Dr. Kiki's Science Hour 30

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Dr. Kiki's Science Hour
Episode 30


Guests

Matthew Baggott, Ph.D. Candidate in Neuroscience, UC Berkeley

Topic

Dr. Kiki's Science Hour talks about the latest research on psychedelic drugs like MDMA, LSD, and Salvia with Matthew Baggott from UC Berkeley.

Links

  • Theassc.org -The Association for the Scientific Study of Consciousness
  • Maps.org -Multidisciplinary Association for Psychedelic Studies
  • Erowid.org -Documenting the Complex Interaction between Humans and Psychoactives


Additional Resources

  • Effects of the psychedelic 3,4-Methylenedioxyamphetamine (MDA) in humans

Jeremy R. Coyle, Jennifer D. Siegrist, Keith Flower, Gantt P. Galloway, Lynn C. Robertson, John Mendelson

3,4-Methylenedioxyamphetamine (MDA) is a psychoactive phenethylamine that is related to MDMA (‘Ecstasy’). Research increasingly supports the idea that this latter drug has emotional effects, including feelings of closeness to others and sociability, that are not shared by most hallucinogens. However, because MDA has not been studied in humans in over 30 years, it is not clear in what ways it is similar to MDMA and in what ways it is similar to hallucinogens like LSD. To better characterize MDA, we conducted a double-blind placebo-controlled study administering MDA to 12 healthy volunteers. We compared effects to those from our studies of MDMA. MDA altered attention to emotional stimuli, consistent with decreased threat vigilance, a hypothesized mechanism of MDMA effects. Changes also included significant increases in closed-eye visuals (CEVs). Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition, supporting a hypothesized link between hallucinations and impairments in sensory or perceptual processing. Overall, MDA produced changes that were similar those of MDMA as well as effects expected from LSD-like hallucinogens.


  • Pharmacodynamic Effects of 3,4-Methylenedioxyamphetamine (MDA)

M.J. Baggott, J. Siegrist, J.R. Coyle, K. Flower, G. P. Galloway, J. Mendelson

Background: MDA is an illicitly used drug that is an analog of MDMA (3,4-methylenedioxymethamphetamine, ‘Ecstasy’). In vivo MDMA is N-demethylated to MDA. Although MDA is often called a hallucinogen, human studies predate widespread use of MDMA, which is not a classical hallucinogen. Thus, it is not clear if MDA pharmacodynamics are more similar to LSD-like hallucinogens or MDMA. We sought to measure its effects in humans in a controlled setting.

Methods: In a placebo-controlled, double-blind, within-subjects study, 12 individuals received a single 98 mg/70 kg bw dose of MDA. This is the molar equivalent of 105 mg/ 70 kg bw MDMA, a well-studied dose. Hormonal (cortisol, prolactin), physiological (HR, BP), and self-report VAS measures of typical MDMA and hallucinogen effects were obtained.

Results: MDA was well-tolerated by all participants (11M/1F; 5 with prior MDA use, 12 with prior MDMA and hallucinogen use). MDA increased cortisol by 16.39 ug/dL (95%CI: 13.03-19.74, P < 1e-3) and prolactin by 18.37 ng/mL (95%CI: 7.39-29.35, P < 1e-3). These hormonal changes are comparable to those seen after MDMA. Heart rate increased by 9.05 bpm (95%CI: 6.10-11.99, P < 1e-5) and blood pressure increased by 18.98 / 12.73 mm Hg (Systolic 95%CI: 16.47 - 21.49, P < 1e-7; Diastolic 95%CI: 10.82 - 14.63, P < 1e-4). Heart rate and systolic changes were significantly less than and greater than seen in a previous study of MDMA (N = 16), respectively (P < 1e-5 and P = 2.42e-7, respectively). There were robust self-report VAS changes in both MDMA-like (e.g., “closeness to others”) and hallucinogen-like (e.g., “familiar things seem unfamiliar”, time distortions, closed-eye visuals) effects that were generally similar to those seen after MDMA.

Conclusions: MDA is a psychoactive sympathomimetic phenethylamine with effects similar to MDMA. Although differences may exist in the magnitude of physiological effects, the overall profiles appear remarkably similar.

Supported by DA 016776


  • MDMA–induced feelings of sociability in humans may have a serotonergic mechanism

KJ Garrison, MJ Baggott, JR Coyle, EK Flower, GP Galloway, and J Mendelson, California Pacific Medical Center Research Institute, San Francisco, CA

Aims: MDMA (3, 4-methylenedioxymethamphetamine, ‘Ecstasy’) is a widely used illicit drug that can induce feelings of sociability and closeness to others. MDMA induces serotonin release by entering the neuron through the serotonin transporter (SERT) and subsequently causing neurotransmitter storage vesicles to release their contents. Blocking the SERT with a selective serotonin reuptake inhibitor (SSRI) interferes with the ability of MDMA to release serotonin and decreases many of its effects in humans and animals. However, it is not clear if the MDMA-induced serotonin release affects sociability.

Methods: We are comparing the effects of MDMA (1.5 mg/kg oral) alone and when given after approximately one week of the SSRI citalopram (20mg/day oral) using a 5-session, double-blind, placebo-controlled, within-subject design. Sociability is measured with the Interpersonal Adjective Scales - Revised (IAS-R) and visual analog (VAS) item “closeness to others”.

Results: A planned interim analysis showed main effects of dosing condition on VAS “closeness to others” (F4,44=13.82, p<0.001) and IAS-R gregariousness-extraversion (F4,44=7.81, p<0.001). MDMA increases both measures compared to placebo (p=0.006 and p<0.001) and citalopram pretreatment significantly attenuates these effects (p=0.032 and p<0.001).

Conclusion: The effects of MDMA on sociability and feelings of closeness to others in humans may be mediated by MDMA interactions with SERT.

Support: R01 DA017716 and DA016776.


  • MDMA Increases Sociability and Oxytocin and Impairs Fear Recognition in Humans

Matthew J. Baggott, B.A. 1,2, §, Gantt P. Galloway, Pharm.D. 1, Hossein Pournajafi Nazarloo M.D., Ph.D.3, C. Sue Carter, Ph.D.3, Ryne Didier, B.S.4, Margie Jang, R.N., Jeremy Coyle, B.A.1,John Mendelson, M.D.1

Abstract

Rationale: MDMA (±3,4-methylenedioxymethamphetamine, ‘Ecstasy’) is said to have unique effects including increased sociability and empathy. These emotional effects and their mechanisms have not been well-studied in a controlled laboratory setting. However, available data suggest they are present and may be produced through mechanisms involving oxytocin. Objectives and Methods: In a placebo-controlled study, we measured self-report sociability, recognition of emotional facial expressions, and plasma oxytocin in 16 participants (8 male, 8 female) after 1.5 mg/kg oral MDMA. Results: MDMA increased self-report sociability and impaired categorization of fearful facial expressions, decreasing accuracy and a signal-detection measure of discrimination (d-prime). MDMA increased plasma oxytocin concentrations, which mediated changes in self-report sociability. Conclusions: MDMA increases sociability, possibly through a mechanism partly involving oxytocin. MDMA may not increase empathic accuracy, but may instead decrease response to threat-related stimuli.

Sponsors

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Production Information

  • Edited by: Erik
  • Notes:
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