Addiction Rehab: Coexistence of Passive and Proton Antiporter-Mediated Processes in Nicotine Transport at the Mouse Blood-Brain Barrier.

Coexistence of Passive and Proton Antiporter-Mediated Processes in Nicotine Transport at the Mouse Blood-Brain Barrier.

Filed under: Addiction Rehab

AAPS J. 2012 Dec 5;
Cisternino S, Chapy H, André P, Smirnova M, Debray M, Scherrmann JM

Nicotine, the main tobacco alkaloid leading to smoking dependence, rapidly crosses the blood-brain barrier (BBB) to become concentrated in the brain. Recently, it has been shown that nicotine interacts with some organic cation transporters (OCT), but their influence at the BBB has not yet been assessed in vivo. In this study, we characterized the transport of nicotine at the mouse luminal BBB by in situ brain perfusion. Its influx was saturable and followed the Michaelis-Menten kinetics (K (m)?=?2.60 mM, V (max)?=?37.60 nmol/s/g at pH 7.40). At its usual micromolar concentrations in the plasma, most (79%) of the net transport of nicotine at the BBB was carrier-mediated, while passive diffusion accounted for 21%. Studies on knockout mice showed that the OCT Oct1-3, P-gp, and Bcrp did not alter [(3)H]-nicotine transport at the BBB. Neither did inhibiting the transporters Mate1, Octn, or Pmat. The in vivo manipulation of intracellular and/or extracellular pH, the chemical inhibition profile, and the trans-stimulation experiments demonstrated that the nicotine transporter at the BBB shared the properties of the clonidine/proton antiporter. The molecular features of this proton-coupled antiporter have not yet been identified, but it also transports diphenhydramine and tramadol and helps nicotine cross the BBB at a faster rate and to a greater extent. The pharmacological inhibition of this nicotine/proton antiporter could represent a new strategy to reduce nicotine uptake by the brain and thus help curb addiction to smoking.
HubMed – addiction


Dopamine Response to Psychosocial Stress in Chronic Cannabis Users: A PET Study With [(11)C]-(+)-PHNO.

Filed under: Addiction Rehab

Neuropsychopharmacology. 2012 Nov 8;
Mizrahi R, Suridjan I, Kenk M, George TP, Wilson A, Houle S, Rusjan P

A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [(11)C]-(+)-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BP(ND)) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in [(11)C]-(+)-PHNO BP (ND)) between CU and HV was tested with analysis of variance. SMCT BP(ND) was significantly higher in CU compared with HV in the AST (F=10.38, p=0.003), LST (F=4.95, p=0.036), SMST (F=4.33, p=0.048), and whole striatum (F=9.02, p=0.006). Percentage of displacement (change in BP(ND) between SMCT and MIST PET scans) was not significantly different across groups in any brain region, except in the GP (-5.03±14.6 in CU, compared with 6.15±12.1 in HV; F=4.39, p=0.049). Duration of cannabis use was significantly associated with stress-induced [(11)C]-(+)-PHNO displacement by endogenous DA in the LST (r=0.566, p=0.044), with no effect in any other brain region. In conclusion, despite an increase in striatal BP(ND) observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release.Neuropsychopharmacology advance online publication, 5 December 2012; doi:10.1038/npp.2012.232.
HubMed – addiction


Mapping human brain fatty acid amide hydrolase activity with PET.

Filed under: Addiction Rehab

J Cereb Blood Flow Metab. 2012 Dec 5;
Rusjan PM, Wilson AA, Mizrahi R, Boileau I, Chavez SE, Lobaugh NJ, Kish SJ, Houle S, Tong J

Endocannabinoid tone has recently been implicated in a number of prevalent neuropsychiatric conditions. [(11)C]CURB is the first available positron emission tomography (PET) radiotracer for imaging fatty acid amide hydrolase (FAAH), the enzyme which metabolizes the prominent endocannabinoid anandamide. Here, we sought to determine the most suitable kinetic modeling approach for quantifying [(11)C]CURB that binds selectively to FAAH. Six healthy volunteers were scanned with arterial blood sampling for 90?minutes. Kinetic parameters were estimated regionally using a one-tissue compartment model (TCM), a 2-TCM with and without irreversible trapping, and an irreversible 3-TCM. The 2-TCM with irreversible trapping provided the best identifiability of PET outcome measures among the approaches studied (coefficient of variation (COV) of the net influx constant K(i) and the composite parameter ?k(3) (?=K(1)/k(2)) <5%, and COV(k(3))<10%). Reducing scan time to 60?minutes did not compromise the identifiability of rate constants. Arterial spin labeling measures of regional cerebral blood flow were only slightly correlated with K(i), but not with k(3) or ?k(3). Our data suggest that ?k(3) is sensitive to changes in FAAH activity, therefore, optimal for PET quantification of FAAH activities with [(11)C]CURB. Simulations showed that [(11)C]CURB binding in healthy subjects is far from a flow-limited uptake.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 December 2012; doi:10.1038/jcbfm.2012.180. HubMed – addiction


Pharmacological Maintenance Treatments of Opiate Addiction.

Filed under: Addiction Rehab

Br J Clin Pharmacol. 2012 Dec 4;
Bell J

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention, and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is minimizing withdrawal symptoms, and attenuating the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been “programmatic”, with a one-size-fits-all approach which in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some “non-responders”, and can be a valuable option in the rehabilitation of demoralised, socially-excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. It represents not only a different medication, but can also be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.
HubMed – addiction


Utilization, measurement, and funding of recovery supports and services.

Filed under: Addiction Rehab

J Psychoactive Drugs. 2012 Sep-Oct; 44(4): 325-33
Cousins SJ, Antonini VP, Rawson RA

An environmental survey was conducted regarding substance abuse recovery supports and services (RSS) delivered across California, where these services are offered, and by whom. Inquiries were made regarding RSS measurement efforts, funding mechanisms, and technical assistance needs. A survey was disseminated to all 57 administrators of county alcohol and other drug or behavioral departments. Results indicate that 62% (23 of 37) of responding counties offer RSS. Overall, certified addiction counselors (CACs) were the staff most utilized to provide RSS, followed by peers, clinicians, and volunteers. Among recovery-community organizations (RCOs), peers, volunteers, and CACs were the most utilized staff. Sober living homes were the most prevalent type of RCO, followed by recovery centers, faith-based/recovery ministries, and recovery schools. Forty-five percent of counties reported funding RSS; 37.8% collect data. RSS may provide valuable support services for individuals recovering from alcohol/drug use; however, the field must further define RSS and develop measurement strategies to justify RSS funding.
HubMed – addiction



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