Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review

Nicolas Salloum; Margot Chouchana; Romain Icick; Vanessa Bloch; Stéphanie Daumas; Salah El Mestikawy; Florence Vorspan; Virgile Clergue-Duval

doi:10.1007/s00213-024-06696-5

Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review

Psychopharmacology (Berl). 2024 Nov;241(11):2205-2222. doi: 10.1007/s00213-024-06696-5. Epub 2024 Oct 21.

Authors

Nicolas Salloum^#^{1

2}, Margot Chouchana^#^{3

4

5

6}, Romain Icick^{1

2

5

6}, Vanessa Bloch^{3

4

5

6}, Stéphanie Daumas^{6

7}, Salah El Mestikawy^{6

7

8}, Florence Vorspan^{1

2

5

6}, Virgile Clergue-Duval^{9

10

11

12}

Affiliations

¹ Département de Psychiatrie et de Médecine Addictologique, Site Lariboisière Fernand-Widal, GHU APHP.Nord - Université Paris Cité, 200 Rue du Faubourg Saint-Denis, Paris, 75010, France.
² UFR de Médecine, Université Paris Cité, 85 Boulevard Saint-Germain, Paris, 75006, France.
³ Service de Pharmacie Hospitalière, Site Lariboisière Fernand-Widal, GHU APHP.Nord - Université Paris Cité, 200 Rue du Faubourg Saint- Denis, Paris, 75010, France.
⁴ UFR de Pharmacie, Université Paris Cité, 85 boulevard Saint-Germain, Paris, 75006, France.
⁵ UMRS-1144 Optimisation Thérapeutique en Neuropsychopharmacologie, INSERM, Université Paris Cité, 4 Avenue de l'observatoire, Paris, 75006, France.
⁶ FHU Network of Research in Substance Use Disorders (NOR-SUD), 4 Avenue de l'observatoire, Paris, 75006, France.
⁷ Neuroscience Paris Seine, Institut de Biologie Paris Seine (NPS- IBPS), INSERM, CNRS, Sorbonne Université, 9 quai Saint Bernard, Paris, 75005, France.
⁸ Départment of Psychiatry, Douglas Research Center, McGill University, 6875 Boulevard Lasalle, Montréal, QC, H4H 1R3, Canada.
⁹ Département de Psychiatrie et de Médecine Addictologique, Site Lariboisière Fernand-Widal, GHU APHP.Nord - Université Paris Cité, 200 Rue du Faubourg Saint-Denis, Paris, 75010, France. [email protected].
¹⁰ UFR de Médecine, Université Paris Cité, 85 Boulevard Saint-Germain, Paris, 75006, France. [email protected].
¹¹ UMRS-1144 Optimisation Thérapeutique en Neuropsychopharmacologie, INSERM, Université Paris Cité, 4 Avenue de l'observatoire, Paris, 75006, France. [email protected].
¹² FHU Network of Research in Substance Use Disorders (NOR-SUD), 4 Avenue de l'observatoire, Paris, 75006, France. [email protected].

^# Contributed equally.

PMID: 39432105
DOI: 10.1007/s00213-024-06696-5

Abstract

Rationale: No drugs are currently validated to treat psychostimulant use disorder (PUD). Pathophysiological studies consistently highlight the contribution of cholinergic mechanisms in psychostimulant use, including the vulnerability to PUD, paving the way for potential therapeutic strategies.

Objectives: The aim of this systematic review is to describe and discuss the efficacy of cholinergic agents in drug trials for patients with PUD.

Methods: A systematic review was conducted on April 4, 2024 in MedLine, Embase and Cochrane Library databases on controlled clinical drug trial of cholinergic agents in humans with PUD, psychostimulant abuse or dependence and psychostimulant use in recent year.

Results: Twenty-eight articles were included, twenty-one on cocaine and seven on amphetamines. Cholinergic agents used in these studies were biperiden (a muscarinic antagonist), mecamylamine (a nicotinic antagonist), nicotinic agonists, acetylcholinesterase inhibitors (AChEI), or citicoline. Two types of trials were identified. There were seventeen randomized controlled clinical trials evaluating cholinergic agents on psychostimulant use reduction in outpatients seeking treatment. Additionally, we retrieved eleven short-term «proof-of-concept» laboratory trials mainly with supervised psychostimulant administration and/or triggered craving challenges. Outpatient trials were heterogeneous and for most, inconclusive. Only two studies on galantamine (AChEI) and citicoline, reported a significant reduction of cocaine consumption. «Proof-of-concept» laboratory trials showed no evidence of efficacy on the selected outcomes, notably on craving.

Conclusions: This review does not support the current prescription of cholinergic agents to treat PUD. Replication clinical trials notably on galantamine or other AChEI, and proof-of-concept trials on comedown symptoms will be necessary to identify a potential therapeutic indication for cholinergic agents in PUD.

Keywords: Acetylcholine; Amphetamines; Cholinergic agents; Cocaine; Psychostimulant use disorder; Psychostimulants.

Publication types

Systematic Review

MeSH terms

Amphetamine-Related Disorders / drug therapy
Central Nervous System Stimulants* / adverse effects
Cholinergic Agents* / pharmacology
Cholinergic Agents* / therapeutic use
Cocaine-Related Disorders / drug therapy
Humans
Randomized Controlled Trials as Topic
Substance-Related Disorders* / drug therapy
Treatment Outcome

Substances

Central Nervous System Stimulants
Cholinergic Agents

Grants and funding

Fédération Hospitalo-Universitaire Network of Research in Substance Use Disorders, Assistance Publique Hopitaux de Paris and Université Paris Cité, Paris, France/Fédération Hospitalo-Universitaire Network of Research in Substance Use Disorders, Assistance Publique Hopitaux de Paris and Université Paris Cité, Paris, France