Fast-acting psychedelic associated with improvements in depression/anxiety

March 18, 2019

Science Daily/Johns Hopkins Medicine

Johns Hopkins researchers have discovered that use of the synthetic psychedelic 5-methocy-N,-N-dimethyltryptamine (5-MeO-DMT) appears to be associated with unintended improvements in self-reported depression and anxiety when given in a ceremonial group setting. 5-MeO-DMT is a psychedelic that is found in the venom of Bufo Alvarius toads, in a variety of plants species, and can be produced synthetically.

In a survey of 362 adults, approximately 80 percent of respondents reported improvements in anxiety and depression after use. These improvements were related to more intense acute mystical effects during the 5-MeO-DMT experience, as well as increases in rating of the personal meaning and spiritual significance of the experience. Improvements were also related to stronger beliefs that the experience contributed to enduring well-being and life satisfaction. These results were published in The American Journal of Drug and Alcohol Abuse.

One of the unique properties of 5-MeO-DMT is the fast action and short duration of the psychedelic effects when compared to other psychedelics. "Research has shown that psychedelics given alongside psychotherapy help people with depression and anxiety. However, psychedelic sessions usually require 7 -- 8 hours per session because psychedelics typically have a long duration of action," says Alan K. Davis, Ph.D., a postdoctoral research fellow in the Behavioral Research Unit, at the Johns Hopkins University School of Medicine. "Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 -- 90 minute session."

Last year, Davis published a study in Frontiers in Psychology that found that 5-MeO-DMT administered in a psychospiritual retreat setting produced comparable ratings of mystical experience as a high-dose psilocybin session in the laboratory setting. Another study by Davis that came out last year in The Journal of Psychopharmacology showed that 5-MeO-DMT had a safe profile of use and low risk for health and legal consequences.

"It is important to examine the short- and long-term effects of 5-MeO-DMT, which may enhance mood in general or may be particularly mood enhancing for those individuals experiencing clinically significant negative mood," says Davis. "Regardless, this research is in its infancy and further investigation is warranted in healthy volunteers."

The authors on this paper were Alan K. Davis, Sara So and Roland R. Griffiths of Johns Hopkins, Rafael Lancelotta of University of Wyoming and Joseph P. Barsuglia of New School Research.

The study was funded by grants from the National Institute on Alcohol Abuse (AA 007747) and the National Institute on Drug Abuse (T32 DA007209, R01 DA003889).

https://www.sciencedaily.com/releases/2019/03/190318132628.htm

Psychedelic drugs promote neural plasticity in rats and flies

June 12, 2018

Science Daily/Cell Press

Psychedelic drugs may have mind-altering powers in the physical sense, too. A new study, published June 12 in the journal Cell Reports, found psychedelics, specifically DOI, DMT, and LSD, can change brain cells in rats and flies, making neurons more likely to branch out and connect with one another. The work supports the theory that psychedelics could help to fight depression, anxiety, addiction, and post-traumatic stress disorder.

"These are some of the most powerful compounds known to affect brain function, it's very obvious to me that we should understand how they work," says senior author David E. Olson, assistant professor in the Department of Chemistry and the Department of Biochemistry & Molecular Medicine at the University of California, Davis.

The idea that depression stems from imbalanced brain chemistry remains popular, but recent studies have revealed evidence that depression manifests as structural changes in brain circuits or atrophy in parts of the brain. This doesn't mean neurons die off during depression, but that neurites retract. Neurites are the sections -- either axons or dendrites -- of a neuron that project out to bridge the gap between two neurons at the synapse to facilitate communication.

"One of the hallmarks of depression is that the neurites in the prefrontal cortex -- a key brain region that regulates emotion, mood, and anxiety -- those neurites tend to shrivel up," says Olson. These brain changes also appear in cases of anxiety, addiction, and post-traumatic stress disorder.

In their paper, Olson and colleagues tested psychedelics from the amphetamine, tryptamine, and ergoline drug classes. In both test tube and animal experiments, the psychedelics showed functional and structural changes like those promoted by ketamine in cortical neurons. Psychedelics increased both the density of dendritic spines and the density of synapses. Some psychedelics tested, including LSD, proved to be more potent and efficacious than ketamine in promoting neurite growth.

The researchers did not do any human experiments, but experiments in both vertebrates and invertebrates showed psychedelics produced similar effects across species. This indicates the biological mechanisms that respond to psychedelics have remained the same across eons of evolution and that psychedelics will likely have the same brain growth (neural plasticity) effects in humans.

Olson and colleagues also set out to test how these psychedelics promoted neural plasticity, meaning they explored which biological pathways psychedelics activate that lead to neural growth. Ketamine's neural plasticity effects were previously shown to be dependent on a protein called brain-derived neurotrophic factor (BDNF). When the researchers blocked BDNF signaling, psychedelics lost their ability to promote neurite growth. BDNF binds to a receptor, called TrkB, that is part of a signaling pathway that includes mTOR, which is known to play a key role in the production of proteins necessary for the formation of new synapses. When the researchers experimented by inhibiting mTOR, it also completely blocked the psychedelics' ability to promote neurite growth. Olson thinks identifying the signaling pathways at play in psychedelic-induced brain changes will help future research identify compounds that could be developed into depression treatments.

"If we fully understand the signaling pathways that lead to neural plasticity, we might be able to target critical nodes along those pathways with drugs that are safer than ketamine or psychedelics," says Olson.

Although most psychedelics aren't considered to be addictive in the same way that cocaine is, they do produce hallucinations. Olson doesn't expect psychedelics to become prescription drugs for depression. "But a compound inspired by psychedelics very well could," he says.

https://www.sciencedaily.com/releases/2018/06/180612185207.htm

Can psychedelic drugs heal?

Psychologists explore potential benefits of hallucinogens for mental health disorders

August 9, 2018

Science Daily/American Psychological Association

Many people think of psychedelics as relics from the hippie generation or something taken by ravers and music festival-goers, but they may one day be used to treat disorders ranging from social anxiety to depression, according to research presented at the annual convention of the American Psychological Association.

"Combined with psychotherapy, some psychedelic drugs like MDMA, psilocybin and ayahuasca may improve symptoms of anxiety, depression and post-traumatic stress disorder," said Cristina L. Magalhaes, PhD, of Alliant International University Los Angeles, and co-chair of a symposium on psychedelics and psychotherapy. "More research and discussion are needed to understand the possible benefits of these drugs, and psychologists can help navigate the clinical, ethical and cultural issues related to their use."

Hallucinogens have been studied in the U.S. for their potential healing benefits since the discovery of LSD in the 1940s. However, research has mostly stalled since psychedelics were outlawed in the late 1960s.

A shift may be coming soon though, as MDMA, commonly known as ecstasy, is beginning its third and final phase of clinical trials in an effort to win Food and Drug Administration approval for treatment of post-traumatic stress disorder, said Adam Snider, MA, of Alliant International University Los Angeles, and co-chair of the symposium.

Findings from one study presented at the symposium suggested that symptoms of social anxiety in autistic adults may be treatable with a combination of psychotherapy and MDMA. Twelve autistic adults with moderate to severe social anxiety were given two treatments of pure MDMA plus ongoing therapy and showed significant and long-lasting reductions in their symptoms, the research found.

"Social anxiety is prevalent in autistic adults and few treatment options have been shown to be effective," said Alicia Danforth, PhD, of the Los Angeles Biomedical Research Institute at the HarborUCLA Medical Center, who conducted the study. "The positive effects of using MDMA and therapy lasted months, or even years, for most of the research volunteers."

Research discussed also explored how LSD, psilocybin (known colloquially as "magic mushrooms") and ayahuasca (a brew used by indigenous people of the Amazon for spiritual ceremonies) may benefit people with anxiety, depression and eating disorders.

Adele Lafrance, PhD, of Laurentian University, highlighted a study of 159 participants who reported on their past use of hallucinogens, level of spirituality and relationship with their emotions.

Using hallucinogens was related to greater levels of spirituality, which led to improved emotional stability and fewer symptoms of anxiety, depression and disordered eating, the study found.

"This study reinforces the need for the psychological field to consider a larger role for spirituality in the context of mainstream treatment because spiritual growth and a connection to something greater than the self can be fostered," said Lafrance.

Other research presented suggested that ayahuasca may help alleviate depression and addiction, as well as assist people in coping with trauma.

"We found that ayahuasca also fostered an increase in generosity, spiritual connection and altruism," said Clancy Cavnar, PhD, with Núcleo de Estudos Interdisciplinares sobre Psicoativos.

For people suffering from life-threatening cancer, psilocybin may provide significant and lasting decreases in anxiety and distress.

When combined with psychotherapy, psilocybin helped a study's 13 participants grapple with loss and existential distress. It also helped the participants reconcile their feelings about death as nearly all participants reported that they developed a new understanding of dying, according to Gabby Agin-Liebes, BA, of Palo Alto University, who conducted the research.

"Participants made spiritual or religious interpretations of their experience and the psilocybin treatment helped facilitate a reconnection to life, greater mindfulness and presence, and gave them more confidence when faced with cancer recurrence," said Agin-Liebes.

Presenters throughout the symposium discussed the need for more research to fully understand the implications of using psychedelics as an adjunct to psychotherapy as well as the ethical and legal issues that need to be considered.

https://www.sciencedaily.com/releases/2018/08/180809141223.htm

Magic mushroom compound psilocybin could provide new avenue for antidepressant research

May 17, 2016

Science Daily/The Lancet

Psilocybin -- a hallucinogenic compound derived from magic mushrooms -- may offer a possible new avenue for antidepressant research, according to a new study published in The Lancet Psychiatry today.

The small feasibility trial, which involved 12 people with treatment-resistant depression, found that psilocybin was safe and well-tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at 3 months post-treatment. The authors warn that strong conclusions cannot be made about the therapeutic benefits of psilocybin but the findings show that more research in this field is now needed.

"This is the first time that psilocybin has been investigated as a potential treatment for major depression," says lead author Dr Robin Carhart-Harris, Imperial College London, London, UK. "Treatment-resistant depression is common, disabling and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments."

Depression is a major public health burden, affecting millions of people worldwide and costing the US alone over $200 billion per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, 1 in 5 patients with depression do not respond to any intervention, and many relapse.

"Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments," says Professor David Nutt, senior author from Imperial College London "Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants."

The trial involved 12 patients (6 women, 6 men) with moderate to severe depression (average length of illness was 17.8 years). The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants (lasting at least 6 weeks). Most (11) had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.

Patients attended two treatment days -- a low (test) dose of psilocybin 10mg oral capsules, and a higher (therapeutic) dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling. Patients had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at 1, 2, 3, and 5 weeks and 3 months after the second dose.

The psychedelic effects of psilocybin were detectable 30 to 60 minutes after taking the capsules. The psychedelic effect peaked at 2-3 hours, and patients were discharged 6 hours later. No serious side effects were reported, and expected side effects included transient anxiety before or as the psilocybin effects began (all patients), some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.

At 1 week post-treatment, all patients showed some improvement in their symptoms of depression. 8 of the 12 patients (67%) achieved temporary remission. By 3 months, 7 patients (58%) continued to show an improvement in symptoms and 5 of these were still in remission. Five patients showed some degree of relapse.

The patients knew they were receiving psilocybin (an 'open-label' trial) and the effect of psilocybin was not compared with a placebo. The authors also stress that most of the study participants were self-referred meaning they actively sought treatment, and may have expected some effect (5 had previously tried psilocybin before). All patients had agreement from their GP to take part in the trial. They add that patients were carefully screened and given psychological support before, during and after the intervention, and that the study took place in a positive environment. Further research is now needed to tease out the relative influence of these factors on symptoms of depression, and look at how psilocybin compares to placebo and other current treatments.

Writing in a linked Comment, Professor Philip Cowen, MRC Clinical Scientist, University of Oxford, Oxford, UK, says: "The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at 3 month follow-up (a comparatively short time in patients with extensive illness duration) are promising but not completely compelling, with about half the group showing significant depressive symptoms. Further follow-ups using detailed qualitative interviews with patients and family could be very helpful in enriching the assessment."

https://www.sciencedaily.com/releases/2016/05/160517083044.htm

How LSD can make us lose our sense of self

April 13, 2016

Science Daily/Cell Press

When people take the psychedelic drug LSD, they sometimes feel as though the boundary that separates them from the rest of the world has dissolved. Now, the first functional magnetic resonance images (fMRI) of people's brains while on LSD help to explain this phenomenon known as "ego dissolution."

As researchers report in the Cell Press journal Current Biology on April 13, these images suggest that ego dissolution occurs as regions of the brain involved in higher cognition become heavily over-connected. The findings suggest that studies of LSD and other psychedelic drugs can produce important insights into the brain. They can also provide intriguing biological insight into philosophical questions about the very nature of reality, the researchers say.

"There is 'objective reality' and then there is 'our reality,'" says Enzo Tagliazucchi of the Royal Netherlands Academy of Arts and Sciences in Amsterdam. "Psychedelic drugs can distort our reality and result in perceptual illusions. But the reality we experience during ordinary wakefulness is also, to a large extent, an illusion."

Take vision, for example: "We know that the brain fills in visual information when suddenly missing, that veins in front of the retina are filtered out and not perceived, and that the brain stabilizes our visual perception in spite of constant eye movements. So when we take psychedelics we are, it could be said, replacing one illusion by another illusion. This might be difficult to grasp, but our study shows that the sense of self or 'ego' could also be part of this illusion."

It has long been known that psychedelic drugs have the capacity to reduce or even eliminate a person's sense of self, leading to a fully conscious experience, Tagliazucchi explains. This state, which is fully reversible in those taking psychedelics, is also known to occur in certain psychiatric and neurological disorders.

But no one had ever looked to see how LSD changes brain function. To find out in the new study, Tagliazucchi and colleagues, including Robin Carhart-Harris of Imperial College London, scanned the brains of 15 healthy people while they were on LSD versus a placebo.

The researchers found increased global connectivity in many higher-level regions of the brain in people under the influence of the drug. Those brain regions showing increased global connectivity overlapped significantly with parts of the brain where the receptors known to respond to LSD are found.

LSD also increased brain connectivity by inflating the level of communication between normally distinct brain networks, they report. In addition, the increase in global connectivity observed in each individual's brain under LSD correlated with the degree to which the person in question reported a sense of ego dissolution.

Tagliazucchi notes in particular that they found increased global connectivity of the fronto-parietal cortex, a brain region associated with self-consciousness. In particular, they observed increased connection between this portion of the brain and sensory areas, which are in charge of receiving information about the world around us and conveying it for further processing to other brain areas.

"This could mean that LSD results in a stronger sharing of information between regions, enforcing a stronger link between our sense of self and the sense of the environment and potentially diluting the boundaries of our individuality," Tagliazucchi said.

They also observed changes in the functioning of a part of the brain earlier linked to "out-of-body" experiences, in which people feel as though they've left their bodies. "I like to think that our experiment represents a pharmacological analogue of these findings," he says.

Tagliazucchi says the findings highlight the value of psychedelic drugs in carefully controlled research settings. He plans to continue to use neuroimaging to explore various states of consciousness, including sleep, anesthesia, and coma. He also hopes to make direct comparisons between people in a dream versus a psychedelic state. Meanwhile, researchers at the Imperial College London are investigating other psychedelic drugs and their potential use in the treatment of disorders including depression and anxiety.

https://www.sciencedaily.com/releases/2016/04/160413135656.htm