William E. Fantegrossi, Ph.D.
Ph.D. – University of Michigan, 2002
In the past few years, a number of relatively obscure compounds have appeared on the illicit drug market. In most cases, these new drugs of abuse have turned out to be established research chemicals that have diffused out of laboratories and scientific journals and onto the streets. As novel pharmacological entities, the legal ramifications for selling and possessing these drugs are initially unclear, and enterprising individuals typically exploit the novelty of these substances to make rapid and substantial profits selling them over-the-counter and online. Indeed, emerging drugs of abuse occupy a legal grey area until emergency scheduling powers are invoked, typically first at the municipal and state level, then nationally.
Research in my laboratory is currently focused on several categories of these drugs, including synthetic cannabinoids (constituents of K2/”Spice” smoking blends), analogues of cathinone (present in “bath salts” preparations), and novel arylcyclohexylamines (related to PCP and ketamine.) In an effort to better understand the biological actions of these emerging drugs of abuse, we use behavioral pharmacology techniques in rodents to compare these compounds with more the well-known drugs of abuse which these emerging drugs are designed to mimic (such as the phytocannabinoid delta9-THC, psychostimulants like MDMA and methamphetamine, and PCP).
Students interested in working in my laboratory will have the opportunity to assist with surgeries (intraperitoneal implantation of biotelemetry probes which simultaneously measure core temperature and locomotor activity), to work with mice or rats in behavioral assays (including operant tests of food- or drug-maintained responding, and assays of drug-elicited effects such as analgesia and catalepsy), and assist with dissections for studies involving tissue distribution and disposition of drug, neurotoxicity, or molecular correlates of tolerance and withdrawal.
Recent Research Support
DEA/FDA HHSF223201610079C (PI) (09/12/16 – 09/11/21)
“In Vivo Pharmacological Studies for abuse liability testing”
NIH/NIDA R01 DA039143 (Co-I) (10/01/15 – 09/30/20)
“Synthetic cannabinoid toxicity: role of biotransformation”
NIH/NIDA R01 DA039195 (Co-I) (05/01/15 – 03/31/20)
“Pharmacology and therapy for MDPV and alpha-PVP like drugs of abuse”
NIH/NIDA T32 DA022981 (Director, Summer Med Stdt Internship) (01/07/15 – 30/06/19)
“Translational Training in Addiction”
NIH/NIDA R01 DA036600 (Co-I) (01/07/14 – 30/06/18)
“Gene therapy for the treatment of methamphetamine abuse”
Rosas-Hernandez H, Cuevas E, Lantz SM, Rice KC, Gannon BM, Fantegrossi WE, Gonzalez C, Paule MG, Ali SF. Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells. Neurosci Lett. 629:125-30, 2016 (PMID: 27320055).
Farrell MS, McCorvy JD, Huang XP, Urban DJ, White KL, Giguere PM, Doak AK, Bernstein AI, Stout KA, Park SM, Rodriguiz RM, Gray BW, Hyatt WS, Norwood AP, Webster KA, Gannon BM, Miller GW, Porter JH, Shoichet BK, Fantegrossi WE, Wetsel WC, Roth BL. In Vitro and In Vivo Characterization of the Alkaloid Nuciferine. PLoS One. 11(3):e0150602, 2016 (PMID: 26963248).
Gannon BM, Williamson A, Suzuki M, Rice KC, Fantegrossi WE. Stereoselective Effects of Abused “Bath Salt” Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. J Pharmacol Exp Ther. 356(3):615-23, 2016 (PMID: 26769917).
Tai S, Hyatt WS, Gu C, Franks LN, Vasiljevik T, Brents LK, Prather PL, Fantegrossi WE. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. Pharmacol Res. 102:22-32, 2015 (PMID: 26361728).
Fantegrossi WE, Gray BW, Bailey JM, Smith DA, Hansen M, Kristensen JL. Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT₂A receptors, in mice. Psychopharmacology. 232(6):1039-47, 2015 (PMID: 25224567).
Baumann MH, Solis E Jr, Watterson LR, Marusich JA, Fantegrossi WE, Wiley JL. Baths salts, spice, and related designer drugs: the science behind the headlines. J Neurosci. 34(46):15150-8, 2014 (PMID: 25392482).
Gannon BM, Reichard EE, Fantegrossi WE. Psychostimulant Abuse and HIV Infection: cocaine, methamphetamine, and “bath salts” cathinone analogues. Curr Addict Rep. 1(3):237-242, 2014 (PMID: 26413453).
Smith DA, Bailey JM, Williams D, Fantegrossi WE. Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice. J Pharmacol Exp Ther, 351(3):485-91, 2014 (PMID: 25271256).
Tai S, Fantegrossi WE. Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential. Curr Addict Rep. 1(2):129-136, 2014 (PMID: 26413452).
Marshell R, Kearney-Ramos T, Brents LK, Hyatt WS, Tai S, Prather PL, Fantegrossi WE. In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection. Pharmacol Biochem Behav. 124:40-7, 2014 (PMID: 24857780).
Norwood AP, Al-Chaer ED, Fantegrossi WE. Predisposing effects of neonatal visceral pain on abuse-related effects of morphine in adult male Sprague Dawley rats. Psychopharmacology. 231(22):4281-9, 2014 (PMID: 24756764).