How Hallucinogens Work (well... at least in mice)

i-27661e83734183f47c87398b90f9c175-hofmann34.jpgHere's the basic story...

New work by a team of researchers has shed light on why hallucinogenic compounds cause altered states in creatures. It has long been known that hallucinogenic compounds have a high affinity for a certain receptor in the central nervous system (5-HT2A, or 2AR), and that when these receptors are blocked, the hallucinogenic side effects are mitigated. What has remained a mystery is why other non-hallucinogenic compounds with a similar affinity for these 2ARs do not produce similar side effects.

How do you know a mouse is tripping balls? It's not like you can show them crazy tapestries and play Pink Floyd and ask them how they feel. It seems that mice exhibit a specific twitch when they are being affected by a hallucinogen.
Does anyone know what else animals do under the influence? I know this kind of research can still happen in Europe and more and more frequently in the U.S. but I really can't say I know much about it. Below the fold is some other pretty recent research on hallucinogens in humans from a mental health perspective.

From the old blog:

From and (obviously) the AP.

NEW YORK (AP)--People who took an illegal drug made from mushrooms reported profound mystical experiences that led to behavior changes lasting for weeks--all part of an experiment that recalls the psychedelic '60s.
Many of the 36 volunteers rated their reaction to a single dose of the drug, called psilocybin, as one of the most meaningful or spiritually significant experiences of their lives. Some compared it to the birth of a child or the death of a parent.... Psilocybin has been used for centuries in religious practices, and its ability to produce a mystical experience is no surprise. But the new work demonstrates it more clearly than before, Griffiths said. Even two months after taking the drug, pronounced SILL-oh-SY-bin, most of the volunteers said the experience had changed them in beneficial ways, such as making them more compassionate, loving, optimistic and patient. Family members and friends said they noticed a difference, too.... Two months later, 24 of the participants filled out a questionnaire. Two-thirds called their reaction to psilocybin one of the five top most meaningful experiences of their lives. On another measure, one-third called it the most spiritually significant experience of their lives, with another 40 percent ranking it in the top five. About 80 percent said that because of the psilocybin experience, they still had a sense of well-being or life satisfaction that was raised either "moderately'' or "very much.''

And the abstract from the article in Psychopharmacology...

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

R. R. Griffiths1, 2 Contact Information, W. A. Richards3, 4, U. McCann1 and R. Jesse4
Rationale Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects.Objectives This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions.Materials and methods The participants were hallucinogen-naïve 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.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.Conclusions When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.

Something else of interest...

Harriet de Wit1 Contact Information
(1) Department of Psychiatry, The University of Chicago, MC3077, 5841 S. Maryland Avenue, Chicago, IL 60637, USA

"The article by Griffiths et al. describes one of the first attempts to study these experiences in a systematic scientific investigation of the reportedly profound and sometimes life-altering experiences induced by the powerful hallucinogen psilocybin. Their study is unique in several ways. First, it applies rigorous, modern methods of psychopharmacological research, including use of controlled, double-blind drug administration with a positive control drug and counterbalanced orders, standardized and replicable testing conditions, and sensitive outcome measures. Second, the study was conducted in specially designed environment, where the drug effects could be experienced safely yet unconstrained by an unnecessarily impersonal laboratory or clinical setting. Third, this is the first modern psychopharmacology study to focus, with healthy volunteers, upon experiences of deeply meaningful insights and understanding. Finally, the study is unique in that the investigators have also begun to study the lasting, life-changing effects that have been attributed to such experiences, using systematic follow-up assessments of mood and overt behavioral changes in the participants' lives."


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I have to admit that this news disappointed me. I've read coherent information processing accounts of what dopamine, norepinephrine and acetylcholine do, but never have I heard a good, integrative theory about serotonin.

If they found out that psychedelics worked on one of the better-characterized neurotransmitters, we would be closer to defining their cognitive effects. Instead, it's serotonin. Grrrreat.

Anybody holding out with an all-encompassing theory of serotonin?

I've got one sitting around somewhere... now if I could just find it...

haha... I don't think I've ever written anything serious on the blog - well except cutting and pasting my own research. I always figured that If I'm spending time writing something with a lot of thought behind it (writing takes me a whole lot of effort) It should be in a peer reviewed journal.