Cholinesterase inhibitors might alleviate methamphetamine-induced delusions, hallucinations and cognitive impairment, while reducing craving and addiction

Abstract

Letters published in this journal do not necessarily reflect the opinions of the Editors or the Editorial Board

Dear Editor, Methamphetamine abuse is a growing epidemic confronting primary care physicians and psychiatrists alike. Especially dangerous are methamphetamine-provoked delusions and hallucinations, both acute and chronic. Methamphetamine psychosis has been successfully treated with atypical anti-psychotic agents such as olanzapine (Misra et al. 2000), but it would be helpful to have other therapeutic options for patients with intolerance or non-response. A new approach is suggested by an intriguing autopsy study of 20 chronic methamphetamine users with 14 normal controls which found that the chronic methamphetamine users had markedly depleted dopamine in the non-motor portion of the basal ganglia system, confirming previous animal data (Moszczynska et al. 2004). Thus, from a neurochemical standpoint, chronic methamphetamine users may resemble Parkinsonian patients. If this is indeed the case, then cholinesterase inhibitors such as donepezil, rivastigmine and galantamine, should diminish hallucinations and delusions in methamphetamine users and also ameliorate any cognitive impairment that might be present, similar to what has been seen for patients with parkinsonian dementia (Fabbrini et al. 2002; Maidment et al. 2006). Perhaps most important of all, cholinesterase inhibitors may actually blunt methamphetamine addiction and so enable users to maintain abstinence. A study in rats found that either nicotine or donepezil significantly attenuated methamphetamine-seeking behaviour, with this being mediated through nicotinic cholinergic receptors (Hiranita et al. 2006). Taking all of the above data together, a logical next step is clinical trials of cholinesterase inhibitors for chronic methamphetamine users, either alone or in combination with atypical anti-psychotic agents, with target symptoms being delusions, hallucinations, cognitive impairment and addiction. Cholinesterase inhibitors could become an important weapon in the fight against methamphetamine.