Psychiatry & the psychedelic drugs. Past, present & future.
Abstract
Rucker, J. J., Iliff, J., & Nutt, D. J. (2017). Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 10.1016/j.neuropharm.2017.12.040
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Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.
Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest.
Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).
Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.
Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2017). Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Frontiers in Pharmacology, 8, 974. 10.3389/fphar.2017.00974
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Ibogaine is an indole alkaloid that comes from the root of the West African shrub Tabernanthe iboga. Ibogaine has been used for centuries in spiritual celebrations, coming of age rituals, and healings among the Babongo and Mitsogo people of West Central Africa. In Africa today, approximately 2–3 million members of the Bwiti religion scattered in groups throughout the countries of the Gabon, Zaire, and the Cameroun take large doses for the “Bwiti initiation ritual”—a powerful “rebirth” ceremony that group members typically undergo before the commencement of their teenage years.
The discovery that ibogaine eliminates the signs and symptoms of opioid withdrawal and diminishes craving for opioids was first made in the 1960s by a group of self-treating individuals with heroin use disorder; a single oral dose administration of ibogaine was associated with a disruption of five addicted individual’s use of opiates for up to 6 months . An underground railroad of individuals in recovery helping others with addictions arose, using ibogaine to help people break their cycle of addiction to heroin, cocaine, and alcohol. Ibogaine is thought to enable individuals with opioid use disorder to transition to abstinence and establish a substance-free recovery through an ibogaine-induced experience that has personal meaning and/or other benefits. Ibogaine’s long-lasting metabolite noribogaine may reset brain circuits to block the intractable cravings and desire to use opioids that set the addiction relapse cycle into motion.
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.
Fattore, L., Piva, A., Zanda, M. T., Fumagalli, G., & Chiamulera, C. (2017). Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology, 1-13. 10.1007/s00213-017-4793-4
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