How to Overcome Depression: From Psychedelics to Brain Stimulation
According to WHO estimates, more than 300 million people worldwide suffer from depression, and this number increases every year. Scientists believe that by 2030, depression will become one of the main public health issues and will rank second among the causes of disability—at least in developed countries. Everyone has a chance of encountering depression, if not in their own life, then in the lives of their loved ones.
Unfortunately, the main methods for treating depressive disorders—antidepressants and cognitive behavioral therapy—do not help everyone. A third of patients remain in a severe state, no matter what medications they try or how many therapists they see. Pharmaceutical companies advertise the benefits of their drugs, but in reality, almost all of them work on the same principle. Fifty years ago, when modern antidepressants appeared, depression was thought to be caused by an imbalance of neurotransmitters in the brain. Drugs like fluoxetine were supposed to restore this balance and relieve symptoms of depression—loss of interest in life, constant fatigue, feelings of worthlessness, and suicidal thoughts.
Today, we understand that this model doesn’t work. We still have a poor understanding of what causes depression and how to eliminate it. In addition, antidepressants have a long list of side effects—people quickly gain weight, suffer from diarrhea, nausea, anxiety, dizziness, insomnia, weakness, and apathy.
But there is good news—for the first time in many years, new methods of treating depression are emerging, based on completely different mechanisms. These may not only change the approach to treating psychological disorders but also help us better understand how consciousness works.
Ketamine: A Fast-Acting Antidepressant
In medicine, ketamine is usually used for anesthesia and pain relief. In high doses, it causes vivid hallucinations and out-of-body experiences. Thanks to these properties, it became popular in counterculture and rave movements—psychoanalyst and neurobiologist John Lilly, for example, popularized ketamine by conducting experiments with it in sensory deprivation tanks.
In the 2000s, ketamine began to be used to treat treatment-resistant depression that does not respond to other methods. Unlike antidepressants, ketamine works very quickly—within hours, not months. For patients with suicidal intentions, this can be a real lifesaver. However, since ketamine was not patented, pharmaceutical companies did not see it as a way to make money and did not fund clinical trials. Only recently has this situation changed.
In March 2019, the FDA approved the use of the ketamine-based nasal spray “Spravato” as a new way to treat severe depression. This decision is called the first major innovation in medical psychiatry in the past half-century.
As an antidepressant, ketamine is used in low doses that do not induce a psychedelic trip but do relieve anxiety and low mood. Several studies have confirmed that ketamine helps patients with severe depression who do not respond to other treatments. However, there are downsides: the effect usually wears off within one to two weeks. To achieve long-term improvement, treatment must be continued for many months or even years—long enough to develop a serious addiction.
Unlike traditional antidepressants, ketamine acts on glutamate NMDA receptors—this triggers a surge in neuronal activity and helps create new synaptic connections between brain cells. Apparently, this helps break the vicious cycle of depressive thoughts and see reality differently. Patients note that ketamine helps them think more clearly and does not dull the range of emotions like regular antidepressants.
Psychiatrists hope that other fast-acting antidepressant drugs will follow the ketamine spray.
Despite its advantages, ketamine has many drawbacks and limitations. “I think using a ketamine nasal spray is rather dangerous: first, the long-term effect of ketamine on depression has not been proven, and second—besides many side effects, including addiction, it will be very difficult to control the dosage,” says Olga Martynova, a researcher at the Center for Neuroeconomics and Cognitive Research at HSE University.
Doctors recommend using ketamine only if other methods do not work, always under medical supervision and in combination with psychotherapy. Perhaps, by studying the positive properties of ketamine, scientists will find other, safer ways to achieve the same effect.
Psychedelics: Psilocybin and the Promise of “Magic Mushrooms”
In 2018, the U.S. Food and Drug Administration granted psilocybin “breakthrough therapy” status. This means the active ingredient in hallucinogenic mushrooms can now be legally used for research. Another substance long associated with mysticism and counterculture is gradually gaining legal status in academic and medical circles.
The effect of “magic” mushrooms in treating depression has been proven repeatedly. In 2016, American scientists found that psilocybin reduced symptoms of depression in 80% of patients with terminal cancer. In 2017, researchers at Imperial College London gave 12 volunteers with severe depression either 10 or 25 milligrams of psilocybin. After three months, five were in complete remission; the rest had significantly reduced anxiety and low mood.
Using brain imaging, scientists showed how psilocybin changes nervous system activity. It strengthens connections between different parts of the brain and stimulates the formation of new synapses—connections between neurons.
Like traditional antidepressants, psilocybin acts on serotonin receptors. It changes the function of brain areas associated with mood—specifically, it reduces the activity of the default mode network, which is linked to obsessive thoughts and depressive states. As a result, people become more aware of hidden patterns in their thinking and behavior. The positive effect of a single “trip” can last for years after use.
“People who regularly take antidepressants often complain of dulled perception. SSRIs suppress both negative and positive emotions. After taking psilocybin, people report the opposite—emotional release and a reset, as if their feelings have become brighter and more responsive,” says Robin Carhart-Harris, one of the leading psychedelic researchers at Imperial College London.
Could psychedelics become the main breakthrough in treating mental disorders? Carhart-Harris believes that even if larger trials prove their effectiveness, they still won’t be a panacea. Unlike antidepressants, psychedelics do not suppress anxiety but force people to confront their repressed emotions and experiences directly. For many, this effect can be too overwhelming. It’s also important to remember the possible side effects and “bad trips.” A future where psilocybin can be bought at a pharmacy by prescription is unlikely to come very soon.
Ayahuasca: Ancient Traditions and Modern Science
Ayahuasca is a traditional drink of Native Americans, used for communicating with spirits and healing. One of its main ingredients contains the powerful psychoactive alkaloid DMT (dimethyltryptamine). It causes vivid visions in which a person returns to their own past or experiences contact with otherworldly beings. Indigenous people believe that the spirits of plants appear to help and guide them.
In most countries, ayahuasca is banned as a strong drug, but in Brazil and Peru, it is considered a sacred drink and a national treasure. Even government officials sometimes admit their fondness for ayahuasca. The governor of the Brazilian state of Acre, Binho Marques, once said: “In times of doubt, when I saw no hope for the future, I found knowledge, enlightenment, and hope with the help of these plants.” Indigenous shamans who use ayahuasca in their rituals receive thousands of people from all over the world every year.
People from Europe and the U.S. have long traveled to the Amazon to get rid of depression, anxiety disorders, and other psychological problems that Western medicine has yet to solve. Scientists usually dismiss such methods as magical superstition. But recently, the healing effect of ayahuasca has been demonstrated in academic research.
Two years ago, Brazilian scientists conducted the first double-blind, placebo-controlled study of ayahuasca for treating severe depression. Before the experiment, all participants had tried several therapies without any effect. A week after the experiment, 64% of those who took ayahuasca felt much better—while in the placebo group, a positive result was observed in only 27% of cases.
On a physiological level, DMT molecules, like psilocybin, act on serotonin 5-HT2A receptors. Recent experiments with rats showed that small doses of DMT help rodents cope better with stress and anxiety. But treating depression in humans is likely related to more than just physiology.
In March of this year, scientists at Johns Hopkins University showed that a fast-acting DMT-based psychedelic eases symptoms of depression and anxiety disorders. Importantly, the greatest effectiveness was achieved when participants reported deep mystical and personal experiences. The intensity of hallucinations did not affect the result.
Apparently, ayahuasca has a healing effect specifically through the psychedelic experience, not just the action of the substance on the body. Like other psychedelics, DMT helps access deep and unconscious thought patterns, which can then be changed to something more stable and positive. Sometimes this looks like a real transformation—enthusiasts compare one ayahuasca experience to ten years of psychotherapy.
Psychedelic therapy may help bridge the gap between modern and traditional treatment methods. Neurobiologist Robin Carhart-Harris believes that by 2024, psychedelic-based medications will radically change psychiatry and be used to treat depression, PTSD, and other conditions. But until that future arrives, ayahuasca remains a hope for the few willing to undergo shamanic rituals. A psychiatrist is unlikely to prescribe it.
Brain Stimulation (tDCS): A Safe and Legal Alternative
Transcranial direct current stimulation (tDCS) is the application of a weak current to the cerebral cortex through electrodes placed on specific areas of the head. This is not a new technology, but it has recently been rediscovered and is now being actively researched. It turns out that brain stimulation leads to a range of positive effects—relieving chronic pain, improving memory and concentration, speeding up learning, and also improving mood and helping to fight depression.
Brain stimulation works at least as effectively as some antidepressants. For example, a double-blind study by Harvard scientists showed that after tDCS sessions, patients with depression recovered even faster than after taking fluoxetine. Two weeks of tDCS therapy produced an effect comparable to four weeks of antidepressant use.
According to a 2016 meta-analysis, active brain stimulation improves the condition of 33% of patients with depression. The results are significantly better than the placebo effect. In control groups using inactive tDCS devices, symptoms decreased in only 19% of people. At the same time, brain stimulation has almost no contraindications or side effects. The only unpleasant sensation patients may experience is a slight burning or itching at the electrode site.
Harvard scientists call brain stimulation one of the most promising and underrated ways to treat depression. In Europe, it has been given a “Class B” status, meaning “probably effective,” approved for depression treatment, and is already used in many clinics. But this method also has limitations. Brain stimulation is not intended for quick results—studies show it provides the most benefits with long-term use.
In an Australian study, after three weeks of daily tDCS sessions, depression symptoms decreased in only 28% of participants. But when the course was extended for another three weeks, the results were much more impressive—42.5% of patients responded to treatment. Many of them had not been helped by medication before.
The principle of tDCS is quite simple. Positively charged electrodes reduce the potential difference on neuron membranes—they become more easily excited and form synaptic connections with other brain cells more readily. Negatively charged electrodes, on the other hand, reduce the activity of neurons in areas that are too active. Thus, brain stimulation helps overcome obsessive thoughts and activates learning mechanisms weakened by depression. In some ways, it is similar to ketamine and some antidepressants, but much safer.
Brain stimulation can also be used by healthy people to improve mood and increase resilience to stress. Modern neuro-gadgets—such as the Russian Brainstorm neurostimulator—allow flexible electrode placement, so the device can be used for several purposes. When used correctly, brain stimulation reduces anxiety, low mood, and hostility toward others, as well as improves memory, concentration, and the ability to handle mental workloads.
Brain stimulation is currently the only new depression treatment method that is legal and safe. Thanks to its low cost, almost anyone can use tDCS devices. While a single ketamine therapy session in the U.S. can cost up to $885, a portable tDCS device from Russian developers is almost ten times cheaper.
Experts recommend using brain stimulation as an adjunct therapy—and, of course, only after consulting a doctor. If you do not have depression, such devices can be used independently.
Depression is not a symptom of a neurotransmitter imbalance, but a serious mental disorder. Depression has not one, but many causes, some of which scientists are only beginning to understand. Perhaps new therapies will lead to a deeper understanding of psychological health and help millions of people return to a full life.