Magic Mushrooms Do The Opposite of Anti-Depressants, But That May Be Why They Work

“I felt so much lighter, like something had been released.”


psychedelic therapy is going through something of a revival right now, and we may now know how one such hallucinogenic drug is seemingly able to alleviate symptoms of depression.


Psilocybin, the active compound in magic mushrooms, has long been known to deliver therapeutic effects to people with depression, and researchers think this is because the drug helps to revive emotional responsiveness in the brain.

What’s so remarkable is this kind of mechanism is actually the opposite effect of a major class of antidepressants used to treat the condition, called selective serotonin reuptake inhibitors (SSRIs).

“Psilocybin-assisted therapy might mitigate depression by increasing emotional connection,” neuroscientist Leor Roseman from Imperial College London explained to PsyPost.

“[T]his is unlike SSRI antidepressants which are criticised for creating in many people a general emotional blunting.”

The new study examined 20 patients diagnosed with moderate-to-severe treatment-resistant depression, to investigate what kinds of effects psilocybin would have on their brain activity and depressive symptoms.

A previous study by some of the same researchers had shown that the drug seems to ‘reset’ brain circuits in depressed people, with patient-reported benefits lasting up to five weeks after treatment.

This time around, the team wanted to examine what impact psilocybin might have on the amygdala – the part of our brain that helps process emotional reactions, including fear – in addition to its effects on participants’ depression.

Before taking the drug, the participants underwent fMRI brain scans, then, in two separate sessions one week apart, they took doses of psilocybin, before again being scanned via fMRI the morning after receiving the second dose.

During the fMRI scans, the group were shown images of faces with either fearful, happy, or neutral expressions, and the researchers wanted to investigate what effect these faces had on the participants’ amygdala after taking psilocybin.

After the experiment, the majority of patients reported that the psilocybin had eased their depressive symptoms, with almost half the group still seeing benefits from the treatment five weeks later – in line with the kinds of benefits other depression studies using the drug have shown.

More intriguingly, the fMRI scans showed the drug heightened activity in the right amygdala, with increased responses to both fearful and happy faces – and the increases to fearful faces were predictive of clinical improvements in depressive symptoms one week after the experiment.

What’s striking is the alleviation of depression occurs from emotional receptivity being enhanced – the opposite of SSRI antidepressants.

“It has been proposed that decreased amygdala responsiveness to negative emotional stimuli under SSRIs is a key component of their therapeutic action,” the researchers explain, “but the present study’s findings suggest that this model does not extend to the therapeutic action of psilocybin for [treatment-resistant depression].”

The researchers don’t know for sure why that is, but after the experiment the patients reported “a greater willingness to accept all emotions post-treatment (including negative ones)” (original emphasis), whereas they felt their previous depression treatments worked to “reinforce emotional avoidance and disconnection.”

“I felt so much lighter, like something had been released, it was an emotional purging, the weight and anxiety and depression had been lifted,” one participant said.

“I have felt a sense of acceptance; more acceptance of agony, boredom, loneliness,” commented another.

“[A] willingness to try to accept the negative times – but also an appreciation of the wonderful times.”

The team acknowledges their study has a number of limitations, including a small sample size, and a lack of controls – including one for SSRIs.

But they say their next trial will try to address those shortcomings, as well as looking further into how this mysterious compound alleviates depression – while seemingly forcing people to confront their emotions, whether good or bad.

“I believe that psychedelics hold a potential to cure deep psychological wounds,” Roseman told PsyPost.

“[A]nd I believe that by investigating their neuropsychopharmacological mechanism, we can learn to understand this potential.”

Neurometabolic Disorders Could Contribute to Depression

Impairments in the production of neurotransmitters may lead to depression in some patients, preliminary results show, opening new avenues for research..

Deficiencies in key compounds that help the body make neurotransmitters may contribute to the intractability of depression in some people.

In 2002, psychiatrist Lisa Pan, a depression and suicide prevention researcher at the University of Pittsburgh Medical Center (UPMC), met Kyle, a 19-year-old suffering from depression (name altered to preserve confidentiality). He was among the estimated 15 percent of depression patients in the U.S. for whom treatments such as antidepressants or therapy do not help. He “had been through every available treatment” including electroconvulsive therapy, but nothing worked, Pan recalls. “At one time, he was on 17 medications simultaneously.” The teenager had attempted suicide, and doctors determined that he was at risk for similar episodes. The next step for him would be state hospitalization.

Having exhausted conventional treatment options, Pan went off script. She enlisted a colleague at UPMC, geneticist David Finegold, to run tests on Kyle’s neurometabolic system, which supplies nutrients necessary to maintain neurons with a healthy supply of neurotransmitters. The tests revealed that Kyle underproduced tetrahydrobiopterin (BH4), a necessary cofactor for enzymes involved in making serotonin, dopamine, and other compounds that modulate emotions and mood. Pan gave him sapropterin, a synthetic form of BH4, to bring his system back into balance. “It took some time, but he got better,” she says. Kyle left the hospital and went on to graduate from college.

“We felt like we might be onto something,” Pan says. She began exploring the possibility that metabolic imbalances affected others for whom standard depression treatment had failed. She and her colleagues conducted an array of blood, urine, and cerebrospinal fluid tests in 33 such individuals, each of whom had shown negligible response to at least three different maximum-dose depression medications administered for six weeks or more. Ranging from teenagers to middle-age adults, the group included some who also suffered post-traumatic stress disorder (PTSD), anxiety, or attention deficit hyperactivity disorder (ADHD).

When the tests came back, about a third of the patients showed a deficiency in the levels of folate in their spinal fluid, another key compound for producing a variety of neurotransmitters. Taking a folate supplement to correct this imbalance improved patients’ depression symptoms, lowering their scores on a questionnaire for suicidal thinking and another for mental and physical signs of depression. And Pan says that as each patient continued to take the supplement, their symptoms continued to improve (Am J Psych, appiajp201615111500, 2016).

Since the publication of these results, “we have gotten hundreds of phone calls from people just asking for help,” she says. As Pan returns these calls, she explains that her findings are preliminary. Her study documents relatively few individual treatment outcomes and is not a formal clinical trial. As the study continues and expands to include more patients, Pan and her colleagues will work to identify the cause of folate deficiency and to investigate whether folate supplementation could become a standard treatment. But these results suggest that treating an underlying neurometabolic imbalance can alleviate depression at least in some cases, which should open a door to new research. Receiving the influx of phone calls “makes me want to work more,” Pan says.

Characterizing depression in broad strokes is almost impossible, cautions David Brent, a former advisor to Pan and coauthor on the study. “There are a lot of people who look the same that probably have very different causes” of depression. Other psychological conditions, including PTSD and anxiety, frequently coincide with and complicate the disorder. “We’re really just at the beginning of extricating” these interacting factors, Pan says, and at this stage, developing solutions that can be standardized for treating many people is difficult.

Even so, Finegold notes that preliminary studies like this one have a way of offering hope to people who have not found a successful depression treatment. He, too, receives phone calls from people living with depression, and some express their gratitude simply to know that new aspects of the problem are being explored.

One avenue of Pan’s further exploration is to search for genetic markers associated with neurometabolic imbalances. Ideally, genetic testing could be used alongside traditional clinical evaluations to provide physicians with as much patient information as possible, says coauthor David Peters, a geneticist at UPMC. Testing spinal fluid is invasive and time-consuming; a quick DNA swab is much more practical, and Peters says incorporating genetic testing is a “very exciting prospect.”

Every six months or so, Pan checks in with Kyle. Having graduated college, he now works in environmental science, and the only medication he takes is sapropterin. In a statement he authorized her to share, Kyle says, “It’s safe to say that I owe my life to the successful diagnosis.”

How to overcome depression without anti-depressants

Depression affects an estimated 14.6 million American citizens. It is typically described as a chemical imbalance in the brain that requires outside assistance, in the same way a heart with an irregular beat requires a pacemaker. As a corollary, many Americans resort to anti-depressants to treat their “mental disorder.”

The problem is, doctors do not have a biological understanding of the mind the same way they have a biological understanding of the heart. Consequently, anti-depressants produce more side effects than cures, which, in turn, requires more drugs to counter balance. In many cases, these side effects actually worsen depression. In other cases, anti-depressants merely numb, rather than treat the underlying problem. It’s a rabbit hole down Big Pharma Avenue.

Depression is so widely defined that nearly everyone qualifies as clinically depressed. This isn’t to say depression is a myth. We all experience blue spells from time to time. But just because you are experiencing a blue spell doesn’t mean you need a blue pill. Here are a few ways to, as the American actress Judy Garland used to sing, “forget your troubles, come on get happy.”

Exercise: Exercise is extremely important when it comes to uplifting your mood. In animal studies, exercise increases the secretion of happy feeling chemicals like serotonin. Some forward thinking agencies have even gone so far as to prescribe exercise, rather than anti-depressants, as a treatment for mild depression.

Charity work: Depressed people are fixated on their problems. Charity work is a great way to see your problems in a new light, from the point of view of the universe. Instead of focusing on your problems, your attention is focused on the problems of other people. Plus, charity work helps you get out of the house, make social connections and feel good in general. Studies have shown that volunteering gives people a deep sense of happiness.

Eat healthy: Depression is believed to be a chemical imbalance. This so-called chemical imbalance may be a product of a poor nutrition. In other words, a depressed mind is a mind deprived of vitamins. To ensure that you are getting your daily vitamin intake, make sure to eat a well-rounded diet consisting of whole foods, mostly plants, consumed in moderation.

Multivitamins are another way to ensure you get your daily vitamin intake. Don’t make multivitamins your primary source of vitamins, however. The bulk of your daily vitamin intake should come from food. Also avoid depressants, like alcohol, which can exacerbate the symptoms of depression.

Get enough sleep: Sleep is essential to human well-being, along with food, water and shelter. Whenever humans are deprived of sleep, it drastically alter ours mood, mostly for the worse. Too little sleep can actually worsen depression. If you’re not getting a standard eight hours of sleep, change your routine. Consider removing distractions in your bedroom that prevent you from getting enough sleep, like your television and computer.

Set goals: Depressed people often feel hopeless. It becomes the focal point of their attention. If you’re depressed, it’s important to keep your mind focused on something other than how depressed you are. This can be achieved by making goals. Goals give you something to look forward to and combat the feeling of hopelessness. Your goals can start out small, such as promising yourself you will run every other day, and build up from there. Depressed thoughts occupy less mental space the more goals you have in mind.

There are instances when depression becomes so severe that outside help is needed. In most cases, however, depression is relatively mild and can be mitigated by some simple lifestyle changes. Even medical doctors who prescribe anti-depressants will recommend you take note of the listed suggestions. With these nuggets of wisdom in mind, you can keep depression out of mind.

Pfizer ‘Hid Link’ Between Anti-Depressants and Birth Defects Alex Jones’ Infowars: There’s a war on for your mind!

Pharmaceutical mammoth Pfizer faces more than 1,000 lawsuits from victims who say that the company knew about the relationship between birth defects and their #1 best-selling anti-depressant. A claim that Pfizer has, of course, battled against.

Report: Pfizer ‘Hid Link’ Between Anti-Depressants and Birth Defects

Now, however, new reports have surfaced that Pfizer’s own scientific advisers were warning of the deadly link for more than a year. Something that my team told you in 2012 was already going on. According to Bloomberg:

“A Pfizer Inc. report shows a scientist warned executives last year about a potential link between the anti-depressant drug Zoloft and birth defects and recommended changes to the medication’s safety warning.
The document from a Pfizer drug-safety official might complicate the company’s efforts to fend off lawsuits brought by parents of children with malformed hearts. Pfizer has consistently rejected suggestions Zoloft caused newborn abnormalities and said Monday the document was taken out of context by lawyers suing the company.”
In other words, Pfizer likely employed a popular Big Pharma tactic: ignore any science that reveals serious side effects, and instead choose to pay some relatively meager fines for the damages. After all, paying a few million (or billion) in fines is often nothing compared to the profits from drugs like Zoloft, which rakes in around $2.9 billion per year alone.

After all, Pfizer has a familiar history with government fines. It was in 2009 when the corporation paid one of the largest health care fraud settlements of all time, shelling out $2.3 billion for “the intent to defraud or mislead” consumers with their painkiller Bextra. Again, a fine that is less than the sales of Zoloft for a single year.

As we read further down into the Bloomberg report, yet again it seems that research indicating serious side effects was simply ignored:

“Pfizer researchers also acknowledged in a 1998 report, which has been introduced into evidence in the Philadelphia trial, they’d found more than a dozen side-effect reports about babies’ birth defects for which their mothers’ Zoloft use couldn’t be ruled out as a cause.”
Sadly, this is nothing new for the mega pharmaceutical conglomerate. Eli Lilly & Co., the manufacturers of Prozac, did their best to hide the link between Prozac and increased risk of suicide for a number of years. Ultimately, it took a Harvard psychiatrist to proclaim that Americans were being treated like ‘guinea pigs’ by Eli Lilly & Co.’s Prozac for real public interest.

Will Pfizer end up paying a couple billion or less in fines for leading to an unknown number of life-threatening birth defects? It is the most likely outcome, for which the company is quite thankful. As long as they can write off the settlement loss and continue to take in the yearly profits, the company will get over it quickly.