Fantastical Fridays: Psychedelic Psilocybin Psychology

Blogging on Peer-Reviewed ResearchAlthough a given scientific paper probably has at least something fairly interesting or unique about it, most people aren't going to be too interested in reading about, for example, the structural details of the protein-protein interactions between cytoplasmic integrin tails and focal adhesion-associated proteins (my work).

But this paper... man, this is completely different. Not only could I not wait to read it, hell, I wished I was there when the experiments were taking place!

i-7522f0de3e8d13394ab11e5c00c52970-shroom.jpgOn July 7th, researchers at Johns Hopkins University School of Medicine published a paper in Psychopharmacology that has been hailed as "the first well-designed, placebo-controlled, clinical study in more than four decades to examine the psychological consequences of the effects of the hallucinogenic (psychedelic) agent known as psilocybin." And for good reason, too.

Since the 1960s, research on mind-altering drugs has largely been considered taboo in the US and elsewhere. Even research on the commonplace drug marijuana has been surprisingly limited, considering its potential therapeutic effects. This has led to a les than thorough understanding of these drugs, their effects, and their mechanisms. This, in turn has for the most part precluded their use in a medical setting and has led to illegal substance laws that are based much more on politics than on science.

i-603c37e242ccb301c12b47f51d2a3004-Psilocybin.pngThe current study (see bottom for full citation), though, attempts to bridge some of these gaps and shine a light into this darkness through the systematic testing of the psychological effects of psilocybin, the active ingredient in mushrooms of the genus Psilocybe ('shrooms, magic mushrooms), which are commonly ingested in recreational drug use. Psilocybin, a hallucinogen, has a chemical structure resembling that of the neurotransmitter serotonin, and it presumably acts by overstimulating serotonin receptors in the brain. For more a more detailed description of the chemistry of psilocybin, visit Paul May's Molecule of the Month site.

In this study, scientists examined the ability of psilocybin to elicit mystical experiences in subjects, and then they had subjects rate the significance of these experiences. The study used double-blind methodology, meaning subjects were randomly assigned to either receive psilocybin or methylphenidate (Ritalin) as a control for the placebo effect, and neither the subject nor the examiner was aware of which the subject had received:

The participants were hallucinogen-naive adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior.

The study design was solid, giving significant credibility to the results:

Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.... When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences.

Here's the thing, though. These people weren't just getting high. They were having life-altering experiences:


Two-thirds of the subjects who received psilocybin rated it as either the single most meaningful experience of their lives or within the top five, and the paper notes that "the volunteers judged the meaningfulness of the experience to be similar, for example, to the birth of a first child or death of a parent." Whoa, that's intense. Even months later, subjects who had taken psilocybin reported overall better mental health and a more positive outlook on life than those how did not receive psilocybin. No long-term negative side effects were observed, although while under the influence of psilocybin some subjects reported fear or paranoia.

These results are impressive, and they apparently surprised the authors of the study as well, according to an AP story. This study demonstrates that, at least under some settings, drug experimentation can have substantially positive effects, and it further validates the centuries-old tradition of some Native Americans using psilocybin in religious ceremonies.

Most importantly, this study demonstrates just how much there is to be learned about currently illegal drugs and just how productive systematic studies of these drugs can be. Hopefully this study will serve as a model for others. As our knowledge base increases, it is likely that we'll find novel uses for some of these drugs. In addition, these studies will provide more evidence to counter the prevailing wisdom behind our misguided and unscientific war on drugs.

In the meantime, though, I guess it's all systems go for recreational drug users. Right?

But don't try this at home, [lead author Griffiths] warned. "Absolutely don't."


R.R. Griffiths, W.A. Richards, U. McCann, R. Jesse, Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance, Psychopharmacology 187 (2006), 268-83.

The psychadelic mushroom photo comes from The Randomness Continues.


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Keep in mind that Hoffman's (and the now assimilated Sandoz's) research on LSD paved the way for the modern era of psychiatric medicines. The fallout from recreational uses of the drug hindered further research on it. It seems that the Johns Hopkins researchers have taken up the banner, but with 'shrooms this time.

The active principal is psilocin, I believe. The phosphorylated psilocybin is a natural prodrug. Although psilocybin may not wind up as a useful therapy, a more thorough understanding of its mechanism of action and impact on behavior may lead to new chemical entities. Can psilocin's agonist activity be modulated? Does it bind to other 5HT receptors? It's a fascinating area, and not just from a recreational point of view.* Just look at endocannabinoid research. That's a hot ticket in the pharma industry now. And just how did we learn about endocannabinoids, hmmmm?

*Although I could comment on the number of pharmaceutical researchers I know who had their interest in ligang-protein interactions sparked by, er, less than controlled experiments, and note that I was an undergrad in the 1970's, well, maybe I'd better shut up now.

Like my SiBling, or should I say "psilo-Sibling," Doc Bushwell, my botanical chemistry interests have me all hot and bothered about this paper.

My interests in this area also stem back to my pharm readings of Hoffmann's experiments at Sandoz, but they lead me to a different idea: are people who are "more spiritual" simply hyperactive in those 5-HT tracts whereby psilocybin acts. Can spirituality and the meaning of life actually have a concrete chemical basis rather than a mystical, inexplicable basis?

These people weren't just getting high. They were having life-altering experiences

Getting high can be a life-altering experience by itself ;)

But don't try this at home, [lead author Griffiths] warned. "Absolutely don't."

He's just covering his bases. First, he's in the US, a zealous anti-drug attitude, and after all, NIDA, which funded the study, didn't like that this research was being done*.

OTOH, in the Netherlands, magic mushrooms, among certain other plant-based drugs, are sold openly in around 120-150 "smartshops". The Dutch Ministry of Health has an agency responsible for monitoring new drugs - Coordination Centre for the Assessment and Monitoring of new drugs(CAM). In 2000, due to the increasing availability of mushrooms, they conducted a risk assessment**.

The executive summary says,

"This drug is not associated with physical or psychological dependency, acute toxicity is largely limited to possible panic and anxiety attacks and, in terms of chronic toxicity, the worst that can happen are flashbacks. Consequently, the use of paddos (hallucinogenic mushrooms) does not, on balance, present any risk to the health of the individual."


(for some reason your spamfilter doesn't like links. Surely, there's a better heuristic than the mere presence of links.)

We've been having some trouble with our spam filter. I'll pass that along, and hopefully we'll get that sorted out.

"Can spirituality and the meaning of life actually have a concrete chemical basis rather than a mystical, inexplicable basis?"

I think that's one of the most important questions we should be asking, Abel Pharmboy, and I think that's where research on these drugs can really prove valuable.

I think that's where research on these drugs can really prove valuable.

I doubt it. One needs to show the emergence of any qualia from physical/chemical activity, before more specialized phenomena are tackled.

""Can spirituality and the meaning of life actually have a concrete chemical basis rather than a mystical, inexplicable basis?""

Maybe our usual "mundane" state is the inaccurate one. I would be curious to know more about interactions between "turned-on" individuals. This is a very interesting subject.

By thomas Barta (not verified) on 17 Jul 2006 #permalink

well. im a young man almost to finish my teens. and i must say i've had some intense experiences with mind altering substances. all the way from mdma to acid. i still havent been able to try dmt. i hope i can soon. and i've had some good times. i learned not to worry so much about death and such, i learned that is just a process to go to another plane of existence. myabe im just a burn out dude from highschool but i have changed alot since i didnt this things and i look at the world with a different pair of glasses. i think this drugs are illegal cuz it takes ppl out of their daily routines and they will no longer be like sheep following what the higher authorities tell us to do. and maybe they re illegal becuz this higher power that controls all know the power of this substances. the power of thought, to question everything. so. yeah. theres drugs that re just bad garbage. but theres other stuff that can maybe take us to a better place. maybe take us humans to our true selves.