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P.6.d.009 Abuse deterrent opiate formulations: an imperfect solution to a perfect storm?
P.6.d. Addiction − Drugs (clinical) presents with a potential for dependence and the anecdotal report on injecting use. A valid cause for concern issued in our research may be its use in conjunction with other psychoactive substances. Globally, the Camfetamine users considered in our analysis, added together, are also intaking Alcohol, Cannabis, Cocaine, Heroin, Amphetamine and Synthetic Amphetamine Derivatives, Piperazine-based Derivatives, Mephedrone, Pipradrol and derivatives, Aminoindane analogues, Ketamine and derivatives, Synthetic Cannabinoid Receptor Agonists, Tryptamines, Benzofurans and Benzodifurans, Natural Product (Fungal and Herbal) Novel Psychoactive Substances, Benzodiazepines, Barbiturates, Anticonvulsant, Antidepressants, Opioid substitution/analgesic therapies. Conclusions: Such a phenomenon constitutes a serious public health challenge since pharmacological, toxicological and psychopathological effects due to interactions between all these sustances may be unpredictable and may be fatal in vulnerable individuals. Moreover, such a polyabuse may lead to deep neurobiochemical CNS alterations that may make these polyabusers extremely difficult to be pharmacologically treated even by expert mental health professionals. More large-scale studies need to be carried out to confirm and better describe both the extent of NPS misuse and possible psychotropic/adverse effects either in complex combinations with other compounds. Health and other professionals should be rapidly and accurately informed about this new and alerting trends of misuse. References [1] King, L.A., Nutt, D.J., 2014. Deaths from ‘legal highs’: a problem of definition. The Lancet, 383: 952. [2] United Nations Office on Drugs and Crime (UNODC), 2013. The challenge of New Psychoactive Substances. A Report from the Global SMART Programme. Available online at http://www.unodc.org/ documents/scientific/NPS_2013_SMART.pdf (accessed on 25/03/2014). [3] Corazza, O., Schifano, F., Simonato, P., et al., 2012. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol Clin Exp, 27: 145–149.
P.6.d.009 Abuse deterrent opiate formulations: an imperfect solution to a perfect storm? E. Sellers1 ° , M. Romach-Sellers2 1 DL Global Partners Inc, Pharmacology, Toronto Ontario, Canada; 2 University of Toronto, Psychiatry, Toronto Ontario, Canada Purpose: In North America, prescription opiate abuse (POA) particularly of extended release (ER) formulations became a serious public health issue with increased prescribing being associated with increasing deaths, overdose, diversion, and treatment admissions. However, POA disproportionately affects lower socioeconomic and marginalized individuals and regions and individuals with comorbidity many whom have chronic pain. We tested the hypothesis that tamper resistant (TR) and abuse deterrent (AD) formulations may ameliorate POA. Methods: We compiled three data sources: Published papers; patents and websites proposing TR/AD formulation technologies; our data compiled from more than 30 studies of TR/AD formulations. Results: Opiate abuse is not a recent phenomenon. Escalation in the 1990s was due to numerous factors including: spread of the internet; marketing of a crushable ER dose form (oxycodone) containing large amounts of drug (i.e., 80 and 160 mg); prescriptions were reimbursable; expansion and promotion of the use of opiates
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to chronic non-cancer pain; behavioral pharmacologic effects of opiates; lax patient selection; lack of awareness of the risks; high comorbidity in chronic pain patients and abusers; profits from diversion; lack of real time monitoring of consequences; normalization of experimentation. Reformulated Oxycontin (ER oxycodone) and Opana (ER oxymorphone) were marketed in 2010 and 2012 respectively. Reformulated ER oxycodone with a dominant market share has had large effects on routes of abuse and POA consequences. More than 20 new TR/AD technologies are currently being develop. These formulation initiatives have not occurred in isolation. Many public health policy and societal responses have transpired including: extensive media coverage; public, policy and political recognition of POA; implementations of prescription monitoring programs; numerous guidelines for use of opiates; more careful patient selection and pain management; targeted interventions (e.g., ‘pill mills’, double doctoring, limiting high dose use and prescribing); implementation of an ER opiate class REMs; mandated ER opiates label changes; publication of an FDA Guidance for TR and AD opiates; enhanced law enforcement and medical standards of care. Paradoxically, concurrent increases of availability of pure and relatively inexpensive heroin has created new issues. Conclusions: While some changes in patterns of abuse are product specific (Oxycontin), other data indicate that prescribing rates (based on per population, number of prescriptions and number of milligrams) and consequences of POA are falling for both ER and immediate release (IR) opiates. These secular trends suggest that a combination of public health interventions and other events are mitigating POA. The public health impact of reformulated Oxycontin on POA is not necessarily generalizable to other TR/AD ER or IR formulations because the opiate market is mainly IR and highly fragmented. Success of non-formulation approaches will erode enthusiasm for TR and AD formulations. As long as POA is perceived as a problem of at risk populations, a general public health benefit will not be evident and reimbursement of TR and AD formulations will be inconsistent. The reimbursement for TR and AD formulations would increase if they were less expensive. Ideally, all ER and IR opiates should be TR/AD.
P.6.d.010 Neural correlates of cue-induced craving for amphetamine J. Guterstam1 ° , N. Jayaram-Lindstr¨om1 , J. Berrebi1 , M. Ingvar1 , J. Franck1 1 Karolinska Institutet, Section of psychiatry, Stockholm, Sweden Purpose: Craving is a central concept in contemporary theories of addiction and an important target for psychological and pharmacological therapies for substance use disorders [1,2]. A deeper understanding of the neurobiology of craving might therefore be of value in the development of new treatments. Previous neuroimaging studies have investigated the neural basis of craving for several different substances, showing activation of limbic and prefrontal brain structures [3]. In some studies, neural cue reactivity has also been linked to risk of relapse to substance use. So far however, there have not been any imaging studies of cue-induced craving for amphetamine, which dominates the heavy drug use in Scandinavia. The aim of this study was to investigate the neural correlates of cue-induced amphetamine craving, using functional magnetic resonance imaging (fMRI) in a sample of amphetamine dependent men.
P.6.d.009 Abuse deterrent opiate formulations: an imperfect solution to a perfect storm? E. Sellers1 ° , M. Romach-Sellers2 1 DL Global Partners Inc, Pharmacology, Toronto Ontario, Canada; 2 University of Toronto, Psychiatry, Toronto Ontario, Canada Purpose: In North America, prescription opiate abuse (POA) particularly of extended release (ER) formulations became a serious public health issue with increased prescribing being associated with increasing deaths, overdose, diversion, and treatment admissions. However, POA disproportionately affects lower socioeconomic and marginalized individuals and regions and individuals with comorbidity many whom have chronic pain. We tested the hypothesis that tamper resistant (TR) and abuse deterrent (AD) formulations may ameliorate POA. Methods: We compiled three data sources: Published papers; patents and websites proposing TR/AD formulation technologies; our data compiled from more than 30 studies of TR/AD formulations. Results: Opiate abuse is not a recent phenomenon. Escalation in the 1990s was due to numerous factors including: spread of the internet; marketing of a crushable ER dose form (oxycodone) containing large amounts of drug (i.e., 80 and 160 mg); prescriptions were reimbursable; expansion and promotion of the use of opiates
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to chronic non-cancer pain; behavioral pharmacologic effects of opiates; lax patient selection; lack of awareness of the risks; high comorbidity in chronic pain patients and abusers; profits from diversion; lack of real time monitoring of consequences; normalization of experimentation. Reformulated Oxycontin (ER oxycodone) and Opana (ER oxymorphone) were marketed in 2010 and 2012 respectively. Reformulated ER oxycodone with a dominant market share has had large effects on routes of abuse and POA consequences. More than 20 new TR/AD technologies are currently being develop. These formulation initiatives have not occurred in isolation. Many public health policy and societal responses have transpired including: extensive media coverage; public, policy and political recognition of POA; implementations of prescription monitoring programs; numerous guidelines for use of opiates; more careful patient selection and pain management; targeted interventions (e.g., ‘pill mills’, double doctoring, limiting high dose use and prescribing); implementation of an ER opiate class REMs; mandated ER opiates label changes; publication of an FDA Guidance for TR and AD opiates; enhanced law enforcement and medical standards of care. Paradoxically, concurrent increases of availability of pure and relatively inexpensive heroin has created new issues. Conclusions: While some changes in patterns of abuse are product specific (Oxycontin), other data indicate that prescribing rates (based on per population, number of prescriptions and number of milligrams) and consequences of POA are falling for both ER and immediate release (IR) opiates. These secular trends suggest that a combination of public health interventions and other events are mitigating POA. The public health impact of reformulated Oxycontin on POA is not necessarily generalizable to other TR/AD ER or IR formulations because the opiate market is mainly IR and highly fragmented. Success of non-formulation approaches will erode enthusiasm for TR and AD formulations. As long as POA is perceived as a problem of at risk populations, a general public health benefit will not be evident and reimbursement of TR and AD formulations will be inconsistent. The reimbursement for TR and AD formulations would increase if they were less expensive. Ideally, all ER and IR opiates should be TR/AD.
P.6.d.010 Neural correlates of cue-induced craving for amphetamine J. Guterstam1 ° , N. Jayaram-Lindstr¨om1 , J. Berrebi1 , M. Ingvar1 , J. Franck1 1 Karolinska Institutet, Section of psychiatry, Stockholm, Sweden Purpose: Craving is a central concept in contemporary theories of addiction and an important target for psychological and pharmacological therapies for substance use disorders [1,2]. A deeper understanding of the neurobiology of craving might therefore be of value in the development of new treatments. Previous neuroimaging studies have investigated the neural basis of craving for several different substances, showing activation of limbic and prefrontal brain structures [3]. In some studies, neural cue reactivity has also been linked to risk of relapse to substance use. So far however, there have not been any imaging studies of cue-induced craving for amphetamine, which dominates the heavy drug use in Scandinavia. The aim of this study was to investigate the neural correlates of cue-induced amphetamine craving, using functional magnetic resonance imaging (fMRI) in a sample of amphetamine dependent men.