Magic Mushrooms
by Mind Over Matter V 13:
Resurgence in Psychedelics Research Reveals Promising Results
There is a resurgence of research underway on psychedelic substances after a decades-long hiatus. Scientists are currently studying the effects of psychedelics on a wide range of conditions, including depression, post-traumatic stress disorder, anxiety, addiction, obsessive-compulsive disorder, anorexia nervosa, and even Alzheimer’s disease, and the results so far look promising.
In this article, we will examine some of the recent findings from research on “serotonergic classic psychedelics” – in particular, psilocybin (found in “magic mushrooms”), ayahuasca (which contains dimethyltryptamine or DMT), and lysergic acid diethylamide (LSD).
These substances each have unique properties but are similar in that they all produce their consciousness-shifting, mind-altering effects primarily by acting on serotonin 2A brain receptors.
STIGMA & SAFETY OF PSYCHEDELICS
Psychedelics garnered much negative attention in the 1960s leading to a long period of prohibition. As a result, there has been significant cultural stigma and, for some people, fear about the use of psychedelics. However, research has demonstrated that in general, when classic psychedelics are used responsibly, they are safe for most people (i.e., not toxic or addictive) and without lasting adverse effects. (Individuals with a personal or family history of psychosis, and those with severe cardiac disease, are the exception and should not take psychedelics.)
Researchers emphasize the importance of “set” and “setting” for safety and a positive experience when using psychedelics. In other words, mindset and intentions matter, as does the environment in which the experience takes place, and the support received before, during, and after the experience. It is also important to keep in mind that researchers using full doses of psychedelic substances are typically studying “psychedelic-assisted therapy,” where the administration of a psychedelic substance is just one component of the complete therapeutic package.
THE PROMISING RESEARCH FINDINGS OCCURRED WHEN PSYCHEDELICS WERE ADMINISTERED IN A CONTROLLED, SUPPORTIVE SETTING IN THE PRESENCE OF TRAINED THERAPY PROFESSIONALS (OFTEN REFERRED TO AS GUIDES).
CLASSIC PSYCHEDELICS & PSYCHIATRY
Much of the research on therapeutic applications of psychedelics has focused on their potential to help individuals with various mental disorders. Recent research (over the last 15 years) has built upon findings from the large body of earlier research (from the 1950s and 1960s, before psychedelics were banned) using rigorous study design.
An example of a recent study using a robust methodology was conducted by Dr. Roland Griffiths and colleagues from Johns Hopkins University, one of several world-class academic institutions conducting psychedelic research.
The researchers looked at the effects of psilocybin on 51 individuals with life-threatening cancer who were experiencing symptoms of depression and/or anxiety, a common occurrence in cancer patients.
JUST ONE HIGH DOSE OF PSILOCYBIN, ADMINISTERED WITH CAREFUL ATTENTION TO SET AND SETTING, WAS FOUND TO PRODUCE SIGNIFICANT DECREASES IN MEASURES OF DEPRESSION, ANXIETY, AND MOOD DISTURBANCE, AS WELL AS INCREASES IN MEASURES OF QUALITY OF LIFE, LIFE MEANING, DEATH ACCEPTANCE, AND OPTIMISM.
Notably, these effects were still present in most participants at the six-month follow-up. These findings were published in 2016 in Journal of Psychopharmacology.
“When administered to carefully-screened, psychologically-distressed cancer patients with support from a trained guide, a single high dose of psilocybin produced large decreases in depression and anxiety,” said Dr. Griffiths, a Professor in the Departments of Psychiatry and Neurosciences at the Johns Hopkins University School of Medicine and Founding Director of the Johns Hopkins Center on Psychedelic and Consciousness Research.
“If psilocybin can help alleviate depression and anxiety in people with life-threatening illnesses, then perhaps it can help others who are living with depression or anxiety, too. We are excited to be exploring that possibility, and we’ve already published one additional study showing large and rapid antidepressant effects of psilocybin in participants with major depressive disorder. We’re also exploring the potential for psychedelics to help with other conditions, in additional research that is underway at our Center.”
In that recent study regarding major depressive disorder (MDD) – published in 2020 in JAMA Psychiatry – Dr. Griffiths and colleagues conducted a randomized clinical trial with 24 participants aged 21 to 75 years who had been diagnosed with MDD and were not currently using antidepressant medications. Fifteen of the participants began psilocybin-assisted therapy immediately, and the remaining 12 (the “waiting list” control group) started after an eight-week delay.
The intervention consisted of two psilocybin sessions with supportive psychotherapy (approximately 11 hours). Results revealed that the participants who received immediate psilocybin-assisted therapy showed improvements in clinician-rated depression severity, as well as self-rated depression and anxiety symptoms, compared to those in the delayed-treatment group.
“This study adds to the growing evidence of psilocybin’s effectiveness in helping people with depression and anxiety. Large and rapid positive effects were seen, and these effects also demonstrated lasting impact. In this study, clinically significant antidepressant effects were still present for 71% of participants at the four-week follow-up,” said Dr. Griffiths.
“And the psilocybin-assisted therapy used in this study yielded effect sizes that were approximately two and a half times greater than those found in psychotherapy, and more than four times greater than the effect sizes found in psychopharmacological depression treatment studies.”
In order to gain a better understanding of the “modern-era” findings on the use of classic psychedelics as a treatment for various psychiatric conditions, Dr. Kristoffer Andersen and colleagues from Imperial College London conducted a systematic review of the research published between January 1, 2000 and May 1, 2020.
The researchers reviewed 16 academic papers about ten psychedelic-assisted therapy clinical trials – seven using psilocybin, two using ayahuasca, and one using LSD – involving 188 participants in total.
COLLECTIVELY, THE STUDIES PROVIDED EVIDENCE OF THE SAFETY OF CLASSIC PSYCHEDELICS, AS WELL AS PROMISING EARLY EVIDENCE OF THEIR EFFECTIVENESS IN TREATING DEPRESSION, ANXIETY, OBSESSIVE-COMPULSIVE DISORDER, AND TOBACCO AND ALCOHOL-USE DISORDERS.
And, for a majority of the participants, the improvements lastedfor several weeks or months, after just one to three treatment sessions. (These findings were published in 2020 in Acta Psychiatrica Scandinavica.)
PSYCHEDELICS & THE BRAIN
What is happening in the brain during a psychedelic experience that might explain why psychedelics appear to help individuals with varied psychiatric conditions?
Brain imaging has shown that when a full dose of psilocybin or other serotonergic psychedelic takes effect, it stimulates the serotonin 2A receptors in the brain, which leads to massive depolarization and rapid repeated firing of the neurons. This activity profoundly alters cortical signaling. Brain activity decreases primarily in one brain network, the default mode network (DMN), which usually plays a role like an orchestra conductor in the brain but goes “offline” during a psychedelic experience.
When DMN activity decreases, the brain “escapes” from its usual tightly constrained, predictable patterns and there is a dramatic increase in new connectivity. So, it is thought that psychedelics likely work by disrupting the brain systems that encode dysfunctional repetitive thoughts and behaviours. In essence, the brain “resets” and creates an opportunity to release long-entrenched patterns like those seen in depression and anxiety, and to develop new insights and habits.
PSYCHEDELICS & ALZHEIMER’S DISEASE
Given the research in humans that has shown classic psychedelics can help alleviate depression and boost the formation of new connections in the brain, as well as findings from animal studies suggesting psychedelics may help improve learning and memory processes, researchers wonder if these substances could help people with Alzheimer’s disease.
At the very least, psychedelics could help with the depression that often accompanies an Alzheimer’s diagnosis, or they could also improve quality of life, and boost cognitive performance or delay cognitive decline. Research is underway to examine these possibilities. In the academic world, for example, the Center for Psychedelics and Consciousness Research at Johns Hopkins is conducting a study on the impact of psilocybin on depression in individuals with mild cognitive impairment or early Alzheimer’s disease. The researchers are currently in the recruitment stage of the study (for more information, visit https://hopkinspsychedelic.org/alzheimers).
The private sector is interested in the potential of psychedelics as a treatment for Alzheimer’s disease as well. For example, biotech company Eleusis is currently investigating the potential for low-dose LSD to target some of the main biomarkers of Alzheimer’s disease.
“Research on the potential of classic psychedelics to help people with Alzheimer’s disease is in the early stages,” explained Dr. Griffiths. “Given the devasting impact of the disease on individuals and society, we obviously hope that our current study will reveal positive findings that lead eventually to a treatment that helps in some way to alleviate the suffering experienced by those with the disease.”
MYSTICAL EXPERIENCE MIGHT BE KEY
When taking a full dose of a psychedelic substance, enough to invoke a hallucinogenic effect, people often have a mystical-type experience – meaning, they experience a profound shift in consciousness where they feel at one with God, the Universe, the Ground of Being (or whatever other term they might prefer to use based on culture or personal preference).
RESEARCH HAS FOUND THAT THE MYSTICAL-TYPE EXPERIENCE APPEARS TO BE AN IMPORTANT FACTOR IN THE LASTING BENEFITS OF PSYCHEDELICS.
“While not all experiences with classic psychedelics are of the mystical type, mystical experiences are highly probable when psychedelics are administered at the right dose, with the proper setting, preparation, and support,” said Dr. Griffiths. “And it looks like there is something about the mystical experience itself that is key to shifting one’s moods, attitudes, and behaviours long-term.”
MICRODOSING PSYCHEDELICS
While much research has focused on the effects of full doses of psychedelics, there is a different line of research that is examining the effects of small doses over time – often referred to as “microdosing.” There is no universally consistent definition of microdosing, but it can be broadly defined as the frequent use of very low doses of psychedelics (i.e., 10% to 20% of a typical full dose, taken one to three times per week, over a varying number of weeks).
Anecdotal evidence and some uncontrolled, observational studies suggest that microdosing may improve well-being, creativity, and cognition (but may also have unpleasant side effects like migraines, physical discomfort, trouble sleeping, and/or feelings of anxiety). Those findings were vulnerable to experimental biases because of the research methods used, and recent studies that were more robust in design have failed to find compelling evidence of the benefits of microdosing.
It is possible that people who microdose report having positive effects (and believe they actually had them) because that is what they were expecting. Laura Kaertner and colleagues recently conducted research to examine that possibility and found that positive expectancy scores at baseline did indeed predict subsequent reports of improvement in well-being, suggesting a significant placebo response among the more than 200 microdosers who took part in the study.
Although more research is needed before reaching firm conclusions, it appears that people’s positive expectations about microdosing are influencing the benefits they perceive. These findings were shared in 2021 in Scientific Reports.
Study design will be critical going forward so that researchers can determine the therapeutic effects of microdosing, if any. In the meantime, current findings highlight the need to be cautious about any claims made regarding the potential therapeutic value of microdosing until more is known.
DON’T SELF-MEDICATE WITH PSYCHEDELICS
As more people learn about the potential benefits of psychedelics, particularly for conditions that are not well-addressed with currently available treatments, there has been growing interest and demand for psychedelics. Along with this shift in cultural acceptance, there have been changes in laws and regulations that affect psychedelics, making it easier to get approval to conduct studies and allowing for expansion of the research at an accelerated pace.
However, there is still much more to learn about the therapeutic use of psychedelics, and in most places, psychedelics remain illegal. Experts in psychedelics routinely advise that individuals should not attempt to self-medicate.
“With all the hype around psychedelics right now, it’s not surprising that there is much enthusiasm and interest in them. However, there are risks associated with psychedelics, and they are not suitable for everyone. Furthermore, one does not know for certain what might be in substances that are obtained illegally,” said Dr. Griffiths. “Thankfully, research on psychedelics is progressing at a rapid pace and I anticipate that it won’t be long until psychedelics become available legally, outside of clinical trials.”