The Effect of Hypnosis on Blood Concentrations of Endocannabinoids

Study Overview
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Brief Summary
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Introduction: Many interventions such as hypnosis, mindfulness meditation, conditioned pain modulation and placebos have been shown to effectively reduce pain both in the laboratory and in clinical settings. However, little is known about their neurophysiological mechanisms of action. Analgesia induced by these techniques is thought to be based on opioidergic and non-opioidergic mechanisms (potentially endocannabinoid mechanisms). Objective: Our main objective is to evaluate the effect of hypnosis, meditation, conditioned pain modulation and placebo on blood concentrations of endocannabinoids (anandamide, 2-arachidonylglycerol, N-palmitoyl-ethanolamine, N-oleoylethanolamide), endogenous opioids (β-endorphins, met / leu-enkephalins, and dynorphins) and norepinephrine in healthy adults. Methods: This study is based on a single-group pre-experimental research design in which two experimental sessions including hypnosis or meditation, conditioned pain modulation and placebo interventions will be completed by all participants. In order to have a better description of the sociodemographic and clinical characteristics of the sample, information will be collected by questionnaires or tests filled by participants at baseline, including: age, sex, language, culture, religion, salary, menstrual cycle of women, medication (if any), mood, anxiety, pain catastrophizing, mindfulness, hypnotic susceptibility, and DNA information. Outcome measures will be collected before, during and after each intervention. The primary outcome is plasma concentrations of endocannabinoids. Secondary measurements include plasma concentrations of endogenous opioids and norepinephrine; change in pain intensity during the thermal noxious stimuli; and autonomic nervous system variability (as measured by heart rate variability). Anticipated results: The investigators expect a positive relationship between the change in pain intensity (analgesia) induced by the interventions (hypnosis, meditation, conditioned pain modulation, and placebo) and the change (increase) in plasma concentrations of endocannabinoids, opioids, and norepinephrine in healthy adults. It is also believed that the interventions will influence heart rate variability. Moreover, it is expected that there will be a relationship between the efficiency of the analgesic intervention and some gene polymorphisms associated to pain modulation and endocannabinoids, opioids or norepinephrine in healthy individuals.

Official Title
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The Role of the Endocannabinoids During the Analgesia Caused by Hypnosis and Meditation

Conditions
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Hypnosis, Endocannabinoids, Analgesia

Intervention / Treatment
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* Behavioral: Hypnosis
* Behavioral: Meditation
* Other: Conditioned pain modulation
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being an healthy adult aged 18-45 years old with no prior experience of hypnosis. Exclusion Criteria: Having difficulty understanding french language Having a vulnerability to dissociative or psychotic episodes Having a diagnosed medical condition or diagnosis of chronic pain leading to kidney, liver, dermatological, respiratory, hematological, immunological, cardiovascular, inflammatory, rheumatologic, endocrine, metabolic, neurological or psychiatric pathologies Being pregnant or breast-feeding Having a body mass index over 40 Using medication, recreational drugs or other agents that affect the central nervous system or the perception of pain (e.g., analgesics, opioids, antiepileptics, muscle relaxers)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Repeated measures on a single group of participants
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intervention<br>Receiving the conditioned pain modulation intervention during the first session and receiving the placebo and the hypnosis or meditation interventions during the second session. | Behavioral: Hypnosis<br>* Hypnosis is a therapeutic method in which the experimenter or therapist make suggestions to individuals after they have undergone a hypnotic induction. This induction is a relaxation procedure designed to focus one's mind and to induce a hypnotic trance in individuals. The hypnotic trance consists in a state of deep absorption, concentration and altered sensations, cognitions and behaviors. Hypnosis can be used for pain control in experimental and clinical settings. In this study, standardized hypnosis including a relaxation technique for the hypnotic induction and a direct hypnotic analgesia technique for the hypnotic suggestions will be used.<br>* Other names: Hypnotic suggestions;Behavioral: Meditation<br>* Meditation is a relaxation method that can be used to reduce pain symptoms and pain perception in clinical and experimental situations. In this study, a standardized mindfulness meditation session of 20 minutes will be used to induce a relaxation and an analgesic effect in participants. Mindfulness meditation is a practice intended to increase mindfulness and awareness of the self and the environment by techniques of controlled breathing, focus on neutral elements, and observation of one's thoughts and emotions without judgment.<br>* Other names: Mindfulness meditation;Other: Conditioned pain modulation<br>* Conditioned pain modulation (CPM) is a pain inhibition mechanism that is used to assess endogenous analgesia capacity. The method to evaluate CPM in healthy individuals and patients with pain includes both a conditioning stimulus (a noxious stimulus that induces CPM) and a test stimulus (a noxious stimulus used to evaluate the analgesic response to the conditioning stimulus). In this study, the conditioning stimulus will be a cold pressor test (two-minutes immersion of one hand in ice water) and the test stimulus will be a two-minutes thermal noxious stimulus delivered by a contact thermode.<br>* Other names: Hetero-segmental counter-irritation;Drug: Placebo Oral Tablet<br>* A placebo is a substance (or treatment) with no active therapeutic effect. The placebo effect (analgesia) in this study will be induced by the oral administration of one inert tablet (sugar pill). The tablet is a round, hard, white, flat-faced tablet with no active ingredient. The participant is told that the tablet is an active drug, more specifically an analgesic or a painkiller, that is used to achieve analgesia, relief from pain. This placebo condition is used to induce a diffuse analgesic effect in participants.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline concentration of endocannabinoids at the end of the intervention | Concentrations (ng/ml) of endocannabinoids (anandamide, 2-arachidonylglycerol, N-palmitoyl-ethanolamine, N-oleoylethanolamide) will be measured in the plasma of participants | Immediately before and after each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline concentrations of opioids at the end of the intervention | Concentrations (ng/ml) of opioids (beta-endorphins, met/leu-enkephalins, and dynorphins) will be measured in the plasma of participants | Immediately before and after each intervention | 
| Change from baseline concentrations of norepinephrine at the end of the intervention | Concentrations (ng/ml) of norepinephrine will be measured in the plasma of participants | Immediately before and after each intervention | 
| Quantitative aspect of pain | Quantitative aspect of pain, or pain intensity, will be measured and averaged for the entire duration (two minutes) of the pain tests on a Computerized Visual Analog Scale (CoVAS). This CoVAS scale ranges from 0% to 100%. Higher values on this scale represent more intense pain. | Immediately before and after each intervention | 
| Measure of the autonomic nervous system | This outcome will be measured by heart rate variability | Immediately before, during and immediately after each intervention | 
| DNA in salivary sample | DNA polymorphisms potentially associated with analgesia, endocannabinoids, opioids or norepinephrine | Immediately after all the interventions have been completed, which will be during the second session after the pill has been ingested | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Hypnosis, Meditation, Conditioned pain modulation, Placebo, Endocannabinoids, Opioid peptides, Norepinephrine, Analgesia, Genes, Heart rate variability