Psychedelic Research

My pace of posting has slowed as I am deep in dissertation writing.  So I have been remiss in failing to celebrate several good new articles, including a study of MDMA-cannabis interactions from Dumont and colleagues and an exciting article that considers one of my favorite topics: hallucinogens from a Bayesian perspective.  However, my primary motivation for this entry is to note the death of psychedelic researcher Abraham Hoffer.
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Here is a list of four human psychedelic studies that are currently recruiting participants. These are all seeking people with specific illnesses. Most of these details were obtained from ClinicalTrials.gov and maps.org
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Torsten Passie and colleagues have published a nice review paper on the pharmacology of LSD. Click through to the full article. There have also been a couple MDMA papers of interest in the last few weeks. I’ll post something about them in the next day or two.
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The Nature News piece on MDMA and PTSD (see my blog entry) wrote:

Swiss psychiatrists have previously reported data on MDMA use in a therapeutic context, but the subjects also received LSD psychotherapy. Although the results were broadly positive, it was not possible to separate the effects of each drug.

Did Nature News really just say that old reports don’t let us conclude MDMA psychotherapy works since maybe it was just the LSD?!

And in any case, isn’t the only citation for those Swiss data the MAPS newsletter?

Today is the birthday of Betty Eisner. Eisner conducted early hallucinogen psychotherapy research with a number of substances. While working on an entry for Eisner in wikipedia, I came across a 1959 paper where Eisner and Cohen say:

During intensive abreactions or at those times when ego disintegration was experienced as a psychotic-like state, it was helpful to have both a male and a female therapist present. They also served as surrogates for inconsistent, manipulating, or rejecting parents and often became a focal point for the projection of intense affectual discharge.

Thus, Eisner, along with Sidney Cohen, appears to have originated the tradition of having both a male and female researcher present during hallucinogen studies. This is something, for example, that Grof recommends in his LSD Psychotherapy book and Johnson et al. mention in their recently published guidelines to human hallucinogen research (blog entry here).

In addition to her many scientific (and some nonscientific) writings, Eisner left us with a very interesting unpublished manuscript, Remembrances of LSD Therapy Past, that fits into a small, important genre with the Shulgins’ PiHKAL, Stolaroff’s Thanatos to Eros, and a few others. To me, these are honest and historic (if sometimes stylistically undistinguished) works. They reveal the successes and failures of smart people trying to understand consciousness and help others. We can learn a lot from them.

Emotions appear to travel by way of the bridge of relationship; relationship is most meager when it exists from mind to mind via words. Is not a much more satisfactory bridge one which leaps from the heart of colour in a painting straight into the solar plexus? Or one which can swing from the psyche straight through a forest into the cosmos? Perhaps the greatest of all bridges of relationship is one which makes a magnificent circle from hand to hand in a group and comes to rest as a transcendental experience in the individual.”

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. (There’s also some nice images in a Figure from Blake & Logothetis’ 2002 Nature Reviews Neuroscience article here).

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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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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Danuta Marona-Lewicka and colleagues have been studying the complex pharmacology of LSD and have previously shown it has an early serotonergic (5-HT2A receptor) phase that lasts about an hour in rats (unclear how to translate the timing to humans) and a later dopaminergic (D2-like receptor) phase. This dopaminergic aspect to LSD may help explain why LSD is more potent than you’d expect based on its interactions with the 5-HT2A receptor.

Marona-Lewicka D, Chemel BR, Nichols DE.
Dopamine D(4) receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI.
Psychopharmacology (Berl). 2008 Jul 6. [Epub ahead of print]

RATIONALE: Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. OBJECTIVE: The present study sought to characterize the effects of several dopamine D(4) agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment times and 2,5-dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT(2A/2C) agonist. MATERIALS AND METHODS: Male Sprague-Dawley rats were trained in a two-lever, fixed ratio (FR) 50, food-reinforced task with LSD-30 (0.08 mg/kg, i.p., 30-min pretreatment time), LSD-90 (0.16 mg/kg, i.p., 90-min pretreatment time), and DOI (0.4 mg/kg, i.p., 30-min pretreatment time) as discriminative stimuli. Substitution and combination tests with the dopamine D(4) agonists, ABT-724 and WAY 100635, were performed in all groups. Combination tests were run using the dopamine D(4) antagonists A-381393 and L-745,870 and two antipsychotic drugs, clozapine and olanzapine. RESULTS: WAY 100635 produced full substitution in LSD-90 rats, partial substitution in LSD-30 rats, and saline appropriate responding in DOI-trained rats. ABT-724 partially mimicked the LSD-90 and LSD-30 cues, but produced no substitution in DOI-trained rats. In combination tests, both agonists shifted the dose-response curve of LSD leftward, most potently for the LSD-90 cue. The D(4) antagonists significantly attenuated both the LSD-90 and LSD-30 cue, but had no effect on the DOI cue. CONCLUSION: Dopamine D(4) receptor activation plays a significant modulatory role in the discriminative stimulus effects in LSD-90-trained rats, most markedly for the later temporal phase of LSD, but has no effect on the cue produced by DOI.