The treatment is here, but are we ready?
- Ketamine is the first hallucinogen approved for therapeutic use in the U.S.
- Research has shown ketamine is effective at treating depression.
- Though ketamine infusion therapy is now being offered at hundreds of North American clinics, there are unaddressed dangers in the current ketamine gold rush.
In March 2019, the FDA approved ketamine, under the trade name Spravato (esketamine), for clinical use in treatment-resistant depression therapy. Alongside racemic ketamine, which is commonly used in ketamine infusion therapy, ketamine is the first hallucinogen approved for therapeutic usage in the United States.
Technically, ketamine is not a psychedelic but rather a hallucinogen and dissociative. (While ketamine has psychedelic effects, traditional psychedelics bind to the 5-HT2B receptor.) Still, advocates for psychedelic therapy recognize ketamine as a gateway for traditional psychedelics, such as psilocybin and LSD, to be considered for therapeutic usage.
To understand the proliferation of ketamine clinics across North America, the origins of this peculiar substance — one that went from battlefields to veterinary clinics to dance clubs in the span of two decades — must be discussed.
History of ketamine
In 1962, chemistry professor Calvin Stevens synthesized ketamine while researching alpha-hydroxyimine rearrangements. The first human tests were conducted on prisoners in 1964. Ketamine soon replaced phencyclidine (PCP) as the go-to anesthetic in hospitals. It was initially used on soldiers during the Vietnam War following FDA approval in 1970. Thanks to its success on the battlefield, ketamine was placed on the World Health Organization's List of Essential Medicines.
Ketamine has been used broadly as a sedative and anesthetic; to aid in emergency surgeries in war zones; as a bronchodilator for severe asthmatics; to treat certain types of seizures; and in postoperative pain management. Now, ketamine infusions and nasal sprays are being used for depression. Ketamine is also showing potential efficacy in treating chronic pain and suicidal ideation, though more research needs to be done.
Of all of those uses, ketamine has predominantly been used as an anesthetic in humans and animals. While it restricts breathing less than other similar medications, ketamine also produces hallucinations (thus, it's labeled as a dissociative anesthetic). The list of potential side effects from using ketamine is long, including nausea, double vision, breathing problems, impaired memory, liver enzyme abnormalities, urinary tract problems, and even increased depression — an alarming possibility given its growing use as an antidepressant replacement.
Small-scale studies on using ketamine to treat depression were conducted in 2000 and 2006. Further research confirmed its role in alleviating depressive symptoms, including the possibility that the antidepressant effects of a single dose can persist for weeks. In 2016, the FDA fast-tracked ketamine trials for depression.
A chair is seen in a therapy room at Field Trip, a psychedelic therapy clinic in Toronto, Ontario, Canada.Credit: Cole Burston/AFP via Getty Images
Ketamine infusion therapy
There has yet to be a consensus on how ketamine addresses depression. Antidepressants act on the body's serotonin and noradrenaline systems. Ketamine seems to interfere with an amino acid derivative, NMDA. As a 2017 study published in the journal Nature explains:
"Ketamine is responsible for blocking the N-methyl-D-aspartate (NMDA) receptor, which causes an immediate alleviation of depressive effects, while another metabolite in the drug helps the effects last for hours. This blockage is also what causes the hallucinogenic effects."
Small intravenous doses of esketamine — an enantiomer of ketamine and the substance actually approved by the FDA — seem to lift depressed patients out of their funk. So does Spravato, a nasal spray that can only be administered under supervision in a doctor's office or clinic.
Patients that have tried two different antidepressant medications with no success (the definition of treatment-resistant depression) can legally receive ketamine infusions or Spravato at clinics located all over the country. Since the therapy is generally not covered by insurance, treatments range from $300 to $2,000 per session; the Field Trip Treatment Program, which includes psychotherapy and six infusions, runs $4,700.
The process of ketamine infusion therapy is varied depending on which clinic you attend. Companies like Field Trip and organizations such as MAPS require psychotherapy sessions to coincide with infusions.
Unfortunately, therapeutic implementation has not always lived up to federal requirements. Reports of patients quitting antidepressants and psychotherapy to use esketamine as their primary source of treatment abound. Since medical professionals with no mental health training, such as nurse practitioners, anesthesiologists, and pain physicians, can legally administer ketamine, patients are left to process the drug's effects with little to no guidance.
Thus far, efficacy has been mixed. As STAT News editor Megan Thielking writes, people with minor depressive issues are likely better candidates for ketamine therapy than those with treatment-resistant depression, the very cohort the drug is purported to target.
"Studies vary but have found response rates to ketamine as high as 70 percent among people with major depression who have failed a few other antidepressants. But the rate is lower for patients with extremely treatment-resistant depression, and how long any improvement lasts varies from one patient to the next."
Was ketamine approved too quickly?
While ketamine therapy is certainly promising, the FDA-approved trials raise a number of red flags. A recent analysis in The British Journal of Psychiatry concludes that we're moving too fast. Author Mark Horowitz writes:
"Out of the three short-term trials conducted by Janssen only one showed a statistically significant difference between esketamine and placebo. These were even shorter than the 6-8 week trials the FDA usually requires for drug licensing."
Trials usually last three months; the approved ketamine trials only lasted four weeks and barely showed efficacy above placebo. More concerning, the FDA allowed Janssen to submit a discontinuation trial with a study design flaw as evidence of efficacy — side effects were treated as evidence of relapse, not withdrawal symptoms. Even more alarmingly, six people in the esketamine group died during the trials, including three by suicide, two of which had previously shown no signs of suicidal ideation.
When Janssen stated that the problem wasn't esketamine but underlying conditions, the FDA accepted the reasoning even though no conclusive evidence was provided. This doesn't mean ketamine therapy isn't potentially therapeutic, though it does suggest that its approval by the FDA was rushed.
Psychiatrist Lori Calabrese, who offers ketamine infusion for depression and anxiety in her clinic, puts it best when stating, "The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish." Time will tell if this treatment proves more beneficial than dangerous in mental health treatments.
Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
A lithium imbalance appears linked to suicide.
- Lithium appears essential to brain activity, but how it works remains a mystery.
- A team of researchers analyzed where in the brain lithium tends to accumulate in two healthy controls and one suicide victim.
- The healthy controls had more lithium in their white matter than gray matter.
Lithium is known to students of chemistry as the lightest solid element, to electronics enthusiasts as a fine material to make a battery out of, and to millions of others as an effective medication. It was initially used as a medicine against a variety of conditions, including "brain gout" and "general nervousness," to some success in the 19th century. It was briefly an ingredient in the soda 7 Up, much like how Coca-Cola once included cocaine. In 1948, the government banned the use of lithium in this way.
Ironically, it was a year after these bans took place that the use of lithium got a dose of science. Its safe use in treating a number of conditions, most notably mania, was demonstrated. It is now widely used to treat bipolar disorder and depression, though it can be toxic in high doses.
Exactly how lithium works in the body isn't known. How the trace amounts of lithium in our bodies, acquired naturally from sources like food and water, affect us is also poorly studied. A new study published in Scientific Reports hopes to fill that gap in the literature. Its findings suggest that lithium is even more important than previously thought, with the body regulating where it is distributed in the brain.
Lithium in the brain of a suicide victim
The researchers used a new technique called neutron-induced coincidence (NIK), which involves shooting neutrons at brain sections and measuring the decay products that form after lithium absorbs a neutron. In this way, they can determine where and how much lithium is in the sample.
This was used to examine a total of 139 samples from the brains of three deceased individuals: the first died a natural death and never took lithium as a medication; the second also never took lithium and died of suicide; and the third took lithium but died a natural death.
The brains of the two subjects who died a natural death contained much more lithium in the white matter than in the gray matter. (Gray matter is involved in higher thought, while white matter is involved in information transfer.) For the suicide victim, there was much less lithium in the white matter compared to the gray matter. The authors concluded that the distribution was "almost diametral to the control collective, where the ratio was well > 1, so that an acute lithium depletion in suicide could be considered."
It appears, therefore, that lithium distribution is controlled in the brain.
What are the implications?
Lead author Jutta Schöpfer explained:
"Our results are fairly groundbreaking, because we were able for the first time to ascertain the distribution of lithium under physiological conditions. Since we were able to ascertain trace quantities of the element in the brain without first administering medication and because the distribution is so clearly different, we assume that lithium indeed has an important function in the body."
The authors note that "our results accordingly support the thesis that lithium may be of essential relevance not only in animal, but also in man." They also mesh well with recent findings suggesting people receiving greater concentrations of lithium in their drinking water are less likely to commit suicide. Additionally, other studies suggest that lithium levels in the water relate to local crime rates and occurrences of neurodegenerative disease.
There is much more to learn about that element in the upper-left corner of the Periodic Table.
A small percentage of people who consume psychedelics experience strange lingering effects, sometimes years after they took the drug.
- LSD flashbacks have been studied for decades, though scientists still aren't quite sure why some people experience them.
- A subset of people who take psychedelics and then experience flashbacks develop hallucinogen persisting perception disorder (HPPD), a rare condition in which people experience regular or near-constant psychedelic symptoms.
- There's currently no cure for the disorder, though some studies suggest medications may alleviate symptoms.
In February 2021, Conor was in his room and looking at his phone when he was struck by a strange feeling.
"The room looked normal, nothing was moving, but I felt as though I was under the influence of a psychedelic," he told Big Think.
As a teenager, Conor had experimented with LSD, mushrooms, and other psychedelics a couple dozen times. Now 25, he had been sober for about a year. He brushed off the incident.
But soon, Conor was struck again by the same strange feeling.
"I had no idea what was going on in my brain at that time and the anxiety and paranoia grew so intense that I became fearful I had developed everything from brain cancer to schizophrenia," he said.
The physical and psychological symptoms he began suffering were "devastating."
"The world [looked] crooked and out of focus, pictures had an eerie quality to them, things would go in and out of focus, at night while falling asleep I would experience vivid and terrifying hypnagogic hallucinations that made rest impossible."
After three weeks, Conor said his visual symptoms amplified with "unbelievable intensity."
"The floors would [breathe], paint on the walls looked wet, visual snow was so intense [that] pure black looked like it was glowing, at night I would see tracers everywhere, halos appeared around text. [...] I did not sleep, my thoughts were anxious and at times deranged, I had unbelievably intense dereliction that made the world seem fake."
What Conor experienced is commonly called an LSD flashback. It's a mysterious phenomenon in which someone who's previously taken a hallucinogenic drug suddenly and temporarily experiences the effects of that drug days, weeks, or even years after consuming it.
Flashbacks can occur after taking a wide range of psychedelic drugs. But compared to other hallucinogens, flashbacks seem to be most common among people who have consumed LSD, according to studies.
Credit Newwup via Adobe Stock
People have reported acid flashbacks for decades. The earliest recorded case may be
Havelock Ellis' 1898 report of taking mescaline and then experiencing sustained heightened sensitization to "the more delicate phenomena of light and shade and color."
But it wasn't until the 1950s, little more than a decade after Albert Hoffman first synthesized LSD, that scientists started researching LSD and its potential long-term effects. While studies have illuminated some aspects of how psychedelics affect the brain, scientists still have much to learn about the nature of LSD flashbacks, what causes them, and how to treat them.
What's certain, however, is that a small percentage of people who consume psychedelics report bizarre and sometimes debilitating effects that emerge long after taking hallucinogens.
Symptoms of LSD flashbacks
Among the most common symptoms of LSD flashbacks are visual distortions. In a 1983 study titled " Visual Phenomenology of the LSD Flashback," the psychiatrist and LSD researcher Dr. Henry David Abraham described 16 common visual disturbances reported by people with LSD flashbacks. To name a few:
- Acquired color confusion: The color of objects changed or presented a newly discovered problem of color confusion.
- Difficulty reading: Text may appear jumbled or leave afterimages of the type against the background of the page.
- Geometric phosphenes: Phosphenes, or eigengrau, are non-specific luminous perceptions that occur when the eyes are closed and may originate from entopic (i.e., arising from within the eye itself) stimuli in normal persons. They also may be induced by gentle pressure on the closed eyelid.
- Pareidolias: This is literally an image within an image. These were described when a subject gazed into a finely reticulated design in linoleum, veneer, or a cloud formation. Besides the abstract pattern of the linoleum, subjects often would be able to see a series of concrete images as well, such as "a fish," "a face," and "a little boy."
- Macropsia: Macropsia is the perception of an object larger than it really is. A characteristic description of this phenomenon came from a subject who noticed that his hand was enormous and then of normal size a few seconds later.
- Micropsia: Micropsia is the perception of an object smaller than reality. One subject said, "My feet looked so tiny, like they were a million miles away."
The effects of LSD flashbacks aren't limited to visual distortions. In a 1970 study called "Analysis of the LSD Flashback," researchers sorted LSD flashbacks into three broad categories: perceptual, somatic (meaning of the body), and emotional.
The emotional flashback is "far more distressing" than the other two, the researchers wrote, providing a case study of a 21-year-old woman who was suffering from LSD flashbacks:
"The patient had these frightening flashbacks during the day, while walking down the street, after smoking marijuana or drinking wine, during the night, and occasionally even while asleep. In one situation she awoke during the middle of the night with a feeling of panic and began running around her house fleeing an imagined threat she could not identify or comprehend. She had taken LSD a number of times, but her last few trips were bad ones with panic and fright followed by loneliness to the point of suicidal despair when she 'came down.' The combination of bad trips and emotional flashbacks made her seek professional help because of her fear that she would harm herself."
To be sure, LSD flashbacks aren't always emotionally distressing. A 2010 survey of 600 hallucinogen users found that, of the minority of users who reported experiencing at least one flashback, only 3 percent described it as a negative experience. In fact, some people enjoyed their flashbacks. On the website Erowid, which promotes research of psychedelic drugs, one user wrote:
"After 2 years of my last acid trip, while on vacation in a very nice wilderness place I was sitting on a rock and then I experienced a clear acid high. I was looking at a very steep hill and suddenly it started moving in nice patterns, exactly as one sees patterns while on acid. It wasn't something uncomfortable. In fact it was really pleasant and there was absolutely no trace of the nasty anxiousness after effects common to LSD. It lasted approximately 2 minutes and I enjoyed it very much."
But some LSD flashbacks are neither brief nor pleasant. A subset of people who use psychedelics develop hallucinogen persisting perception disorder (HPPD), a rare and poorly understood condition in which people experience omnipresent or recurring flashbacks. While the symptoms of HPPD vary, the condition can cause intense pain, irreversible perceptual distortions, emotional and psychological distress, and even suicidal thoughts.
HPPD: The never-ending trip
HPPD is estimated to affect between one to five percent of LSD users, though the actual figure is impossible to determine without better data. The disorder was first described formally in 1986 by the American Psychiatric Association's Diagnostic & Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R). The current edition of the manual (DSM-5) says patients need to meet several criteria to be diagnosed with HPPD:
- Patients must reexperience perceptual symptoms they experienced while intoxicated with the hallucinogen.
- These symptoms must cause "significant distress or impairment in social, occupational, or other important areas of functioning."
- These symptoms aren't due to a separate medical condition or mental disorder.
So, what's the difference between a flashback and HPPD? Mainly frequency and duration. A 2017 review published in Frontiers in Psychiatry noted that while "a flashback is usually reported to be infrequent and episodic, HPPD is usually persisting and long-lasting."
A 2014 review published in the Israel Journal of Psychiatry and Related Sciences outlined two types of HPPD. The first, HPPD I, is the "flashback type," which is a generally short-term, non-distressing, benign and reversible state accompanied by a pleasant affect. The severity of HPPD I varies, with some people describing their mild flashbacks as annoying, while others say it's like getting "free trips."
But HPPD II is a different beast. The condition can be permanent, with perceptual distortions and other symptoms manifesting irregularly or almost constantly.
"The symptoms usually include palinopsia (afterimages effects), the occurrence of haloes, trails, akinetopsia, visual snows, etc.," according to the aforementioned 2017 review. "Sounds and other perceptions are usually not affected. Visual phenomena have been reported to be uncontrollable and disturbing. Symptomatology may be accompanied by depersonalization, derealization, anxiety, and depression."
What causes flashbacks and HPPD?
When asked what causes flashbacks and HPPD, Dr. Abraham told Popular Science, "I've spent my life studying this problem and I don't know, is the short answer."
But researchers have proposed explanations. One centers on memory. Because psychedelics can cause extremely powerful and emotional experiences, it's theoretically possible that certain environmental stimuli can remind people of those experiences, and then memory "transports" them back into that subjective mindset — similar to how a soldier with post-traumatic stress disorder might suffer an episode after hearing a loud, sudden noise.
Another hypothesis involves how LSD interacts with the brain's visual processing center. Dr. Abraham proposed that HPPD may arise due to "disinhibition of visual processing related to a loss of serotonin receptors on inhibitory interneurons," which may be caused by consuming LSD.
The basic idea is that LSD somehow changes the way the brain interprets visual stimuli. That might explain why people with HPPD have difficulty properly "disengaging" from the things they see around them. For example, a red stoplight might appear not as a discrete red circle but as a streak of red light painted across their field of vision; or a strobe light might not appear as a flickering light but a light that's constantly on.
Credit Yurok Aleksandrovich via Adobe Stock
"Such a locking of visual circuitry into an 'on' position following perception of a visual stimulus would explain such diverse complaints as trailing, color intensification, positive afterimages, phosphenes, and color confusions, each of which may represent a failure of the respective visual function to turn off the brain's response to the stimulus once the stimulus is gone," Dr. Abraham
It's also possible that people are genetically predisposed to HPPD and that ingesting LSD is the key that unlocks the disorder. This hypothesis would help explain why people have reportedly developed HPPD after taking a single, moderate dose of LSD.
Ultimately, the exact causes of HPPD are unclear. Partially as a result, there's currently no cure for the disorder, though studies show that people with HPPD have reported improvements in symptomatology after taking benzodiazepines. There's also anecdotal evidence that fasting can alleviate the disorder.
Despite uncertainty over the causes of HPPD, researchers do have a good idea of what can trigger "flare-ups" of HPPD. Dr. Abraham's 1983 study listed the most common triggers, some of which include:
- Emergence into a dark environment
- Intention (intentionally inducing visual aberrations by, say, staring at a blank wall)
People with HPPD describe the condition
To get a better understanding of HPPD, Big Think posted a questionnaire to the HPPD community on Reddit. Here are some of the responses:
How did HPPD first manifest for you?
"First I noticed highly enhanced creativity and intense visuals when [high on] weed and I really enjoyed that part. The realization that this is not going to go away soured the whole experience tho."
"My enhanced creativity left me after about a week and what I was left with was mild visual snow. I hardly knew anything about HPPD at the time and just didn't really care about my symptoms and still thought they were just going to vanish at some point, which they didn't. I kept taking drugs simply because I was addicted and felt like life is no fun without them. My HPPD got gradually worse over time and more symptoms appeared. First, I noticed mild tracers, which got worse over time (again due to continued drug use) and then tinnitus and brain fog. But primarily my symptoms are visual."
Are your symptoms episodic or constant?
"Both constant and episodic," wrote user LotsOfShungite. "A stressful event can trigger my symptoms off into the deep end."
"Except the brain fog and head pressure that varies, my visual disturbances are constant. The most debilitating ones are the visual snow, especially when I'm inside except if I watch the TV since it filters some of it out. It's also VERY frustrating that I no longer can focus on objects/details (can't stare) and the astigmatism-like symptoms that I got, like blurriness, especially in the distance and ghosting (double vision) plus starbursts from strong light sources. When I'm outside, the pattern glare is really annoying, same with the excessive amount of floaters that came with this. I also see halos from light sources."
"My symptoms are mostly constant and only change through rather obvious outside influences, such as certain drugs (almost all drugs), stress, lack of sleep, etc. Although my HPPD is quite pronounced, I have learned to accept it and almost only notice it when I pay attention to it. I always [know] it's there and it somewhat bugs me but I get along."
What are some common misconceptions about HPPD?
"I think the most common misconception about hppd is when people refer to it as "tripping permanently". There is a massive distinction between those two things. Generally with hppd, your vision may be altered, but to call it "tripping" is incredibly misleading. Tripping entails a massively altered state of mind and visual perception that is not seen with hppd. There are psychological symptoms like panic attacks, anxiety and dpdr, but those stem from the stress of dealing with the condition. Not because you have trapped lsd molecules flying around your brain for decades (another common myth) A person with hppd is capable of thinking clearly and acting the same as any other sober minded person. A lot of us have jobs, can hold conversations, are capable of being productive members of society. The "burnt out acid junkie" stuck in a "permanent trip" is an extremely toxic trope that creates stigmas around people who already feel intense regret and emotional distress caused by a poorly understood condition. We are not the drugs that we took, and are capable of growing past the mistakes we made in life."
"One of if not the biggest 'misconception' is that many people believe that HPPD does not exist. But I guess there is no way to prove to another person that it does, so this is gonna stay the case until HPPD enters the public consciousness of the psychedelic community."
"They usually don't understand anything about it since most haven't heard about it, which really is crazy considering how debilitating this disorder is for many. And as Dr. Abraham said: in the medical field it's highly under- and misdiagnosed. Often as psychosis."
Lopyriev via Adobe Stock
Hope for HPPD
Since experiencing his first acid flashback in February, Conor has found a few helpful strategies to minimize symptoms, including seeing a psychologist, staying sober, getting enough sleep, staying productive, and talking regularly with friends.
He's currently training to be in the military.
"The symptoms will lessen with time and sobriety, and HPPD provides an opportunity to improve yourself. That being said, because thoughts of suicide are apparently common with people that have HPPD, the medical community should take the condition seriously. Especially given how many people use psychedelics today."
While the future of HPPD research remains unclear, general psychedelics research is going through something of a renaissance. In recent years, researchers have published a growing body of studies showing how psychedelics like psilocybin, LSD, and MDMA can help treat conditions like depression, anxiety, post-traumatic stress disorder, and existential distress.
But, among people with HPPD, opinions on the utility of psychedelics vary. Conor advised caution:
"I would not recommend [hallucinogenic] drugs be taken for recreational purposes. They are tools to help us treat illnesses and should be treated as such. If someone has depression or other mental health issue, maybe psychedelics administered in a clinical setting by a doctor is appropriate, but otherwise, playing with your brain like it's a chemistry playset is asking for trouble down the road."
Two different studies provide further evidence of the efficacy of psychedelics in treating depression.
- A phase 2 clinical trial by Imperial College London found psilocybin to be as effective at treating depression as escitalopram, a commonly prescribed antidepressant.
- A different study by the University of Maryland showed that blocking the hallucinogenic effects of magic mushrooms in mice did not reduce the antidepressant effect.
- Combined, these studies could lead to new ways of applying psychedelics to patient populations that don't want to trip.
Due to stigma, their illegal status and difficulty in finding control groups, research with psychedelics has been a challenge. But research increasingly shows that this class of drug has legitimate medicinal uses, and they may be just as good or even better than more traditional therapies.
Now, the Centre for Psychedelic Research at Imperial College London reports in the New England Journal of Medicine that when pitted against escitalopram (brand name: Lexapro), psilocybin was as effective as the popular SSRI (selective serotonin reuptake inhibitor) in treating moderate to severe depression. Perhaps most significantly, these results were obtained when comparing 6 weeks of daily doses of escitalopram to just two administrations of psilocybin.
Robin Carhart-Harris, head of the center who has published over 100 papers on psychedelics, is confident this study represents another step forward in applying psychedelics to mental health treatment protocols while also reducing fears a lot of citizens have around these substances. In a press release, he said:
"One of the most important aspects of this work is that people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study. Psilocybin performed very favorably in this head-to-head."
Credit: Robin Carhart-Harris et al, NEJM, 2021.
As depicted above, the phase 2 clinical trial included 59 volunteers. The escitalopram (control) group received six weeks of daily escitalopram in addition to two tiny (1-mg) doses of psilocybin — a dose so low that it is unlikely to produce hallucinogenic effects. The psilocybin (experimental) group received two 25-mg doses of psilocybin three weeks apart with placebo given on all the other days.
At the end of the study, both groups saw a decrease in depressive symptoms, though the results were not statistically significant. (That isn't necessarily bad because if the two drugs have similar effects, then they would not produce statistically significant results. Still, a larger study is needed to confirm that psilocybin is "just as good as" escitalopram.)
Additionally, several other outcomes favored psilocybin over escitalopram. For instance, 57 percent in the psilocybin group saw a remission of symptoms compared to 28 percent in the escitalopram group. This result was significant.
Psychedelics without tripping
As psychedelics become decriminalized and potentially legalized for therapeutic use, however, a large population of people might desire the antidepressant effects without the hallucinations. For example, the psychedelic ibogaine may be useful for treating addiction, so the company Mindmed is developing an analog that works without producing the unwanted hallucinogenic side effects.
A new research article, published in the journal PNAS, investigated the antidepressant effects of psilocybin on a group of chronically stressed mice. (Under immense stress, mice develop something resembling human depression.) As with humans, depressed mice lose a sense of joy, which can be assessed by determining their preference for sugar water over tap water. Normal mice prefer sugar water, but depressed mice simply don't care.
Once the mice were no longer juicing up on the sweetened water, the team dosed them with psilocybin alongside a drug called ketanserin, a 5-HT2A serotonin receptor antagonist that eliminates psychedelic effects. Within 24 hours of receiving the dose, the mice were rushing back to the sugar water, indicating that tripping is not necessary for psilocybin to work as an antidepressant.
While the team is excited about these results, they realize it needs to be replicated in a different population.
"The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression."
Photo: Cannabis_Pic / Adobe Stock
The future of psychedelic therapy
Psychedelics such as psilocybin and LSD have a long track record of efficacy in clinical trials and anecdotal experiences. Almost all volunteers of the famous Marsh Chapel experiment claimed their experience on Good Friday in 1962 was one of the most significant events of their lives — and this was a quarter-century after the fact. A more recent, controlled study found that a single dose of psilocybin showed antidepressant effects six months later.
Proponents of macrodosing and ritualistic experiences sometimes argue that the full-blown mystical trip is the therapy, though this is anecdotal, not clinical research. As the Maryland team noted, a number of people are contraindicated for psychedelics, whether through a family history of schizophrenia or current antidepressant treatments.
Senior author Scott Thompson is excited for future research on this topic. As he said of his team's findings:
"The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate… These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice."
Hopefully, with more research occurring in psychedelics than even in the 1950s (when studies predominantly relied on anecdotal evidence and little government support), the longstanding stigmatization of psychedelics is beginning to recede. This could open up new possibilities for both clinical research and, for those curious about the ritual effects, a continuation of introspective experiences.
Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Children with pre-existing mental health issues thrived during the early phase of the pandemic.
- While COVID-19 physically affects adults more than children, mental health distress has increased across all age groups.
- Children between 5 and 17 sought help for mental health issues at much higher rates in 2020.
- However, a new study found children with pre-existing mental health issues experienced reduced symptoms when lockdowns began.
While the physical effects of COVID-19 have dominated headlines for the last 13 months, mental health effects are considered a simultaneous pandemic that could outlast the virus. Children have generally been resilient against the novel coronavirus (though at least one variant is hitting that demographic harder). In terms of depression and anxiety, however, children are on par with adults.
Emergency hospital visits for mental health issues in the 12-to-17-year-old demographic have jumped 31 percent since the pandemic began. Younger children have fared only slightly better: a 24 percent increase for children ages 5 to 11. In Germany, one in three children has suffered anxiety or depression over the past year. On top of this, children are having trouble learning in remote education environments.
However, at least one demographic fared better than normal, at least during the early phase of lockdowns. According to a new study, published in the Journal of the American Academy of Child and Adolescent Psychiatry, middle school children from a predominantly Latinx community with higher-than-normal levels of mental distress experienced a reduction in symptoms.
Children with previous mental health problems saw reduced internalizing (behaviors including being withdrawn, nervous, lonely, unwanted, or sad), externalizing (behaviors including lying, acting irresponsibly, breaking the law, or displaying lack of remorse), and other problems.
Those without mental health issues benefited as well, at least in terms of internalizing and overall behavior; there was no change in attentional issues or externalizing.
The researchers began tracking 322 children (average age 12) in January 2020, before the pandemic took hold in America. They were studied until May 2020. While this only represents a sliver of time in lockdown, senior author Carla Sharp, a psychology professor at the University of Houston, says the results have important clinical implications.
"First, promoting family functioning during COVID-19 may have helped protect or improve youth mental health during the pandemic. Further, it is important to consider cultural factors, such as familism and collectivism in Latinx communities that may buffer the early effects of disasters on mental health to COVID-19 stress."
Seven-year-old Hamza Haqqani, a 2nd-grade student at Al-Huda Academy, uses a computer to participate in an E-learning class with his teacher and classmates while at his home on May 01, 2020 in Bartlett, Illinois.Photo by Scott Olson/Getty Images
Many have decried what we've lost during this past year. Indeed, the issues are many and complex. Yet we've also seen reductions in environmental damage (including noise pollution) and increased savings. We also have a greater awareness of how factory farming helps viruses proliferate. And, despite the obvious challenges of earning a living with so many businesses and industries shuttered, this time has afforded some an opportunity to reconnect with their family.
Study co-author Jessica Hernandez Ortiz says this research could inspire new avenues of addressing mental health issues in children.
"Our findings underline the importance of the family environment and Latinx collectivist values of community connection for promoting child resilience and brings into stark focus the possibility that school environments may exacerbate mental health difficulties. Removal from that context into a less pressured environment immediately and positively impacts mental health."
Since the study ended shortly into the pandemic, the novelty of family togetherness could have diminished as families became economically strained and realized that spending all their time together was more taxing than initially imagined. That said, humans are social animals that require regular contact with family and peers. The latter group might not have been available, but at least for some children, their families filled in the gaps, especially for those that did not thrive in a traditional school environment.
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