From trip to treatment – the science of psychedelic drugs

You will rarely see me get up early and bike through the rain to make it to church on time. I made an exception for the Interdisciplinary Conference on Psychedelic Research (ICPR2012), a two-day event hosted in the Moses and Aaron Church in Amsterdam. Here I outline some of the talks I went to.

Marco Reeuwijk_ICPR_Church

ICPR is organized by the OPEN foundation, which is an interdisciplinary foundation aiming to facilitate research on psychedelics. The atmosphere is clearly different from what you would expect at a regular conference. The audience is pretty diverse and the media coverage is impressive which says something about a great public interest for this topic in the Netherlands. The talks were broad, covering fields such as philosophy, anthropology, psychology, and neuroscience.

I was particularly interested in the two sessions on the neuropharmacology of psychedelic drugs. The first talk was by Dr Robin Carhart-Harris (Imperial College London). He and colleagues did an fMRI study of the brain on psilocybin, the psychedelic compound in magic mushrooms. Just as the drug lights up your senses, you might expect that the brain would be full of activations. Actually the opposite happened: Carhart-Harris found decreases in cerebral blood flow in the thalamus, posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC). These deactivations were also correlated with the reported intensity of the drug’s effects. The deactivated regions are typically thought to integrate information. Carhart-Harris suggested that psychedelics might decrease the connectivity of the brain’s connector regions, which leads to a state of unconstrained cognition. The mPFC is often overactive in patients with depression. Both psilocybin and several other psychedelic drugs such as MDMA and ketamine seem to deactivate this region.

Vivid memories

Both Mendel Kaelen (Ph.D. candidate at Imperial College London, and a graduate from Groningen University) and Carhart-Harris presented on-going research on memory and MDMA, also known as ecstasy. The results point towards therapeutically useful effects of MDMA. The drug appears to make negative memories feel less painful and enhance memories of positive episodes. In the MRI scanner, participants were asked to think of some of their most positive and negative memories. The memories were rated for vividness during the scan and later in the day. Participants in the MDMA group rated positive memories as more positive and vivid compared to the placebo group. There was also more activity in visual cortex. Mendel Kaelen is currently looking at the effective connectivity between visual and memory related regions. He presented modeling data (dynamic causal modeling) which show that during MDMA effects input from visual cortex drives activation in the parahippocampal region. It seems like enhanced sensory processing provides input that makes memory recall more detailed and vivid. After reading this, you might be worried about how participants responded to drugs in the MRI scanner. It can seem like a claustrophobic place, but participants described it as “a nice warm buzzing tube”, “a cocoon for blissed-out meditation” and the annoying sounds from the scanner “turned into a choir of chanting monks”.

The dualist drug

Dr Ruud Kortekaas (University Medical Center Groningen) outlined his plans for an ambitious study. Together with profs Schoevers and Aleman he plans to investigate the effects of ketamine on patients with treatment-resistant depression. Ketamine is a medically approved dissociative anesthetic and is also used as a party drug. One of the curious effects of ketamine is the dissociative effect – it literally separates the mind from the body. It is often described as a trip deep into the mind where the external world seems distant.

Marco Reeuwijk ICPR_Kortekaas (2)

Kortekaas presented a study protocol, which involves 52 patients and will look at the effects of three weeks treatment over a period of twenty weeks in total. The patients in the experimental group will take low doses of oral ketamine, and all patients will continue with their on-going treatment as well. Previous studies have already shown that patients with depression improve within a few hours after ketamine administration. For some, the effects persist for more than a week. Up until now, the doses of ketamine have been quite high and given by injections. This means that the patients have to come to a hospital and that they will be tripping for an hour or so. In the study planned by Kortekaas, the goal is to see if positive effects can be achieved with a much lower amount of ketamine given as a pill on a daily basis. If that is the case, ketamine would be a serious alternative to conventional antidepressants.

I am curious about the outcome of the ketamine study. One issue that kept coming up during the conference was whether the actual psychedelic experience is necessary for an effective treatment. Perhaps the trip reflects some form of plasticity or underlying restructuring in the brain that is crucial for the effectiveness of the treatment. For instance, Dr Matthew Johnson (John Hopkins, Boston, USA) found that the effect of psilocybin on mood and attitudes was related to the rating of the psychedelic experience rather than the amount of drugs received. In other words: having an eye opening, mind-blowing, spiritual experience mattered more than the dose of the drug that facilitated it. I wonder if the psychedelic experience itself reflects that neural changes are taking place. Or can you have the same effects without the trip? To me, the psychedelic effect could be essential for the treatment, but the trip is also a challenge for this field of research. You could argue that psychedelic studies rarely are double blind: if you are in the experimental condition, you will know. The study by Kortekaas will definitely contribute to this debate, because the ketamine dose given is too low to have any psychedelic effects. If the treatment is successful, it will be a lot easier to rule out a placebo effect.