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

/pdf/combined-pharmacotherapies-and-behavioral-interventions-for-2vogia99j0.pdf

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

Background and Objectives: TaqI-A polymorphism, related to D2 dopamine receptor (DRD2), and event-related P300 potentials have been considered markers of alcohol dependence. The effect of alcohol use variables and TaqI-A on P300 in a single sample have been hardly analysed previously. This study examined changes in P300 parameters after six months of abstinence in alcohol-dependent subjects classified by their TaqI-A genotype. Methods: 102 men with alcohol dependence were studied at baseline and at 6 months of continued abstinence. P300 was recorded using an auditory paradigm. TaqI-A polymorphism was genotyped: 34.3% of sample was classified as A1[TaqI-A1/TaqI-A1and TaqI-A1/TaqI-A2] and 65.7% as A2 [TaqI-A2/TaqI-A2]. The association between P300 and TaqI-A and the correlation with age and alcohol consumption were considered. Results: The abstinence period was not associated to differences in neither P300 latency (F[1, 99] = 1.154 p = 0.285) nor amplitude (F[1, 99] = 1.453, p = 0.231). A1 subgroup was related to a longer latency (F[1, 99] = 5.055 p = 0.027), an early abuse age onset (F[1, 100] = 14.552 p < 0.001) and close to be significant to an early dependence age onset (F[1, 100] = 3.868 p = 0.052). Other drinking pattern variables were not associated to p300 measures. Family history for alcoholism and TaqI-A were not related (X[1] = 0.327 p = 0.568) and no association was found with p300 measures. Current age correlated positively with P300 latency (F[1, 99] = 26.082, p < 0,001) and negatively with amplitude (F[1, 99] = 5.297 p = 0.023). P300 amplitude was not influenced by alcohol use variables nor TaqI-A polymorphism. Conclusions: P300 latency could be a biological marker of vulnerability to alcohol dependence related to TaqI-A1 polymorphism, irrespective of alcohol use variables. Received: 11 November 2008 Revised: 10 August 2009 Accepted: 14 September 2009 Background and Objectives P300 is a positive electrical deflection recorded at maximal amplitudes over the midline centroparietal scalp in response to rare attended events within a sequence of similar, but discriminate, stimuli. Although the functional significance of P300 is still debated1, 2, its amplitude indexes the allocation of resources for the evaluation of stimuli and its sensitivity to instrumental manipulation indicates that it reflects a neural substrate of controlled information processing strategies3. Reduced P300 amplitude has been reported in many psychiatric disorders, including schizophrenia4, depression5, and alcoholism6. Various studies have related the presence of lower P300 amplitude or longer P300 latency with alcoholism7-10. Many of these studies have been carried out on children of alcoholics, so P300 alterations have been considered a genetic marker of vulnerability to alcoholism11 or an endophenotype of an alcoholism subtype12-15. The brain dopaminergic system, which is centrally involved in reward and learning, has been widely studied in substance use disorders. The TaqI-A single-nucleotide polymorphism (SNP) (rs1800497) located near the 3 ́region of the dopamine D2 receptor gene (DRD2; chromosome 11q22–q23) has been considered a genetic marker of alcoholism1619. TaqI-A SNP consists of the substitution of C > T, also called the A2 and A1 alleles, respectively, which affects a previously unidentified protein kinase gene called ANKK1 (ankyrin repeat and kinase domain containing 1)20. There is no consensus about the role of the A1 allele and A1 genotype (heterozygous or homozygous for A1 allele) in addictive behaviour, but three meta-analyses have shown a robust association between TaqI-A SNP and alcoholism21, 22. In addition, the P300 wave has been associated with dopaminergic activity23 and TaqI-A polymorphism has been associated with P300-wave changes. The relationship between P300 wave and TaqI-A has been examined in non alcoholic sons of alcoholics. Longer latencies24 and amplitude attenuation have been observed in A1 subjects25, 26. We found that A1 alcohol-dependent males had longer P300 latencies than A2 alcohol dependents and healthy controls27. Nonetheless, other studies have not found any differences between the A1 and A2 subgroups28. To further examine P300 capability to measure possible differences associated to the TaqI A1 and A2 subgroups and to ethanol toxic effect in alcohol dependence, we studied changes in the P300 wave after a period of abstinence in a sample of alcohol-dependent males classified by TaqI-A genotype. There have been published several works that had taken into account an abstinency period and the influence of family history for alcoholism on P300wave measures but not the TaqI A polymorphism29-32.

http://scielo.isciii.es/pdf/ejpen/v23n4/original3.pdf

P300 in alcohol dependence: Effects of TaqI-A genotype

[Cardiovascular changes during alpha-2 agonist treatment of opiate withdrawal syndrome].

Effect of chronic alcohol consumption on brain structure in males with alcohol use disorder without a familiar history of alcoholism.

Programas de disminución del daño en la dependencia alcohólica: el reto de la alcohología moderna

Digiusto E, Shakeshaft A, Ritter A, et al. Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Addiction 2004;99:450–60. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

/pdf/individuals-with-opioid-dependence-who-leave-drug-treatment-td8tmuyvj2.pdf

Gabriel Rubio

Papers

P300 in alcohol dependence: Effects of TaqI-A genotype

[Cardiovascular changes during alpha-2 agonist treatment of opiate withdrawal syndrome].

Effect of chronic alcohol consumption on brain structure in males with alcohol use disorder without a familiar history of alcoholism.

Programas de disminución del daño en la dependencia alcohólica: el reto de la alcohología moderna

Individuals with opioid dependence who leave drug treatment have higher overdose and death rates than those still in treatment