Magic mushrooms for depression, MDMA for PTSD: the 21st century revolution in psychedelic psychotherapy

It does not seem to be an exaggeration to say that psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for biology and medicine or the telescope is for astronomy.

Stanislav Grof (1980)

From the CIA’s secret experiments with LSD on unsuspecting “participants” in the 50s and 60s, to psychotherapists who studied and used LSD extensively while it was legal to do so, through to clandestine therapists who continued to use LSD (and other psychedelics) after its ban in the late 60s, research into psychedelic drugs has a long and complicated history.

But talk to people in the field, and they will rightly insist that this time round it’s different rigorous scientific enquiry has taken over and it intends to take psychedelic research into the mainstream.

Psychedelics are increasingly proving their worth as tools in psychotherapy. But, as Charles Grob - a professor of psychiatry and researcher of the psychopharmacology of hallucinogens and MDMA at UCLA - explains: “At this point [we don’t] have a definitive answer as to the specifics of central nervous modulation.”

So no-one quite knows exactly what is going on at the moment, but that shouldn’t stop us approaching this tricky but fascinating topic with a broad brush explanation.

This time round, rigorous scientific enquiry has taken over, and it intends to take psychedelic research into the mainstream.

Broadly speaking, there are two major avenues of psychedelic research in the modern era: direct studies into the value of psychedelic drugs as tools for psychotherapy; and brain imaging studies seeking to understand the neurobiological mechanisms that underlie the psychedelic brain state. We might (simplistically) characterise the former as asking whether psychedelics are useful tools for psychotherapy, and the latter as how they might be useful.

To bridge the explanatory gap between these two areas of study, let’s look at the neurological mechanisms that might underlie the potential effectiveness of psychedelic-assisted therapy in patients with depression and post-traumatic stress disorder (PTSD).

The building of the mind

Let’s start with an analogy - as with all analogies, its ability to highlight certain material means that it necessarily fails to highlight everything.

Imagine a small, windowless building above ground. It is equipped with extraordinarily sophisticated recording equipment, strategically placed around the external walls. These cameras, olfactory sensors, heat monitors and touch receptors, among a plethora of other sensory gadgets, are able to convey a sense of the “world out there” to its inhabitant. When the camera films something, the information is sent for interpretation and converted into an image that is displayed on a giant projection in front of the building’s main occupant: Norman (yes, we are calling him Norman). Something similar happens when the microphone picks up a sound, and when the olfactory sensors “smell” something. The narrative that has been presented to Norman is then sent to a media unit, where it is processed, condensed and sent away for storage.

Below this building lies a vast multi-floor basement. It is almost unimaginably complex. With the help of the administrator (more on him later), this “depot” organises and stores decades’ worth of information that it receives, in part, from the media processing unit. The complexity, speed and dynamism of this basement would make a FedEx sorting depot look like the early stages of a slow game of hot potato). As a result of the sheer amount of information being exchanged, the administrator finds practical ways to increase efficiency – this means that over time, the basement moves towards patterns of information exchange that are repeatable and efficient.

Sitting between the ground floor and the basement is a trapdoor; this is where the administrator sits. In addition to his other duties, he acts as gatekeeper to the basement, ensuring that only the most necessary exchanges take place between Norman and the floors below him. So, part of his job is to communicate with Norman in order to determine which files or constellation of files should be sent up for him to make use of.

This structure is the human mind (and its accompanying sensory paraphernalia). Norman represents the small part of our brain that makes up our conscious awareness; the basement is our unconscious, or subconscious mind. But the bit we are really interested in is the administrator. This we can give many names: the self, the ego, the regulator, or to use the jargon of modern neuroscience: the default mode network (DMN). It can be described in various ways (and fulfils various rolls), but it is essentially a top-down control mechanism that determines how various parts of the mind communicate with each other – it is the gatekeeper of the subconscious and the regulator of experience.

Dr Robin Carhart-Harris - who, as part of the Beckley/Imperial Psychopharmacological Research Programme is conducting the first ever brain imaging study with patients under the influence of LSD, boldly puts it into plain language for us: “The default mode network … is really YOU.”

It helps to think of the DMN as a “reducing valve” (a term Aldous Huxley presciently coined in The Doors of Perception), or a pragmatic filter designed for survival in an inherently overwhelming world. Imagine how impossibly tricky life would be if we were always constantly aware of all the memories and experiences that we had formed over our lifetimes, or if every time you sat down in a crowded bar to talk to a friend, you couldn’t help but tune in to all the conversations going on around you. This is a necessary filter for our normal functioning in the world.

So far, so good. So where do the psychedelic drugs come in? The answer has to do with the unusual activity of the DMN - and therefore the brain as a whole - in those people with particular pathologies.


From a neuroscientific perspective, we know that people with major depression are unable to reduce the activity of the DMN in certain contexts, such as when trying to engage in externally focused tasks. Their DMN essentially works overtime, in a way that tends to manifest as entrenched and rigid patterns of introspective negativity (inescapable and deep-seated negative thoughts about oneself).

Based on information garnered from brain imaging studies, Carhart-Harris suggests that in depression, “the brain gravitates towards states that can become very entrenched and stereotyped, and it’s these states that are very difficult for patients to remove themselves from…”

This might be seen as the administrator being a little over-officious. It is useful to have access to efficient patterns of thought for various activities within our daily lives, but if the processes of our mind become too structured, too rigid and too introspective, we lose the possibility of accessing a broader range of brain states, which, in a damaging spiral, makes escaping these negative and entrenched patterns of thought particularly difficult.

So, cognition in depression can be characterised as entrenched, inflexible and negatively introspective. Brain imaging studies suggest that this is strongly correlated with the increased activity of the DMN.

Post-Traumatic Stress Disorder

In normal circumstances, our experience of the world is processed before it is stored as memory in one of the rooms in the basement (the hippocampus). But when we experience a particularly extreme and traumatic event (like those that can give rise to PTSD), it can overwhelm the mind’s innate ability to process. Instead of being stored as a normal memory, the experience bypasses processing and is locked away in the basement of the mind as a sort of raw, unprocessed experience. This is a poisonous prisoner to have locked in the psyche.

Sensing this memory and its potential escape as a constant threat, part of the DMN (specifically, the amygdala) works very hard to suppress it, to keep it locked up. And this is where it stays… most of the time.

However, the suppression is far from perfect, so when something consciously or otherwise associated with the initial trauma occurs, the raw memory comes flooding back and the patient is forced, to some extent, to relive the experience of the original trauma. This can also happen without the influence of obvious external stimuli and can result in nightmares, terrifyingly realistic flashbacks and an ambiguous but very real sense of constant threat.

Psychedelics and their therapeutic potential

So, how can psilocybin (the primary active ingredient in magic mushrooms) help people with depression and how can MDMA [1] help people with PTSD?

One of the major discoveries in the world of psychedelic science over the past decade or so has come as something of a surprise to many researchers. Measuring blood flow in the brains of volunteers who have been given psilocybin intravenously, researchers working in the Beckley/Imperial Research Programme discovered that rather than increasing the flow of blood (and thus the capacity for increased neuro-activity), psilocybin actually decreased the flow of blood to a particular area - the DMN.

The potential implications of this discovery for the study of consciousness, psychology and psychiatry are difficult to overstate. Here we have a substance that can temporarily knock out the regulator of the mind, the gatekeeper of the subconscious. No longer functioning at full capacity, the gatekeeper leaves the door open and loosens its grip on some of the rigid patterns of thought for which it is normally responsible.

Under the influence of psilocybin, the gatekeeper of the subconscious leaves the door open and loosens its grip on the mind…

Treating depression with psilocybin

Given what we know about the biological underpinnings of depression, it is clear, in a superficial sense, why temporarily disabling the DMN might be helpful as an aid to therapy for depression. More specifically, Carhart-Harris explains that these substances seem to “increase the flexibility of the brain … increasing the range of states which the brain can visit”.

This is difficult to conceptualise, but if we imagine that part of the cognitive problem in depression is being stuck with one particular way of seeing the world and one’s role within it, psilocybin seems to offer a new perspective, a way out of this rigid pattern of thinking. This descriptio,n though, seems to unable to encapsulate the characteristically numinous experience of so many subjects in experiments with psilocybin. Grob points out that researchers administering psilocybin can “reliably replicate mystical states”, and that “positive therapeutic outcomes appear to correlate with having had a strong psycho-spiritual experience”. Can there be a better description of a truly new way of experiencing the world than through the lens of a mystical or spiritual brain state?

There does seem to be something even more special going on. Patients who undergo therapy with psilocybin seem to show signs of improvement a long time after the psychopharmacological effects of the drug have elapsed. There are early signs, from studies on animals, that psychedelic drugs may induce a plasticity of the brain’s neural pathways, but in terms of explaining their impressive enduring impact, Carhart-Harris warns there is still a “huge amount of conjecture” about how this might work. More studies are needed.

Treating PTSD with MDMA

Standard treatment practices for PTSD often involve attempting to allow the patient to recall the original trauma in such a way that it can be therapeutically processed and re-stored as a more normal memory, thus removing the horrific PTSD hallmark of being forced to relive the trauma.

Without the aid of psychedelic tools, though, PTSD is exceptionally difficult to treat for at least two reasons. First, the initial memory resides deep in the subconscious, and is being held there by the amygdala as part of a powerful but imperfect protective mechanism. Second, being forced to relive or recall the experience, if this becomes possible, is likely to be so overwhelmingly upsetting or stressful that processing it in a therapeutically useful way may be impossible.

With these two problems in mind, we consider MDMA, which seems to do two incredibly useful things as an aid to treating PTSD. Firstly, because of the reduced blood flow to the DMN, the area responsible for the suppression of the traumatic memory - the amygdala - is partly disabled. This action alone might actually be counterproductive, as it might simply allow for the PTSD symptoms to come instantly to the surface, overwhelming the patient and inducing a fearful response.

But MDMA does something else. By increasing the levels of the neurotransmitters serotonin and dopamine in the brain, it gives the patient a powerful sense of security and emotional warmth, making them more trusting and open and, crucially, allowing them to experience the world - including the recollection of memories - in a more positive (or less negative) light. Ideally, this allows the patient to access an unusual “sweet spot” of memory reprocessing: the memory is allowed past the slumbering administrator, through the trapdoor to conscious awareness and, when it reaches that point, it is perceived as being less overwhelmingly negative, allowing the patient a crucial period in which they can process it in a way that wasn’t possible first time round.

In a recent MAPS sponsored pilot study, 83% of the subjects receiving MDMA-assisted therapy no longer met the criteria for PTSD at a two-month check up. By any standard, this is an incredible indication of the potential value of MDMA therapy, although many further studies are required before any regulator could consider it safe and effective.

Although we have only looked at psilocybin and MDMA, and their potential utility in therapy for depression and PTSD, it seems that there is a remarkable commonality that pervades across the spectrum of psychedelic tools, including, for example, ayahuasca and LSD.

Unlike most normal psychiatric medicines currently in use, psychedelic-assisted therapy seems to be addressing the causes and not just the symptoms of these pathologies. At the risk of sounding a bit new-age about it all, after much research, it struck me as possible that psychedelic drugs help us to tap into an innate healing ability. I put this to Charles Grob, expecting to receive a stern warning about not mixing up science with guesses and nonsense. To my surprise, he seemed to agree: “Yes… we may have the latent capacity to access innate neurobiological and psychological mechanisms that facilitate healing.”

That’s worth repeating; humans may have an inbuilt ability to heal their own psychological complications, and the administration of psychedelic drugs, with the help of skilled therapists, may be one of the keys to accessing it.

We may have the latent capacity to access innate neurobiological and psychological mechanisms that facilitate healing.

Why should the world care?

Part of the reason that all of this matters, is the sheer number of people we are talking about. In both cases, the numbers seem likely to rise.

PTSD affects men and women from across the world. Military personnel are by no means the only people affected, but for obvious reasons, they are commonly at risk for PTSD.

Military veterans make up around 10% of the US population. The Department for Veteran Affairs (VA) estimates that PTSD afflicts nearly one in three US veterans from the Vietnam war, one in five from Iraq and more than one in 10 from Afghanistan. A recent VA report shows that in 2012, the number of US military veterans dying from suicide had increased from 18 to 22 a day in less than a decade; this is likely to be an underestimation. That’s one US veteran committing suicide every hour in 2012. President Obama has referred to suicide among veterans and soldiers in the US forces as an “epidemic”.

US government bodies continue to spend billions of dollars trying to treat veterans suffering with PTSD, while doing absolutely nothing to lower the incredibly high barriers to studying MDMA as an aid to therapy.

No matter what statistics you look at, depression is reaching epic proportions in some parts of the world. In a number of countries, doctors are writing antidepressant prescriptions for more than one in 10 adults (in the US, the figure is around 11% of those aged 12 and over). In 2013 in the UK, 53 million prescriptions for antidepressants were issued. This is a 92% increase since 2003. Whether this represents a growing depression epidemic, or inappropriate prescription practices is not always clear. Regardless, the WHO puts the point starkly - “depression affects more than 350 million people” and “is the leading cause of disability worldwide”. It’s a pretty big deal, however you look at it.

Depression affects more than 350 million people … and is the leading cause of disability worldwide.

MDMA and psilocybin cannot be patented and they will never be prescribed as “take home” medicines. No one will become rich producing these substances for a regulated medicinal market, which means that pharmaceutical companies have no incentive to pay the remarkable costs involved in jumping through all the relevant regulatory hoops to bring them to market. By far the biggest hurdle in getting these studies to fruition is funding, or the lack of it.

If you want to help get this research to the next stage, please consider checking out the websites below. Even talking about the topic, sharing this article, will help move the world towards an understanding that psychedelic drugs are – in the right hands – potentially powerful tools for psychological healing. This alone will be a major boost for this fascinating and crucial area of study.


[1] “MDMA isn’t a psychedelic!” I hear you cry. The truth is, the term psychedelic is not a hard and fast classification. The etymology of the word is a combination of Greek words that together mean “mind manifesting”. In this broad sense at least, it seems reasonable to refer to it as a psychedelic, especially when being used in this particular therapeutic context. Inevitably many will disagree, but this is an argument about terminology without a broad academic consensus. My dirty little secret: I prefer the term entactogen, but it would have made the title much more of a mouthful. [twitter: @BeckleyDrugs] [twitter: @MAPSnews] Image credit -, published under a Creative Commons License (A bottle of LSD from a Swiss clinical trial sponsored by MAPS)

How this article was made

  • 345 points
  • 11 backers
  • 5 drafts
  • 1 comment
Creative Commons License

Also in this issue