Glutamatergic medications for the treatment of drug and behavioral addictions

Olive, M. Foster; Cleva, Richard M.; Kalivas, Peter W.; Malcolm, Robert

doi:10.1016/j.pbb.2011.04.015

Cited by 190 publications

(133 citation statements)

References 199 publications

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“…Similarly, gabapentin has been indicated for the treatment/ management of drug (e.g. opiates [41]; cannabis [42]), behavioural [43] and alcohol [44] addictions.…”

Section: Gabapentinoids As a Treatment For Addiction?mentioning

confidence: 99%

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

2014

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Gabapentinoids (e.g. pregabalin and gabapentin) are widely used in neurology, psychiatry and primary healthcare but are increasingly being reported as possessing a potential for misuse. In fact, increasing levels of both prescriptions and related fatalities, together with an anecdotally growing black market, have been reported from a range of countries. This article reviews the current evidence base of this potential, in an attempt to answer the question of whether there is cause for concern about these drugs. Potent binding of pregabalin/gabapentin at the calcium channel results in a reduction in the release of excitatory molecules. Furthermore, gabapentinoids are thought to possess GABA-mimetic properties whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system. Overall, pregabalin is characterized by higher potency, quicker absorption rates and greater bioavailability levels than gabapentin. Although at therapeutic dosages gabapentinoids may present with low addictive liability levels, misusers' perceptions for these molecules to constitute a valid substitute for most common illicit drugs may be a reason of concern. Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable. Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication. Key pointsGabapentinoids are thought to possess GABAmimetic properties, whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system.Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable.Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate for a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication.

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“…Similarly, gabapentin has been indicated for the treatment/ management of drug (e.g. opiates [41]; cannabis [42]), behavioural [43] and alcohol [44] addictions.…”

Section: Gabapentinoids As a Treatment For Addiction?mentioning

confidence: 99%

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

2014

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“…Other regimens, including ShA regimens that do not lead to CP-AMPAR accumulation, provide insight into strategies for decreasing addictive behavior under different conditions. The most striking example concerns the drug N-acetylcysteine, which reduces cocaine-related behaviors after non-contingent cocaine exposure and ShA cocaine self-administration and has shown promise in clinical trials (Mardikian et al, 2007;Amen et al, 2011;Olive et al, 2012).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Purgianto

Scheyer

Loweth

et al. 2013

Neuropsychopharmacol

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Ca 2 þ -permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens (NAc) after B1 month of withdrawal from a long-access cocaine self-administration regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate the 'incubated' cue-induced cocaine craving produced by this regimen. Our present goal was to determine if other commonly employed cocaine selfadministration regimens also elicit CP-AMPAR accumulation. We compared four regimens, named according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats began with 10 days of ShA and then entered a differential phase (10-14 days) in which ShA sessions either continued or switched to LgA. Controls self-administered saline. After 440 days of withdrawal, whole-cell patch-clamp recordings were performed in NAc core medium spiny neurons to assess the contribution of CP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bath application of the selective CP-AMPAR antagonist naspm (100 mM). Naspm produced a non-significant (B10%) attenuation of electrically evoked local excitatory postsynaptic current in the saline and ShA groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%) was observed in both the LgA groups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgA groups is associated with increased baseline responsiveness of MSN to excitatory drive. Together with data on cocaine infusions in each group, our results show that CP-AMPAR accumulation and enhanced glutamate transmission is associated with longer sessions (6 h), rather than the number of sessions or cocaine infusions.

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“…2,3 Recently, changes in glutamatergic neurotransmission have been implicated in the pathophysiology of addiction. 4 Preclinical studies showed reduced basal glutamate levels in the nucleus accumbens of rodents chronically treated with cocaine, and that this reduction appears to be associated with pleasure-seeking behavior. [5][6][7][8] Reinstatement of cocaine-seeking behavior was also related to a reduction in baseline extracellular concentrations of glutamate, resulting in a lower tonic activation of group 2 metabotropic glutamate receptors (mGluR2/3), which usually inhibit presynaptic release of glutamate.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of N-acetylcysteine in the treatment of addictions

Asevedo

Mendes

Berk

et al. 2014

Rev. Bras. Psiquiatr.

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Objective: To conduct the first systematic literature review of clinical trials of N-acetylcysteine (NAC) for the treatment of substance abuse disorders and addictive behaviors. Methods: A search of the MEDLINE, Embase and PsycINFO databases was conducted. The inclusion criteria for the review were clinical trials that used NAC in the treatment of a disorder related to substance use and/or addictive behaviors, limited to texts in English, Spanish, or French. The selected studies were evaluated with respect to type of trial, sample size, diagnostic input, intervention, length of follow-up, outcome variables, and results. Results: Nine studies analyzing a total of 165 patients met the eligibility criteria and were included in qualitative analysis. These studies evaluated the role of NAC in cocaine dependence (three studies), cannabis dependence (two studies), nicotine dependence (two studies), methamphetamine addiction (one study), and pathological gambling (one study). Five of these trials were double-blind, randomized, and placebo-controlled. Conclusions:The studies analyzed suggest a potential role for NAC in the treatment of addiction, especially of cocaine and cannabis dependence. These results are concordant with the hypothesis of the involvement of glutamatergic pathways in the pathophysiology of addiction.

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Glutamatergic medications for the treatment of drug and behavioral addictions

Cited by 190 publications

References 199 publications

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Systematic review of N-acetylcysteine in the treatment of addictions

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