Open-Label Study of a Proprietary Treatment Program Targeting Type A γ-Aminobutyric Acid Receptor Dysregulation in Methamphetamine Dependence

Urschel III, Harold C.; Hanselka, Larry L.; Gromov, Irina; White, Lenae; Baron, Michael
October 2007
Mayo Clinic Proceedings;Oct2007, Vol. 82 Issue 10, p1170
Academic Journal
OBJECTIVE: To evaluate the safety and efficacy of the pharmacological component of a proprietary medical treatment program targeting type A γ-aminobutyric acid receptor dysregulation in adults who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for methamphetamine dependence. PARTICIPANTS AND METHODS: A prospective, open-label, single-group study of the medication portion of a proprietary treatment program for methamphetamlne dependence was conducted from July 1, 2005, to May 10, 2006, at Research Across America, an outpatient private, for-profit, clinical research company in Dallas, TX. In the study, flumazenil, hydroxyzine, and gabapentin, all of which were approved by the US Food and Drug Administration for indications other than drug dependence, were used off-label for the treatment of methamphetamine dependence. Fifty persons who had used methamphetamine within 7 days of study entry were enrolled and received the treatment. Treatment lasted 4 weeks, followed by 8 weeks of weekly follow-up visits to monitor for methamphetamine use via urine drug tests and self-reporting. RESULTS: Participant retention was higher than expected, with 85% of participants completing the program. Significant decrease in methamphetamine use (P<.001) was noted at 84 days after vs 90 days before treatment. If missing data are counted as days of methamphetamine use, a 47% reduction in use was observed for the entire sample (P<.001) and a 65% reduction for the 36 who completed the 8-week evaluation phase (P<.001). Urine test results and self-reported use were positively correlated (Pearson r=-0.72, P<.001). The frequency of cravings was reduced on average by 66% (P<.001), with 30 of 31 (97%) of the 36 who completed the study reporting reduction in cravings. CONCLUSION: Substantial reductions in methamphetamine cravings and use were observed in all phases of treatment, and the retention rate of participants was high. These findings suggest that the efficacy of the medications and of the entire program in treating methamphetamine dependence should be examined in controlled trials.


Related Articles

  • Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series. Onugoren, M. Dogan; Deuretzbacher, D.; Haensch, C. A.; Hagedorn, H. J.; Halve, S.; Isenmann, S.; Kramme, C.; Lohner, H.; Melzer, N.; Monotti, R.; Presslauer, S.; Schäbitz, W. R.; Steffanoni, S.; Stoeck, K.; Strittmatter, M.; Stögbauer, F.; Trinka, E.; von Oertzen, T. J.; Wiendl, H.; Woermann, F. G. // Journal of Neurology, Neurosurgery & Psychiatry;Sep2015, Vol. 86 Issue 9, p965 

    Background: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABABR) and α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the...

  • New Evidence for an Important Role of Endogenous GABA in Seizure Generation in the Immature Hippocampus. Dudek, F. Edward // Epilepsy Currents;Jul2003, Vol. 3 Issue 4, p142 

    Comments on a study by V. I. Dzhala and K. J. Staley which examined the role of endogenous γ-aminobutyric acid (GABA) in seizure generation in the immature hippocampus. Susceptibility of neonates and young children to seizures; Relevance of the effects of GABA [subA]-receptor activation to...

  • GABAB-receptor subtypes assemble into functional heteromeric complexes. Kaupmann, Klemens; Malitschek, Barbara; Schuler, Valerie; Heid, Jakob; Froesti, Wolfgang; Beck, Pascal; Mosbacher, Johannes; Bischoff, Serge; Kulik, Akos; Shigemoto, Ryuichi; Karschin, Andreas; Bettler, Bernhard // Nature;12/17/1998, Vol. 396 Issue 6712, p683 

    Describes a gamma-aminobutyric acidB (GABAB) receptor subtype, GABABR2, which does not bind available GABAB antagonists with measurable potency. Evidence for the assembly of heteromeric GABAB receptors in vivo and the demonstration that GABABR2 and GABABR1a/b proteins immunoprecipitate and...

  • Neurological disorders: Changes away from the synapse. Jones, Rachel // Nature Reviews Neuroscience;Nov2004, Vol. 5 Issue 11, p824 

    Presents information on a study which examined the expression of specific gamma-aminobutyric acid (GABA) receptor subunits in a mouse model of epilepsy. Use of a single treatment with pilocarpine to induce a chronic epileptic condition with spontaneous seizures; Information on GABA receptors...

  • Pressure-sensitive and -insensitive coupling in γ-aminobutyric acid[sub a] receptors. Davies, Daryl L.; McCauley, Linda D.; Bolger, Michael B.; Alkana, Ronald L. // Psychopharmacology;2001, Vol. 157 Issue 4, p401 

    Rationale: Previous behavioral and biochemical studies suggest that allosteric coupling processes initiated by benzodiazepines, barbiturates and neuroactive steroids can be sub-categorized on the basis of their sensitivities to antagonism by increased atmospheric pressure. However, biochemical...

  • Mutational analysis of molecular requirements for the actions of general anaesthetics at the γ-aminobutyric acidA receptor subtype, α1β2㬲. Siegwart, Roberta; Krähenbühl, Karin; Lambert, Sachar; Rudolph, Uwe // BMC Pharmacology;2003, Vol. 3, p1 

    Background: Amino acids in the β subunit contribute to the action of general anaesthetics on GABAA receptors. We have now characterized the phenotypic effect of two β subunit mutations in the most abundant GABAA receptor subtype, α1β2γ2. Results: The β2(N265M) mutation in M2...

  • Expression of Rice Glutamate Decarboxylase in Bifidobacterium Longum Enhances γ-Aminobutyric Acid Production. Ki-Bum Park; Geun-Eog Ji; Myeong-Soo Park; Suk-Heung Oh // Biotechnology Letters;Nov2005, Vol. 27 Issue 21, p1681 

    Bifidobacteria are important for the production of fermented dairy products and probiotic formulas but have a low capacity for γ-aminobutyric acid (GABA) production. To develop a Bifidobacterium strain with an enhanced GABA production, we transformed Bifidobacterium longum with a rice...

  • Looking for GABA in All the Wrong Places: The Relevance of Extrasynaptic GABAA Receptors to Epilepsy. Richerson, George B. // Epilepsy Currents;Nov/Dec2004, Vol. 4 Issue 6, p239 

    It comes as no surprise that a high concentration ofγ-aminobutyric acid (GABA)A receptors exists across the synapse from presynaptic terminals that contain GABA. Oddly, though, many GABAA receptors also are far away from synapses. These extrasynaptic GABAA receptors are tonically activated by...

  • Astrocytes as GABA-ergic and GABA-ceptive Cells. Yoon, Bo-Eun; Woo, Junsung; Justin Lee, C. // Neurochemical Research;Nov2012, Vol. 37 Issue 11, p2474 

    GABA (gamma-aminobutyric acid) is considered to be the major inhibitory neurotransmitter that is synthesized in and released from GABA-ergic neurons in the brain. However, recent studies have shown that not only neurons but astrocytes contain a considerable amount of GABA, which can be released...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics