Cane2TheLeft: aripiprazole probably produces (some) increase in methamphetamine's effects because of its affinity for autoreceptor partial agonism/blockade.
Behav Brain Res. 2011 Jan 20;216(2):621-5. Epub 2010 Sep 15.
Repetitive administration of aripiprazole enhances locomotor response to methamphetamine in mice.
Cheng MC, Hsu SH, Chen CH.
Department of Psychiatry, Yuli Mental Health Research Center, Yuli Veterans Hospital, Hualien, Taiwan.
Dopamine receptor partial agonists have been proposed as potential candidate agents to treat psycho-stimulant abuse. Aripiprazole is a dopamine D2/D3 receptor partial agonist that is currently used as an antipsychotic drug in clinical settings. This study aimed to examine whether aripiprazole can suppress the methamphetamine-induced locomotor response in mice that is used as an indicator for potential clinical use. In ICR mice pre-exposed to methamphetamine (1mg/kg subcutaneous injection once daily for 7 days), we found that mice receiving repetitive treatments with aripiprazole (1, 5, and 10mg/kg, respectively; intraperitoneal injection once daily for 1 week) showed a significantly enhanced locomotor response upon re-exposure to methamphetamine (0.5mg/kg), compared with animals that received a vehicle treatment. Furthermore, we found that methamphetamine-naïve mice receiving repetitive treatment with aripiprazole (5mg/kg intraperitoneal injection once daily for 1 week) also showed a significantly enhanced locomotor response to acute challenge with methamphetamine (0.5mg/kg), compared with animals receiving the vehicle treatment. The enhanced locomotor response to methamphetamine in both methamphetamine-pre-exposed and methamphetamine-naïve mice lasted at least four weeks in this study. Our data suggest that aripiprazole may enhance the effects of methamphetamine, so caution should be exercised when prescribing to individuals with histories of stimulant use.
Haloperidol has also been shown to increase dopamine release from m-amphetamine caused by blockade at the D2 autoreceptor.
Toxicol Mech Methods. 2010 Mar;20(3):127-32.
Effects of dopamine antagonists on methamphetamine-induced dopamine release in high and low alcohol preference rats.
Nishiguchi M, Kinoshita H, Kasuda S, Takahashi M, Yamamura T, Matsui K, Ouchi H, Minami T, Hishida S, Nishio H.
Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
[email protected]
The authors have previously shown that high alcohol preference rats (HAP) have a significantly higher sensitivity than low alcohol preference rats (LAP) for methamphetamine (MA). In this study, changes in dopamine and serotonin release induced by MA (1 mg/kg, intraperitoneally) after pre-treatment with D1 and D2 receptor antagonists were examined in the striatum of rats with different alcohol preferences to elucidate differences in receptor levels between the two rat strains. D1 receptor antagonist SCH23390 or D2 receptor antagonist haloperidol were administrated intracerebroventricularly 10 min before MA stimulation. This study investigated the effect of methamphetamine-induced dopamine and serotonin release in striatum using microdialysis of freely moving rats coupled to ECD-HPLC. With haloperidol treatment both strains of rats showed a significantly greater maximum increase on MA-induced dopamine release compared with respective control rats. However, after SCH23390 treatment only HAP rats showed a significantly greater increase in dopamine release compared with controls. SCH23390 blocks mainly D1 receptors only in the post-synaptic membrane, whereas haloperidol blocks D2 receptors in both the pre-synaptic and post-synaptic membranes. The MA-induced increase in dopamine release following haloperidol pre-treatment was greater than SCH23390 pre-treatment in both strains. This result indicates that D2 receptors (autoreceptors) in the pre-synaptic membrane were blocked, leading to the elimination of the feedback function that regulates dopamine release. These data suggested that alcohol preference is associated with the action of MA, and the dopaminergic mechanism, specifically the D1 system in the striatum, might have a different pathway dependent on alcohol preference.
In humans however, aripiprazole does not always increase subjective "liking". N=6 is pretty small for a sample size, but that would sure be an "interesting" study, getting trained to discriminate meth from saline... I was unaware such "frontier pharmacology" goes on today in the US.
J Clin Psychopharmacol. 2011 Aug;31(4):470-80.
Discriminative-stimulus, subject-rated, and physiological effects of methamphetamine in humans pretreated with aripiprazole.
Sevak RJ, Vansickel AR, Stoops WW, Glaser PE, Hays LR, Rush CR.
Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY 40536-0086, USA.
Methamphetamine is thought to produce its behavioral effects by facilitating release of dopamine, serotonin (5-HT) and norepinephrine. Results from animal studies support this notion, whereas results from human laboratory studies have not consistently demonstrated the importance of monoamine systems in the behavioral effects of methamphetamine. Human drug-discrimination procedures are well suited to assess neuropharmacological mechanisms of the training drug by studying pharmacological manipulation. In this human laboratory study, 6 participants with a history of recreational stimulant use learned to discriminate 10 mg oral methamphetamine. After acquiring the discrimination (ie, ≥ 80% correct responding on 4 consecutive sessions), the effects of a range of doses of methamphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with 0 and 20 mg aripiprazole (a partial agonist at D2 and 5-HT1A receptors), were assessed. Methamphetamine alone functioned as a discriminative stimulus, produced prototypical stimulant-like subject-rated drug effects (eg, increased ratings of Good Effects, Talkative-Friendly, and Willing to Pay For) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion methamphetamine-appropriate responding or produce subject-rated effects but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of methamphetamine, as well as some of the subject-rated drug effects. These results indicate that monoamine systems likely play a role in the behavioral effects of methamphetamine in humans. Moreover, given the concordance between past results with d-amphetamine and the present findings, d-amphetamine can likely serve as a model for the pharmacological effects of methamphetamine.
Risperidone on the other hand blocks most of the effects of m-amphetamine, it seems.
Drug Alcohol Depend. 2010 Oct 1;111(3):241-9. Epub 2010 Jun 11.
Effect of risperidone on acute methamphetamine-induced hyperthermia in rats.
Shioda K, Nisijima K, Yoshino T, Kato S.
Department of Psychiatry, Jichi Medical University, Tochigi, Japan.
[email protected]
The abuse of methamphetamine (METH) is popular in many parts of the world. The number of fatal cases related to METH-induced hyperthermia is increasing, but no definitive therapy has yet been found. In the present study, we investigated the ability of risperidone to attenuate acute METH-induced hyperthermia and the mechanism of its action. When administered before and after a single high METH dose (10 mg/kg), risperidone significantly suppressed acute METH-induced hyperthermia in a dose-dependent manner. The same effect was produced by dopamine-1 (DA(1)) and serotonin-2A (5-HT(2A)) receptor blockers, but not by D₂, 5-HT(1A), 5-HT(2B/2C), or 5-HT(2C) receptor blockers, demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D(1) and 5-HT(2A) receptors. A microdialysis study showed that when METH (10 mg/kg) was subcutaneously injected into rats, the levels of DA, 5-HT, glutamate, and the nitric oxide (NO) metabolites NOx (NO₂⁻+ NO₃⁻) in the anterior hypothalamus increased. Risperidone pretreatment significantly attenuated increases in the levels of DA, 5-HT, glutamate, and NOx. The present study indicates that risperidone may be an effective drug for treating METH-induced hyperthermia in humans and that METH influences the DA and 5-HT neuron systems as well as other neuron systems, including the glutamate and NO systems.
I did a search but all I found was using antipsychotics for the come down. I want to know if after the peak effect of an antipsychotic was over would meth still be effective?
I haven't heard about any atypicals having stimulant or euphoric effects alone or in combination with other drugs and have only seen others report the opposite so I am curious to learn more about this.
