Uncovering the Therapeutic Potential of Psychedelics

Research Resurgence Points to Mental Health Benefits

As a graduate student studying psychoanalysis, Robin Carhart-Harris, PhD, came across research on the use of LSD (lysergic acid diethylamide) in psychotherapy that brought clarification and direction to his subsequent career. “I realized that key principles of psychoanalysis were most likely valid because the phenomenology of the psychedelic experience seemed to verify them in quite a compelling way,” he told Psych Congress Network. “In my view, marrying psychoanalysis and psychopharmacology by way of psychedelics promises to yield major advances for psychiatry and psychology…People have good reason to be very excited about this.”

Dr. Carhart-Harris, who will speak at Psych Congress 2018, is the head of psychedelic research for the center for neuropsychopharmacology at Imperial College London in England. Here, he addresses misconceptions surrounding psychedelics, discusses their potential therapeutic utility, and namedrops a prominent US politician who once noted “LSD can be very, very helpful in our society if used properly.”

Q: What are some of the biggest misconceptions you encounter about psychedelic drugs?

A: There are several misconceptions, although it does seem the public and mental health professionals are wising up to “the truth” about psychedelics. One specific misconception I’ve encountered on several occasions is the idea that psychedelics are particularly dangerous compounds that can lead to addiction and/or insanity. The truth is that psychedelics have little-to-no addiction potential and have only been associated with enduring psychotic responses in very rare, individual cases that sometimes receive a disproportionate amount of press attention.

If we look at the scientific data, psychedelics are actually treated as aversive by animals, meaning they actively avoid them. A nottoo- dissimilar phenomenon is seen in humans, where people often do not wish to repeat a psychedelic experience for quite some time, if ever, after having had one. Somewhat ironically, psychedelics are showing promise as treatments for drug and alcohol addiction—with impressive results. Similarly, meta-analyses and population studies have not found a relationship between psychedelic use and negative mental health outcomes. Rather, a trend in the opposite direction was found in at least 1 large population study. Those who had a history of use of psychedelics had lower levels of psychological distress and lower suicidality scores.

Register now for Psych Congress 2018, taking place Oct. 25-28 in Orlando, Fla.

These findings reflect what we see in the lab with controlled studies of healthy individuals and patients with psychiatric disorders such as treatment-resistant depression. They also mirror what we have seen when sampling people using psychedelics in a naturalistic way, such as web-based questionnaires with a prospective design. It is important to emphasize we have found evidence that context is important for determining response. People who have a therapeutic intention experience greater improvement in well-being post-use. But we have also seen that people can report benefits even if they are not using these compounds for a specific psychiatric purpose, such as if they report using them for self-exploration.

Granted, anomalous responses and side effects occur with all drugs. But the point here is to address your question, and the data say that, contrary to a common misconception, psychedelics are not particularly dangerous or harmful compounds. They may, in fact, have beneficial effects if taken in a responsible way.

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Q: What drew you to the field of psychedelic drug research?

A: I was studying psychoanalysis prior to my PhD and discovered literature on the use of LSD in psychotherapy. This changed everything for me. I realized that key principles of psychoanalysis were most likely valid because the phenomenology of the psychedelic experience seemed to verify them in quite a compelling way. For example, people commonly report a dissolution of their egos under psychedelics. This is an experience that is typically met with struggle, as the ego does not relinquish control easily. However, if control is ceded, people appear to experience remarkable insight into the depths of their psyches under psychedelics. Indeed, psychedelic means “mind-revealing,” and this, in my view, is a valid term.

The mind-revealing effects of psychedelics can sometimes be unpleasant if people are faced with dealing with painful psychological material they have omitted from conscious awareness. But they can also be profoundly cathartic and blissful. Discovering this literature triggered a sea change in my thinking about the mind, but I have also always been as much drawn to biological accounts of the mind as deep psychological ones. For me, neurobiology provides a grounding for psychology, particularly if that psychology is abstract. In my view, marrying psychoanalysis and psychopharmacology by way of psychedelics promises to yield major advances for psychiatry and psychology in the coming years and decades. People have good reason to be very excited about this.

Q: Which mental health disorders are psychedelic compounds offering hope for?

A: Psychedelics are showing potential for a range of different disorders. Recent news has tended to focus on depression. We published a small-scale study on psilocybin (“magic mushrooms”) for treatmentresistant depression in 2016, which was followed by 2 larger and more rigorously designed US studies showing improvements in anxiety and depression scores after psilocybin therapy for existential distress linked to life-threatening illness. This work was preceded by other notable studies. However, over the last 12 years, papers have been published about psychedelics for obsessive compulsive disorder, end-of-life anxiety, depression (including treatment-resistant depression), and tobacco and alcohol addiction. Added to this are papers showing lasting improvements in well-being in healthy individuals after just 1 or 2 dosing sessions with a psychedelic, MDMA-assisted psychotherapy for post-traumatic stress disorder, and conceptual work positing efficacy for functional neurological disorders and eating disorders.

Also Coming up at Psych Congress 2018:

A New Generation of Depression Treatment Approaches
Future Opportunities in the Treatment of Schizophrenia
Looking at Depression Through an Evolutionary Lens

Despite all this literature, it should be acknowledged that these data derive mostly from small-scale studies. One interpretation of the collective excitement they are now generating is that we are witnessing a bias that can happen in the early phase of research in which effect sizes are inflated for a number of reasons. While this may be so, another not mutually exclusive interpretation is that psychedelics do indeed have considerable therapeutic potential efficacy for a broad range of different psychiatric disorders because they have an exceptional ability to address something common to all of them.

Q: Can you give a simplified overview of what happens in the brain after a person takes a psychedelic compound? What is your research showing?

A: A variety of different evidence supports the view that activation of the serotonin 2A receptor subtype is key to the action of psychedelics. If you give a drug that blocks this receptor before you give a psychedelic, essentially the psychedelic won’t work.

Serotonin 2A receptors appear to mediate neural and behavioral plasticity. They are heavily expressed on excitatory neurons, particularly in the cortex, and activation of these receptors increases excitability but in an irregular way, so that the activity of large populations of neurons is dysregulated under psychedelics.

When we use electroencephalogram (EEG) or magnetoencephalography (MEG), we see brain activity become less organized and more complex under psychedelics. Indeed, we have found measures of the complexity or entropy of brain activity provide a remarkably reliable index of the intensity of the subjective effects of psychedelics.

Using functional magnetic resonance imaging (fMRI) to measure brain activity at an even broader temporal scale, we can look at the properties of large-scale brain networks and how these change under psychedelics. When we do, we see 2 main effects: a decrease in the integrity of these large-scale networks, and an increase in the cross-talk between them. A valid summary description of the brain effects of psychedelics, therefore, is they broaden the state space in which the mind and brain can wander, and they do this by breaking down conventional, ordinarily dominant modes of brain functioning.

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Q: What are the potential dangers of psychedelic compounds, and how do you ensure participants in your studies are as safe as possible?

A: There may be potential dangers not known to us. Although some cultures have been using psychedelic plants for several hundred years, scientific research into their effects has never really been allowed to flourish. What we do know, however, is that psychedelics can potently alter the quality of conscious experience, and this can be frightening for some people. If this occurs in a stressful environment, or if it happens to someone with latent or manifest psychological vulnerabilities, then this could, in theory, trigger a negative psychological response with potentially lasting negative consequences. Relatedly, if a psychedelic is taken in a suboptimal environment without proper supervisory care, individuals may put themselves in dangerous situations and suffer physical injury.

One potential complication is so-called “hallucinogen persisting perception disorder” (HPPD). HPPD refers to cases in which individuals report residual perceptual abnormalities after a psychedelic has been metabolized from the body. Although this condition appears to be rare and associated with certain psychedelics (LSD) more than others (psilocybin), it can be distressing for those who suffer from it, and there are no obvious effective treatments other than conventional psychiatric interventions such as psychotherapy and pharmacotherapy (antipsychotic medication). In our recent clinical trial with psilocybin for depression, the main side effects were anxiety on drug-onset, some associated nausea (but no vomiting), some expected changes in cognition that can create a temporary sense of confusion, and headaches the next day or sometimes 2 days after the higher-dose session. No clear cases of HPPD have been reported in modern research with psychedelics.

We ensure people are safe in our studies through careful screening, the provision of psychological support before, during, and after the experience, the provision of a safe and comfortable environment for the experience, and having in place a number of contingency measures if adverse responses are observed. These mainly take the form of psychological intervention from experienced staff trained for such situations.

Q: Psychedelic compounds generated a lot of interest in the mid-1900s but then fizzled out until recently. What happened to dull the initial excitement, and what’s fueling the recent renewed scholarly interest?

A: A combination of factors led to the downfall of psychedelic research and therapy in the late 1960s. Some have blamed excessive proselytising from psychedelic figureheads such as Timothy Leary, once a Harvard professor in psychiatry, who, after “turning on” to the effects of psychedelics, decided to drop academic pursuits in favor of dedicating himself to a more political campaign in which he energetically and provocatively promoted indiscriminate use of psychedelics. This, unsurprisingly, created a political backlash, which, with the help of alarmist media reporting, involved the dissemination and promotion of misinformation about the harms of psychedelics.

This backlash had impacts on those who would otherwise supply the drug for this research, most notably Sandoz (now Novartis), causing them to cease supply, and other bodies important for sanctioning and/or funding psychedelic research. Not all mainstream figures were complicit in this “bail out” however, as exemplified by a fascinating US Senate committee meeting in 1966 in which Sen. Robert Kennedy commented, “Perhaps to some extent we have lost sight of the fact that LSD can be very, very helpful in our society if used properly.” Unfortunately for psychedelic science, such rational voices were drowned out by those of the ill-informed but nevertheless maddened crowd.

Q: What do you hope Psych Congress attendees will take away from your session?

A: I hope attendees will take away some new learnings about the short- and long-term brain and mind effects of psychedelics and perhaps an increased curiosity and openness to learn more about their therapeutic potential. I wouldn’t want or expect people to become overnight converts. As Carl Jung said, “Skepticism is the mother of all scientific truths.” So I hope people go away with a heightened interest in the topic but with no less skepticism than when they arrived.

—Jolynn Tumolo