Psychedelics and Plasticity: Doors of Reception

The  fascinating thesis "Doors of Reception" provides an interesting view of psychedelic research.  I found the information about gene expression, plasticity, and attention to be particularly compelling.  A slight bit on the technical side, but readable. Some quotes:

Even more notably, they found that there were certain gene expressions that were induced by the hallucinogenic agonists but not by the non-hallucinogenic ones (Gonzalez-Maeso et al. 2003). These particular genes mainly belong to the family of early growth response (EGR) elements which are primarily known to be involved with neural growth and plasticity (Leah & Wilce 2002).

The hallucinogen-specific transcript for the protein Egr-2 showed particularly robust expression.

Gene expression of neural growth and plasticity helps explain the long term benefits that have been seen with psychedelics.

The level of Egr-2 expression was proportional to the magnitude of attentional demand.

Meditation has a great deal to do with attentional demand.

As neuroplasticity-based therapies emerge and begin their refinement, the two novel and central attributes they entail, that of qualitative activity-dependence and potentially permanent curative capability, parallel precisely the two key aspects of psychedelic therapy that have, over the past six decades, been a conceptual and ideological challenge for conventional medical science to address and antithetical to its economic landscape.

Skepticism about fMRI analysis

As reported in "Stanford psychologists uncover brain-imaging inaccuracies," apparently the smoothing techniques used to make sense of fMRI data may cause researchers to miss activity from smaller scale structures and thus possibly assign that activity to larger structures nearby.

Skepticism about Meditation Research

The article "Research on TM and Other Forms of Meditation Stinks" highlights some of the flaws in meditation research.  An important point to be made is the difficulty of precisely defining meditation itself.

Even more difficult would be capturing details of brief, spontaneous peak experiences.

My sense is that we are slowly getting better at this, with some of the older research being more of a stone knives and bearskins kind of thing.  Many people are aware that private research funded by a group with an agenda (such as Transcendental Meditation) may not constitute the highest expression of reasonable investigation.

Skepticism about EEG biofeedback

In the article "Read this before paying $100s for neurofeedback therapy" the author points out a number of reasons to be skeptical about alpha biofeedback.

Certainly one should be skeptical when paying thousands for neurofeedback, as in the case of Biocybernaut.

I do think there are a surprising number of not so well informed practitioners out there providing neurofeedback with little knowledge or sense of scientific discipline, and in some cases bordering on outright charlatanism.  So there is definitely a case for skepticism.

But I would add a couple of points.  The initial research cited, from the 80s and 90s, is quite a long ways from modern biofeedback.  Personal computers with the necessary speed and processing ability, software, equipment, and protocols had not been developed at that time.  It was after that time period that EEG biofeedback exploded.

The article seems to focus a bit more on alpha biofeedback than biofeedback targeted to specific anomalies (although ADHD is mentioned).  In some ways it is easy to slough off the alpha training of the sixties as hippie nonsense.  My take would be that alpha training, in general, is akin to meditation.  And if you don't go about meditation in the right way *, for example, you could spend decades and not attain stream entry, i.e. in some way be wasting your time.  Off the top of my head I can point to the addiction rehab studies of Peniston and later Scott as examples of successful alpha-theta training.

However, overall the article does have a balance to it, and I would agree generally with the skeptical attitude.  The problem is when skepticism becomes knee jerk.  I am reminded of an old researcher who commented on Tibetan monks meditating, and expressed the opinion that they were simply wasting their time.

I can say that EEG biofeedback definitely helped me, but for my particular set of conditions I suspect proper meditation would have done about the same thing.  For certain disorders, I think EEG biofeedback does have the ability to produce miraculous results.  Hopefully more and better research will point the way.

* One proven way, The practical meditation instructions of Mahasi Sayadaw (~40 minutes mp3).

Meditation: Alpha Brain Wave Control

Researchers studied a group of meditators who were initially taught a body scanning technique (similar to Goenka), moving on to other forms of mindfulness.  The researchers seemed to be focused on the somatosensory cortex, what I think of as the central strip running from ear to ear (C3-C4).  Researchers believe that top down control of alpha leads to "faster and more sensitive filtering of sensory information in the brain," which may explain many of the benefits of meditation.

As reported in the article "Controlling Brain Waves May Be Key to Meditation's Benefits," the original paper is "Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation"

Mindfulness shifts mid-frontal alpha asymmetry

In the article "Approaching dysphoric mood: State-effects of mindfulness meditation on frontal brain asymmetry" two groups of women with recurring depression were exposed to meditation via a mindfulness support group and showed positive shifts in alpha asymmetry (i.e. more alpha on the right).

Highlights

► mindfulness meditation has a protective effect in remitted recurrently depressed patients.
► anterior EEG alpha asymmetry is associated with depressive vulnerability and motivation.
► meditation has a state-effect on alpha asymmetry, yielding an adaptive, approach-related pattern.

Video: Understanding How Psychedelics Work In The Brain

Video: [1/4] Dr. David Nichols - Advances In Understanding How Psychedelics Work In The Brain.

Interesting talk, here are a few highlights.  LSD hits many receptors, unlike, say psilocybin or MDMA, including dopamine receptors.  Rats can be taught to discriminate between drugs, which allows us to do some forms of testing without humans.  LSD may have a longer effect (than say psilocybin) based on a metabolite which seems more active on the dopamine receptors.

Some researchers found that the second half of the LSD experience was often marked by paranoia or unsatisfactory qualities, Nichols believes this may be due to the metabolite.  With my buddhist geek background, I'd give another hypothesis and say people got up in the "ecstatic" range of the 4th nana/2nd jhana early in the trip and then moved on to the unsatisfactory dukkha nanas (5th-10th nana, 3rd jhana) as the trip continued.

Description from youtube:

This talk presented a brief overview of what psychedelics are, and several significant events in this field in the past four decades. A comparison will be made between molecular structures, and how they were related to the structure of the neurotransmitter serotonin. The receptors that have been identified as targets for psychedelics were discussed, and their brain localization noted, followed by a brief description of where the receptors are located, and what happens inside the cell after the receptor is activated by a psychedelic. Comments included about the different intracellular signaling pathways that can be activated, and which one(s) may be important for altering consciousness. A diagram of connectivity between key brain regions was discussed, which will show how some of the effects of psychedelics may be induced. Particular note will be made of the difficulty in identifying psychedelic molecules in the absence of human experimentation, which is illegal. There will then be a discussion of the use of drug discrimination to identify "LSD-like" molecules, and an example from the author's laboratory of the use of rigid analogues to identify important structural features of molecules such as LSD. Finally, a discussion was presented of the unique psychopharmacology of LSD, which occurs in two time-dependent phases, and the hypothesis that LSD may be converted in the body into an active metabolite that may be responsible for this time-dependent activity.

Psychedelic Science in the 21st Century, a conference in San Jose, California, April 15-18 2010, organized by MAPS - the Multidisciplinary Association for Psychedelic Studies in collaboration with: the Heffter Research Institute, The Council on Spiritual Practices, & the Beckley Foundation