OPEN Foundation

MDMA

Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry

Abstract

Without researching psychedelic drugs for medical therapy, psychiatry is turning its back on a group of compounds that could have great potential. Without the validation of the medical profession, the psychedelic drugs, and those who take them off-license, remain archaic sentiments of the past, with the users maligned as recreational drug abusers and subject to continued negative opinion. These two disparate groups—psychiatrists and recreational psychedelic drug users—are united by their shared recognition of the healing potential of these compounds. A resolution of this conflict is essential for the future of psychiatric medicine and psychedelic culture alike. Progression will come from professionals working in the field adapting to fit a conservative paradigm. In this way, they can provide the public with important treatments and also raise the profile of expanded consciousness in mainstream society.

Sessa, B. (2014). Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry. Journal of Psychoactive Drugs, 46(1), 57–62. http://dx.doi.org/10.1080/02791072.2014.877322
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MDMA and the “Ecstasy Paradigm”

Abstract

For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The “precautionary principle” suggests that, in the absence of knowing for certain, “experts” should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The “ecstasy paradigm” is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

Cole, J. C. (2014). MDMA and the “Ecstasy Paradigm”. Journal of Psychoactive Drugs, 46(1), 44–56. http://dx.doi.org/10.1080/02791072.2014.878148
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The Potential Dangers of Using MDMA for Psychotherapy

Abstract

MDMA has properties that may make it attractive for psychotherapy, although many of its effects are potentially problematic. These contrasting effects will be critically reviewed in order to assess whether MDMA could be safe for clinical usage. Early studies from the 1980s noted that MDMA was an entactogen, engendering feelings of love and warmth. However, negative experiences can also occur with MDMA since it is not selective in the thoughts or emotions it releases. This unpredictability in the psychological material released is similar to another serotonergic drug, LSD. Acute MDMA has powerful neurohormonal effects, increasing cortisol, oxytocin, testosterone, and other hormone levels. The release of oxytocin may facilitate psychotherapy, whereas cortisol may increase stress and be counterproductive. MDMA administration is followed by a period of neurochemical recovery, when low serotonin levels are often accompanied by lethargy and depression. Regular usage can also lead to serotonergic neurotoxicity, memory problems, and other psychobiological problems. Proponents of MDMA-assisted therapy state that it should only be used for reactive disorders (such as PTSD) since it can exacerbate distress in those with a prior psychiatric history. Overall, many issues need to be considered when debating the relative benefits and dangers of using MDMA for psychotherapy.

Parrott, A. C. (2014). The Potential Dangers of Using MDMA for Psychotherapy. Journal of Psychoactive Drugs, 46(1) , 37–43. http://dx.doi.org/10.1080/02791072.2014.873690
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History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS)

Abstract

This article describes the teenage vision of the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) that humanity’s future would be aided by the therapeutic and spiritual potential of psychedelic substances. The article traces the trajectory of MAPS from inception in 1986 to its present, noting future goals with respect to research, outreach, and harm reduction. MAPS was created as a non-profit psychedelic pharmaceutical company in response to the 1985 scheduling of 3,4-methylenedioxymethamphetamine (MDMA). Overcoming many hurdles, MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) and plans for FDA prescription approval in 2021. MAPS’ program of research expanded to include a trial of lysergic acid diethylamide (LSD)-assisted psychotherapy for anxiety when facing life-threatening illness, observational studies of ibogaine in the treatment of addiction, and studies of MDMA for social anxiety in people with autism spectrum disorders. MAPS meets the challenges of drug development through a clinical research team led by a former Novartis drug development professional experienced in the conduct, monitoring, and analysis of clinical trials. MAPS’ harm-reduction efforts are intended to avoid backlash and build a post-prohibition world by assisting non-medical users to transform difficult psychedelic experiences into opportunities for growth.

Emerson, A., Ponté, L., Jerome, L., & Doblin, R. (2014). History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS). Journal of Psychoactive Drugs, 46(1), 27–36. http://dx.doi.org/10.1080/02791072.2014.877321
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MDMA decreases the effects of simulated social rejection

Abstract

3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6. https://dx.doi.org/10.1016/j.pbb.2013.11.030

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The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labelling and Blood Oxygen Level-Dependent Resting-State Functional Connectivity

Abstract

Background
3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

Methods
MDMA was orally administered to 25 physically and mentally healthy individuals in a double-blind, placebo-controlled, balanced-order study. Arterial spin labelling (ASL) and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA. Participants underwent two ASL and two BOLD scans in a 90 minute scanning session and the MDMA and placebo study days were separated by one week.

Results
MDMA produced marked increases in positive mood. Only decreased CBF was observed after MDMA and this was localised to the right medial temporal lobe (MTL), thalamus, inferior visual cortex and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of MDMA’s global subjective effects. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

Conclusions
The MTLs appear to be specifically implicated in the mechanism of action of MDMA but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … Nutt, D. J. (2014). The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labelling and Blood Oxygen Level-Dependent Resting-State Functional Connectivity. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2013.12.015
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IJTS Special Topic Section: Ketamine ● Psychedelic Experiential Pharmacology: Pioneering Clinical Explorations with Salvador Roquet

Abstract

Richard Yensen was a research fellow at the Maryland Psychiatric Research Center from 1972 to 1976. He studied psychedelic psychotherapy with Stanislav Grof, M.D. and other senior staff. During this time he treated patients with substance abuse disorders, cancer, neurosis, and other health professionals seeking a training experience. Dr. Yensen did his Ph.D. dissertation on the use of MDA in psychotherapy with neurotic outpatients and conducted his research at the MPRC. Through many years of experience in governmentsanctioned psychedelic research, he has evolved a non-drug shamanistic psychotherapy called Perceptual Affective Therapy. In the 1990’s Richard was co-holder of IND 3250, an investigational new drug permit issued by the U.S. Food and Drug Administration to study LSD and psychotherapy until 2006. He is currently a licensed psychologist in California and director of the Orenda Institute in Vancouver and Cortes Island, British Columbia, Canada and president of the Salvador Roquet Psychosynthesis Association. He has served on the faculties of Harvard Medical School, Johns Hopkins University and the University of Maryland Medical School in Baltimore.

Wolfson, P. E. (2015). Psychedelic Experiential Pharmacology: Pioneering Clinical Explorations with Salvador Roquet. International Journal of Transpersonal Studies.
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Help pay for MDMA PTSD research

Recently, MAPS officially launched an Indiegogo campaign to help complete their crucial study of MDMA-assisted psychotherapy for people suffering from post-traumatic stress disorder (PTSD). OPEN supports MAPS in their efforts to raise both funds and awareness. Money is needed to progress vital research on these substances, while increasing awareness on the human and economic costs of PTSD can show that viable alternatives exist that can transform the lives of PTSD-sufferers.

The first published studies have shown that MDMA-assisted psychotherapy can be an effective treatment for people who did not respond to conventional therapies for post-traumatic stress disorder. MAPS’ studies are supported by the US government; their ongoing study in military veterans, firefighters, and police officers is halfway complete, and early results are promising. For some recent articles on MDMA-assisted PTSD-treatment, see here, here and here.

Donations will help pay the costs of conducting our ongoing clinical trial, a critical part of our international research program to develop MDMA-assisted psychotherapy into a prescription treatment for PTSD. Visit the Indiegogo page here,

A video-interview with one of the first subjects can be watched here:

The induction of synaesthesia with chemical agents: a systematic review

Abstract

Despite the general consensus that synaesthesia emerges at an early developmental stage and is only rarely acquired during adulthood, the transient induction of synaesthesia with chemical agents has been frequently reported in research on different psychoactive substances. Nevertheless, these effects remain poorly understood and have not been systematically incorporated. Here we review the known published studies in which chemical agents were observed to elicit synaesthesia. Across studies there is consistent evidence that serotonin agonists elicit transient experiences of synaesthesia. Despite convergent results across studies, studies investigating the induction of synaesthesia with chemical agents have numerous methodological limitations and little experimental research has been conducted. Cumulatively, these studies implicate the serotonergic system in synaesthesia and have implications for the neurochemical mechanisms underlying this phenomenon but methodological limitations in this research area preclude making firm conclusions regarding whether chemical agents can induce genuine synaesthesia.

Luke, D. P., & Terhune, D. B. (2013). The induction of synaesthesia with chemical agents: a systematic review. Frontiers in Psychology, 4, 1-11. http://dx.doi.org/10.3389/fpsyg.2013.00753
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Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

Abstract

There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

de Kleine, R. A., Rothbaum, B. O., & van Minnen, A. (2013). Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review. European Journal of Psychotraumatoly, 17(4), 1-15. http://dx.doi.org/10.3402/ejpt.v4i0.21626
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30 April - Q&A with Rick Strassman

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