Liana Fattore1, Alessandro Piva2, Mary Tresa Zanda3, Guido Fumagalli2, Cristiano Chiamulera4. 1. National Research Council of Italy, Institute of Neuroscience-Cagliari, Cagliari, Italy. 2. Sezione Farmacologia, Dipt. Diagnostica e Sanità Pubblica, Università degli Studi di Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy. 3. Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cittadella Universitaria di Monserrato, SP 8, Km 0.700, 09042, Monserrato, Italy. 4. Sezione Farmacologia, Dipt. Diagnostica e Sanità Pubblica, Università degli Studi di Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy. cristiano.chiamulera@univr.it.
Abstract
RATIONALE: Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial "psychedelic effect," which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy. OBJECTIVE: Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories. RESULTS: We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition. CONCLUSIONS: Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.
RATIONALE: Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial "psychedelic effect," which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy. OBJECTIVE: Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories. RESULTS: We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition. CONCLUSIONS: Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.
Authors: Agnes Norbury; Sarah B Rutter; Abigail B Collins; Sara Costi; Manish K Jha; Sarah R Horn; Marin Kautz; Morgan Corniquel; Katherine A Collins; Andrew M Glasgow; Jess Brallier; Lisa M Shin; Dennis S Charney; James W Murrough; Adriana Feder Journal: Neuropsychopharmacology Date: 2021-07-31 Impact factor: 7.853