Constructing the ecstasy of MDMA from its component mental organs: Proposing the primer/probe method.
Medical Hypotheses February 1, 2016 DOI: 10.1016/j.mehy.2015.12.018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | Mental organs Neuron groups Specific mental states Complex brain states Neuropharmacology Neurotransmitter release Pharmacological effects Receptor activation Serotonin-2 receptors Specific receptor Primer/probe method Research methodology Experimental method Test |
| Citations | 6 |
| Key points | Proposes that the entactogenic mental state of MDMA is due to simultaneous direct activation of imidazoline-1 and serotonin-2 receptors, and introduces a primer/probe method to test this and related hypotheses. |
Abstract
The drug MDMA, commonly known as ecstasy, produces a specific and distinct open hearted mental state, which led to the creation of a new pharmacological class, "entactogens". Extensive literature on its mechanisms of action has come to characterize MDMA as a "messy" drug with multiple mechanisms, but the consensus is that the distinctive entactogenic effects arise from the release of neurotransmitters, primarily serotonin. I propose an alternative hypothesis: The entactogenic mental state is due to the simultaneous direct activation of imidazoline-1 (I1) and serotonin-2 (5-HT2) receptors by MDMA. This hypothesis emerges from "mental organ" theory, which embodies many hypotheses, the most relevant of which are: "Mental organs" are populations of neurons that all express their defining metabotropic receptor, and each mental organ plays a distinct role in the mind, a role shaped by evolution as mental organs evolve by duplication and divergence. Mental organs are the mechanism by which evolution sculpts the mind. Mental organs can be in or out of consciousness. In order for a mental organ to enter consciousness, three things must happen: The mental organ must be activated directly at its defining receptor. 5-HT2 must be simultaneously activated. One of the functions of activated 5-HT2 is to load other simultaneously activated mental organs fully into consciousness. In some cases THC must be introduced to remove long-term blocks mediated by the cannabinoid system. I propose the "primer/probe" method to test these hypotheses. A "primer" is a drug that selectively activates 5-HT2 (e.g. DOB or MEM) or serotonin-1 (5-HT1) and 5-HT2 (e.g. DOET or 2C-B-fly). A "probe" is a drug that activates a receptor whose corresponding mental organ we wish to load into consciousness in order to understand its role in the mind. The mental organ is loaded into consciousness when the primer and probe are taken together, but not when taken separately. For example, the blood pressure medications rilmenidine and moxonidine are selective for imidazoline-1 and can be used to test the hypothesis that the entactogenic mental effects of MDMA are due to loading the imidazoline-1 mental organ into consciousness. The primer/probe method is not limited to testing the specific hypothesis about MDMA and imidazoline, but is a general method for studying the role of mental organs in the mind. For example, the role of dopamine mental organs can be studied by using Parkinson's drugs such as ropinirole or pramipexole as probes.
Comparable studies
Other theoretical and historical papers on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens | 1986 | Theoretical or philosophical paper | |
| The Background and Chemistry of MDMA | 1986 | Historical analysis | |
| The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents* Original documents in Merck's historical archive in Darmstadt, Germany, years 1900–1960 | 2006 | Historical analysis | |
| Distinct neural mechanisms for the prosocial and rewarding properties of MDMA | 2019 | Theoretical or philosophical paper | |
| How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale | 2009 | Theoretical or philosophical paper |
Citations in the library
Cited by 4
- Unifying Theories of Psychedelic Drug Effects Frontiers in Pharmacology March 2, 2018
- The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology Frontiers in Neuroscience September 28, 2017
- Why MDMA therapy for alcohol use disorder? And why now? Neuropharmacology November 1, 2018
- An ontology of psychedelic entity experiences in evolutionary psychology and neurophenomenology Journal of Psychedelic Studies March 26, 2018
Cites 50
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens Journal of Psychoactive Drugs October 1, 1986
- Subjective Reports of the Effects of MDMA in a Clinical Setting Journal of Psychoactive Drugs October 1, 1986
- Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug British Journal of Addiction August 1, 1992
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
and 45 more in the library