Addiction Rehab: Attenuation of Cocaine and Heroin Seeking by ?-Opioid Receptor Antagonism.

Attenuation of cocaine and heroin seeking by ?-opioid receptor antagonism.

Filed under: Addiction Rehab

Psychopharmacology (Berl). 2013 Jan 9;
Giuliano C, Robbins TW, Wille DR, Bullmore ET, Everitt BJ

RATIONALE: Evidence has implicated the endogenous opioids, in particular ?-opioid receptors, in emotional behavior and regulation of reward circuits, especially in the context of heroin addiction and hedonic responses to ingestive rewards. The ?-opioid receptor antagonist naltrexone (NTX) has been reported to be effective in preventing relapse to alcoholism and in reducing alcohol and cocaine craving during abstinence. OBJECTIVES: The aim of the present experiments was to investigate the effects of a novel selective ?-opioid receptor antagonist GSK1521498 on cocaine and heroin seeking and the primary reinforcement of drug self-administration behavior. METHODS: Rats were first trained to self-administer cocaine or heroin and then to seek the drugs over prolonged periods of time under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a drug-associated conditioned reinforcer. On a stable baseline, animals were treated with either GSK1521498 (0.1, 1, 3 mg/kg; IP) or NTX (0.1, 1, 3 mg/kg; SC) before each test session. RESULTS: Cocaine seeking was dose-dependently decreased following GSK1521498 treatment. However, the same treatment had no effect on cocaine self-administration under a continuous reinforcement schedule. Treatment with NTX had a less pronounced but similar effect. GSK1521498, but not NTX, dose-dependently reduced heroin seeking both before and after infusion of the drug although both increased heroin self-administration under continuous reinforcement. CONCLUSIONS: These data suggest that GSK1521498, by reducing opioid receptor signaling at the ?-opioid receptor, may have therapeutic potential to reduce the propensity to seek cocaine or heroin and, additionally, to diminish the consequence of an initial relapse to heroin taking.
HubMed – addiction

Commentary on Griffith-Lendering et al: [title tbc].

Filed under: Addiction Rehab

Addiction. 2013 Jan 8;
Lewis G, Heron J

Deciding whether an exposure causes a disease is a difficult and uncertain task in epidemiology. That association is not causation is well known, yet Griffith-Lendering and colleagues (1) claim that their study “suggests that there is a bi-directional causal association between [cannabis use and psychosis vulnerability]”. This is a strong claim to make based upon the data presented. TRAILS is a cohort study of adolescents recruited at age 11 from schools in the Northern area of the Netherlands who have now been followed up to 25 years. The data used in the paper was from 13, 16 and 19 years and both cannabis use and “psychosis vulnerability” were collected at all time points. The analysis that is presented is a cross lagged model using structural equation modelling. Their results indicated that psychosis vulnerability at both 13 and 16 years was associated with later cannabis use while there was evidence that cannabis use at 16 was associated with psychosis vulnerability at 19, but no evidence of an association between cannabis use at 13 and psychosis vulnerability at 16 years. The association between cannabis use and psychotic symptoms is well established. Though it is worth noting that the authors do not find that early cannabis use is more likely to lead to psychosis than later use, at least at these ages (2). Of more note perhaps is the possibility that psychotic symptoms may lead to cannabis use.
HubMed – addiction

Extended release methylphenidate for treatment of amphetamine/methamphetamine dependence: a randomised, double-blind, placebo controlled trial.

Filed under: Addiction Rehab

Addiction. 2013 Jan 8;
Miles SW, Sheridan J, Russell B, Kydd R, Wheeler A, Walters C, Gamble G, Peta H, Maree J, Kuoppasalmi K, Tuomola P, Föhr J, Kuikanmäki O, Vorma H, Salokangas R, Mikkonen A, Kallio M, Kauhanen J, Kiviniemi V, Tiihonen J

AIMS: To assess the efficacy of methylphenidate as a substitution therapy for amphetamine/methamphetamine dependence in Finland and New Zealand. DESIGN: parallel group, double-blind, randomised placebo controlled trial. SETTING: outpatient care. PARTICIPANTS: amphetamine/methamphetamine dependent, aged 16-65. MEASUREMENTS: The primary outcome measure was presence/absence of amphetamine/methamphetamine in urine samples collected twice weekly. Secondary measures included treatment adherence, alterations in craving scores and self-reported use. Primary analysis was by intention to treat (ITT). Study drug: methylphenidate (as Concerta(®) ) was up-titrated over two weeks to a maximum dose of 54 mg daily and continued for a further 20 weeks. Doses were given under daily supervision at the clinics. FINDINGS: Seventy nine participants were randomised (40 methylphenidate; 39 placebo); 77 received allocated treatment and 27 completed the trial. ITT analysis (N=78) showed no statistically significant difference in the percentage of positive urines between the methylphenidate and placebo arms (OR 0(.) 95, 95% CI 0(.) 83 – 1(.) 08). However, there was a significant difference (p< 0(.) 05) between the active and placebo arms in retention, the placebo arm displaying a significantly lower retention from six weeks that persisted until trial end. CONCLUSIONS: The trial failed to replicate earlier findings suggesting that methylphenidate was superior to placebo. The low retention rate confounded the ability to draw firm conclusions about efficacy. The higher retention rate was observed in the methylphenidate arm. Any replication of this work would need to consider alternatives to the rigid clinic attendance criteria, and consider an increased dose. HubMed – addiction

A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders.

Filed under: Addiction Rehab

Addiction. 2013 Jan 8;
Levin FR, Mariani J, Brooks DJ, Pavlicova M, Nunes EV, Agosti V, Bisaga A, Sullivan MA, Carpenter KM

AIM: To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. DESIGN: This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. SETTINGS: The trial was conducted at two university research centers in the United States. PARTICIPANTS: One hundred and three cannabis dependent adults participated in the trial. MEASUREMENTS: The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. FINDINGS: The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X(1) (2) =0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X(1) (2) =7.46, p-value<0.01; OR = 4.51, 95% CI: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F(1,179) =30.49, p-value<0.01), but not the VEN-XR group (F(1,186) =0.02, p-value=0.89). CONCLUSIONS: For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. HubMed – addiction

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