Edward Cone - Academia.edu (original) (raw)

Papers by Edward Cone

Journal of Analytical Toxicology, 2019

As cannabis has become more accessible, use of alternative methods for cannabis administration su... more As cannabis has become more accessible, use of alternative methods for cannabis administration such as vaporizers has become more prevalent. Most prior controlled pharmacokinetic evaluations have examined smoked cannabis in frequent (often daily) cannabis users. This study characterized the urinary excretion profile of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), the primary analytical outcome for detection of cannabis use, among infrequent cannabis users following controlled administration of both smoked and vaporized cannabis. Healthy adults (N = 17), with a mean of 398 (range 30–1,825) days since last cannabis use, smoked and vaporized cannabis containing 0, 10, and 25 mg of Δ9-tetrahydrocannabinol (THC) across six outpatient sessions. Urinary concentrations of THCCOOH were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity, and agreement between three immunoassays (IA) for THCCOOH (with cutoffs of 20, 50, and 100 ng/mL) and gas chroma...

Journal of Analytical Toxicology, Oct 1, 1998

PubMed, Sep 1, 1984

Buprenorphine, a powerful mixed agonist-antagonist analgesic which shows promise of providing mai... more Buprenorphine, a powerful mixed agonist-antagonist analgesic which shows promise of providing maintenance pharmacotherapy for heroin addicts, is metabolized in male human subjects to norbuprenorphine and to conjugated buprenorphine and norbuprenorphine. Following subcutaneous, sublingual, and oral buprenorphine administration to a single subject, total metabolite excretion in urine was 2, 13.4, and 12.1%, respectively. No free parent drug was detected in urine. The amount of norbuprenorphine metabolite excreted in urine generally exceeded that of conjugated buprenorphine. In contrast, free and conjugated buprenorphine equaled or greatly exceeded total norbuprenorphine content in fecal samples following oral or sublingual administration. The greatest amount of drug and metabolite eliminated in feces occurred at 4 to 6 days following buprenorphine administration at times when there was very little urinary excretion of conjugated buprenorphine. This latter evidence indicates an enterohepatic circulation of buprenorphine in humans.

PubMed, Apr 1, 1998

Levo-alpha-acetylmethadol (LAAM) is a long-acting opioid agonist approved for use as a maintenanc... more Levo-alpha-acetylmethadol (LAAM) is a long-acting opioid agonist approved for use as a maintenance treatment for opioid dependence. Previous clinical studies report that the onset of the effects of LAAM is slower after parenteral administration than oral administration; however, preclinical studies suggest otherwise. This study examined the pharmacodynamic and pharmacokinetic profile of LAAM when given orally and intravenously to humans. Opioid-experienced volunteers (n = 6), who were not physically dependent on opioids, received LAAM (20 and 40 mg/70 kg i.v. and p.o.) and placebo under double-blind, double-dummy conditions during five weekly experimental sessions. Behavioral, physiological, subjective and pharmacokinetic measures were collected before and for 96 hr after drug administration. Intravenous LAAM produced significant subjective and physiological effects that appeared within 5 min, whereas the effects of oral LAAM appeared more slowly within 1 to 2 hr after drug administration. Pharmacokinetic data indicate that the immediate effects of intravenous LAAM are largely attributable to the parent drug rather than the active metabolites, nor-LAAM and dinor-LAAM. LAAM produced prototypic opioid agonist effects (i.e., miosis, subjective ratings of high, nodding) that were of equal magnitude across routes, dose-related and of long duration (up to 60 hr). These data are in contrast to previous clinical reports and indicate that LAAM produces effects of immediate onset when administered parenterally, which suggests that intravenous LAAM possesses greater abuse potential than previously believed.

PubMed, 1990

A diuretic effect of the pentapeptide BW942C [Tyr-D-Met(O)-Gly-pNO2-Phe-Pro-NH2 HCl] was demonstr... more A diuretic effect of the pentapeptide BW942C [Tyr-D-Met(O)-Gly-pNO2-Phe-Pro-NH2 HCl] was demonstrated in humans and rats; it was characterized pharmacologically using whole animal, isolated tissue and in vitro binding studies. A single 2-mg dose of BW942C increased urine output 5-fold over control values in humans. In Long-Evans rats, BW942C produced a biphasic dose-response curve for urine output with lower doses increasing and higher doses suppressing output. Low doses of naltrexone antagonized the antidiuresis, and high doses antagonized the diuresis produced by BW942C. BW942C was less efficacious in producing diuresis than the full kappa agonists bremazocine and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate, hydrate). Furthermore, BW942C antagonized the diuretic effects of bremazocine and U50,488H. Rats tolerant to U50,488H-induced diuresis were cross-tolerant to BW942C. In Brattleboro rats, which are unable to synthesize vasopressin, BW942C failed to produce a diuretic effect, demonstrating the necessity of vasopressin for its diuretic response. In the kappa-selective rabbit vas deferens bioassay, BW942C was less efficacious than a full agonist, it was antagonized by naloxone and BW942C in nondepressant doses antagonized a full agonist. In binding studies, BW942C had the highest affinity for mu and delta opioid receptors and an intermediate affinity for kappa opioid receptors. The data suggest that BW942C has the property of a partial kappa opioid agonist in addition to being a mu agonist.

Journal of Analytical Toxicology, Jul 1, 1988

Clinical Pharmacology & Therapeutics, Sep 1, 1986

Five healthy men were passively exposed under pre- and postplacebo controlled conditions to sides... more Five healthy men were passively exposed under pre- and postplacebo controlled conditions to sidestream smoke from four and 16 standard marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [delta-9-THC]) for 1 hour each day for 6 consecutive days. Subjective effects produced by the 16-cigarette exposure conditions were similar to those observed after active smoking of one 2.8% delta-9-THC marijuana cigarette. Effects after the four-cigarette condition were less pronounced. Concurrent physiologic measurements showed no clear trends or effects of smoke exposure for either condition. Daily mean plasma levels of delta-9-THC ranged from 2.4 to 7.4 ng/ml with an individual high of 18.8 ng/ml for the 16-cigarette condition. With the use of EMIT cannabinoid assays with 20 ng/ml (EMIT 20) and 100 ng/ml (EMIT 100) cutoffs, urines positive per subject under the four- and 16-cigarette passive exposure conditions were 4.6 +/- 2.2 and 35.2 +/- 3.8, respectively, for the EMIT 20 and 0.0 and 1.0 +/- 0.8, respectively, for the EMIT 100 assay. From the results of these studies, caution is clearly indicated for individuals who might be substantially exposed to heavy marijuana cigarette smoke environments and for those interpreting marijuana screening data.

Clinical Pharmacology & Therapeutics, Sep 1, 1989

Addiction, Apr 1, 1998

Aims. Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations w... more Aims. Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject‐reported withdrawalsymptomatology during buprenorphine dose induction, maintenance treatment (daily and alternate‐day dosing) and withdrawal . Design. Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate‐day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52 . Setting. Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD . Participants. Eleven male, heroin‐dependent volunteers participating in a research study . Intervention. Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine) . Measurements. Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter . Findings. The mean steady‐state buprenorphine plasma concentration (24 hours) after daily administration of sublingual buprenorphine for study days 21‐35 was 0.80 ng/ml, and the mean alternate day steady‐state buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady‐state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady‐state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady‐state (days 21‐35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half‐lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively . Conclusions. During daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half‐life of buprenorphine suggested that increasing the buprenorphine dose with alternate‐day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.

Journal of Analytical Toxicology, 2022

There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and va... more There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and vaporized formulations. This within-subject, double-blind, double-dummy, placebo-controlled laboratory study analyzed the pharmacokinetic profile of CBD, ∆9-tetrahydrocannabinol (∆9-THC) and related metabolites in blood and oral fluid (OF) after participants (n = 18) administered 100 mg of CBD in each of the following formulations: (1) oral CBD, (2) vaporized CBD and (3) vaporized CBD-dominant cannabis containing 10.5% CBD and 0.39% ∆9-THC (3.7 mg); all participants also completed a placebo condition. Oral CBD was administered in three formulations: (1) encapsulated CBD, (2) CBD suspended in pharmacy-grade syrup and (3) Epidiolex, allowing for pharmacokinetic comparisons across oral formulations (n = 6 per condition). An optional fifth experimental condition was completed for six participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg of CBD. Blood and OF...

Clinical Pharmacology & Therapeutics, 2001

Clinical Pharmacology & Therapeutics, 1997

Journal of Analytical Toxicology, 2020

Oral cannabis products (a.k.a. “edibles”) have increased in popularity in recent years. Most prio... more Oral cannabis products (a.k.a. “edibles”) have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5–2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (...

Journal of Analytical Toxicology, 2021

The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacoki... more The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC–MS-MS. Urinary CBD concentrations (ng/mL...

Drug and Alcohol Dependence, 2020

Journal of Opioid Management, 2017

The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulatio... more The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of ...