The Tug-of-War on Drugs, Part 1

In celebration of Washington and Colorado's first quasi-legal 4-20, I spent days writing a series of heavily-referenced posts on why certain drugs are illegal -- which somehow disappeared from cyberspace. So, here's my best paraphrase...

Strolling through the suburbs on a gray November's day, I couldn't help but notice a blue spruce surrounded by red dinner plate-sized mushrooms. Immediately, I recognized these as the fruiting bodies of the European Amanita muscaria ("fly agaric") which form a mycorrhizal relationship with the tree's roots.

Hello there, stupid primates! Let us play with your brains!

These "edible" (or, alternately, "poisonous") Amanitas can cause quasi-psychedelic states of mind (and possibly gnomes), thanks to the active ingredient muscimol. These mushrooms are traditionally "deactivated" when eaten as food in some countries, and are technically legal to consume in the U.S..
` More interestingly, this same suburban neighborhood was likely home to thousands of small, drab fruiting bodies of Psilocybe cyanescens. This species is chock full of psilocybin and its breakdown product psilocin, which is a powerful, LSD-like drug.
` The mushrooms of active Psilocybe species are illegal to gather in most states, even from one's own flower bed.

So, why are some "magic" mushrooms legal and others not? One might naively suppose that the illegal species must be worse for people's health, but as Ben Goldacre might say, "I think you'll find it's a bit more complicated than that."

As I shall discuss further in this post, the so-called "psilocybin mushrooms" are seemingly impossible to overdose on, even on purpose. Long-term use also does not correlate with any negative physiological effects, or mental illnesses, aside from exacerbating symptoms in people already inclined to psychotic breaks.
` Compared to A. muscaria (and the more potent A. pantherina), the psilocybin mushrooms are generally much easier to dose according to one's preferences, and have little to no unpleasant physical effects.
` So, the concern with the psilocybin mushrooms is not for the health of the people who take them. Instead, I found that psilocybin was banned at least in part for its role in the 1960's social revolutions -- and I am saving that part for next time.

In this article I will discuss the science of psilocin and LSD as "boundary-dissolving" drugs, meaning that they shut down the ego process: With the ego gone, so goes the misleading and limiting effects that others have on us by appealing to and manipulating one's sense of self.
` This experience reveals that all of the power we think others have over us is only an illusion. Conflict and prejudice arise mainly because of the barriers that are "programmed" into the ego. When people use these drugs specifically for the purposes of erasing such damage, compassion and self-actualization can blossom far beyond what was previously possible.
` This can be extremely empowering and therapeutic to an individual, and is also why LSD completely backfired in the U.S. military's attempt to create 'super-soldiers': Once the subjects realized that authority and social pressure really are "all in your head", they laughed in the face of orders.

Psychedelics are also bad news for politicians who want to distract the populace from the real issues (such as the pointlessness of the Viet Nam war) by ensnaring people's identities in political propaganda that turns them against one another.
` Timothy Leary's experiment in releasing psychedelics to masses of young people resulted in revolutionary and often naive inspiration to rebel against the system.
` Not surprisingly, these drugs became identified with anti-war groups, hippies, feminists, socialists, communists, anarchists and other people with "funny ideas". (Also, Charles Manson, though he wasn't very funny.)

To Nixon, all this meant trouble, so it is no wonder that he banned psychedelics and spread massive amounts of misinformation to scare people away from them.
` Other governments followed suit, effectively shutting down all psychedelic research in the entire world for decades, thus delaying new and valuable discoveries until recent years.

If any of this surprises you, then you really should read on:

Like most Americans, I grew up believing the whole "drugs are bad, m'kay?" mantra, but as a Skeptic I must ask, "What does the science say?"
` The first thing I learned was that not all "recreational" drugs are the same, and that many even have therapeutic benefits.

This was not at all surprising to me, since I knew that cocaine and heroin used to be sold as medicine (including Coca-Cola!) until these substances were found to be addictive.
` Heroin and other opiates (morphine, codeine, oxycodone, etc.) are still used as painkillers, while derivatives of cocaine are commonly used as local anesthetic, as in cold sore cream and injections at the dentist's office.
` While I agree that excessive opiate and cocaine use commonly leads to health problems, addiction, and death (as do barbiturates, methamphetamine, etc.), some illegal and therapeutic drugs are comparatively safe.

Cannabis is probably the best-known of these, and drugs based on its many cannabinoids are being developed and prescribed for a considerable variety of indications -- see Grotenhermen & Müller-Vahl 2012 for more on cannabinoid uses.
` Yet, in the U.S. all but one of these drugs are classified as Schedule I under the Controlled Substances Act. This category is for substances associated with:
` 1: A high potential for abuse. 2: No currently accepted medical use in the United States, and 3: Lack of safety for use under medical supervision.

I am not certain what is meant by "abuse", although the likelihood of a user developing cannabis dependence appears to be around one in ten, which is even less than the rate of caffeine dependence. As for "currently accepted medical use" in this country, here are but a few examples:
` Cannabis and certain cannabinoids are prescribed for combating glaucoma (Tomida, Pertwee Azuara-Blanco 2004), relieving nausea (Parker, Rock & Limebeer 2011), and most famously, killing pain (again, see Grotenhermen).
` It's also used to treat a range of mental disorders, from anxiety to anorexia (more on this in Part 2). This should not be surprising for the casual observer, considering the origins of such phrases as "don't worry, be happy" and "I've got the munchies".

As for "lack of safety", cannabis itself isn't really toxic: There is not a single known death via cannabis toxicity, which is not surprising since a lethal overdose would probably require smoking thousands of joints at the same time (Hall & Solowij, 1998).
` Lab animals are notoriously hard to kill with the buds of this plant, whether eaten or inhaled, and even their brains are hard to damage (that is, unless they suffer asphyxiation and carbon monoxide poisoning from excessive smoke).
` That being said, there are some rare adverse reactions, such as allergies or a dangerously-rapid heartbeat, so it is not completely without risk of death.

In contrast, alcohol poisoning claims 80,000 lives each year, and drunk driving accidents account for 31% of traffic fatalities in 2011. Medically, alcoholic beverages are repeatedly found to be far more addictive and toxic than many other recreational drugs (including cannabis and psilocybin). 
` Additionally, it is alcohol (but not the other two) that increases the likelihood of risky behavior, violence, and partner abuse. It even has more potential to cause brain damage in adolescents, and even cancer, as compared to cannabis. Yet, you will note, Prohibition has not made a comeback in the U.S.

Despite cannabis' fairly benign track record, its research and treatments continue to be severely constrained in the U.S. The same goes for another Schedule I drug, psilocybin, along with mushrooms containing it.

My first clue that psilocybin doesn't belong in this category came to my attention years ago: I was reading articles about how psilocybin can be used to treat obsessive compulsive disorder (Moreno et al 2006), especially for otherwise-untreatable cases.
` Since then, I've been noticing articles here and there on the benefits of psychedelics -- in fact, the current issue of Scientific American Mind has an article on psilocybin therapy to help terminally ill people deal with their condition.

For the longest time I wondered, how could hallucinating and losing touch with reality help with certain mental disorders? Eventually, I caved in to my curiosity and did some research:
` Contrary to what I had thought, a person who is moderately high on psilocybin or LSD does not lose their rationality, nor do they have problems distinguishing what is real and what isn't.
` Although "heroic" doses can be disorienting, a mid-range dose allows one to take a step back from one's everyday life (e.g. habits, relationships, and ways of thinking), and "look down" on them from an oblique perspective.
` That's not something I would have guessed, and it has to do with the way these drugs "turn down" the ego:

The neurological effect behind this seems to be a reducing of activity in some parts of the brain, such as the thalamus, whose job it is to block out signals that seem unimportant.
` Without this "reality filter" in the way, one can have access to information that one normally would not be aware of. As Yale psychologist Andrew Sewell explains in this LiveScience article:

"...[Y]our perception of the world is governed by a combination of 'bottom-up' processing, starting ... with incoming signals, combined with 'top-down' processing, in which selective filters are applied by your brain to cut down the overwhelming amount of information to a more manageable and relevant subset that you can then make decisions about.

"In other words, people tend to see what they've been trained to see, and hear what they've been trained to hear."

With increased information flow, says Sewell, "Colors become brighter, people see things they never noticed before and make associations that they never made before."
` Aldous Huxley described this phenomenon as opening "the reducing valve" of conscious awareness, and this appears to be a scientifically valid model, according to current research.

Psilocybin breaks down into psilocin, which gains access to one's 5-HT2A serotonin receptors because of its similarity to the neurotransmitter serotonin. It also apparently de-activates parts of the brain that would block out information from one's awareness.
` Carhart-Harris, Erritzoe & Nutt, (2012) claim to have found such correlations with the action of psilocybin. They were surprised to find less, rather than more activity in the fMRI scans, especially in regions that coordinate activity between various parts of the brain.
` There have been many criticisms of this proposed mechanism, but further research seems to back it up. Decreased activity in two regions (the anterior cingulate and medial prefrontal cortices) also corresponded with the intensity of the subjects' reported psychedelic experiences.
` The authors wrote:

These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

The brain regions affected in this way also make up the default-mode network, which is important in high-level concepts such as the ego. That drop in activity would explain the experience of ego dissolution that psilocybin users report.
` The team also found that although these experiences are often ineffable, that the language centers in the brain are still functioning. Perhaps such ineffable experiences really are that difficult to describe?

Another fMRI study (Carhart-Harris et al 2012), although small, seems to show that psilocybin can make memories more vivid. The authors suggest that psilocybin "may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases."
` This makes sense because the insights people gain from such psychedelic "trips" often change the way they look at the world. In fact, psilocybin is not the only "unconventional" experimental treatment for depression (see Young 2013).
` Another thing; if psilocybin reduces activity in the medial prefrontal cortex, which causes the brooding thoughts characteristic of depression, this may also help to explain how it helps sufferers to break free of their emotional chains.

Yet another finding of Carhart-Harris' team was that psilocybin calms the hypothalamus, which is highly active during cluster headaches. This would explain the findings of Sewell, Halpern & Pope (2006), who found that psilocybin and LSD abort cluster headaches, which is such a severely painful and unpredictable condition that sufferers tend to isolate themselves from other people and some even kill themselves.
` At least preliminary studies show that the non-psychedelic 2-bromo-LSD can keep cluster headaches away for months at a time. "Compared to what these headache sufferers currently have available to them, this is quite remarkable. It could lead to a near-cure-like treatment", Halpern says.

So, there are doctors who use either psilocybin or LSD to help pull people out of emotional ruts, and even some who experimentally use them to banish "suicide headaches".
` Not as much research has been done on the muscimol contained in A. muscaria, (the mushroom that's widely legal to consume), although there are some therapeutic applications quite different than those of psilocybin, such as a strong painkilling effect.
` In any case, the muscimol does not seem to have the same "opening the reducing valve" type of effect, although its own distinct mental effects could be useful in other ways.
` Psilocybin's therapeutic uses are at least cautiously accepted in the U.S., although federal lawmakers probably find these even easier to ignore than the more widespread and better-understood uses of cannabis.

Moving on, does psilocybin have a "high potential for abuse"? If "abuse" includes recreational/therapeutic use without medical supervision, then alas, it is quite likely to be abused. But if "abuse" means "destructively excessive use", then this is not very realistic:
` Many psychedelics such as psilocybin are quite difficult to become dependent on, in part because just one use causes a week's worth of resistance to a second "trip". (In contrast, muscimol doesn't induce such resistance, although one would also not expect to find a muscimol junkie.)
` It is also worth noting that most cases of substance dependence happen when the person tries to kill some sort of pain. When one takes psilocybin, negative emotions and other stressful sensations can easily lead to a "bad trip", so it even discourages dependence in "drug addict" types.
` Though this be true, some multi-drug abusers do manage to include psychedelics in with the rest of their addictive regimen. (Now that's hardcore.)

Finally, is psilocybin unsafe under medical supervision, as required for a Schedule I drug? As it turns out, the worst of typical worries with this substance is having a traumatically-bad trip which is not resolved before the drug wears off.
` Decades of research consistently show that bad trips are induced by a bad mood, unpleasant or "clinical" surroundings, as well as susceptibility of mental illness. (More on this in Part 2.)
` Doctors who use this drug to help people cope with, say, a terminal illness, know to make the patient's surroundings both comfortable and cheerful. They may even play music to help guide the patient's experience, keeping it as pleasant as possible. 
` Even so, this drug is not recommended for use in people who are prone to psychosis, as they may not "find their way home" again. This is especially true with higher-than-average doses.

Besides mental and neurological effects, is psilocybin strongly toxic? Not at all: As any Skeptic would know, what makes any substance toxic is its dose. For example, everyone's body naturally produces molecules such as formaldehyde and hydrochloric acid, and these are in such low percentages that they aren't harmful.
` On the other hand, a lethal overdose of salt is about one gram for every kilogram of body weight, and it is also possible to overdose on water, or even breathe too much oxygen! Technically, any substance in a high enough concentration can overwhelm one's cells to the point of toxicity.

Compared to salt (or aspirin, for that matter), Psilocybe mushrooms are virtually non-toxic -- at least in lab animals. (To date, there is only one, possibly two fatalities that might have been caused by Psilocybe overdose.) Even caffeine is a deadlier drug -- something to keep in mind when ordering espresso shots.
` Depending on the species and desired level of effect, a proper dose of Psilocybe is somewhere around a handful fresh or a few grams dry. (The amount of actual psilocybin is around 4 to 10 milligrams.) No long-term physiological effects have been discovered from such use -- at least, not yet.

Interestingly, the legal Amanita muscaria mushrooms are toxic enough to make vomiting a common story for users, partly because their potency is difficult to gauge. Even so, it typically takes more than a few of these huge mushrooms to kill a person, and serious harm is rare, thanks in part to modern medical treatment.
` So, the illegal mushrooms are practically non-toxic, and the legal mushrooms have less predictable effects and are more likely to cause severe nausea.

One may astutely point out an obvious and serious danger -- death by eating the wrong mushroom. For example, a species called Conocybe filaris, as well as three species of Galerina, contain excessively lethal levels of amatoxin and are commonly seen growing in the same flower beds as Psilocybe cyanescens.
` Although these mushrooms are similar-looking enough to be confused with one another (sometimes with tragic consequences), this is mostly due to ignorance in mushroom identification. (Strange fact: One of these genera typically "bleeds" bluish psilocin, the other two don't, with one known -- and vanishingly rare -- exception.)
` Fatal though these small look-alikes may be, the amatoxin-filled Amanita phalloides (a.k.a. "death cap") is the number-one cause of mushroom-related deaths. It can be easy to mistake the pale A. phalloides for edible Amanita species, although at least this is not so true with the brightly-colored psychoactive species.

To summarize; the illegal mushrooms have far more known benefits and fewer known risks than the legal ones. Overall, Psilocybe are the more desirable mushrooms for medical researchers, doctors, as well as casual users in general.

And, as I have found, psilocybin's popularity is a large part of why it has been listed as a Schedule I drug. So, how did psilocybin become so popular, and what exactly happened in the 60's that led to its being banned?
` For that matter, why is there also a prohibition on cannabis, whereas the most harmful drugs of all -- alcoholic beverages and tobacco products -- are sold in grocery stores?

These questions will be answered in my next post, which I must similarly paraphrase from what I had before.