynine at α-Adrenoceptors

  ACS Chemical Neuroscience · 2025-11-21 · 1 citations

  articleOpen access

  R partial agonist pharmacology might contribute to mitragynine's psychostimulant-like properties.

  PublisherDOI

• Diagnostic performance of a human over-the-counter urine test to detect kratom alkaloids and metabolites in canine urine

  American Journal of Veterinary Research · 2025-12-22

  articleOpen access

  Objective: To use liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis to quantify kratom alkaloids and metabolites in the urine of healthy dogs following a single oral dose of an encapsulated kratom extract and evaluate the accuracy of an over-the-counter (OTC) human kratom urine test for identifying the presence of kratom alkaloids and metabolites in canine urine. Methods: Urine samples were collected from 8 healthy female Beagles following a single oral dose of an encapsulated kratom extract (8 mg) every 4 hours for 24 hours. Urine concentrations of kratom alkaloids and metabolites were measured using LC-MS-MS analysis. Urine samples were tested with an OTC human kratom urine test for identification of mitragynine and/or 7-hydroxymitragynine. Results: In this small cohort of dogs, the OTC human kratom urine test demonstrated 100% sensitivity (6 of 6; 95% CI, 60.97% to 100.00%) and 100% specificity (7 of 7; 95% CI, 64.57% to 100.00%) for identifying kratom alkaloids and/or metabolites. Kratom metabolite 7-hydroxymitragynine had higher urine concentrations compared to the parent alkaloid mitragynine. Conclusions: Kratom is primarily excreted as metabolites in canine urine following oral administration of a single dose. Although these results are limited by the small sample size and wide CIs, the OTC human kratom urine test reliably detected kratom metabolites in canine urine when compared with LC-MS-MS. Clinical Relevance: The results of this study provide a better understanding of kratom elimination in dogs and support the potential utility of an OTC kratom urine test as a diagnostic tool for suspected kratom exposure; however, larger studies are needed to validate diagnostic performance.

  PublisherDOI

Recent grants

• NIH Grant R03DA017360

  NIH · $141k · 2005

• Opioid use disorders: UF Pharmacy medications discovery and development

  NIH · $4.5M · 2018–2024

• Kratom alkaloids: in vitro and in vivo pharmacological mechanisms

  NIH · $2.9M · 2019–2025

• Opioid use disorders: UF Pharmacy medications discovery and development

  NIH · $3.6M · 2018–2020

• Kratom alkaloids: in vitro and in vivo pharmacological mechanisms

  NIH · $693k · 2019–2024

Frequent coauthors

• Lance Richard McMahon

  Texas Tech University

  226 shared

• Takato Hiranita

  The University of Texas Health Science Center at Houston

  217 shared

• Francisco León

  University of Florida

  204 shared

• Samuel Obeng

  University of Florida

  193 shared

• Avi Patel

  Samford University

  176 shared

• Jenny L. Wilkerson

  Texas Tech University Health Sciences Center

  175 shared

• Abhisheak Sharma

  University of Florida

  172 shared

• Nicholas P. Ho

  University of Florida

  164 shared

Labs

• Department of Cellular and Systems PharmacologyPI

Education

• Ph.D., Medicinal Chemistry

  University of Georgia

  1998

• BSPh, College of Pharmacy

  Ohio Northern University

  1994

Awards & honors

• F.A.A.P.S. (Fellow of the American Association of Pharmaceut…