Antianxiety and antidepressant effects from a single dose of psychedelic drug persist years later in cancer patients
January 28, 2020
Science Daily/New York University
Following up on their landmark 2016 study, researchers at NYU Grossman School of Medicine found that a one-time, single-dose treatment of psilocybin, a compound found in psychedelic mushrooms, combined with psychotherapy appears to be associated with significant improvements in emotional and existential distress in cancer patients. These effects persisted nearly five years after the drug was administered.
In the original study, published in the Journal of Psychopharmacology, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual well-being, and increased quality of life. At the final 6.5-month follow-up assessment, psilocybin was associated with enduring antianxiety and antidepressant effects. Approximately 60 percent to 80 percent of participants continued with clinically significant reductions in depression or anxiety, sustained benefits in existential distress and quality of life, as well as improved attitudes toward death.
The present study, publishing online Jan. 28 in the same journal, is a long-term follow-up (with assessments at about 3 years and 4.5 years following single-dose psilocybin administration) of a subset of participants from the original trial. The study reports on sustained reductions in anxiety, depression, hopelessness, demoralization, and death anxiety at both follow-up points.
Approximately 60 percent to 80 percent of participants met criteria for clinically significant antidepressant or anxiolytic responses at the 4.5 year follow-up. Participants overwhelmingly (71 to 100 percent) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives.
"Adding to evidence dating back as early as the 1950s, our findings strongly suggest that psilocybin therapy is a promising means of improving the emotional, psychological, and spiritual well-being of patients with life-threatening cancer," says the 2016 parent study's lead investigator, Stephen Ross, MD, an associate professor of psychiatry in the Department of Psychiatry at NYU Langone Health. "This approach has the potential to produce a paradigm shift in the psychological and existential care of patients with cancer, especially those with terminal illness."
An alternative means of treating cancer-related anxiety and depression is urgently needed, says Ross. According to statistics from several sources, close to 40 percent of the global population will be diagnosed with cancer in their lifetime, with a third of those individuals developing anxiety, depression, and other forms of distress as a result. These conditions, experts say, are associated with poorer quality of life, increased rates of suicide, and lowered survival rate. Unfortunately, conventional pharmacologic treatment methods like antidepressants work for less than half of cancer patients and tend to not work any better than placebos. In addition, they have no effect whatsoever on existential distress and death anxiety, which commonly accompany a cancer diagnosis and are linked to a hastened desire for death and increased suicidality, says Ross.
The researchers say psilocybin may provide a useful tool for enhancing the effectiveness of psychotherapy and ultimately relieving these symptoms. Although the precise mechanisms are not fully understood, experts believe that the drug can make the brain more flexible and receptive to new ideas and thought patterns. In addition, previous research indicates that the drug targets a network of the brain, the default mode network, which becomes activated when we engage in self-reflection and mind wandering, and which helps to create our sense of self and sense of coherent narrative identity. In patients with anxiety and depression, this network becomes hyperactive and is associated with rumination, worry, and rigid thinking. Psilocybin appears to acutely shift activity in this network and helps people to take a more broadened perspective on their behaviors and lives.
How the Original Research and Follow-up Were Conducted
For the original study, the NYU Langone team provided 29 cancer patients with nine psychotherapy sessions, as well a single dose of either psilocybin or an active placebo, niacin, which can produce a physical flush sensation that mimics a psychedelic drug experience. After seven weeks, all participants swapped treatments and were monitored with clinical outcome measures for anxiety, depression, and existential distress, among other factors.
Although researchers found that the treatment's antianxiety and antidepressant qualities persisted 6.5 months after the intervention, little was known of the drug's effectiveness in the long term. The new follow-up study is the longest-spanning exploration of psilocybin's effects on cancer-related psychiatric distress to date, the study authors say.
"These results may shed light on how the positive effects of a single dose of psilocybin persist for so long," says Gabby Agin-Liebes, PhD candidate, lead investigator and lead author of the long-term follow-up study, and co-author of the 2016 parent study. "The drug seems to facilitate a deep, meaningful experience that stays with a person and can fundamentally change his or her mindset and outlook," she says.
Agin-Liebes, who is pursuing her PhD in clinical psychology at Palo Alto University in California, cautions that psilocybin does not inherently lead to positive therapeutic effects when used in isolation, and in uncontrolled, recreational settings, and "should be taken in a controlled and psychologically safe setting, preferably in conjunction with counseling from trained mental health practitioners or facilitators," she adds.
Next, the researchers plan to expand this research with larger trials in patients from diverse socioeconomic and ethnic groups who have advanced cancer-related psychiatric and existential distress.
"This could profoundly transform the psycho-oncologic care of patients with cancer, and importantly could be used in hospice settings to help terminally ill cancer patients approach death with improved emotional and spiritual well-being," says Ross.
https://www.sciencedaily.com/releases/2020/01/200128115423.htm
'Ego-dissolving' psychedelic drugs could assist with mental health
August 8, 2017
Science Daily/University of Adelaide
The altered state of consciousness and temporary lack of ego that results from using psychedelic drugs could help some mental health patients recover from their symptoms, according to academics at the University of Adelaide.
Researchers in the University's Department of Philosophy have been studying the body of evidence around the use of psychedelic drugs such as LSD and magic mushrooms, and the impact they have on people's sense of "self."
In a new article published online in Aeon (https://aeon.co/essays/psychedelics-work-by-violating-our-models-of-self-and-the-world), authors Professor Philip Gerrans and recent PhD graduate Dr Chris Letheby say there is growing evidence to suggest that psychedelic experiences can be truly "transformative" -- including helping some people with anxiety, depression, or addiction.
"We know quite a lot about the neurochemistry of psychedelic drugs and how they work on the brain. What's poorly understood is the more complex relationship between the brain, our sense of self, and how we perceive the world," says Professor Gerrans, who has been researching self-representation in psychiatric disorders.
In a recent paper published in the journal Neuroscience of Consciousness, Professor Gerrans and Dr Letheby explain how users of psychedelic drugs often report that their sense of being a self or 'I' -- distinct from the rest of the world -- has diminished or completely "dissolved."
"This 'ego dissolution' results in a moment of expanded awareness, a feeling in which the mind is put more directly and intensely in touch with the world," Professor Gerrans says.
"Through this experience it may be possible to re-engineer the mechanisms of self, which in turn could change people's outlook or world view. The profound sense of connection produced by this experience has the potential to be beneficial for people suffering from anxiety, depression, and some forms of addiction," he says.
Dr Letheby says one of the reasons why psychiatric disorders are so hard to shake is that it's almost impossible for sufferers to view things differently.
"People who go through psychedelic experiences no longer take it for granted that the way they've been viewing things is the only way," Dr Letheby says.
"Psychedelics can assist in enlightening people about the processes behind their subjectivity. Ego dissolution offers vivid experiential proof not only that can things be different, but that there is an opportunity to seek change."
The researchers do not advocate unsupervised recreational use of psychedelic drugs.
"These drugs were originally researched and used as treatments for various psychiatric conditions in the mid-20th century, with psychiatrists in the 1950s claiming success in treating alcoholism and other mental health conditions.
"It may be time for these drugs to make a psychiatric comeback, under controlled circumstances. More research would be needed to establish just how important they could be as part of an overall treatment program," Professor Gerrans says.
https://www.sciencedaily.com/releases/2017/08/170808145443.htm
Magic mushrooms' effects illuminated in brain imaging studies
January 24, 2012
Science Daily/Imperial College London
Brain scans of people under the influence of the psilocybin, the active ingredient in magic mushrooms, have given scientists the most detailed picture to date of how psychedelic drugs work. The findings of two studies being published in scientific journals this week identify areas of the brain where activity is suppressed by psilocybin and suggest that it helps people to experience memories more vividly.
In the first study, published January 23 in Proceedings of the National Academy of Sciences (PNAS), 30 healthy volunteers had psilocybin infused into their blood while inside magnetic resonance imaging (MRI) scanners, which measure changes in brain activity. The scans showed that activity decreased in "hub" regions of the brain -- areas that are especially well-connected with other areas.
The second study, due to be published online by the British Journal of Psychiatry on January 24, found that psilocybin enhanced volunteers' recollections of personal memories, which the researchers suggest could make it useful as an adjunct to psychotherapy.
Professor David Nutt, from the Department of Medicine at Imperial College London, the senior author of both studies, said: "Psychedelics are thought of as 'mind-expanding' drugs so it has commonly been assumed that they work by increasing brain activity, but surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas. These hubs constrain our experience of the world and keep it orderly. We now know that deactivating these regions leads to a state in which the world is experienced as strange."
The intensity of the effects reported by the participants, including visions of geometric patterns, unusual bodily sensations and altered sense of space and time, correlated with a decrease in oxygenation and blood flow in certain parts of the brain.
The function of these areas, the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), is the subject of debate among neuroscientists, but the PCC is proposed to have a role in consciousness and self-identity. The mPFC is known to be hyperactive in depression, so psilocybin's action on this area could be responsible for some antidepressant effects that have been reported. Similarly, psilocybin reduced blood flow in the hypothalamus, where blood flow is increased during cluster headaches, perhaps explaining why some sufferers have said symptoms improved under psilocybin.
In the British Journal of Psychiatry study 10 volunteers viewed written cues that prompted them to think about memories associated with strong positive emotions while inside the brain scanner. The participants rated their recollections as being more vivid after taking psilocybin compared with a placebo, and with psilocybin there was increased activity in areas of the brain that process vision and other sensory information.
Participants were also asked to rate changes in their emotional wellbeing two weeks after taking the psilocybin and placebo. Their ratings of memory vividness under the drug showed a significant positive correlation with their wellbeing two weeks afterwards. In a previous study of 12 people in 2011, researchers found that people with anxiety who were given a single psilocybin treatment had decreased depression scores six months later.
Dr Robin Carhart-Harris, from the Department of Medicine at Imperial College London, the first author of both papers, said: "Psilocybin was used extensively in psychotherapy in the 1950s, but the biological rationale for its use has not been properly investigated until now. Our findings support the idea that psilocybin facilitates access to personal memories and emotions.
"Previous studies have suggested that psilocybin can improve people's sense of emotional wellbeing and even reduce depression in people with anxiety. This is consistent with our finding that psilocybin decreases mPFC activity, as many effective depression treatments do. The effects need to be investigated further, and ours was only a small study, but we are interested in exploring psilocybin's potential as a therapeutic tool."
The researchers acknowledged that because the participants in this study had volunteered after having previous experience of psychedelics, they may have held prior assumptions about the drugs which could have contributed to the positive memory rating and the reports of improved wellbeing in the follow-up.
Functional MRI measures brain activity indirectly by mapping blood flow or the oxygen levels in the blood. When an area becomes more active, it uses more glucose, but generates energy in rapid chemical reactions that do not use oxygen. Consequently, blood flow increases but oxygen consumption does not, resulting in a higher concentration of oxygen in blood in the local veins.
In the PNAS study, the volunteers were split into two groups, each studied using a different type of fMRI: 15 were scanned using arterial spin labelling (ASL) perfusion fMRI, which measures blood flow, and 15 using blood-oxygen level-dependent (BOLD) fMRI. The two modalities produced similar results, strongly suggesting that the observed effects were genuine.
The studies were carried out with a Home Office licence for storing and handling a schedule 1 drug and were approved by NHS research ethics committees. All the volunteers were mentally and physically healthy and had taken hallucinogenic drugs previously without any adverse response. The research involved scientists from Imperial, the University of Bristol and Cardiff University and was funded by the Beckley Foundation, the Neuropsychoanalysis Foundation, Multidisciplinary Association for Psychedelic Studies, and the Heffter Research Institute.
https://www.sciencedaily.com/releases/2012/01/120123152043.htm
LSD Finds New Respectability
September 1, 2005
Science Daily/McMaster University
It was the drug of choice on university campuses, the drug that spawned psychedelic culture as well as countless jail sentences and fines, but LSD actually has respectable roots—roots that a McMaster University researcher is uncovering.
"Far from being fringe medical research, trials of LSD were once a legitimate branch of psychiatric research," explains Erika Dyck, a doctoral researcher in the Department of History at McMaster. "LSD produced a "model psychosis," meaning people who took the drug exhibited symptoms of illnesses such as schizophrenia. Doctors used this as a new method for studying mental illness."
In a recent issue of the Canadian Journal of Psychiatry, Dyck traces the history of LSD—and its eventual withdrawal from medical research. LSD, ord-lysergic acid diethylamide, first appeared in scientific literature in 1943. For nearly a decade, it gave psychiatrists insight into experiences of schizophrenic patients and showed potential as a cure for alcoholism.
In the 1960s, as the media increasingly associated the drug with love-ins, anti-war demonstrations and the counterculture, governments intervened to criminalize LSD, restricting and then terminating medical research into its potential therapeutic effects.
Now, therapeutic uses of psychedelic drugs are resurfacing. Research groups in the United States are currently examining the usefulness of MDMA, or "ecstasy," in treating pain in medical conditions such as Parkinson's disease and cancer.
This makes Dyck optimistic that LSD may become a valid area of research again. "Many illegal drugs are used in medical settings. Scientists who studied LSD made important contributions to psychiatry, and found it helped many people cope with mental illness."
Dyck discovered another interesting fact while researching LSD: The term "psychedelic”, it turns out, was a Canadian invention – coined in Weyburn, Sask. in the 1950s.
The paper is available online at
www.cpa-apc.org/Publications/Archives/CJP/2005/june/InRevDyck.asp.
McMaster University, named Canada's Research University of the Year by Research Info Source, has world-renowned faculty, and state-of-the-art research facilities. McMaster's culture of innovation fosters a commitment to discovery and learning in teaching, research and scholarship. Based in Hamilton, the University has a student population of more than 23,000, and an alumni population of more than 115,000 in 128 countries.
https://www.sciencedaily.com/releases/2005/09/050901073759.htm