Pharmacological treatments for methamphetamine addiction: current status and future directions

Abstract

Methamphetamine (MA) abuse remains a global health challenge despite intense research interest in the development of pharmacological treatments. This review provides a summary of clinical trials and human studies on the pharmacotherapy of methamphetamine use disorder (MUD). Areas covered: We summarize published clinical trials that tested candidate medications for MUD and also conducted PubMed and Google Scholar searches to identify recently completed clinical trials using the keywords 'methamphetamine' 'addiction' 'pharmacotherapy' and 'clinical trial.' To determine the status of ongoing clinical trials targeting MUD, we also searched the ClinicalTrials.gov online database. We conclude this review with a discussion of current research gaps and future directions. Expert commentary: Clinical trials examining the potential for pharmacotherapies of MUD have largely been negative. Future studies need to address several limitations to reduce the possibility of Type II errors: small sample sizes, high dropout rates or multiple comorbidities. Additionally, new treatment targets, such as MA-induced disruptions in cognition and in the neuroimmune system, merit trials with agents that selectively modulate these processes.

The Main Molecular Mechanisms Underlying Methamphetamine- Induced Neurotoxicity and Implications for Pharmacological Treatment

“…Immunotherapies reduce the amount of drug in the CNS by triggering the production of antibodies binding the drug molecule after systemic absorption of METH ( Ballester et al, 2017 ). Miller et al (2013) found that, in rats receiving a KLH-conjugated METH-like hapten vaccine (MH6-KLH) and the vaccine succinyl MA (SMA–KLH), higher antibody titer-dependent METH serum concentrations, yet lower METH concentrations, in the CNS were observed, which suggested reduced METH concentrations in the brain.…”

“…In addition, it was shown that anti-METH/AMP mAb4G9 therapy protected maternal and fetal rat brains from METH-induced damage ( Gentry et al, 2006 ; White et al, 2014 ). Another study reported that a human–mouse monoclonal antibody binding to methylphenidate, named anti-METH antibody (mAB7F9), elicited a significant reduction in the METH concentration ( Ballester et al, 2017 ). In particular, a combined approach using monoclonal and polyclonal antibodies was more effective in reducing the METH concentration in the brain ( Hambuchen et al, 2015 ).…”

“…Long-term exposure to METH leads to DA depletion, impairment of dopaminergic markers, and neuronal degeneration ( Barr et al, 2002 ; Ballester et al, 2017 ). Therefore, extensive investigations, including those of several drugs in clinical trials, have been performed to explore efficacious pharmaceutical interventions for recovery from neural injury resulting from METH use.…”

Exposure to far‐infrared ray attenuates methamphetamine‐induced impairment in recognition memory through inhibition of protein kinase C δ in male mice: Comparison with the antipsychotic clozapine

“…Methamphetamine (MA) is a highly addictive psychoactive drug (Ballester, Valentine, & Sofuoglu, ). Chronic use of MA leads to psychosis, with symptoms similar to those of paranoid schizophrenia, such as hallucination and delusion (Yui, Goto, Ikemoto, & Ishiguro, ; Yui et al, ).…”

Update on methamphetamine: an old problem that we have recently encountered

“…A recent systematic review found no effect of psychostimulant agents on sustained abstinence or retention in treatment (58). Novel approaches for the treatment of methamphetamineuse disorder include neuroimmune modulators (minocycline, ibudilast), cognitive enhancers (rivastigmine, galantamine, atomoxetine, modafinil, citicoline), vaccines, and oxytocin (59).…”