Given those earlier findings, the fMRI data reported by Dr. Nutt’s group are somewhat surprising. Methodological issues (such as route of administration, dose, and the spectrum and extent of psilocybin-induced symptoms) may be at least partially responsible for these differences, since the processes being measured are not identical. It is also important to consider that the 5-HT2A receptor is not the only type of serotonin receptor that is activated by psilocybin. Dr. Vollenweider’s experiments have confirmed that the increase in metabolic activity detected by PET is mediated by the 5-HT2A receptor (the serotonin receptor responsible for the psychedelic effects of psilocybin). Because Dr. Nutt’s group did not conduct a similar test to verify that the effects they observed are mediated by the 5-HT2A receptor, this would be a logical next step.
Hopefully, follow-up studies will provide an explanation for these discrepant findings, and will settle the debate over whether hallucinogens act by increasing or reducing brain activity. Clinical trials are currently being conducted to investigate whether hallucinogens can be used to relieve stress and anxiety in terminal cancer patients, to attenuate the symptoms of obsessive-compulsive disorder, and to reduce the frequency of cluster headaches, so it is important to determine the mechanism for the therapeutic effects of hallucinogens. Additionally, there appears to be some overlap between the effects of hallucinogens and the symptoms of psychosis, so understanding how hallucinogens work could potentially provide insight into the causes of schizophrenia and facilitate the development of more effective treatments. In any event, it is important to note that studies have consistently identified the mPFC and ACC as playing key roles in mediating the effects of hallucinogens. In light of what is known about the core functions of these brain regions, it is not unreasonable that they would be involved in mediating the effects of hallucinogenic drugs. Therefore, although it is not yet clear whether hallucinogens act on the mind through the mechanism proposed by Huxley, it appears that we have succeeded in identifying some of the key brain regions targeted by these powerful agents.
Adam Halberstadt is a postdoctoral fellow in the Department of Psychiatry at the University of California San Diego. He studies the serotonin system and its involvement in psychiatric disorders. Mark Geyer is a Distinguished Professor of Psychiatry and Neurosciences at the University of California San Diego. His laboratory uses animal models to study human drug effects and schizophrenia. He is also a co-founder of the Heffter Research Institute, an organization that promotes scientific research with hallucinogens.
Are you a scientist who specializes in neuroscience, cognitive science, or psychology? And have you read a recent peer-reviewed paper that you would like to write about? Please send suggestions to Mind Matters editor Gareth Cook, a Pulitzer prize-winning journalist at the Boston Globe. He can be reached at garethideas AT gmail.com or Twitter @garethideas.
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Add CommentLiterally, the contradictory results of the fMRI studies directly indicated that psilocybin reduced blood flow to the mPFC and ACC, that may mediate the results of numerous other processing regions, while previous PET studies found that psilocybin increased the metabolic activity of certain cells in many regions of the brain, including the mPFC and ACC.
Reply | Report Abuse | Link to thisPerhaps psilocybin reduces total nutrient intake of the mediating mPFC and ACC structures (by constricting blood vessels, for example) while increasing the activity of certain cells within. If the mPFC and ACC mediate the results of numerous processing regions, perhaps a reduction in their moderating effects increase their communication activity.
That hallucinogens' effects are generally analogous to drinking water from a fire hose seems incontravertible.
...acid, being the end-product from that marvellous fungus which produces the ergot-infection in rye...like psilocybin, peyote, marijuana and the host of hallucinogenic natural medicines...a common thread sews these fun party-'gals' tightly together in purposeful familiarity...in my humble lay-mans' opinion...
Reply | Report Abuse | Link to thisThe "trip" is really the actuation of these various plants'/fungus' defense-mechanisms...all fine-tuned either by Father Creator and/or the natural, on-going, evolutionary processes...whichever one desires to believe in -is irrelevant and inconsequential in comparison to what's comin' after one drops a few hits...as is with tomatoes reproducing like red-wabbits -which is the tomatoes' time determined defense...these(psychedelic) living-elements developed a non-lethal and indirect way of letting animals know that if you eat these(or their host) you may very well stroll off of a cliff...or be rendered incapable of finding/hunting food and/or fleeing/fighting deadly enemies...the brains' ability to 'filter-out' unessential information is temporarily altered...such as, reflected-light...the geometric-patterns(not experienced by people who were blind from birth) and the myriad of visible-energies from one end of the scale(infra-ultra) to the other are experienced in full...and quantum...say-y, in normal-sight one sees a ball-park, w/game in progress...and an active picnic-area near-by...Lady Acid/Mesc/Psilocybe/THC/Etc...'sees' chemically, that ones'(the trippers') brain is set a few levels 'up' with a number of select sensual neurotransmitter 'filters'...
Which are either temporarily shut'off' or re-directing these 'messengers' to layers of receptors, then activating their counter-part neurons with information, not regularly handled by these facilities...
-sending a constant interpretation to the cognitive-brain that is relatively 'confused' in continuity, perception, reasoning & etc...to the tripper...
The baseball game, park and picnic-ers all blend into an undulating, flowing cognitive ballet of emotional euphoria, visions of surreal colour, sound, touch...a brain-blast...fun!
--all of which, WHEN OCURRED WITHIN THE WILD...puts the veggies 'attackers' health & life at risk...
A defense for in-the-wild survival...however, many species of animals from insects to mammal(including man) to the aviary families...very actively seek out these hallucinogenic, living medicines...i.e. Lapp-land reindeer sniff-out a certain lichen which contains a potent psychedelic -just for the fun of tripping...& so do I...
We societal humans DON'T live 'in the wild'...planet Earth does...
P.S...Salvinorin-A is one...umm,...of a kind! Amen.
"Clinical trials are currently being conducted to investigate whether hallucinogens can be used to relieve stress and anxiety in terminal cancer patients, to attenuate the symptoms of obsessive-compulsive disorder, and to reduce the frequency of cluster headaches, so it is important to determine the mechanism for the therapeutic effects of hallucinogens."
Reply | Report Abuse | Link to thisHow can you 'determine the mechanism for the therapeutic effects of hallucinogens' before you've determined whether or not they have therapeutic effects?
@jtdwyer - If both fMRI & PET data are accurate, then psilocybin is simultaneously decreaseing bloodflow to the mPFC & ACC and increasing metabolic acitvity in those same areas. This would seem to call into question fMRI's usefulness as a measure of neural activity.
@SittingMooseShaman - Were you tripping when you wrote that?
It is encouraging to see psychedelics taken seriously again; as usual there is much reinventing of the wheel. While we certainly need and respect the nuts 'n bolts research approach, this is like describing the picture on your TV with all the associated emotions and conceptual connections one makes, by examining the motherboard and chips.
Reply | Report Abuse | Link to thisWe've been hashing these approaches over since the 50's. If you think that the effects of sex can be understood by describing engorement and nerve endings, without having sex; or that the taste of a fine cake can be known by weighting carbohydrates, oils, sugars, etc., you are a machine.
Be an adult! take the mushroom. It is not just about intensified broadband data streams, it is also an aweful ("full of awe") immersion into a direct experience of the connectivity of the intertwining Mind of the biosphere. There are so many ancient threads in us that percolate below the surface of our little waking consciousness, the one that enters the lab to do these experiments. This is something one needs to explore from the inside out as well as the outside in. Find out more about WHO you really are and then you will even find directions from that Mind on how to better reveal it through your lab work.
People that don't want to learn are destined to be dominated by those that do. I hope you are not as foolish as you comments.
Reply | Report Abuse | Link to thisHow can poisoning yourself help to heal your brain?
Getting wasted kills useful brain cells.
I had three friends die from brain tumors, when the body starts to die from toxins, it's the same feeling.
Huxley is turning in his grave nearly 100 years after his visionary prophecies began to form into his own mode of fiction. He is one of my favorite authors and raised serious issues and made world-wide breakthroughs in the research of psychedelics as well as our cognitive liberties. I drew a portrait as homage to the man and his works. See the him roll with the mushrooms, the pills and the doors of perception at http://dregstudiosart.blogspot.com/2010/07/aldous-huxley-rolls-in-his-grave.html
Reply | Report Abuse | Link to thisYep, good point. I agree...
Reply | Report Abuse | Link to thisNot that I tripped often but when I did saw a pattern where, first thing, my vision went 2 dimensional. This can be done by closing one eye as well and losing depth of field but, when tripping, this happened with both eyes open. So, it seems very feasible to me that brain function is reduced since the synchrony of the eyes first becomes impaired.
Reply | Report Abuse | Link to thisUm, you might want to check the purity of whatever you have been using in your research, Moose. For my own part, in my limited experience with LSD, the most significant effect I found was the removal of previous perceptual blinders. That is, the 'comedic' representation of the tripping individual staring at their own hand and saying "Wow-w..." is because they are actually 'seeing' their own hand for the first time since they were an infant. It is entirely new and unfamiliar. And, not a loss of 'memory', but a loss of perceptual filtration or, as it's otherwise known, prejudice. I seem to recall that what limited my own (youthful) experiences with LSD was happening to look in a mirror. For me, it wasn't lack of reality, it was TOO MUCH reality.
Reply | Report Abuse | Link to thisHmm - I never heard anyone say that before...
Reply | Report Abuse | Link to thisI'm sorry for your loss.
Reply | Report Abuse | Link to thisHaving survived some incidence of cancer and, more to the point, the quite separate and distinct toxic effects of many months of chemotherapy (poisoning myself to heal my body), in my experience the effects of hallucinogens are not at all similar to those of most toxins.
While I suspect that few therapeutic applications can be found for hallucinogens, the basic research should be conducted, since the potential benefits of whole classes of important psychoactive drugs have been ignored for many years. IMO, one of the most critical tasks of the medical field is to minimize the suffering (pain and anxiety) of terminal and chronic care patients.
While I'm just an ignorant lay person, I have to question the medical protocol employed in the Carhart-Harris fMRI experiments. The article states:
Reply | Report Abuse | Link to this"In this study, intravenous administration of 2 mg of psilocybin induced a moderately intense psychedelic state that was associated with reductions of neuronal activity in brain regions such as the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC)."
I think that injection of psilocybin is a very unusual method of ingestion. Also, as I understand, psilocybin is a 'prodrug' that is metabolized by the body to produce psilocin, the actual psychoactive compound. As I understand, it has been established that the psychedelic effects actually persist for a shorter duration when psilocybin is intravenously injected. While I have no clinical expertise in this area, I have to wonder if different fMRI results might have been obtained if the psilocybin had been orally ingested.
The results of these studies considered with the known complexity of the brain suggest that we still have no idea how they work. This is hardly surprising since we have very little understanding of even normal states of consciousness.
Reply | Report Abuse | Link to thisIn the absence of an understanding of these mechanisms all we have to work with is at best epidemiological data (thin on the ground) and anecdotal reports (inherently unreliable).
Personally I would like to have the option of using these drugs if I had a terminal illness or was suffering chronic pain. I was lucky enough to experience pharmaceutical grade LSD in my youth and while it is not something that should be taken lightly it had a powerful positive emotional impact on me.
In terms of palliative care this is much more important than considerations of the validity of its spiritual, social, or emtional revelations. Bliss out and die!
Clinical studies using LSD and psylocybin therapy with severly schizophrenic children was carried out in the early sixties by two different groups. The work of Fisher et al was particularly amazing. Subjects chosen for the experimental therapy were withdrawn and/or self destructive to the point of death. In one of the more desperate cases the individual was attending public school within 2 years of beginning the therapy. The published report includes the case histories of 12 children of which all exhibited marked if not miraculous improvement.
Reply | Report Abuse | Link to thisAlso, very promising studies with alcoholics was carried out in Toronto and Amsterdam around this same time. Unfortunately all of this valuable work was aborted in the mid sixties due to public hysteria and political paranoia.
A great resource to access these publications and more is online at "the psychedelic library".
Yeah! Hallucinogens seem inhibiting or knocking down for a while, in some persons a longstanding fact, the inhibitory brain circuitry, so the wild part in your mind has a way of showing, and the stop signals the subject receives from others, and from the internalized social an ethical values, are disregarded; in chimps if they give an LSD to one in the herd, the whole group becomes extremely upset, as the stoned animal no longer reacts to the hierachy positions and signals in the group. In mandrills, a way for an old male to impose its power on a young one may be farting in the young's face, but going so deeply in humiliating others may be not accepted in humans, LSD can trigger this kind of behavior. Other drugs act in a different way, I was told about a nurse that after having taken a Datura tea got an offer from a ward mate in the hospital: "Hey, go home and I'll do your work shift, you're too high to work". The D-tea-drinker: How did you notice I was high? Answer: you were measuring the blood pressure of the leg of a cabinet!
Reply | Report Abuse | Link to thisVery entertaining.
Reply | Report Abuse | Link to thisI have never used psychedelic’s, but as a severe Migraine sufferer who gets what can only be described as psychedelic dreams at times which are a prelude to a massive Migraine I very much doubt I would ever want to try these drugs unless I was assured the side affects were no longer a part of the therapy.
Reply | Report Abuse | Link to thisSome of the dreams I have had have left me feeling as if I was literally climbing the walls and having my skin eaten off my bones by insects while I had no control over my body, my mind would wonder into unknown and mostly horrific places, so if these are the affects of these drugs you can count me out! That is from the same Serotonin effect on the brain.
Anyone with thoughtful experience of LSD can tell you that it likely works by helping the brain "let go" of its inhibiting, sensorial-sensual orientation to the phenomenal world. It is like getting rid of boulevard sensibilities so that one can appreciate Picasso. The "deepest" trips occur when wearing blindfolds and listening to music or even to stereo "pink noise" so that all attempts to maintain brain coherence are gonzo.
Reply | Report Abuse | Link to thisThe question remains what sort of "reality" emerges when the brain is freed of sensory input, but is not asleep/dreaming. One passes through "vistas" or "scenarios" like the often grisly scenes suddenly lit up in an amusement park "Tunnel of Love" that are supposed to make you grab your partner. Are these insights or arbitrary fantasies?
Losing synchronicity of the eyes (as result of hallucinogens' effects) very well may indicate reduced brain activity.. Good point RobRob2
Reply | Report Abuse | Link to thisGlad to see psilocybin being studied in a test environment. Utilizing the more testing machinery available, (MRI, PET, EEG) to see the end result might help with the assurance that it is helping or hindering the patient.
Reply | Report Abuse | Link to thisPossibly some type of mental test would be useful as well during the test of medication. A patient may or may not be able to successfully test, or even want to.
Further testing is in order, in my opinion, to see what and if psilocybin could do for our brains. Plenty of people have tested it on their own...