FDA OKs Breakthrough Designation For “Magic Mushrooms” In Depression Treatment

by NCN Health And Science Team Posted on November 25th, 2018

Houston, Texas, USA : The US Food and Drug Administration (FDA) has approved mushrooms with psilocybin, a psychedelic compound, for its “Breakthrough Therapy” designation for depression treatment.

The FDA has given a group of psychiatrists its blessing to dose patients with magic mushrooms in therapy sessions. The FDA granted “Breakthrough Therapy” designation to COMPASS Pathways’ psilocybin-assisted therapy for treatment-resistant depression.

The London-based life sciences company, backed in part by Peter Thiel, will use the psychedelic drug psilocybin, the active chemical extracted from psychedelic mushrooms, to treat patients in Europe and North America in a Phase 2b trial to determine the optimal dose of the drug. 216 patients in 12 to 15 research sites across Europe and North America will be dosed with psilocybin. Trials will begin in the UK this month with other sites joining in later. Regulatory approvals for the trial have already been given in the UK, the Netherlands and Canada.

The release says the dosed patients will also receive “psychological support.” Researchers have known for some time that psilocybin showed promising usefulness as a safe treatment for depression.

The new study, undertaken by Compass Pathways, is a phase IIb study, meaning it is a rigorously controlled trial that demonstrates whether or not a treatment works. If the trial is successful, it will be followed by phase III studies, which compare the new treatment with the traditional treatment standards.

“We are excited to be starting this landmark trial which has the potential to transform lives,” said George Goldsmith, Compass Pathways’ chairman and co-founder. “Depression is the leading cause of ill-health and disability worldwide, and treatment-resistant depression affects more than 100 million people. It is a huge unmet need and the trial will teach us more about how this new approach might address it.”

Ekaterina Malievskaia, Chief Medical Officer and Co-founder of COMPASS, said: “The design of this study has been a truly collaborative effort, with scientists, clinicians, patient representatives and regulators from Europe and North America working together with the goal of helping patients suffering with treatment-resistant depression.”

UC Berkeley Wellness explained how psilocybin can help with emotional regulation. Untreated patients with depression generally experience increased blood flow to the amygdala, a part of the brain which controls emotion. After treatment with psilocybin, researchers observed reduced blood flow to the amygdala, which they correlated with a decrease in depressive symptoms in all 19 subjects one week after treatment, and in nearly half of participants five weeks later. This mechanism wasn’t previously understood. UC Berkeley Wellness also reports that the FDA is considering approving the drug MDMA for treatment of PTSD because it increases feelings of trust and compassion.

For scientists that study psychedelic drugs, the FDA’s move is welcome news. The Breakthrough Therapy designation, first established in 2012, allows the FDA to closely assist researchers in the development of a promising drug to treat serious conditions or diseases.

Roland Griffiths, Ph.D., a professor of psychiatry and behavioral sciences at Johns Hopkins University, heads the lab that conducted the first contemporary FDA-approved clinical trial on psilocybin in 2000. He’s encouraged by the news.

“This is a significant positive development in the potential future regulatory approval of psilocybin, a classic psychedelic drug, for medicinal purposes,” Griffiths tells Inverse. “After a decades-long hiatus of research with psilocybin and related psychedelic drugs, investigators in the United States and Europe have demonstrated the safety and preliminary signs of efficacy of psilocybin for a variety of therapeutic applications.”

Kelan Thomas, Pharm.D., an associate professor of clinical sciences at Touro University California, co-authored a Journal of Psychoactive Drugs review of psilocybin-assisted therapy in 2017, in which he and his team predicted the compound’s role in the future of psychiatry.

“I was very surprised that the FDA has already granted Breakthrough Therapy designation just two months after they approved the study design,” Thomas tells Inverse. “Usually the FDA wants to evaluate data from the drug sponsor’s phase 2b trials before granting Breakthrough Therapy designation, but perhaps data from the previous psilocybin clinical trials that were summarized in my 2017 review article were sufficient evidence.”

But Griffiths explains that the Breakthrough Therapy designation doesn’t necessarily indicate that the FDA will approve psilocybin for widespread human use. What it does mean is that the FDA sees psilocybin-assisted therapy as a novel approach to specifically treating treatment-resistant depression, a condition that affects as many as 50 percent of patients with clinical depression.

Matthew Johnson, Ph.D., an associate professor of psychiatry and behavioral sciences at Hopkins who works with Griffiths on psilocybin research, agrees that this news is significant.

“FDA Breakthrough status is a big deal,” he tells Inverse. “It implies that the FDA recognizes the treatment is potentially one with a large impact on a largely under-treated condition. It also means that the FDA works more closely with the sponsor given the potential public health benefit, and goes beyond the typical ‘Just the facts, ma’am’ relationship they typically have with a pharmaceutical sponsor.”

This means that instead of just scrutinizing the results of COMPASS’s clinical trials, the FDA will make constructive recommendations in a more timely manner than it would with typical drug trials.

The FDA would not offer any comment on the news, citing the confidential status of Breakthrough Therapy applications. But COMPASS Pathways announced the development itself on Tuesday.

To Johnson and Griffiths, the news suggests that the FDA has grown willing to look at psilocybin from the perspective of science and public health, rather than a stance of fear or misunderstanding. This change has been slow, as the psychedelic heyday of the ‘60s sparked a culture of fear around psychedelic drugs, which meant mainstream scientists couldn’t touch them for decades.

“We don’t have an area of science — except possibly chemical weapons or germ warfare — where there’s a cultural consensus that this is so dangerous that we shouldn’t do anything with them,” says Griffiths. But due to the work done in the past 18 years at Johns Hopkins, Imperial College London, New York University, and other academic institutions around the world, this cultural consensus is shifting, and the FDA’s decision is evidence. Johnson says the Breakthrough Therapy designation indicates the FDA will not be “prejudiced against [psilocybin] for non-scientific, political reasons.”

“I think this is an important advance in bringing these compounds out of the dark ages into the light of potential cultural acceptability to systematically explore further applications,” says Griffiths.

All of this is becoming possible because scientists have established enough of a basic understanding of psilocybin to confidently move forward with human trials, knowing that there’s a low likelihood that they’ll do serious harm to volunteers.

This summer, Griffiths, Johnson, and their colleagues published a lengthy analysis of psilocybin’s potential to harm people in the journal Neuropharmacology. In the paper, they conclude that psilocybin has a very low potential for abuse and addiction, and a low potential to harm people who take it.

They also recommended that psilocybin should be moved to Schedule IV of the Controlled Substances act — the category that includes drugs like Xanax and Ambien. Currently the drug is designated Schedule I — along with heroin — meaning it has no medicinal value and high potential to harm people. But as the research piles up, the law will be forced to catch up.

Griffiths is keen to caution, though, that psilocybin is not always harmless. In a 2016 survey in the Journal of Psychopharmacology, the Hopkins team found that out of 1,993 people who had had challenging psychedelic experiences (“bad trips”), 7.6 percent of them ended up seeking professional treatment for psychological symptoms that lasted long after the drugs wore off.

“Although the addiction liability of these drugs is low,” Griffiths says, “that doesn’t mean they’re safe, and they certainly need to be regulated in some fashion. FDA will ultimately be responsible for determining the parameters of that regulation.”

It remains to be seen whether this looks like a central pharmacy that dispenses drugs directly to psychiatrists, or perhaps something else, but Griffiths is pretty sure of one thing:

“It seems unlikely that these are compounds that will be dispensed at a pharmacy.”

EARLIER : Reclassification Recommended For Drug In Magic Mushrooms To Treat Depression, Anxiety

Researchers at Johns Hopkins University have recommended that psilocybin, the compound found in hallucinogenic mushrooms (magic mushrooms) , be reclassified so it can be used to treat anxiety and depression.

In an evaluation of the safety and abuse research on the drug in hallucinogenic mushrooms, Johns Hopkins researchers suggest that if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug—one with no known medical potential—to a schedule IV drug such as prescription sleep aids, but with tighter control.

“We want to initiate the conversation now as to how to classify psilocybin to facilitate its path to the clinic and minimize logistical hurdles in the future,” says Matthew W. Johnson, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “We expect these final clearance trials to take place in the next five years or so.”

Following the Controlled Substances Act of 1970, any drug with the potential for abuse is categorized based on criteria that take into account whether the drug has accepted medical use, and its safety and the potential for abuse. Although preliminary research studies suggest that psilocybin may be effective for smoking cessation and for disorders such as cancer-specific depression and anxiety, it must clear phase III clinical trials before the Food and Drug Administration can be petitioned to reclassify it.

Studies in animals and humans both show low potential for abuse, the researchers say. When rats push a lever to receive psilocybin, they don’t keep pushing the lever like they do for drugs such as cocaine, alcohol or heroin. When it comes to human studies, people who have used psilocybin typically report using it a few times across their lifetime.

As for safety, studies show it frequently falls at the end of the scales with the least harm to users and society, say the researchers. Psilocybin also is lowest in the potential for lethal overdose as there is no known overdose level.

“We should be clear that psilocybin is not without risks of harm, which are greater in recreational than medical settings, but relatively speaking, looking at other drugs both legal and illegal, it comes off as being the least harmful in different surveys and across different countries,” says Johnson.

That being said, although psilocybin is relatively less harmful than other drugs and not prone to compulsive abuse, the researchers don’t recommend releasing psilocybin into patients’ hands even with a prescription. “We believe that the conditions should be tightly controlled and that when taken for a clinical reason, it should be administered in a health care setting monitored by a person trained for that situation,” says Johnson. The researchers foresee that the process for psilocybin use in the clinic would be similar to how an anesthesiologist prescribes and administers a drug, minimizing the potential for abuse or harm.

The researchers summarize their analysis in the print issue of Neuropharmacology.

Study :  Matthew W. Johnson et al. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act, Neuropharmacology

In a separate study the American Psychological Association explored the potential benefits of hallucinogens for mental health disorders

Psychologists explore potential benefits of hallucinogens for mental health disorders

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, Ph.D., 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, Ph.D., 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, Ph.D., 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, Ph.D., 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.

A separate analysis by the conversation (below) examined the potential for medical use of LSD, MDMA and mushrooms.

The real promise of LSD, MDMA and mushrooms for medical science

Psychedelic science is making a comeback.

Scientific publications, therapeutic breakthroughs and cultural endorsements suggest that the historical reputation of psychedelics —such as lysergic acid diethylamide (LSD), mescaline (from the peyote cactus) and psilocybin (mushrooms) —as dangerous or inherently risky have unfairly overshadowed a more optimistic interpretation.

Recent publications, like Michael Pollan’s How to Change your Mind, showcase the creative and potentially therapeutic benefits that psychedelics have to offer —for mental health challenges like depression and addiction, in palliative care settings and for personal development.

Major scientific journals have published articles showing evidence-based reasons for supporting research in psychedelic studies. These include evidence that pscilocybin significantly reduces anxiety in patients with life-threatening illnesses like cancer, that MDMA (3,4-methylenedioxy-methamphetaminecan; also known as ecstasy) improves outcomes for people suffering from PTSD and that psychedelics can produce sustained feelings of openness that are both therapeutic and personally enriching.

Other researchers are investigating the traditional uses of plant medicines, such as ayahuasca, and exploring the neurological and psychotherapeutic benefits of combining Indigenous knowledge with modern medicine.

I am a medical historian, exploring why we now think that psychedelics may have a valuable role to play in human psychology, and why over 50 years ago, during the heyday of psychedelic research, we rejected that hypothesis. What has changed? What did we miss before? Is this merely a flashback?

Healing trauma, anxiety, depression

In 1957, the word psychedelic officially entered the English lexicon, introduced by British-trained and Canadian-based psychiatrist Humphry Osmond.

Osmond studied mescaline from the peyote cactus, synthesized by German scientists in the 1930s, and LSD, a laboratory-produced substance created by Albert Hofmann at Sandoz in Switzerland. During the 1950s and into the 1960s, more than 1,000 scientific articles appeared as researchers around the world interrogated the potential of these psychedelics for healing addictions and trauma.

But, by the end of the 1960s, most legitimate psychedelic research ground to a halt. Some of the research had been deemed unethical, namely mind-control experiments conducted under the auspices of the CIA. Other researchers had been discredited for either unethical or self-aggrandizing use of psychedelics, or both.

Timothy Leary was perhaps the most notorious character in that regard. Having been dismissed from Harvard University, he launched a recreational career as a self-appointed apostle of psychedelic living.

Drug regulators struggled to balance a desire for scientific research with a growing appetite for recreational use, and some argued abuse, of psychedelics.

In the popular media, these drugs came to symbolize hedonism and violence. In the United States, the government sponsored films aimed at scaring viewers about the long-term and even deadly consequences of taking LSD. Scientists were hard-pressed to maintain their credibility as popular attitudes began to shift.

Now that interpretation is beginning to change.

A psychedelics revival

In 2009, Britain’s chief drug adviser, David Nutt, reported that psychedelic drugs had been unfairly prohibited. He argued that substances such as alcohol and tobacco were in fact much more dangerous to consumers than drugs like LSD, ecstasy (MDMA) and mushrooms (psilocybin).

He was fired from his advisory position as a result, but his published claims helped to reopen debates on the use and abuse of psychedelics, both in scientific and policy circles.

And Nutt was not alone. Several well-established researchers began joining the chorus of support for new regulations allowing researchers to explore and reinterpret the neuroscience behind psychedelics. Studies ranged from those looking at the mechanisms of drug reactions to those revisiting the role of psychedelics in psychotherapy.

In 2017, Oakland, Calif., hosted the largest gathering to date of psychedelic scientists and researchers. Boasting attendance of more than 3,000 participants, Psychedelic Science 2017 brought together researchers and practitioners with a diverse set of interests in reviving psychedelics —from filmmakers to neuroscientists, journalists, psychiatrists, artists, policy advisers, comedians, historians, anthropologists, Indigenous healers and patients.

The conference was co-hosted by the leading organizations dedicated to psychedelics —including the Multidisciplinary Association for Psychedelic Studies (MAPS) and The Beckley Foundation —and participants were exposed to cutting-edge research.

Measuring reaction, not experience

As a historian, however, I am trained to be cynical about trends that claim to be new or innovative. We learn that often we culturally tend to forget the past, or ignore the parts of the past that seem beyond our borders.

For that reason, I am particularly interested in understanding the so-called psychedelic renaissance and what makes it different from the psychedelic heyday of the 1950s and 1960s.

The historic trials were conducted at the very early stages of the pharmacological revolution, which ushered in new methods for evaluating efficacy and safety, culminating in the randomized controlled trial (RCT). Prior to standardizing that approach, however, most pharmacological experiments relied on case reports and data accumulation that did not necessarily involve blinded or comparative techniques.

Historically, scientists were keen to separate pharmacological substances from their organic cultural, spiritual and healing contexts —the RCT is a classic representation of our attempts to measure reaction rather than to interpret experience. Isolating the drug from an associated ritual might have more readily conveyed an image of progress, or a more genuine scientific approach.

Today, however, psychedelic investigators are beginning to question the decision to excise the drug from its Indigenous or ritualized practices.

Over the past 60 years, we have invested more in psychopharmacological research than ever before. American economists estimate the amount of money spent on psychopharmacology research to be in the billions annually.

Rethinking the scientific method

Modern science has focused attention on data accrual —measuring reactions, identifying neural networks and discovering neuro-chemical pathways. It has moved decidedly away from larger philosophical questions of how we think, or what is human consciousness or how human thoughts are evolving.

Some of those questions inspired the earlier generation of researchers to embark on psychedelic studies in the first place.

We may now have more sophisticated tools for advancing the science of psychedelics. But psychedelics have always inspired harmony between brain and behaviour, individuals and their environments, and an appreciation for western and non-western traditions mutually informing the human experience.

In other words, scientific pursuits need to be coupled with a humanist tradition —to highlight not just how psychedelics work, but why that matters.

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