The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

http://www.phytecs.com/wp-content/uploads/2015/02/Pharmacol-Rev-2006-Pacher-389-462.pdf

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

ContextAlcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.ObjectivesTo evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.Design, Setting, and ParticipantsRandomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.InterventionsEight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.Main Outcome MeasuresPercent days abstinent from alcohol and time to first heavy drinking day.ResultsAll groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.ConclusionsPatients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.Trial Registrationclinicaltrials.gov Identifier: NCT00006206

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Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence: The COMBINE Study: A Randomized Controlled Trial

Inhibition and impulsivity: Behavioral and neural basis of response control

http://homepages.se.edu/cvonbergen/files/2013/01/Fifty-Years-of-the-Barratt-Impulsivenss-Scale_An-Update-and-Review.pdf

Fifty years of the Barratt Impulsiveness Scale: An update and review

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the br...

Endocannabinoid-Mediated Control of Synaptic Transmission

Executive function in schizophrenia: Influence of substance use disorder history

The role of psychopharmacology in the medical abuses of the Third Reich: From euthanasia programmes to human experimentation

Modulation of impulsivity by topiramate: Implications for the treatment of alcohol dependence

The present study explored the reliability and validity of a Spanish version of the Readiness to Change Questionnaire (RCQ) (12-item short form) as it might be used for opportunistic intervention. The test has three scales to allocate patients to a stage of change: pre-contemplation (P), contemplation (C) or action (A). The RCQ was translated and back-translated prior to pilot administration to 15 patients. From two settings (a general hospital ward and a primary health care centre), 201 patients were identified as excessive drinkers on the Alcohol Use Disorders Identification Test. Patients known to be alcohol-dependent and attending for alcohol-related reasons were excluded. Patients completed the RCQ. Test-retest reliability after 2 days was assessed in 35 patients. A components analysis was performed. Patients were classified on RCQ scores to a stage of change. Two experts separately interviewed the patients and made an allocation to stage of change, blind to the RCQ score. Test-retest reliability was good (P: r = 0.81; C: r = 0.87; A: r = 0.86). Within the three scales, RCQ items showed fair consistency in terms of Cronbach's alpha (P: 0.58, C: 0.75, A: 0.80). Component analysis showed that together the scales accounted for 57. 4% of the variance. The experts agreed between themselves on patients' stage of change (weighted kappa 0.92) but much less with the stage of change according to RCQ (expert A, kappa = 0.44; expert B, kappa = 0.52). Omitting patients with low consumption did not improve internal reliability, and omitting those with low educational level who might have filled in the questionnaire wrongly did not improve internal reliability or agreement between RCQ and the experts. We conclude that the Spanish RCQ did not function efficiently in a population of opportunistically identified excessive drinkers.

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Readiness to change questionnaire: reliability study of its Spanish version.

Introduction Anticonvulsant drugs have been used in the treatment of alcohol detoxification. The purpose of the present study was to evaluate the efficacy and safety of zonisamide in a sample of patients presenting alcohol withdrawal syndrome. Method In this 3-week, randomized, flexible-dose trial, 40 inpatients with alcohol dependence disorder received zonisamide or diazepam for detoxification. Zonisamide was started at a dose of 400-600 mg/day (week 1), tapering to a minimum dose of 100-300 mg/day (week 3). Diazepam was administered using a similar regimen (from 130-50 mg/day tapering to 5-15 mg/day). Subjects were treated initially (weeks 1 and 2) in an inpatient unit and for the final week in an outpatient facility. During the inpatient period, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) was used to assess the efficacy of each substance. During the outpatient period the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and a craving scale were used. Results All subjects completed the study. During the inpatient period both drugs reduced alcohol withdrawal symptoms, but the decrease was more marked in the zonisamide group. At the end of the study (week 3) participants treated with zonisamide showed lower CIWA-Ar scores than subjects receiving diazepam. Also, individuals in the zonisamide group had less craving for alcohol, less anxiety, and less daytime sedation compared with participants treated with diazepam. Conclusion Zonisamide can be a valuable alternative to benzodiazepines in the prevention of alcohol withdrawal syndrome.

Gabriel Rubio

Papers

Executive function in schizophrenia: Influence of substance use disorder history

The role of psychopharmacology in the medical abuses of the Third Reich: From euthanasia programmes to human experimentation

Modulation of impulsivity by topiramate: Implications for the treatment of alcohol dependence

Readiness to change questionnaire: reliability study of its Spanish version.

Zonisamide versus diazepam in the treatment of alcohol withdrawal syndrome