- Study reveals how psychedelic psilocybin improves long-term creative thinking
- One Dose of This Illegal Drug Can Stop Depression for Months
- Scientists Discover New Compounds in Magic Mushrooms
- Study Finds ß-Carboline Compounds in Magic Mushrooms
- Magic Mushrooms Synthesize Several ß-Carbolines
- The Effects of Magic Mushrooms vs. Individual Molecules
Study reveals how psychedelic psilocybin improves long-term creative thinking
Psilocybin, the primary psychoactive compound in magic mushrooms, is currently the focus of an exciting new wave of clinical research.
Promising experimental results are revealing the psychedelic compound to be remarkably effective in treating an assortment of mental health issues, from major depression to anxiety related to a terminal illness diagnosis.
Other research is also finding the compound potentially quite effective in helping treat drug dependence issues.
Underlying all this research is the idea that single doses of psilocybin result in enduring and positive psychological changes, persisting past the acute phase of intoxication.
How the drug is generating these long-lasting effects is motivating a great deal of current research, for if these medicines become legal and widely deployed, we need to understand how they fundamentally work and what the best way is to administer them in clinical settings.
A new study, led by psychopharmacology researchers from Maastricht University in the Netherlands, has delivered a fascinating insight into the longer-term, sub-acute effects of a single psilocybin dose on creative thinking.
The experiment revealed unexpected temporal alterations to different creative thinking constructs that could lead to a therapeutic “window of opportunity” in the days following a single dose, whereby certain follow-up therapy interventions could be most clinically effective.
The research followed more than 50 subjects who consumed the drug at a psilocybin retreat in the Netherlands.
The drug was administered in the form of a mushroom-infused tea and participants were free to roam the house and property during the acute phase of intoxication.
Tests on creative thinking, empathy and life satisfaction were undertaken before ingestion, the morning after and seven days later.
The temporal effects of the drug on creative thinking were perhaps the most intriguing results from the research. In an email to New Atlas, Natasha Mason, one of the lead authors on the new study, explained the dual facets of creativity the study focused on.
“Creativity is a multicomponent construct, consisting of divergent (DT) and convergent (CT) thinking,” Mason explains.
“Whereas DT is a process used to generate many new ideas, in a context where more than one solution is correct, CT is considered a process of generating a single optimal solution to a particular problem, emphasizing speed, accuracy, and logic.
The best example of these two processes in play is probably a brainstorming session. DT allows you to come up with various ideas or solutions to a problem, and CT allows you to pick the best solution.
Although both are aspects of creativity and necessary in the creative process, it has been suggested by previous research that DT is a better predictor of creative potential, as it allows for assessment of original ideas (vs CT which leads to conventional, “correct” ideas).”
The morning following the psilocybin dose, participants displayed increases specifically in divergent thinking, but not convergent thinking.
Most interesting were the seven-day follow up reports showing DT performance had returned to normal levels, but CT performance had unexpectedly increased.
This strange result leads the researchers to hypothesize a potential “window of opportunity” whereby certain sub-acute phases, following a psilocybin dose, could be targeted with different types of therapeutic interventions.
“This time- and construct- related differentiation of effects of psilocybin on creativity is really interesting, when thinking of how it can be utilized in a therapeutic process,” says Mason. “Specifically, it has been suggested that DT can enhance psychological flexibility by allowing individuals to generate new, more effective coping strategies.
Thus the ability of psilocybin to enhance DT sub-acutely could help patients to relive events, recall various associations, and consider their situation from another perspective.
Longer-term effects on CT could then be utilized in a subsequent integration session where patients discuss their acute experiences and decide on a strategy to help them cope with intensive emotions.”
So conceivably, future treatment structures could consist of morning-after therapy sessions that capitalize on DT enhancements, followed up by integration sessions a week later that are framed around CT enhancements.
It is still early days for understanding these long-term cognitive shifts manifested by psilocybin.
This particular study only worked on a seven-day timeframe but Mason does suggest that prior work with the psychedelic ayahuasca has found CT enhancements lasting up to one month following a single dose.
The researchers are fundamentally aware of the limitations in the study and readily admit much more work needs to be done to understand how these long-term cognitive alterations induced by psilocybin are influenced by set, setting and individual expectations. The team has recently completed a placebo-controlled iteration of this same experiment with the results yet to be published, as well as looking at these same creative thinking factors for other psychedelic compounds such as ayahuasca and 5-MeO-DMT.
Perhaps the most fundamental takeaway from this compelling new study is the insight into how changes to creative thinking could play a major role in explaining why these psychedelic compounds are proving useful in treating a variety of mental health conditions.
It's becoming increasingly clear these psychedelic agents manifest interesting sub-acute effects beyond the initial few hours of intoxication, and the better we can understand those post-dose transitory phases, the better we can organize effective treatment plans that utilize those beneficial periods.
“These findings highlight the possible underlying role of enhanced creativity and empathy in the therapeutic potential of psychedelics,” says Mason.
“Importantly, the effects outlast the acute state, potentially opening up a “window of opportunity” where therapeutic interventions could prove more effective.
These findings add further support to growing evidence suggesting that psychedelics may hold therapeutic value for treating stress-related mood disorders.”
The new study was published in the Journal of Psychoactive Drugs.
One Dose of This Illegal Drug Can Stop Depression for Months
The results of Vincent’s mushroom trip—and those of 79 other study subjects her—are now being made public, and they’re very encouraging.
A pair of randomized, blinded studies published Thursday in The Journal of Psychopharmacology provide the most robust evidence to date that a single dose of psilocybin can provide relief from the anxiety and gloom associated with cancer for at least six months.
Roughly 40 percent of people with cancer suffer from a mood disorder, which increases their risk of suicide and impairs treatment. Evidence they can be helped by antidepressants is weak.
“People are facing their own mortality, their own demise,” said Roland Griffiths, a professor at the the Johns Hopkins University School of Medicine and the lead author of one of the studies.
“That’s a very special and quite poignant vulnerability that many people have in facing life-threatening illnesses.”
Two teams of researchers, one led by Griffiths and the other by psychiatrist Stephen Ross at the New York University Langone Medical Center, simultaneously ran the studies on participants who had life-threatening cancers as well as a psychiatric diagnosis of anxiety or depression.
For the treatment sessions, guides would bring the participants into a comfortable, living-room- lab and equip them with an eye mask and headphones connected to a playlist of instrumental music. In New York, the guides held the participants’ hands and told them to state their intention for the day.
The guides at Johns Hopkins told Vincent, “If you see something scary, open up and walk right in,” she said. Then, they gave her a dose of psilocybin inside a gelatin capsule and stood back.
Vincent describes her six-hour trip as “spectacularly gorgeous” and “beyond words.
” She saw a sea of green and purple shapes, then a deep-space emptiness with a monolithic presence, similar to the Borg Collective from Star Trek.
At one point, a series of Egyptian ships and Russian dolls paraded before her. As she laughed and wept, something popped out at her from the mental kaleidoscope: A small, creamy-white, animated crab.
“It’s Cancer the crab,” she thought later, referring to the zodiac sign. “It could have been a big, horrifying monster crab that was about to tear me up and eat me. But it wasn’t, it was comic relief. There is still humor in life, there’s still beauty in life.”
In the Johns Hopkins study, half of the 51 participants were given a low dose of psilocybin as control, followed by a high dose five weeks later. (For the other half, the order of the doses was reversed.) The results were remarkable: Six months later, 78 percent of the participants were less depressed than they started, as rated by a clinician, and 83 percent were less anxious.
Furthermore, 65 percent had almost fully recovered from depression, and 57 percent from their anxiety, after six months. By comparison, in past studies antidepressants have only helped about 40 percent of cancer patients, performing about as well as a placebo.
At the six-month follow-up, two-thirds of the participants rated the experience as one of the top five most meaningful of their lives. They attributed their improvements to positive changes in their attitudes about their lives and their social relationships.
Their quality of life improved, as did their feelings of “life meaning” and optimism—even though several of them would later die. “People will say, ‘I know I’m dying, I’m sad that I’m dying, but it’s okay,” Griffiths said. “Things are going to be alright.”
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Scientists Discover New Compounds in Magic Mushrooms
Image from Shutterstock.
There are many mysteries surrounding psychedelic mushrooms (aka psilocybin mushrooms or magic mushrooms).
One of the most critical questions is very basic; what compounds do these mushrooms contain? Historically, psilocybin (the most abundant compound) has received much of the attention.
Psilocybin is a prodrug that the body metabolizes to psilocin, the compound that acts at the serotonin 5-HT2A receptor to produce the psychedelic effect.
Over the years, researchers have identified other compounds in magic mushrooms such as psilocin, baeocystin, norbaeocystin, and aeruginascin. Now, with the renewed interest in the possible therapeutic uses of psychedelics, scientists are revisiting magic mushrooms at a fundamental level—figuring out what compounds are in them.
Study Finds ß-Carboline Compounds in Magic Mushrooms
German scientists have identified new compounds in four species of magic mushrooms and studied their roles in biosynthetic pathways the mushrooms use.1 The researchers isolated the known magic mushroom compounds psilocybin, psilocin, baeocystin, norbaeocystin, and norpsilocin. The new compounds they isolated belong to a family of chemicals known as ß-carbolines.
ß-carbolines are naturally occurring alkaloid compounds.2 They are most commonly known as components of the psychotropic beverage ayahuasca. Examples of ß-carbolines include harmine, harmane, and harmaline (ß-carboline is also another name for the compound norharmane).
Much of the effect of ayahuasca is due to the ability of ß-carbolines to inhibit MAO (monoamine oxidase) enzymes.2,3 This inhibition makes it possible for the psychedelic compound DMT (dimethyltryptamine, another compound in ayahuasca) to pass the digestive system and enter the circulation.
ß-carbolines has some psychotropic effects on their own. Still, without their ability to inhibit MAO enzymes, the full effects of ayahuasca are not realized.
ß-carbolines also inhibit the uptake of serotonin, dopamine, epinephrine, and norepinephrine via competitive inhibition of the receptors4,5 (Keep in mind that the interactions between an enzyme and a molecule are different from how an allosteric modulator interacts with a molecule).
From a disease standpoint, ß-carbolines are known to play a role in the development of essential tremor (uncontrolled shaking) and have been implicated in Parkinson’s disease.6
Magic Mushrooms Synthesize Several ß-Carbolines
Using 1D and 2D NMR (nuclear magnetic resonance) spectroscopy, Blei et al. analyzed extracts from Psilocybe cubensis, P. mexicana, P. cyanescens, and P. semilanceata.
They identified these ß-carbolines in the extracts: Cordysinin C, Cordysinin D, Harmane, Harmol, Norharmane, and Perlolyrine. Figure 1 shows their chemical structures.
These compounds have previously been isolated from fungi and plants in genera such as Cordyceps, Peganum, and Banisteriopsis.7
Figure 1: The chemical structures of newly discovered beta-carboline compounds in some species of magic mushrooms1 (click to enlarge).
As part of this study, the researchers used stable-isotope labeling with 13C11-L-tryptophan to show the ß-carbolines were biosynthetic products of the Psilocybe species. This means that ß-carbolines in magic mushrooms may contribute to the entourage effect along with the known compounds. As the researchers put it,
We conclude that Psilocybe mushrooms produce an ayahuasca- and potentially similarly synergistic set of metabolites that may impact upon onset and duration of their effects. 1
Also, using MALDI-MS (matrix-assisted laser desorption/ionization mass spectroscopy), the researchers showed that the ß-carbolines accumulated at the hyphal apices (the outer edges of the mycelium).
The Effects of Magic Mushrooms vs. Individual Molecules
The Blei et al. paper is a pioneering step in studying the chemistry and variability of the compounds in magic mushrooms. This work highlights the chemical complexity of naturally occurring compounds.
It helps with the understanding that ingesting magic mushrooms is very different from taking pure psilocybin (or any other single compound isolated from magic mushrooms).
The pharmacology of mushrooms is different than individual compounds and understanding this is critical for optimizing the effects of formulations of magic mushroom compounds.
As is often the case with scientific discovery, these study results answer some questions but also pose more. The presence and known effects of ß-carboline compounds in the Psilocybe species they studied, displays the entourage effect in magic mushrooms in a new light. The study authors sum this up well by saying,
Future pharmacological research is therefore warranted to determine to what extent Psilocybe β-carbolines contribute to the actual psychotropic effects of magic mushrooms.
In a recent interview, Paul Stamets, the world-famous magic mushroom expert told Joe Rogan,
…looking at the natural form of these mushrooms, standardized to psilocybin at a certain concentration versus the pure molecule, I think that is the wave of the future.
- Blei F, Dörner S, Fricke J, et al. Simultaneous Production of Psilocybin and a Cocktail of β-Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms. Chemistry – A European Journal. doi:10.1002/chem.201904363
- McKenna D, Callaway J, Grob C. The scientific investigation of ayahuasca. A review of past and current research. The Heffter Review of Psychedelic Research. 1998;1:65-77.
- Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol. 2010;48(3):839-845. doi:10.1016/j.fct.2009.12.019
- Buckholtz NS, Boggan WO. Monoamine oxidase inhibition in brain and liver produced by β-carbolines: structure-activity relationships and substrate specificity. Biochemical Pharmacology. 1977;26(21):1991-1996. doi:10.1016/0006-2952(77)90007-7
- Pähkla R, Rägo L, Callaway JJ, Airaksinen MM. Binding of Pinoline on the 5-Hydroxytryptamine Transporter: Competitive Interaction with [3H] Citalopram. Pharmacology & Toxicology. 1997;80(3):122-126. doi:10.1111/j.1600-0773.1997.tb00384.x
- Louis ED, Zheng W, Jurewicz EC, et al. Elevation of blood β-carboline alkaloids in essential tremor. Neurology. 2002;59(12):1940-1944. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992345/. Accessed November 20, 2019.
- Callaway JC, Brito G de S, Neves ES. Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. Journal of psychoactive drugs. 2005;37(2):145-150. doi:10.1080/02791072.2005.10399795