Interest in the potential therapeutic benefits of psychedelic agents has recently increased. In addition to psilocybin, a wide variety of agents with psychedelic properties have been proposed and ...partially tested. However, the challenges of obtaining approval to market a restricted psychotomimetic agent are formidable.
Abstract This paper summarizes the background and origins of pharmaceutical risk management and minimization principles and approaches as reflected in FDA statute, policy, and practice. It describes ...the history of early “risk management” programs, such as the patient package inserts (PPIs) introduced for oral contraceptives in 1976 and medication guides developed for products with safety concerns over the past decade. Exemplary products and programs that include restricted distribution systems such as the early clozapine “blood for drug” program are discussed. The principles and tools described in the US Food and Drug Administration (FDA) risk management guidances of 2005 are likely to be relied upon as the REMS (Risk Evaluation and Mitigation Strategies) mandated by the FDA Amendments Act (FDAAA) of 2007 are implemented.
Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and ...play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges.
While the varied psychedelic agents described in this chapter share some properties, they have a range of pharmacologic effects that are reflected in the gradation in intensity of hallucinogenic effects from the classical agents to DMT, MDMA, ketamine, dextromethorphan and new drugs with activity in the serotonergic system. The common link seems to be serotonergic effects modulated by NMDA and other neurotransmitter effects. The range of hallucinogens suggest that they are distinct pharmacologic agents and will not be equally safe or effective in therapeutic targets. Newly synthesized specific and selective agents modeled on the legacy agents may be worth considering.
Defining therapeutic targets that represent unmet medical need, addressing market and commercial issues, and finding treatment settings to safely test and use such drugs make the human testing of psychedelics not only interesting but also very challenging.
This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.
•Safe conduct.•Pharmacodynamic measures.•Study design weaknesses.•Regulatory approval.
ABSTRACT
Aims To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.
Design ...A 10‐week out‐patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.
Setting This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.
Participants Participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence. Sixty‐seven participants were enrolled with 55 completing final study measures.
Intervention The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.
Measurements Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale–Observer and self‐report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.
Findings Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5–8 (P = 0.10) and non‐significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.
Conclusions The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.
Research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties ...of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies.
Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies.
Cannabis for Medical Use Eisenberg, Rebecca S.; Leiderman, Deborah B.
Food and drug law journal,
01/2019, Letnik:
74, Številka:
2
Journal Article
Recenzirano
A majority of Americans now live in states that purport to authorize medical use of cannabis, although federal law continues to prohibit both recreational and medical use. The current legal regime ...for cannabis is unstable and may be more effective at deterring research than it is at deterring medical use. Lack of data on medical cannabis products poses public health risks as well as policy and legal challenges. Modified regulatory approaches for other kinds of products provide alternative models for encouraging safety and effectiveness research and providing better information about cannabis products already in clinical use.
ABSTRACT
Aims To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence.
Design ... A 10‐week out‐patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.
Setting The study was conducted at the Cincinnati Medication Development Research Unit (MDRU).
Participants Participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures.
Intervention The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.
Measurements Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale—observer and self‐report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests.
Findings Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non‐significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well.
Conclusions The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.
ABSTRACT
Aims The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine ...dependence.
Design A multi‐arm, modified blinded, placebo‐controlled design was used.
Setting The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).
Participants Participants met criteria for cocaine dependence during a 2‐week screening period.
Intervention Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.
Measurements Urine benzoylecgonine (BE) concentrations, self‐report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.
Findings None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end‐point compared to the placebo group. Significant within‐group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self‐reported cocaine use declined over the study period. Overall, the active medications were well tolerated.
Conclusions This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.
Opiate dependence remains a fundamental challenge confronting health delivery systems and is often characterized as a social and moral issue. The impact of this disorder on healthcare policy is ...changing with the increased incidence of HIV, hepatitis C, and tuberculosis infections in opiate-dependent patients. These medical illnesses have substantial effect on escalating healthcare costs, and, therefore, also affect healthcare policy priorities, which are responsive to these costs. Pharmacological treatments for opiate dependence have had limited success; often the consequence of limited access to care. Hence, there is a need to develop new pharmacotherapies for opiate dependence that extend the range of clinical options, including new first-line treatment approaches. This paper will focus on the safety and health policy considerations related to the use of buprenorphine and buprenorphine/naloxone based on data derived from clinical trials and post-marketing surveillance that provide evidence for the use of the medications as first-line treatments in an office-based environment. The evaluation of this evidence formed the basis by the National Institute on Drug Abuse to support and pursue the evaluation and registration of buprenorphine/naloxone and buprenorphine in a public/private sector cooperative effort to become an office-based, first-line treatment for opiate dependence.
This paper summarizes the background and origins of pharmaceutical risk management and minimization principles and approaches as reflected in FDA statute, policy, and practice. It describes the ...history of early 'risk management' programs, such as the patient package inserts (PPIs) introduced for oral contraceptives in 1976 and medication guides developed for products with safety concerns over the past decade. Exemplary products and programs that include restricted distribution systems such as the early clozapine 'blood for drug' program are discussed. The principles and tools described in the US Food and Drug Administration (FDA) risk management guidances of 2005 are likely to be relied upon as the REMS (Risk Evaluation and Mitigation Strategies) mandated by the FDA Amendments Act (FDAAA) of 2007 are implemented. Copyright Elsevier Ireland Ltd.
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