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Differences in cannabis withdrawal symptoms between individuals with and without attention deficit hyperactivity disorder
Abstracts / Drug and Alcohol Dependence 140 (2014) e2–e85
Opioids with lower brain uptake are less recognizable in rat drug discrimination tests and thus potentially less subject to abuse Stephen D. Harrison 1 , H. Gursahani 1 , J. Pfeiffer 1 , K. Gogas 1 , J. Riggs 1 , T. Riley 1 , D. Gauvin 2 , S. Doberstein 1 1
Nektar Therapeutics, San Francisco, CA, United States 2 MPI Research, Inc., Mattawan, MI, United States Aims: Prescription opioids are the mainstay of analgesic therapy, although their abuse is rising to epidemic proportions. A solution to this problem would be to separate opioid analgesia from abuse potential. Drugs that are readily recognized as opioids are considered more prone to abuse. We have tested whether lowering the rate of brain entry of an opioid will make it less recognizable in rat drug discrimination assays. Methods: Various mu-opioid agonists were assessed for different properties: (1) potency by receptor binding and elicitedfunction in vitro; (2) brain-uptake rate relative to an antipyrine control compound by in situ brain perfusion; (3) potential to be recognized as a mu-opioid agonist by rats trained to recognize oxycodone in the drug discrimination assay. Correlations between these parameters were made to establish underlying relationships between them. Results: The rate of brain uptake and potency of mu-opioid agonists both correlate inversely with the minimum discriminable dose (MDD) in the rat drug discrimination assay. The highest MDD was observed for opioids with dramatically reduced brain uptake rates (between 0.01 and 0.1 relative to antipyrine) compared to commercially used opioids (brain uptake rates between 0.5 and 10 relative to antipyrine). Conclusions: Opioid agonists that have a high potency against the mu-opioid receptor and which have a high rate of entry into the brain are more likely to be recognized as a mu-opioid agonists. A low MDD is considered to be reflective of potential abuse liability and consequently opioids with low brain entry rates, and thus higher MDD values, may have less abuse potential. Consequently it may be possible to maintain analgesic efficacy and yet reduce the potential for the abuse, by reducing brain entry rate. Mu-opioid agonists with an engineered reduction in brain uptake rate offer a potential approach to achieving this goal. Financial support: Nektar Therapeutics. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.239 Differences in cannabis withdrawal symptoms between individuals with and without attention deficit hyperactivity disorder Karen Hartwell 1,2 , E. Chauchard 3,4 , D.A. Gorelick 3 , Aimee McRae-Clark 1 1 Department of Psychiatry, MUSC, Charleston, SC, United States 2 Ralph H. Johnson VAMC, Charleston, SC, United States 3 Intramural Research Program, NIDA, Bethesda, MD, United States 4 Toulouse University Octogone-CERPP, Toulouse, France
Aims: Individuals with attention deficit hyperactivity disorder (ADHD) have greater cannabis use than the general population. Differences in cannabis withdrawal symptoms were examined between cannabis-dependent adults with and without ADHD.
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Methods: Treatment-seeking, cannabis-dependent adults with (n = 30) and without (n = 23) ADHD enrolled in two pharmacotherapy treatment studies completed the Marijuana Quit Questionnaire, a 176-item semi-structured instrument, to assess withdrawal symptoms during their “most serious” (self-defined) quit attempt without formal treatment. Data were analyzed with chi-square Kruskal–Wallis tests for independent samples with statistical significance of two-tailed alpha value p < 0.05. Results: No significant differences between the two groups in sociodemographic or cannabis use characteristics were found. Majority of subjects were male (84%), white (84%), single (67%); average (SD) age 31.2 (10.6) years. Age of first cannabis use was 15.3 (3.0) years, of first regular use 17.4 (3.9) years. In month prior to quit attempt, 71.4% of subjects smoked cannabis at least daily; 97.5% at least weekly. Ninety-five percent of subjects reported at least one withdrawal symptom, most commonly craving for marijuana (68%), initial insomnia (65%), boredom (57%), restlessness (55%), anxiety (51%), angry (49%), and irritability (49%). Non- ADHD subjects were significantly more likely than those with ADHD to report decreased appetite or weight loss (50% vs. 17%, 2 = 5.18, p = 0.023). 45% of the non-ADHD group met proposed DSM-5 criteria for cannabis withdrawal syndrome compared to 30.4% of the ADHD group. Conclusions: Results suggest that more severe withdrawal symptoms may not account for higher rates of cannabis dependence among individuals with ADHD. Financial support: Supported by the Intramural Research Program, NIH, NIDA (DAG), 5R21DA018221 (ALM-C), 5R01DA026782 (ALM-C), and French Interministerial Mission for the Fight against Drugs and Drug Addiction (EC). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.240 Workshop training in contingency management: Initial effects on the attitudes, knowledge, self-efficacy, and adoption readiness of community addiction treatment personnel Bryan Hartzler Alcohol & Drug Abuse Institute, University of Washington, Seattle, WA, United States Aims: While the efficacy of contingency management (CM) in addiction treatment is well-established, little is known about impacts of training for community based treatment personnel. This study reports initial impacts of workshop training among staff at a community-based opiate treatment program (OTP). Methods: OTP staff (N = 17) were recruited to participate in a 16-h CM training workshop, dispersed as four weekly half-day sessions at their clinic, and complete training outcome assessments one week prior and one week following training. Assessments measured positive/negative attitudes, conceptual and applied knowledge, self-efficacy for implementation, and adoption readiness. To account for assessment reactivity, a subsample (n = 10) were randomly-assigned to twice complete the pre-training assessment seven days apart. General linear models (GLM) first assessed assessment reactivity in this subsample, and then training impacts in the full sample. Results: Across outcome measures, GLM effects targeting assessment reactivity were nonsignificant (all p-values > .25) with effect sizes below threshold for educational significance. GLM revealed significant training effects for increases in conceptual knowledge (p < .001), applied knowledge (p < .01), self-efficacy for implementation (p < .05), and adoption readiness (p < .05). GLM
Opioids with lower brain uptake are less recognizable in rat drug discrimination tests and thus potentially less subject to abuse Stephen D. Harrison 1 , H. Gursahani 1 , J. Pfeiffer 1 , K. Gogas 1 , J. Riggs 1 , T. Riley 1 , D. Gauvin 2 , S. Doberstein 1 1
Nektar Therapeutics, San Francisco, CA, United States 2 MPI Research, Inc., Mattawan, MI, United States Aims: Prescription opioids are the mainstay of analgesic therapy, although their abuse is rising to epidemic proportions. A solution to this problem would be to separate opioid analgesia from abuse potential. Drugs that are readily recognized as opioids are considered more prone to abuse. We have tested whether lowering the rate of brain entry of an opioid will make it less recognizable in rat drug discrimination assays. Methods: Various mu-opioid agonists were assessed for different properties: (1) potency by receptor binding and elicitedfunction in vitro; (2) brain-uptake rate relative to an antipyrine control compound by in situ brain perfusion; (3) potential to be recognized as a mu-opioid agonist by rats trained to recognize oxycodone in the drug discrimination assay. Correlations between these parameters were made to establish underlying relationships between them. Results: The rate of brain uptake and potency of mu-opioid agonists both correlate inversely with the minimum discriminable dose (MDD) in the rat drug discrimination assay. The highest MDD was observed for opioids with dramatically reduced brain uptake rates (between 0.01 and 0.1 relative to antipyrine) compared to commercially used opioids (brain uptake rates between 0.5 and 10 relative to antipyrine). Conclusions: Opioid agonists that have a high potency against the mu-opioid receptor and which have a high rate of entry into the brain are more likely to be recognized as a mu-opioid agonists. A low MDD is considered to be reflective of potential abuse liability and consequently opioids with low brain entry rates, and thus higher MDD values, may have less abuse potential. Consequently it may be possible to maintain analgesic efficacy and yet reduce the potential for the abuse, by reducing brain entry rate. Mu-opioid agonists with an engineered reduction in brain uptake rate offer a potential approach to achieving this goal. Financial support: Nektar Therapeutics. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.239 Differences in cannabis withdrawal symptoms between individuals with and without attention deficit hyperactivity disorder Karen Hartwell 1,2 , E. Chauchard 3,4 , D.A. Gorelick 3 , Aimee McRae-Clark 1 1 Department of Psychiatry, MUSC, Charleston, SC, United States 2 Ralph H. Johnson VAMC, Charleston, SC, United States 3 Intramural Research Program, NIDA, Bethesda, MD, United States 4 Toulouse University Octogone-CERPP, Toulouse, France
Aims: Individuals with attention deficit hyperactivity disorder (ADHD) have greater cannabis use than the general population. Differences in cannabis withdrawal symptoms were examined between cannabis-dependent adults with and without ADHD.
e81
Methods: Treatment-seeking, cannabis-dependent adults with (n = 30) and without (n = 23) ADHD enrolled in two pharmacotherapy treatment studies completed the Marijuana Quit Questionnaire, a 176-item semi-structured instrument, to assess withdrawal symptoms during their “most serious” (self-defined) quit attempt without formal treatment. Data were analyzed with chi-square Kruskal–Wallis tests for independent samples with statistical significance of two-tailed alpha value p < 0.05. Results: No significant differences between the two groups in sociodemographic or cannabis use characteristics were found. Majority of subjects were male (84%), white (84%), single (67%); average (SD) age 31.2 (10.6) years. Age of first cannabis use was 15.3 (3.0) years, of first regular use 17.4 (3.9) years. In month prior to quit attempt, 71.4% of subjects smoked cannabis at least daily; 97.5% at least weekly. Ninety-five percent of subjects reported at least one withdrawal symptom, most commonly craving for marijuana (68%), initial insomnia (65%), boredom (57%), restlessness (55%), anxiety (51%), angry (49%), and irritability (49%). Non- ADHD subjects were significantly more likely than those with ADHD to report decreased appetite or weight loss (50% vs. 17%, 2 = 5.18, p = 0.023). 45% of the non-ADHD group met proposed DSM-5 criteria for cannabis withdrawal syndrome compared to 30.4% of the ADHD group. Conclusions: Results suggest that more severe withdrawal symptoms may not account for higher rates of cannabis dependence among individuals with ADHD. Financial support: Supported by the Intramural Research Program, NIH, NIDA (DAG), 5R21DA018221 (ALM-C), 5R01DA026782 (ALM-C), and French Interministerial Mission for the Fight against Drugs and Drug Addiction (EC). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.240 Workshop training in contingency management: Initial effects on the attitudes, knowledge, self-efficacy, and adoption readiness of community addiction treatment personnel Bryan Hartzler Alcohol & Drug Abuse Institute, University of Washington, Seattle, WA, United States Aims: While the efficacy of contingency management (CM) in addiction treatment is well-established, little is known about impacts of training for community based treatment personnel. This study reports initial impacts of workshop training among staff at a community-based opiate treatment program (OTP). Methods: OTP staff (N = 17) were recruited to participate in a 16-h CM training workshop, dispersed as four weekly half-day sessions at their clinic, and complete training outcome assessments one week prior and one week following training. Assessments measured positive/negative attitudes, conceptual and applied knowledge, self-efficacy for implementation, and adoption readiness. To account for assessment reactivity, a subsample (n = 10) were randomly-assigned to twice complete the pre-training assessment seven days apart. General linear models (GLM) first assessed assessment reactivity in this subsample, and then training impacts in the full sample. Results: Across outcome measures, GLM effects targeting assessment reactivity were nonsignificant (all p-values > .25) with effect sizes below threshold for educational significance. GLM revealed significant training effects for increases in conceptual knowledge (p < .001), applied knowledge (p < .01), self-efficacy for implementation (p < .05), and adoption readiness (p < .05). GLM