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Humans have been eating hallucinogenic, or “magic,” mushrooms
in ritual and spiritual contexts since at least 3,000 BCE.
But despite how long we’ve known about magic mushrooms,
we actually barely know anything, well, about magic mushrooms.
Or, more specifically, about psilocybin,
the molecule that makes these mushrooms so special.
There’s over 200 species of fungi that produce psilocybin,
which makes them hallucinogenic.
But this molecule itself isn’t the one that causes hallucinations in humans.
You see, the body strips off a phosphate molecule
from the psilocybin to form a different molecule called psilocin.
And it’s psilocin that actually sends people on a trip,
because it binds to one of the same receptors as serotonin,
which is the molecule involved in things from sleep and
blood pressure to mood regulation and depression.
The receptor is 5HT2A, which is also targeted by other
psychedelic drugs like LSD, MDMA, and mescaline.
And scientists still don’t know how or if molecules binding to the
5HT2A receptor result in hallucinations,
but they think it’s related to how parts of the brain communicate with each other.
And a way they think that psilocybin is doing this is by strengthening the
connections between brain networks,
even for areas that weren’t strongly connected before taking psilocybin.
In mice, for example, psilocybin may actually be creating entirely new connections.
In people, psilocybin increases the strength of the connections responsible for how
you sense the world, while also decreasing the connections
responsible for how we understand signals from our environment.
And some scientists think this mix and match on how we sense and understand
signals from our surroundings is what may cause
an altered state of consciousness.
One of the side effects of magic mushrooms.
But right now, this research about connectivity is still fuzzy and sometimes
conflicting, in large part because research into the effects of psilocybin is so new.
Policy changes in the last 10 to 15 years have let researchers finally start studying
not just the basic effects of psilocybin, but also the possible therapeutic benefits.
These studies typically involve giving one or two moderate to high doses of
psilocybin in the presence of at least one psychiatrist.
The idea is for the patient to have a good trip experience,
where the lines between themselves and the world around them break down.
This lets them feel connected with the world.
One of the areas of therapeutic interest is for
people with treatment-resistant depression.
This type of depression occurs in about 10 to 30 percent of people with depression,
and it’s what it sounds like: people whose depression either doesn’t respond or
keeps coming back after they start taking antidepressants.
In one early study, researchers treated participants with treatment resistant
depression and about two-thirds of them responded to psilocybin one week after
treatment, and 60 percent still showed
improved depression scores three months later.
Only a few studies have been done so far,
but they seem to suggest that psilocybin can improve depression scores pretty
dramatically, and that there are pretty large improvements
when compared to a placebo.
And compared to traditional antidepressants, which require a daily dose,
hallucinogens can show months of benefit after just one.
It also seems like, when it’s combined with therapy,
psilocybin can be pretty good at helping treat addiction too.
So, researchers have looked at alcohol and cigarette addiction also.
And again, all of these studies are pretty preliminary,
but in a study of people with alcohol dependence,
participants drank less frequently and had fewer heavy
drinking days for up to two months after getting psilocybin treatment.
Which is less compared to just doing traditional therapy once a week.
And for smoking cessation, one study showed that 80 percent of participants were
smoke-free after six months, and 60 percent were still smoke-free
up to 57 months later, after just two or three doses of psilocybin.
That’s almost five years.
But one big question for future psychedelic research is whether
it’s possible to get the benefits without actually tripping.
So scientists looked into microdosing, which involves regularly
taking super-small doses of psychedelics,
small enough not to trip, but enough to feel a positive mood boost.
And a team of researchers has been exploring the possibility of a
non-hallucinogenic psilocybin-like molecule that also binds with the 5HT2A
receptor that might give the antidepressant benefits without the high.
And while it might seem feasible to have some of the good effects without the trip,
other researchers aren’t sure that tripless psychedelics will work as well.
That’s because there’s some evidence that people with more intense tripping
experiences have better therapeutic responses.
On the other hand, getting the benefits without the trip would be great, because
while psilocybin is non-addictive and really difficult to overdose on,
there can still be side effects.
Things like paranoia and anxiety while tripping can put people at risk of physical
harm, and sometimes, even more, long-term psychological problems.
But it’s hard to really draw any firm conclusions, because of the drug laws that
make psilocybin hard to study, which means there
just hasn’t been a lot of research done.
And the studies that have been done tend to be pretty small.
Importantly, the clinical trials of psilocybin that have been done involve having a
therapist present for the entire trip, and then more therapy in the days that follow.
But it seems that research on psilocybin bodes a promising future, but only time
will tell if it will go mainstream as a formal therapeutic.
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