Psychoactive Mushrooms Presentation

What with the hol­i­days and the decision to move all the art­icles from Coffeesh0p over here, it’s about time I posted some­thing with a bit more meat. Having said that, this post is also suit­able for veget­arians, so read on!

As I men­tioned briefly before, I had to give another present­a­tion to my neuro­phar­ma­co­logy class in a similar vein to the one on Salvia divinorum I pub­lished earlier. In the end, I chose to talk about psy­cho­active mush­rooms, so here’s the slides and a bit of blog­gi­fied talking along with each. Before we begin though, I’ll just say this was the worst present­a­tion I’ve ever given — I (prob­ably) had the most severe case of flu ever recorded and only managed to summon the courage to deliver it with Beechams flu plus, aspirin and a cheeky dihydro­codeine. Without these unsung heroes, this talk would not have been possible!

Oh, you can also click on the slides to enlarge them. Without further ado:

I’ll be talking about both the tra­di­tional “Magic Mush­rooms” and the fly agaric mush­room, which is less well known, but is actu­ally pretty cul­tur­ally sig­ni­ficant. For both of these, I’ll touch on a bit of history and tra­di­tion, phar­ma­co­logy and a few other inter­esting bits and pieces.
The typical magic mush­rooms are actu­ally many species of the Psilo­cybe genus with each species having its own subtle dif­fer­ences. There are 60 species of Psilo­cybe mush­rooms growing throughout the united states, of which 25 are hal­lu­cino­genic. These mush­rooms will grow in nearly any kind of habitat, apart from arid deserts, so are found throughout the world. The greatest species diversity falls within the neo­tropic climate zones, encom­passing much of South America.

These mush­rooms were tra­di­tion­ally used by the native peoples of middle America for divin­a­tion & healing pur­poses as well as reli­gious com­mu­nion. In fact, these people referred to the mush­rooms as “God flesh” in their native lan­guage. Tra­di­tional use con­tinued until the Spanish invaded, bringing European culture with them in the 14-​​1500s which pushed mush­room use under­ground. In 1955, Robert Gordon Wasson was the first west­erner to take the mush­rooms, and since then, western interest has exploded.

Some of the pos­itive effects brought on by these mush­rooms include a euphoric change in mood accom­panied by gig­gling and laughter, as well as an increased flow of ideas and tend­ency to think “deep”. Objects and lights also appear more inter­esting and col­ourful. The neutral effects include a general shift in con­scious­ness, as with most other psy­cho­active sub­stances, but also an increased emo­tional sens­it­ivity, pupil dila­tion & pho­to­sensit­ivity, leth­argy and time dila­tion – the feeling that time is passing faster than it actu­ally is. The neg­ative effects of mush­room use can include intense fear, a head­ache as the effects begin to wane, gastrointest­inal dis­com­fort such as cramps & nausea, anxiety, con­fu­sion and fainting. There has been no evid­ence of organ damage fol­lowing use.

The phar­ma­co­logy – The important con­stitu­ents are two com­pounds in the trypt­amine family, psilo­cybin and psi­locin. Psilo­cybin is not actu­ally bio­lo­gic­ally active – rather, it’s a prodrug that gets dephos­phorylated by the body to form psi­locin, which is psy­cho­active. I’ve also put a model of 5-​​HT on there for com­par­ison. Psi­locin is an agonist at 5-​​HT 2A, 2C and 1A receptors, but it’s hal­lu­cin­atory effects are due to the binding to 5-​​HT2A receptors in the brain. Psi­locin shows no effect on dopam­in­ergic path­ways, and only affects norad­ren­ergic path­ways in high doses. It is believed to be the degrad­a­tion of psi­locin into some kind of blue pigment respons­ible for the char­ac­ter­istic blue/​black bruising of these mush­rooms fol­lowing hand­ling. The ease at which they bruise is a good indic­ator of the mushroom’s potency. One species will even turn blue from just blowing on it.

While there are no recog­nised medical uses of magic mush­rooms, they have been used as an exper­i­mental treat­ment for a number of dis­orders. There’s sig­ni­ficant anec­dotal evid­ence to suggest that mush­rooms can abort the period where people with cluster head­aches are prone to attacks and also prevent relapses. Cluster head­aches are quite a serious con­di­tion, being described as more painful than child­birth (by women!), so it’s no wonder people are willing to break the law to treat them­selves. There are also cur­rently studies under way on the effect of these mush­rooms at easing the psy­cho­lo­gical suf­fering asso­ci­ated with cancer.

There’s not a lot more to say about these mush­rooms, only that making them illegal nat­ur­ally hampers research into a poten­tially useful drug.

The Amanita mus­caria mush­room is a whole dif­ferent kettle of fish. Here’s a few pic­tures so you know what I’m talking about.

Also known as the Fly agaric, this mush­room is the archetypal toad­stool of the fairy tales, and is native to many places throughout the northern hemi­sphere, where it has been used cere­mo­ni­ally and recre­ation­ally for thou­sands of years. The mush­room, when freshly picked, is pois­onous, but with careful pre­par­a­tion, the mush­room loses its tox­icity. Unlike its psilo­cybin con­taining coun­ter­part, this mush­room is com­pletely legal.

Amanita have a long past, appearing in artwork from as long ago as 3500 BC. They also appear in paint­ings from the renais­sance period, becoming more prom­inent during the Vic­torian era. This mush­room is asso­ci­ated in par­tic­ular with fairies, elves and little people in general. They also began appearing on Christmas cards as a symbol of luck, and models of the mush­room were hung on Christmas trees as dec­or­a­tions. This could be due to the natural asso­ci­ation between these mush­rooms and pine forests.

It’s also been sug­gested that Santa Clause himself is mod­elled after the fly agaric mush­room, with his red ‘n’ white suit. Reindeer have also been observed eating this mush­rooms in the wild and becoming intox­ic­ated, so could that be behind the stories of flying reindeer? In fact, here’s another article on Amanita mus­caria & Christmas — a very inter­esting read. Alice in Won­der­land by Lewis Carol seemed to draw it’s inspir­a­tion from Amanita mus­caria too.

Here’s a few images of this mush­room appearing in art through time. The top left one is from Disney’s Fantasia from 1940 — another example of just how wide­spread this mush­room has become within our culture.

Use of these mush­rooms has been as wide­spread as their geo­graphic dis­tri­bu­tion, but heavy use has been recorded in Siberia in par­tic­ular. The Siberian shamans use the fly agaric as an altern­ative method to drum­ming and chanting to enter a trance state, but in eastern Siberia, the mush­rooms were used by everyone both reli­giously and recreationally.

These mush­rooms have a much more of a sed­ative effect with less hal­lu­cin­a­tions than the psilo­cybin con­taining coun­ter­parts. The pos­itive effects include euphoria, anal­gesia, trance-​​like states being achieved, syn­aes­thesia, and seeing “little people”. Maybe that one’s not so pos­itive… The neutral effects include sed­a­tion, although some people can feel par­tic­u­larly ener­getic, along with changes in body per­cep­tion, blurred vision and such. The most common neg­ative effects asso­ci­ated with fly agaric use are nausea & gastrointest­inal dis­com­fort, but a powerful dis­so­ci­ation and deli­rium can occur at higher doses.

The active com­pounds in Amanita mus­caria are Ibotenic acid and it’s deriv­ative, muscimol. Ibotenic acid is a neur­o­toxin, which has since found a use in research, being a good inducer of brain lesions. This is the com­pound respons­ible for the toxic deli­rium res­ulting from inges­tion of the fresh mush­rooms. When dried in a par­tic­ular manner, the ibotenic acid is decarboxylated into muscimol, making the mush­rooms a lot safer to eat.

Muscimol itself is a selective agonist at the GABA-​​A receptor and a partial agonist at the GABA-​​C receptor. Muscimol’s effect profile is the sum of its actions at both these receptors, where it binds to the GABA site rather than that of an allos­teric mod­u­lator, such as ben­zo­diazepines or bar­bit­ur­ates. These GABAergic effects alter neur­onal activity in many regions of the brain including the cerebral cortex, the hip­po­campus and the cere­bellum. Muscimol is not meta­bol­ised further by the body, but is excreted in large quant­ities, as we shall see…

Time for some inter­esting bits and pieces about muscimol. Alcohol with­drawal can lead to hal­lu­cin­a­tions of little people much like muscimol. Since alcohol also acts on GABAergic path­ways, maybe the effects could be related?

Siberian tribes used to drink the urine of their shaman, as it con­tains a high con­cen­tra­tion of muscimol after cere­mo­nial fly agaric use. I can’t think of any reason someone might find this out in the first place though.

And despite the name, Amanita mus­caria have neg­li­gible mus­car­inic effects. They do contain mus­carine, but in such tiny quant­ities to not make a difference.

Muscimol has also found use as a phar­ma­co­lo­gical tool, being a GABA agonist. GABA itself plays an inhib­itory role, so GABA agon­ists applied to the brain will also have an inhib­itory role. This is a useful method of sim­u­lating axon-​​sparing brain lesions, making revers­ible inac­tiv­a­tion of brain areas a great way to study brain-​​behaviour rela­tion­ships, such as where and when neur­onal events for learning and memory take place.

And that’s that!

At this point I handed round a fly agaric cap for extra cool points.

The slides are avail­able as a PDF here: Psy­cho­active Mush­rooms Present­a­tion [1.79 MB]

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