As your eyes close, a kaleidoscopic vision of pattern, color, and sense of deep meaning engulfs your entire field of experience. Thirty minutes ago you were given a controlled dose of a highly potent, and highly illegal, hallucinogenic compound—all in the name of science. Months from now, you will say that this was one of the most profound experiences of your life [5]. You have joined a small but growing number of human subjects participating in an exciting new wave of research. The aim of this work is to understand how an infamous class of mind-altering substances—the psychedelics—may actually be a powerful tool for treating certain forms of psychological suffering.

Psychedelics are a special class of substances known for the vivid perceptual and cognitive changes they induce. Most are classified as Schedule I controlled substances. Legally, this means the U.S. federal government believes they have a high potential for abuse, no currently accepted medical use, and are unsafe to consume even under medical supervision. Despite this legal classification, a variety of psychedelics are currently being studied in laboratory and clinical settings. The results of this research suggest that they are non-toxic, pose no significant risk of dependence, and show great promise in treating a variety of psychiatric ailments [1]. But how do they actually exert their effects in the brain?

What do psychedelics actually do?

The classical psychedelics include, psilocybin, an organic molecule found in a variety of fungi (“magic mushrooms”), lysergic acid diethylamide (LSD), originally synthesized from components of a wheat fungus, and dimethyltryptamine (DMT), an especially potent psychedelic produced by many plant species [2]. The chemical structures of these compounds resemble serotonin, an important chemical messenger in the nervous system (Figure 1). One of their primary effects is to stimulate neurons in the brain that are naturally responsive to serotonin. These serotonin-sensitive brain cells are widespread in the wrinkly outer layer of the brain known as the cerebral cortex. This structure is disproportionately large in humans compared to other mammals, and is widely believed to endow us with many of our higher cognitive abilities.

Figure 1 ~ Psychedelic compounds such as psilocybin, dimethyltryptamine (DMT) and lysergic acid diethylamide (LSD) have chemical structures that resemble the neurotransmitter serotonin. This structural similarity to serotonin allows them to stimulate serotonin-sensitive neurons in the brain. (Source: ChemDraw)

Although psychedelics typically share similar chemical properties, the effective doses, routes of administration, and duration of their effects vary dramatically. The subjective effects also depend strongly on a person’s environment and expectations [14]. At low to moderate doses these typically include mild to moderate distortions in cognition and sensory perception. At higher doses, profound, life-altering experiences are commonly reported, often described as having a mystical or transcendental character [11].

Unlike psychedelics, drugs of abuse such as cocaine, methamphetamine, and nicotine strongly stimulate the brain’s dopamine system (Figure 2), which is critical for their habit-forming potential. The ability of psychedelics to act primarily on the serotonin system is thought to be important for their unique subjective effects and negligible habit-forming potential. Preventing their ability to stimulate serotonin-sensitive neurons also prevents their hallucinogenic effects [21]. But what is going on in the brain as a whole during the psychedelic experience? In just the past few years, the tools of modern neuroscience have allowed researchers to begin to answer this question.

Psilocybin: effects on brain activity and conscious experience

Neuroscientists have recently studied the effects of psilocybin on the brain activity of healthy human participants [4]. They found that psilocybin caused changes in activity across the entire cerebral cortex. These changes were especially pronounced in areas of the cerebral cortex that make up the default-mode network. The default-mode network is composed of a group of brain areas that is most active when we are not actively engaged in a task, and is thought to be important for aspects of cognition such as introspection, mind-wandering, and self-referential thought.

Another study using functional brain imaging also found psilocybin-induced changes in brain activity [15]. In particular, they observed that psilocybin led to decreased activity in several brain regions, with some of the largest decreases in default-mode areas like the medial prefrontal cortex and posterior cingulate cortex (Figure 2). These same brain regions harbor many of the serotonin-sensitive neurons that psychedelics interact with, and show increased activity during self-related thinking under normal conditions. Could one of the major effects of psilocybin and other psychedelics be to decrease activity in certain brain regions, thereby changing the very sense of self that typically frames our everyday conscious experience?

Figure 2 ~ Illustration of the dopamine and serotonin pathways in the human brain. Many drugs of abuse act directly on specific parts of the dopamine pathway, whereas psychedelics act primarily through the serotonin pathway. Note that the serotonin pathway extends throughout the entire cerebral cortex, including default-mode areas such as the medial prefrontal cortex and posterior cingulate cortex, highlighted in pink. Figure by Brian Chow.

Intriguingly, default-mode areas also become less active in other altered states of consciousness, such as meditation [12]. Indeed, people often use similar language to describe the psychedelic experience and non-ordinary states of consciousness like meditation and sensory deprivation [8,9]. These include experiences of depersonalization, frequently verbalized in terms of “ego disintegration,” “boundlessness,” or the feeling that all things are intimately connected [5]. Meditation and sensory deprivation have also been implicated as treatments for depression and anxiety [16], which is an area where psychedelics like psilocybin show great promise. 

Psychedelic psychotherapy

Psychedelics (mainly LSD) were originally studied in the mid-twentieth century, and had shown promise in treating alcoholism and end-of-life anxiety [20]. The original impetus for this research came in part from psychiatrists’ own experience with these substances, and the idea that they might work by allowing patients to see their condition from a new perspective [13]. But after passage of the US Controlled Substances Act in 1970, research halted. In the past several years, however, the potential therapeutic applications of psychedelics have once again become an active area of research.

Psilocybin was recently been given to healthy volunteers in order to study its acute and long-lasting effects. The main finding was that, in most people, psilocybin could induce highly profound, “mystical-type” experiences [11]. In interviews and questionnaires administered after these sessions, participants rated their psilocybin experiences high in qualities such as ineffability (difficult to describe in words), unity (feeling that all things are connected), and having a deeply felt positive mood. Two months after these sessions, the vast majority of participants rated their psilocybin experience as one of the top five most meaningful experiences of their life and as having increased their sense of well-being and life satisfaction. To help put things into clearer perspective, participants sometimes compared the significance of their experience to the death of a parent, or birth of their first child.

Psilocybin has also been administered to terminally ill cancer patients with the hope of alleviating their psychological distress. For many people, learning of a terminal diagnosis can lead to debilitating depression and anxiety. An initial study demonstrated that psilocybin could be safely administered to such patients without inducing adverse effects [18]. Cancer patients in a more recent study at NYU Medical School have seen dramatic and long-lasting reductions in depression and anxiety. Remarkably, these effects were achieved after just a single dose of psilocybin [20], and it is astounding to hear personal testimonies from patients: “I don’t think I’ve experienced—ever—the gratitude that I felt. Gratitude for what? It was just gratitude. I don’t like to talk about it, because it’s really beyond words.” [17]

Figure 3 ~ Dried specimens of Psilocybe cubensis, one of many species of “magic mushrooms.” Mushrooms belonging to the genus Psilocybe contain psychoactive compounds such as psilocybin, which has recently been studied for its potential therapeutic uses. (Photo by Erik Fenderson:

 A major theme of this research so far is that psilocybin can, under appropriate conditions, reliably induce profound and potentially life-altering experiences; it seems to be able to change brain activity in ways that radically shift our sense of self, reinforcing the original intuition that psychedelics may help reframe a person’s typical thought patterns. “Cognitive reframing” is a common strategy in traditional psychotherapy, and psychedelics may provide a means for kick-starting the reframing process. In the words of one researcher, “individuals transcend their primary identification with their bodies and experience ego-free states [during the psychedelic experience]… and return with a new perspective and profound acceptance [20].”  In this spirit, pilot studies investigating the potential use of psilocybin as an addiction therapy aid have been very encouraging, with success rates as high as 80% in an initial smoking cessation study, and larger studies currently underway [7].

Despite a variety of promising results, researchers urge extreme caution. They stress that this area of research in its infancy, and that experiments have been conducted under carefully controlled, comfortable, and supervised conditions. Disturbing psychedelic experiences (“bad trips”) have been reported by recreational users [19], and participants in psychedelic research are carefully screened for mental health issues before being selected. Nonetheless, there is optimism that psychedelics may one day become part of the legal psychiatric toolkit. More research is sorely needed, and some researchers have recommended that the federal government reclassify these substances in order to facilitate future efforts [20]. No matter what the future holds for the place of these substances in society, the work currently being done suggests that, for some people, the psychedelic experience may be well worth the trip.

Nick Jikomes is a Ph.D. candidate in the Harvard University Program in Neuroscience

Follow @njikomes on Twitter

News references

 [2] Sledge, Matt. & Grim, Ryan (2013, December 9). If You Haven’t Heard Of DMT Yet, You Might Soon. The Huffington Post

[3] Bone, Eugenia (2014, November 29). Can Mushrooms Treat Depression? The New York Times.

[7] Lawrence, Janna (2014, October 27). Psychedelics: entering a new age of addiction therapy. The Pharmaceutical Journal.

[9] Harris, Sam (2007, January 8). Selfless Consciousness Without Faith. The Washington Post.<>

[20] Pollan, Michael (2015, February 9). The Trip Treatment. The New Yorker

[13] Costandi, Mo (2014, September 2). A brief history of psychedelic psychiatry. The Guardian.

[18] “How Psychedelic Drugs Can help Patients Face Death. The New York Times. 


 [5] “Blisshrooms.” Radiolab.

[8] (2013, April 30). Sensory Deprivation Tanks. Vice.

[11] Griffiths, Roland (2009, November 9). TEDxMidAtlantic.

[16] Sensory Deprivation: An Altered State of Mind. ABC News.

[17] “Magic Mushrooms and the Healing Trip.” The New Yorker (2015).

Technical references

[1] Nichols, D.E. (2004). Hallucinogens. Pharmacology & Therapeutics. 101, 131-181.

[4] Muthukumaraswamy, S.D., et al. (2013). Broadband Cortical Desynchronization Underlies the Human Psychedelic State. J. Neuroscience. 33(38):15171-15183

[10] Johnson, M.W., et al. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacology. 28(11):983-992

[12] Brewer, J.A., et al. (2011). Meditation experience is associated with differences in default mode network activity and connectivity. PNAS. 108(50):20254-9

[15] Carhart-Harris, R.L., et al. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. PNAS. 109(6):2138-43

For further information

[14] Psychoactive Basics. Erowid.

[19] Harris, Sam. (2011, July 4). Drugs and the Meaning of Life.

[21] Nichols, David (2011, January 6). David Nichols – Psychedelic Science.


7 thoughts on “Worth the trip: psychedelics as an emerging tool for psychotherapy

  1. “Despite a variety of promising results, researchers urge extreme caution. They stress that this area of research in its infancy, and that experiments have been conducted under carefully controlled, comfortable, and supervised conditions. Disturbing psychedelic experiences (“bad trips”) have been reported by recreational users [19], and participants in psychedelic research are carefully screened for mental health issues before being selected.”

    I’d rather have the drugs remain illegal than have MDs in charge of them. An MD is a University degree holder. What is a University? It is a corporation, that is, it is a fictitious entity. So they’re screening users for mental illness, are they? Using what definition? The WHO’s definition, which is more or less that you can be as crazy as you like, as long as you show up for work, don’t make waves? That is, you can believe in completely fictitious entities, like Universities, Medical Boards, etc. and be “mentally well.” In fact, to protect their privilege, the psychiatric community has a dreadful habit (somewhat improved in recent years) of labelling people who understand that they’re loonies “psychotic.” That’s right, if you don’t believe in invisible, intangible beings like Universities and medical colleges, many psychiatrists think that’s evidence of “psychosis.”

    LSD and psilocybin are less harmful than marijuana—anyone in this line knows David Nutt’s research. Acting like LSD and psilocybin are dangerous and that we need to keep them from the “mentally ill” is nonsense—if anything, we need to keep them from the institutionalized physicians, who are quite off their rockers, believing in invisible, immortal bodies politic. And all of this information was standard kit by the 18th century, so, like, it’s obvious why psychedelics were banned—they increase awareness of the body and reality and that so much of “society” (that’s just another word for corporation, by the way) is flimflam.

    Nobody should be forced to believe in Universities or Colleges any more than Artemis—and the idea that the High Priests of Artemis should decide who gets to use psychedelics or not should be very troubling to anyone who believes in a free and democratic society—in a democratic society, the people rule themselves, they’re not ruled by oligopolies of medical professionals, legal professionals, etc.

    The problem is that by any reasonable definition, University people are mentally ill. They believe in invisible, immortal, incorporeal bodies, called Universities. If that isn’t mental illness, I don’t know what is. I’ll govern my own drug use, thanks, I don’t need some mentally ill Barber College graduate doctoring me.

    1. What is this horse shit. Psychonaut here. When you stop fighting your invisible war, feel free to join the rest of the world. If you hate institutionalized education then don’t use it.

  2. Hi all, I just want to askl if someone ever tried using shrooms or truffles for medical purposes? I was reading some articles about this magic truffles and shrooms before engaging my self for the first time. Like this one from: .They say that it has a very potent effect on the brain and hallucination. Unlike marijuana does it have any medical use? In one article that I’ve read magic truffles or shrooms are use on reducing the symptoms of obsessive-compulsive disorder and anxiety. It can also help people to quit smoking and alcohol addiction. Some studies also suggest the property of magic shrooms/truffles can be useful for cancer patients. I would really want to hear other insights regarding this new possible alternative meds. Thanks

    1. Daniel S Lennox Shrooms and most drugs have medical application including marijuana
      Even heroin cocaine and meth have medical uses

    2. A little nugget of wisdom from my university database for you: “Accumulating evidence suggests that psilocybin with accompanying psychological support can be used safely to treat a range of psychiatric conditions, including: end-of-life anxiety and depression, alcohol and tobacco addiction, obsessive compulsive disorder, and most recently from our group, treatment-resistant major depression.”
      — From “Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms” by Robin L Carhart-Harris et al.

  3. Does anyone know if there’s a specific psychedelic best in treatment for chronic alcohol addiction and if they might helpful treating BPD and anxiety by addressing the traumas that caused it ?

  4. I have known many people in my area who uses this as cure to their mental disorder. Psychedelic mushrooms has a great potential to medical world as it has its own way of treating the illness of the people who is experiencing stress, anxiety and etc.

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