Psychedelics Research Recap October 2021

October brought us 26 novel publications on psychedelics as medicine. Several studies explored the effects of low doses of LSD, others investigated the positive outcomes of ketamine, whilst some dove into the outcomes of MDMA. Some of the papers published describe interesting experiments and surveys, although many are reviews.

The most interesting studies this month were a deep dive into psychedelics for chronic pain (an interview study), a survey that found that more than 50% of those with eating disorders would take part in research with psychedelics, and the first look at patents and psychedelics.

You can find all the papers in our database, and the ones that weren’t added in our October Link Overview.

Experiments that take a peak inside the brain

Several interesting experiments were published this month. One experiment gave people a medium dose of LSD (50μg) and found that LSD similarly affected the passive and active stream of thought towards deviant but meaningful thought patterns. Another LSD study (13μg and 26μg) found that microdoses of LSD produced desynchronization patterns similar to those reported with higher doses of psychedelics, leading the authors to believe that microdoses of LSD may produce therapeutic effects in the absence of a full psychedelic experience.

The study above used EEG to measure brain patterns, with EEG being a good tool for measuring brain activity over time. A study in rats found that several psychedelics (psilocybin, LSD, mescaline, DOB) all produced desynchronization patterns and argues that these results were nearly identical to those in humans. In other words, experiments that look at EEG measures in rats/mice (which are easier to undertake), maybe a good proxy for humans (it has ‘robust translational validity’).

Another study in rats, this time with the lesser-known psychedelic DOI, found long-lasting changes in synaptic plasticity after a single dose of the psychedelic. The study looked both at the connections between brain cells (dendrites) as well as how genes are expressed (epigenetics).

Back to humans, a study looked at the pro-cognitive effects of six infusions of (es)ketamine. It was found that ketamine has a pro-cognitive effect on processing speed and that this effect may be independent of ketamine’s effect on mood. Interestingly, the authors argue that the clinical outcomes related to ketamine may be in part mediated by improvements in cognition.

Looking at the long-term effects of ketamine, a follow-up study investigated the antidepressant effects five years after at least one dose of ketamine. Patients who had been taking the neuroleptic (an antipsychotic medication) quetiapine had a significantly longer time to relapse than patients taking other neuroleptics. Mitigating the negative (overdose) effects of ketamine (from recreational use, but possibly also high-dose therapeutic use) is further investigated in a novel study with mice.

Surveys find support from parents and positive outcomes of frequent psychedelic use

A survey of nearly 300 parents asked them about their perceptions on using ketamine to treat mood disorders and suicidality in adolescents. Most parents had positive attitudes towards using ketamine for suicidality, major depressive disorder and bipolar disorder in adolescents. Some did raise concerns about potential side effects and lack of (specific) FDA approval.

Does feeling ‘existential isolation’ correlate with lower levels of meaning in life? For the average person, this is true, but a survey of over 2000 people finds that the previously reported negative impact levels of existential isolation have on a person’s levels of meaning in life was not present in those who have had a mystical experience.

The third survey featured this month looked at the associations between frequency of psychedelic use, self-reported spirituality, and difficulties with emotion regulation. The study finds that classic psychedelic use predicted greater spirituality, which predicted better emotion regulation, ultimately leading to lower levels of anxiety, depressed mood and disordered eating.

Of those suffering from eating disorders (EDs), queried in the final survey this month, more than half would be open to participating in psychedelic research, whilst six out of ten think it’s worthwhile to continue research in this area.

Not a survey, but an interview study, investigates how people are currently using psychedelics to self-medicate for chronic pain. Scores on pain were substantially improved during and after psychedelic use, two processes are identified that underly these effects (Positive Reframing & Somatic Presence).

Researching psychedelics, with care

Early research on psychedelics from the 1960s and ’70s was abandoned for a multiplicity of reasons. A commentary paper investigates the reasons besides the ‘War on Drugs’ and concludes that tighter regulation of the pharmaceutical industry, failure of psychedelic experiments to live up to expectations and a lack of interest from the pharmaceutical industry to fund trials were all contributing factors.

Now that research is in full swing again, the commercialization of psychedelics and associated patents is being critically evaluated. The first paper coming out of the POLAR initiative at Harvard Law School explores issues regarding the patenting of psychedelics given their controversial history and offers suggestions on how to reduce the risk of biopiracy and the issuance of meritless psychedelic patents. Patent pledges, prior art repositories (e.g. Porta Sofia), and tighter patenting requirements on novel psychedelics are three of those suggestions.

Care for indigenous communities should be taken and several initiatives are being undertaken to protect both culture and cultivation of psychedelic plants. But the worldview through which Western medicine (and recreational use) looks at psychedelics may not be commensurable with that of indigenous use argues a commentary paper. Though other authors argue that traditional use of psychedelics may be complementary to Western use, and could be a way for more people to experience relief from suffering.

Let’s review shall we?

At Blossom, we’re somewhat hesitant to publish reviews. Some are made for a specific audience (e.g. nurses in New Zealand), others just recap what we already know. That being said, this month we’ve still included nine reviews that have added substantially to the literature or focused on a specific area of a topic.

Three reviews looked at where we stand with MDMA-assisted therapy. The first review concludes that MDMA significantly reduces a measure of PTSD and is well tolerated and generally safe. A second review, and meta-analysis, grouped data from 27 placebo-controlled studies and finds that MDMA has a moderate-to-large effect on self-reported sociability outcomes. Not only useful for making friends at a rave, but sociability is also one of the elements that can support MDMA-assisted therapy. A third review investigates if the neurological changes are permanent (i.e. neurotoxic), but finds they are potentially reversible.

Ketamine is currently the only psychedelics being used within the medical setting at scale. A review of reviews across 11 studies finds that ketamine alleviated symptoms of depression 40 min to 1 week while esketamine improved symptoms at 2 hours to 4 weeks. The methodological quality of most reviews was, unfortunately, described as “critically low.” No better news is reported in a review of ketamine in the treatment of migraines, which finds inconclusive evidence for its efficacy.

An understudied psychedelic, 5-MeO-DMT, gets a bit more attention in the excellent review of the state of research. Though human studies are far and between, the first results are pointing towards positive effects on scores of depression and addiction. And a review of psilocybin for end-of-life anxiety symptoms finds positive effects on anxiety, in the absence of serious adverse effects.

The neurological mechanisms that happen after psychedelic use are highlighted in a review of neural plasticity. New connections (dendrites) can be made (new branches/spine formation) within the brain, and these new connections may outcompete the ‘bad’ previously established connections. Still, we are only scratching the surface and not much is known about where the majority of neuronal changes take place or how these differ between the different psychedelics. Another review looked specifically at thalamic activity (‘the brain’s gateway’), but also here there is not enough detailed information yet.