This research briefing is co-published with the excellent Report on Psychedelics.

June 24th, 2021

In The Research Briefing:

• Are patients ready for psychedelics as medicines? A survey study provides answers
• Microdosing for creativity still not catching a break
• Ketamine helps those with chronic migraines find temporary relief

SURVEY

Psychedelic perceptions of patients

When psychedelics become available as medicines, will the general public accept them? And more specifically, will patients accept them? If they don’t, then the whole enterprise of researching these compounds is mute. If they do, researchers and companies will know that there is a market to service. This survey study asked those who use mental health services about their attitudes regarding psychedelics as medicines.

The researchers sent participants a survey (via the post because of Covid) and got almost all of them to send it back. The participants in the study were suffering from depression, bipolar disorder, addiction, or personality disorders (e.g. OCD). Only a third of participants knew what psychedelics were, and that same percentage (but not per see the same respondents) thought it could be a good treatment option for them.

The researchers also found the following

• 72% supported further research
• 59% supported psilocybin as a medical treatment
• 55% would accept it as a treatment if a doctor recommended it

Among the 99 participants, those who were younger, less religious, or who had used psychedelics before responded more positively than the average. So case closed? Not so fast. Of those surveyed, 20% viewed psychedelics as addictive and unsafe, even when used under medical supervision. There is still a lot of educating to be done.

MICRODOSING

Still a mixed bag for microdosing and creativity

Microdosing remains a controversial topic within psychedelic science. The practice has been shown to be beneficial to many and is practiced by a large number of people. It has positive effects on mood, creativity, productivity, amongst other positive changes. But, much of that can be attributed to placebo or expectancy effects. Researchers have been struggling to find a common ground between the lived experience of thousands of microdosers and double-blind placebo-controlled studies.

This pre-print meta-analysis grouped the data of three of those studies and analyzed the creativity scores of 171 participants. Two commonly used creativity tasks (Picture Concept Task, Alternative Uses Task) were used to measure the convergent (honing in on a solution) and divergent (finding multiple possibilities/solutions/uses) creativity.

This is what we know about creativity and microdosing in the lab

• The microdosing group scores higher on the ratio of original responses, which indicates an improvement in the quality of divergent answers
• But no effect was found on the other sub-scales of divergent creativity, nor on the convergent creativity scale
• The study did control for expectation effects, making the findings more robust

The current study finds that the effects of microdosing are still very subtle. One explanation could be that the participants were already using psychedelics for a longer time, which may have reduced the effects found in the current study. A way around this is to research those who haven’t used psychedelics before. Another reason could be the mismatch between the measure (the two tasks) and ‘real life’ creativity. Whereas the tasks are well-defined, creativity in the broadest sense may still be helped by someone engaging in microdosing (or going on a full trip to work on a problem).

The jury is still out, but this is one more point for team placebo.

KETAMINE

Refractory Chronic Migraine decreased with ketamine

Psychedelics are known for their ability to relieve mental pain. From depression to PTSD, different molecules have proven to be effective in the reduction of suffering. Now researchers are asking themselves if the same can be done for physical pain.

Ketamine has been used for aneasthetics and pain reduction purposes for many decades now. Studies find that ketamine reduces pain in the body. But what about some of the worst pain that people can experience, refractory chronic migraines.

On a scale of 1 to 10, people rate this pain at a (constant!) 7. Not all patients are being helped with the current methods and some are already turning towards psychedelics. Studies on LSD and psilocybin are showing favorable results.

The current study investigated the potential of ketamine to treat refractory chronic migraines. Ketamine was pitted against lidocaine, a local anaesthetic. The hypothesis is that a metabolite, a molecule that is formed when ketamine is being broken down, named (2R,6R)-hydroxynorketamine reduces pain as it has been shown to be effective in animal studies.

What made the pain go away?

• The pain level decreased from 7.4 to 3.7 at the end of hospitalization
• The numbers were slightly less pronounced for the lidocaine group (7.6 to 4.8)
• But in both groups, six weeks later the pain was back at the same (high) level

The difference in pain between both groups was significant, with the ketamine group experiencing less pain after treatment. Alas, for patients this difference might not be clinically significant (it would then have to be 2.0 or greater contrast). What the study did find is that ketamine reduced pain within 3 days, whilst for lidocaine it took until the end of treatment (5 days).

The current study is very small (6 participants) but provides another data point that psychedelics can be a tool to help with some of the worst pain that people suffer from.

Research Report Readout

A review investigates the therapeutic rationale behind the use of psilocybin and MDMA in the treatment of PTSD and depression. Both compounds and the possible treatment modalities (the combination with talk therapy) are discussed.

A pre-print study uses high density EEG, Bayesian modelling, and machine learning to show that predictions (measured as reaction times) depend on alpha activity in higher order cortex (brain), beta feedback, and NMDA receptors. Ketamine blocks access to learned predictive information (i.e. also negative predictive models underlying depression).

Interviews with nine gay men with AIDS, who participated in group therapy with psilocybin, found two major thematic change processes. The first was breaking free from ‘autopilot’ and becoming more mindful and thus allowing for better emotional processing. The second was meaning-making and posttraumatic growth.

Ketamine improved responses to rewards two hours after depressed patients had received ketamine (35mg/70kg) treatment. This correlated with several neurological observations.