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