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Dual blockade of endocannabinoid hydrolyzing enzymes reveal a CB1 receptor-mediated interoceptive stimulus
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Abstracts / Drug and Alcohol Dependence 156 (2015) e102–e182
Dual blockade of endocannabinoid hydrolyzing enzymes reveal a CB1 receptor-mediated interoceptive stimulus Robert Owens 1 , Patrick Beardsley 1 , Benjamin cravatt 3 , Aron Lichtman 2 1
VCU, Richmond, VA, United States Virginia Commonwealth University, Richmond, VA, United States 3 The Scripps Research Institute, La Jolla, CA, United States 2
Aims: The observation that dual blockade of endogenous cannabinoid degradative enzymes monoacylglycerol (MAGL) and fatty acid amide hydrolase (FAAH) elicits THC-like psychotropic effects suggest FAAH & MAGL function as dual brakes in curtailing the pharmacological effects of endogenous cannabinoids. To test this hypothesis, we examined whether blockade of FAAH and MAGL would produce an interoceptive stimulus in mice, using the drug discrimination paradigm. Drug discrimination is an assay used to infer the subjective effects of drugs. Here we tested whether elevating levels of the naturally occurring endogenous cannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) via inhibition of both degradative enzymes would serve as an interoceptive stimulus in mice, N = 7–8. Towards this end, we employed the dual FAAH & MAGL inhibitor SA-57 as the training drug. Methods: Mice were trained using a double alternation between SA-57 and vehicle (DDVVDD) and acquired the task over 40 days. Results: The discriminative stimulus effects of 10 mg/kg SA57 were dose-related (ED50 (95% CI) = 4.49 (3.77–5.35) mg/kg) and were antagonized by the CB1 receptor antagonist rimonabant (3 mg/kg), but not the CB2 receptor antagonist SR144528 (3 mg/kg). CP55, 940 as well as the dual FAAH/MAGL inhibitor JZL195 substituted for SA-57, and rimonabant blocked the substitution of both. Low doses of SA-57 (<3 mg/kg), which completely inhibit FAAH, but not MAGL, did not substitute for SA-57. Conclusions: These findings suggest that inhibition of FAAH alone is not sufficient to elicit SA-57-like subjective effects. Taken together, this study represents the first example that elevating levels of naturally occurring endogenous cannabinoids serves as a discriminative stimulus. Thus, MAGL and possibly FAAH serve as brakes in curtailing the psychotropic effects of endogenous cannabinoids. Financial support: Dr. Aron Lichtman, Virginia Commonwealth University. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.456 Using cellphone technology to monitor and increase dosing adherence Mark Oyama 1 , Maureen P. Hillhouse 1 , Christie Thomas 1 , Jeffrey Annon 1 , Albert Hasson 1 , Larissa Mooney 1 , Robrina Walker 2 , Linda Chang 3 , Steve Sparenborg 4 , Walter Ling 1 1
UCLA, Los Angeles, CA, United States UT Southwestern Medical Center, Dallas, TX, United States 3 University of Hawaii, Honolulu, HI, United States 4 Center for the Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, United States 2
Aims: Cellphone technology has become ubiquitous in substance abuse research over the last few years. Cellphone text reminders and status assessments allow a virtual 24-h assessment
window; previous research used cellphones to remind participants to take their study medication and to take photos when dosing. Methods: A current study conducted under the auspices of the NIDA Clinical Trials Network, the Accelerated Development of Additive Pharmacotherapy (ADAPT) trial, extends the usefulness of cellphone technology. Participants are provided with smartphones to capture medication dosing in video format, and reimbursement is given for each valid video submitted. Results: Cellphones were provided to 49 study participants at three study sites. Smartphone use in this study addresses several concerns typically in research on participants with substance use disorders: (1) provides a method of contact with participants outside the clinic visit; (2) serves as a reminder to take study medication; (3) encourages adherence by incentivizing submission of valid dosing videos; (4) allows participant to enter clinic appointments in cellphone calendar and set reminders; (5) confirms self-reported medication adherence; and (6) may increase retention as participants keep smartphones at study completion. Including cellphones in the study design has also introduced some challenges: (1) ensuring privacy and confidentiality of study data; (2) difficulties in teaching participants how to use the device; and (3) navigating new ground in terms of regulatory approvals. Conclusions: Cellphone technology as used in the treatment studies may improve treatment or medication adherence, participant engagement and retention, serving to improve collection and validation of study data. Financial support: DA13045. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.457 The impact of nicotine dose assignment on affect and depression during extended exposure to experimental Spectrum cigarettes: Findings from CENIC Project 1 Study 1 Lauren R. Pacek 3 , Ryan Vandrey 2 , Jennifer W. Tidey 1 , David J. Drobes 5 , Joseph Koopmeiners 6 , Annie Umbricht 4 , Dorothy Hatsukami 7 , Eric Donny 8 1 Center for Alcohol & Addictions Studies, Brown University, Providence, RI, United States 2 Johns Hopkins University, Baltimore, MD, United States 3 Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States 4 Johns Hopkins University School of Medicine, Baltimore, MD, United States 5 Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, United States 6 Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, United States 7 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, United States 8 Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
Aims: To explore how nicotine dose assignment impacts affect and depression status during 6-week exposure to experimental cigarettes. Methods: Data came from the Center for Evaluation of Nicotine in Cigarettes (CENIC) Project 1 Study, a randomized clinical trial among general population current cigarette smokers in the U.S. (2013–2014). Descriptive statistics were used to describe the sample, and logistic regression and linear mixed models were used
Abstracts / Drug and Alcohol Dependence 156 (2015) e102–e182
Dual blockade of endocannabinoid hydrolyzing enzymes reveal a CB1 receptor-mediated interoceptive stimulus Robert Owens 1 , Patrick Beardsley 1 , Benjamin cravatt 3 , Aron Lichtman 2 1
VCU, Richmond, VA, United States Virginia Commonwealth University, Richmond, VA, United States 3 The Scripps Research Institute, La Jolla, CA, United States 2
Aims: The observation that dual blockade of endogenous cannabinoid degradative enzymes monoacylglycerol (MAGL) and fatty acid amide hydrolase (FAAH) elicits THC-like psychotropic effects suggest FAAH & MAGL function as dual brakes in curtailing the pharmacological effects of endogenous cannabinoids. To test this hypothesis, we examined whether blockade of FAAH and MAGL would produce an interoceptive stimulus in mice, using the drug discrimination paradigm. Drug discrimination is an assay used to infer the subjective effects of drugs. Here we tested whether elevating levels of the naturally occurring endogenous cannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) via inhibition of both degradative enzymes would serve as an interoceptive stimulus in mice, N = 7–8. Towards this end, we employed the dual FAAH & MAGL inhibitor SA-57 as the training drug. Methods: Mice were trained using a double alternation between SA-57 and vehicle (DDVVDD) and acquired the task over 40 days. Results: The discriminative stimulus effects of 10 mg/kg SA57 were dose-related (ED50 (95% CI) = 4.49 (3.77–5.35) mg/kg) and were antagonized by the CB1 receptor antagonist rimonabant (3 mg/kg), but not the CB2 receptor antagonist SR144528 (3 mg/kg). CP55, 940 as well as the dual FAAH/MAGL inhibitor JZL195 substituted for SA-57, and rimonabant blocked the substitution of both. Low doses of SA-57 (<3 mg/kg), which completely inhibit FAAH, but not MAGL, did not substitute for SA-57. Conclusions: These findings suggest that inhibition of FAAH alone is not sufficient to elicit SA-57-like subjective effects. Taken together, this study represents the first example that elevating levels of naturally occurring endogenous cannabinoids serves as a discriminative stimulus. Thus, MAGL and possibly FAAH serve as brakes in curtailing the psychotropic effects of endogenous cannabinoids. Financial support: Dr. Aron Lichtman, Virginia Commonwealth University. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.456 Using cellphone technology to monitor and increase dosing adherence Mark Oyama 1 , Maureen P. Hillhouse 1 , Christie Thomas 1 , Jeffrey Annon 1 , Albert Hasson 1 , Larissa Mooney 1 , Robrina Walker 2 , Linda Chang 3 , Steve Sparenborg 4 , Walter Ling 1 1
UCLA, Los Angeles, CA, United States UT Southwestern Medical Center, Dallas, TX, United States 3 University of Hawaii, Honolulu, HI, United States 4 Center for the Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, United States 2
Aims: Cellphone technology has become ubiquitous in substance abuse research over the last few years. Cellphone text reminders and status assessments allow a virtual 24-h assessment
window; previous research used cellphones to remind participants to take their study medication and to take photos when dosing. Methods: A current study conducted under the auspices of the NIDA Clinical Trials Network, the Accelerated Development of Additive Pharmacotherapy (ADAPT) trial, extends the usefulness of cellphone technology. Participants are provided with smartphones to capture medication dosing in video format, and reimbursement is given for each valid video submitted. Results: Cellphones were provided to 49 study participants at three study sites. Smartphone use in this study addresses several concerns typically in research on participants with substance use disorders: (1) provides a method of contact with participants outside the clinic visit; (2) serves as a reminder to take study medication; (3) encourages adherence by incentivizing submission of valid dosing videos; (4) allows participant to enter clinic appointments in cellphone calendar and set reminders; (5) confirms self-reported medication adherence; and (6) may increase retention as participants keep smartphones at study completion. Including cellphones in the study design has also introduced some challenges: (1) ensuring privacy and confidentiality of study data; (2) difficulties in teaching participants how to use the device; and (3) navigating new ground in terms of regulatory approvals. Conclusions: Cellphone technology as used in the treatment studies may improve treatment or medication adherence, participant engagement and retention, serving to improve collection and validation of study data. Financial support: DA13045. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.457 The impact of nicotine dose assignment on affect and depression during extended exposure to experimental Spectrum cigarettes: Findings from CENIC Project 1 Study 1 Lauren R. Pacek 3 , Ryan Vandrey 2 , Jennifer W. Tidey 1 , David J. Drobes 5 , Joseph Koopmeiners 6 , Annie Umbricht 4 , Dorothy Hatsukami 7 , Eric Donny 8 1 Center for Alcohol & Addictions Studies, Brown University, Providence, RI, United States 2 Johns Hopkins University, Baltimore, MD, United States 3 Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States 4 Johns Hopkins University School of Medicine, Baltimore, MD, United States 5 Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, United States 6 Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, United States 7 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, United States 8 Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
Aims: To explore how nicotine dose assignment impacts affect and depression status during 6-week exposure to experimental cigarettes. Methods: Data came from the Center for Evaluation of Nicotine in Cigarettes (CENIC) Project 1 Study, a randomized clinical trial among general population current cigarette smokers in the U.S. (2013–2014). Descriptive statistics were used to describe the sample, and logistic regression and linear mixed models were used