Psychedelic Research

For some reason, this article by Stephen Szára only recently appeared on PubMed, despite having a 2007 publication date. It gives a brief overview of the author’s perspective on DMT research. Szára is from the first generation of psychopharmacology researchers and did key experiments on the pharmacology of psychoactive tryptamines, first in Hungary and then in the U.S. where he worked with Julius Axelrod, among others. Szára was the first to scientifically study DMT in humans.
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Perceptual rivalry is one of the neatest ways to study the neural correlates of the contents of consciousness. If you’re not familiar with this phenomenon, you can read Olivia Carter’s online tutorial on binocular rivalry, one commonly studied type of perceptual rivalry.

Perceptual rivalry should fascinate anyone with an interest in consciousness research. It is also a rare area where scientific studies of consciousness and hallucinogens converge. Carter has done groundbreaking studies (links below) of how psilocybin and possibly LSD affect perceptual rivalry, including some research using the amazing phenomenon of motion-induced blindness (demo here), my favorite visual illusion. Carter’s research is consistently inspiring: She uses rigorous quantitative tools to measure the effects of pharmacological manipulations on consciousness. Her work is one reason I consider perceptual rivalry among the most interesting directions to pursue in future human hallucinogen research, even if (as Carter and Dittrich’s data suggest) hallucinogens do not affect rivalry through a 5-HT2A mechanism.

Two noteworthy developments in non-hallucinogenic rivalry research are a paper by Jakob Hohwy and colleagues giving an elegant theory for why rivalry occurs and a great paper by Joel Pearson and colleagues showing that mental imagery influences rivalry.
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Jörg Daumann and colleagues have published a functional magnetic resonance imaging (fMRI) study comparing the effects of N,N-Dimethyltryptamine (DMT) and S-Ketamine on fMRI-measured neural activity and performance during an attention task. Although the main findings aren’t dramatic, this paper is noteworthy in another way: I believe it is the first publication to combine fMRI and serotonergic hallucinogen administration in humans. This makes their use of ultra-short-duration DMT impressive.
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Adam Halberstadt and colleagues have found that, if rats are pretreated with MAOA inhibitors, then 5-MeO-DMT displays biphasic locomotor effects that it doesn’t normally have. With this drug combination, the initial reduction in locomotion is followed by a later 5-HT2A-mediated increase in activity. The obvious questions, which the authors also raise, are how this lines up with LSD research from the Nichols group at Purdue and others finding early and late phases of LSD effects (previously mentioned here) and the extent to which this might explain the different phases of ayahuasca phenomenology, which Benny Shanon has described at length (see below).
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In this clinical MDMA study, Felix Hasler and colleagues gave volunteers MDMA alone and in combination with the beta-adrenoreceptor blocker and 5-HT1A antagonist pindolol. The role of 5-HT1A receptors in the effects of MDMA in people is particularly interesting given Thompson et al.’s research (see below) on the prosocial effects of MDMA in rodents.
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I remember sitting in Heinrich Waelsch’s study overlooking the Hudson in August 1951, just before returning to England to take up my newly-created post. “What is experimental psychiatry?” asked Heinrich Waelsch, giving me that whimsical penetrating look of his. The newly named professor did not rightly know. “I suppose,” I said, hesitatingly, “it is the application of experimental research method to clinical psychiatry.” — Joel Elkes

July 16th was the anniversary of Gordon Alles’ first self-experiment with MDA in 1930 —to my knowledge the first experience with an MDMA-like drug. Much later, at a 1959 conference at UCSF, he described his experience. If you’ve ever wondered what a hallucinogen/MDMA-like experience would be like to someone without any expectations aside from an interest in finding treatments for allergies and congestion, here is his remarkably observant account:
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Here is an interesting pharmacodynamics paper from Erin Koldrich and colleagues. These investigators recently published a MDMA pharmacokinetics paper (previously blogged here) with a larger N (17 with 7 female before, 8 with 2F for most measures here). One could speculate that the current participants are a subset of that larger sample and the others were busy in an fMRI experiment. In this new paper, some measures include a ninth participant, from whom only a partial battery of measures was collected for this reason. So we may have an MDMA fMRI paper soon. Not a surprise given the author list, but still something to look forward to!
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Flickering light can give rise to remarkable hallucinations. There is a long history of scientific study of this phenomenon, continuing productively to this day. Here are two interesting new papers:
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