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MDMA

A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens

June 1, 2018 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

Recent years have seen renewed interest and research about the use of hallucinogens as possible agents in the treatment of psychiatric disorders. However, we are unaware of studies assessing the current attitudes of American psychiatrists regarding hallucinogens. Therefore, we e-mailed surveys to 1000 members of the American Psychiatric Association-250 resident-fellows and 750 attending psychiatrists. The response rate was 32.4%. Respondents tended to perceive hallucinogens as potentially hazardous and appropriately illegal for recreational purposes. However, a large minority expressed optimism about the potential use of hallucinogens for psychiatric treatment. Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic. Optimism among trainees and younger psychiatrists may possibly reflect greater exposure to recent positive publications about hallucinogens and less awareness of more negative past reports.
Barnett, B. S., Siu, W. O., & Pope Jr, H. G. (2018). A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens. The Journal of nervous and mental disease, 206(6), 476-480. 10.1097/NMD.0000000000000828
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A Survey of American Psychiatrists' Attitudes Toward Classic Hallucinogens

June 1, 2018 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

Recent years have seen renewed interest and research about the use of hallucinogens as possible agents in the treatment of psychiatric disorders. However, we are unaware of studies assessing the current attitudes of American psychiatrists regarding hallucinogens. Therefore, we e-mailed surveys to 1000 members of the American Psychiatric Association-250 resident-fellows and 750 attending psychiatrists. The response rate was 32.4%. Respondents tended to perceive hallucinogens as potentially hazardous and appropriately illegal for recreational purposes. However, a large minority expressed optimism about the potential use of hallucinogens for psychiatric treatment. Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic. Optimism among trainees and younger psychiatrists may possibly reflect greater exposure to recent positive publications about hallucinogens and less awareness of more negative past reports.
Barnett, B. S., Siu, W. O., & Pope Jr, H. G. (2018). A Survey of American Psychiatrists’ Attitudes Toward Classic Hallucinogens. The Journal of nervous and mental disease, 206(6), 476-480. 10.1097/NMD.0000000000000828
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Psilocybin and MDMA reduce costly punishment in the Ultimatum Game

May 29, 2018 / MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Disruptions in social decision-making are becoming evident in many psychiatric conditions. These are studied using paradigms investigating the psychological mechanisms underlying interpersonal interactions, such as the Ultimatum Game (UG). Rejection behaviour in the UG represents altruistic punishment – the costly punishment of norm violators – but the mechanisms underlying it require clarification. To investigate the psychopharmacology of UG behaviour, we carried out two studies with healthy participants, employing serotonergic agonists: psilocybin (open-label, within-participant design, N = 19) and 3,4-methylenedioxymethamphetamine (MDMA; placebo-controlled, double-blind, crossover design, N = 20). We found that both MDMA and psilocybin reduced rejection of unfair offers (odds ratio: 0.57 and 0.42, respectively). The reduction in rejection rate following MDMA was associated with increased prosociality (R2 = 0.26, p = 0.025). In the MDMA study, we investigated third-party decision-making and proposer behaviour. MDMA did not reduce rejection in the third-party condition, but produced an increase in the amount offered to others (Cohen’s d = 0.82). We argue that these compounds altered participants’ conceptualisation of ‘social reward’, placing more emphasis on the direct relationship with interacting partners. With these compounds showing efficacy in drug-assisted psychotherapy, these studies are an important step in the further characterisation of their psychological effects.
Gabay, A. S., Carhart-Harris, R. L., Mazibuko, N., Kempton, M. J., Morrison, P. D., Nutt, D. J., & Mehta, M. A. (2018). Psilocybin and MDMA reduce costly punishment in the Ultimatum Game. Scientific reports, 8(1), 8236. 10.1038/s41598-018-26656-2
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Are Ecstasy Induced Serotonergic Alterations Overestimated For The Majority Of Users?

May 7, 2018 / MDMA, Papers, Psychology, Publications / By / , ,

Abstract

BACKGROUND:
Neuroimaging studies imply that the regular use of ±3,4-methylenedioxymethamphetamine (MDMA), the major constituent of ecstasy pills, alters the brain’s serotonergic system in a dose-dependent manner. However, the relevance of these findings remains unclear due to limited knowledge about the ecstasy/MDMA use pattern of real-life users.
AIMS:
We examined the representativeness of ecstasy users enrolled in neuroimaging studies by comparing their ecstasy use habits with the use patterns of a large, international sample.
METHODS:
A systematic literature search revealed 10 imaging studies that compare serotonin transporter levels in recreational ecstasy users to matched controls. To characterize the ecstasy use patterns we relied on the Global Drug Survey, the world’s largest self-report database on drug use. The basis of the dose comparison were the Usual Amount (pills/session), Use Frequency (sessions/month) and Dose Intensity (pills/year) variables.
RESULTS:
Both the average Usual Amount (pills/session) and Use Frequency (sessions/month) of neuroimaging study participants corresponded to the top 5-10% of the Global Drug Survey sample and imaging participants, on average, consumed 720% more pills over a year than the Global Drug Survey participants.
CONCLUSIONS:
Our findings suggest that the serotonin brain imaging literature has focused on unusually heavy ecstasy use and therefore the conclusions from these studies are likely to overestimate the extent of serotonergic alterations experienced by the majority of people who use ecstasy.
Szigeti, B., Winstock, A. R., Erritzoe, D., & Maier, L. J. (2018). Are Ecstasy Induced Serotonergic Alterations Overestimated For The Majority Of Users?. Journal of Psychopharmacology, 0269881118767646.
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3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

May 1, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

BACKGROUND:
Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population.
METHODS:
We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405.
FINDINGS:
Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen’s d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment.
INTERPRETATION:
Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders.
FUNDING:
Multidisciplinary Association for Psychedelic Studies.
Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J., … & Doblin, R. (2018). 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry, 5(6), 486-497, 10.1016/S2215-0366(18)30135-4
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The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

April 11, 2018 / MDMA, Papers, Psychology, Publications / By /

Abstract

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.
Passie, T. (2018). The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985). Drug Science, Policy and Law, 4, 2050324518767442., 10.1177/2050324518767442
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MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?

March 7, 2018 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear- and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD.

Feduccia, A. A., & Mithoefer, M. C. (2018). MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?. Progress in neuro-psychopharmacology and biological psychiatry. 10.1016/j.pnpbp.2018.03.003
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The re-emergence of hallucinogenic research

February 20, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

Due to the intractability, at times, in the treatment of PTSD, clinicians and researchers continue to explore different options for treatment. This article discusses the renewed interest in hallucinogens for such treatment.
Begola, M. J., & Dowben, J. S. (2018). The re‐emergence of hallucinogenic research. Perspectives in psychiatric care. 10.1111/ppc.12263
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Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation

February 14, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

The word “psychedelic” derives from the Greek terms for mind—psyche—and “delos” which means “clear, manifest,” so in essence, psychedelic drugs can be seen as the prototype “window on the mind” concept. The term was originally coined in the 1950s to describe lysergic acid diethylamide (LSD), mescaline, and other hallucinogens, drugs that profoundly alter human experience. These have subsequently been shown to act primarily as agonists at the 5-HT2Areceptor in the brain. Research into the therapeutic potential and mechanisms of action of psychedelic and related drugs peaked in the late 1960s but then stagnated for 50 years after the 1971 UN Psychotropics Convention made psychedelic research with humans almost impossible to carry out (Kyzar et al. 2017).

Recently, however, this area is experiencing a renaissance as drugs often associated with recreational use—such as LSD, ketamine, and cannabis/cannabinoids—have been shown to have therapeutic potential in a range of disorders such as treatment-resistant depression, suicidal ideation, and some pediatric epilepsies. Further, recent pilot studies suggest that MDMA as well as the classic psychedelics, LSD, and psilocybin may contribute to the pharmacopeia for post-traumatic stress disorder (PTSD) and other difficult-to-treat psychiatric disorders. Research has also been stimulated by functional neuroimaging studies of single doses of psychedelics showing that they produce widespread changes in brain connectivity as well as profound alterations to perception and cognition. At the same time, as one would expect from a relatively fledgling area, many questions remain about mechanisms of action, safety, and efficacy. These include what type of psychological therapies best combine with which type of psychedelic drug, whether some types of drug have benefits even without psychological treatment, what the optimal doses are, from single dose through to intermittent or repeated dosing. The current renaissance in empirical psychedelic research stimulated this Special Issue of Psychopharmacology. The articles are grouped into three sections: Clinical efficacy and clinical issues; Effects and Mechanisms of action; Regulation and history.

Curran, H. V., Nutt, D., & de Wit, H. (2018). Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation. 10.1007/s00213-017-4822-3
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