Microdosing for mental health

The following are the latest statistics available from the National Institute of Mental Health Disorders, part of the National Institutes of Health:
  • Mental health disorders account for several of the top causes of disability in established market economies, such as the U.S., worldwide, and include: major depression (also called clinical depression), manic depression (also called bipolar disorder), schizophrenia, and obsessive-compulsive disorder.
  • An estimated 26% of Americans ages 18 and older (about 1 in 4 adults) suffers from a diagnosable mental disorder in a given year.
  • Many people suffer from more than one mental disorder at a given time. In particular, depressive illnesses tend to co-occur with substance abuse and anxiety disorders.
  • Approximately 9.5% of American adults ages 18 and over, will suffer from a depressive illness (major depression, bipolar disorder, or dysthymia) each year.
    • Women are nearly twice as likely to suffer from major depression than men. However, men and
      women are equally likely to develop bipolar disorder.
    • While major depression can develop at any age, the average age at onset is the mid-20s.
    • With bipolar disorder, which affects approximately 2.6% of Americans age 18 and older in a given year — the average age at onset for a first manic episode is during the early 20s.
  • Most people who commit suicide have a diagnosable mental disorder — most commonly a depressive disorder or a substance abuse disorder.
    • Four times as many men than women commit suicide. However, women attempt suicide more often than men.
    • The highest suicide rates in the U.S. are found in Caucasian men over age 85. However, suicide is also one of the leading causes of death in adolescents and adults ages 15 to 24.
  • Approximately 1% of Americans are affected by schizophrenia.
    • In most cases, schizophrenia first appears in men during their late teens or early 20s. In women, schizophrenia often first appears during their 20s or early 30s.
  • Approximately about 18% of people ages 18- 54 in a given year, have an anxiety disorder in a given year. Anxiety disorders include: panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and phobias (social phobia, agoraphobia, and specific phobia).
    • Panic disorder typically develops in late adolescence or early adulthood.
    • The first symptoms of OCD often begin during childhood or adolescence.
    • GAD can begin at any time, though the risk is highest between childhood and middle age.
    • Individuals with OCD frequently can have problems with substance abuse or depressive or eating disorders.
    • Social phobia typically begins in childhood or adolescence.

Depression:

Overview
Depression affects more than 264 million people of all ages globally. The World Health Organization ranks depression as one of the most debilitating diseases to society.
It is the leading cause of disability worldwide and the psychiatric diagnosis most commonly associated with suicide, which accounts for nearly 800,000 deaths globally each year.
Individuals suffering from depression may face an inability to manage life’s demands and maintain social connections, affecting all aspects of their experiences, from school and employment to relationships and overall quality of life.
Treatment-resistant depression is a chronic condition that places an increased emotional, functional and economic burden on the individual, their loved ones and society. It is also associated with greater morbidity, higher health care costs and various comorbid conditions.
In the United States, approximately 10% of the adult population has been diagnosed with Major Depressive Disorder (MDD) in the past 12 months, and the yearly economic burden of MDD is estimated to be $210 billion.
Although effective pharmacotherapies for depression are available, these drugs have limited efficacy, produce adverse effects, and are associated with patient adherence problems.
While any patients with depression showed reduced or remitted symptoms after treatment with existing pharmacotherapies, approximately 30% to 50% of patients did not respond fully and as many as 10% to 30% of patients were considered treatment-resistant, resulting in average effects that were only modestly larger than the effects of placebo.
Most of the current pharmacotherapies for MDD, including the widely used selective serotonin reuptake inhibitors (SSRIs), increase levels of brain monoamine neurotransmitters such as serotonin and norepinephrine (typically by blocking reuptake).
A growing body of evidence suggests that newer ketamine-like medications exert therapeutic efficacy in MDD through effects on glutamate neurotransmission.
Ketamine hydrochloride, a nonselective N-methyl-d-aspartate receptor antagonist, is the most well-researched of these newer medications. Several studies have demonstrated the efficacy of a single ketamine infusion in rapidly (within hours) reducing depression symptoms and, when effective, lasting from a few days to about 2 weeks. However, ketamine has high abuse liability, and its administration involves moderate physiological risk that requires medical monitoring.
The combined serotonergic and glutamatergic action of psilocybin and the preliminary evidence of the antidepressant effects of psilocybin-assisted therapy (among patients with life-threatening cancer or patients with treatment-resistant depression) indicate the potential of psilocybin-assisted therapy as a novel antidepressant intervention.
Moreover, psilocybin has lower addiction liability and toxic effects compared with ketamine and is generally not associated with long-term perceptual, cognitive, or neurological dysfunction.
The substantial negative public health impact of MDD underscores the importance of conducting more research into drugs with rapid and sustained antidepressant effects. Current pharmacotherapies for depression have variable efficacy and unwanted adverse effects. Novel antidepressants with rapid and sustained effects on mood and cognition could represent a breakthrough in the treatment of depression and may potentially improve or save lives.
The findings from a new study suggest that psilocybin may be effective in the much wider population of patients who suffer from major depression than previously appreciated.
“The magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market,” says Alan Davis, Ph.D., adjunct assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Because most other depression treatments take weeks or months to work and may have undesirable effects, this could be a game changer if these findings hold up in future ‘gold-standard’ placebo-controlled clinical trials.” The published findings cover only a four-week follow-up in 24 participants, all of whom underwent two five-hour psilocybin sessions under the direction of the researchers.
“Because there are several types of major depressive disorders that may result in variation in how people respond to treatment, I was surprised that most of our study participants found the psilocybin treatment to be effective,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Center for Psychedelic and Consciousness Research. He says the major depression treated in the new study may have been different than the “reactive” form of depression in patients they studied in the 2016 cancer trial. Griffiths says his team was encouraged by public health officials to explore psilocybin’s effects in the broader population of those with major depressive disorder because of the much larger potential public health impact.

 

The Johns Hopkins Psilocybin Study

In a small study of adults with major depression, Johns Hopkins Medicine researchers report that two doses of the psychedelic substance psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms, with most participants showing improvement and half of study participants achieving remission through the four-week follow-up.
Psilocybin (in high doses) produces visual and auditory hallucinations and profound changes in consciousness over a few hours after ingestion. In 2016, Johns Hopkins Medicine researchers first reported that treatment with psilocybin under psychologically supported conditions significantly relieved existential anxiety and depression in people with a life-threatening cancer diagnosis.
Now, the findings from the new study, published Nov. 4 in JAMA Psychiatry, suggest that psilocybin may be effective in the much wider population of patients who suffer from major depression than previously appreciated.
“The magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market,” says Alan Davis, Ph.D., adjunct assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
“Because most other depression treatments take weeks or months to work and may have undesirable effects, this could be a game changer if these findings hold up in future ‘gold-standard’ placebo-controlled clinical trials.”
“Because there are several types of major depressive disorders that may result in variation in how people respond to treatment, I was surprised that most of our study participants found the psilocybin treatment to be effective,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Center for Psychedelic and Consciousness Research.
He says the major depression treated in the new study may have been different than the “reactive” form of depression in patients they studied in the 2016 cancer trial. Griffiths says his team was encouraged by public health officials to explore psilocybin’s effects in the broader population of those with major depressive disorder because of the much larger potential public health impact.
For the new study, the researchers recruited 24 people with a long-term documented history of depression, most of whom experienced persisting symptoms for approximately two years before enrolling in the study. The average age of participants was 39; 16 were women; and 22 identified themselves as white, one person identified as Asian and one person identified as African American.
Participants had to taper off any antidepressants prior to the study with the help of their personal physician to ensure safe exposure to this experimental treatment.
Thirteen participants received the psilocybin treatment immediately after recruitment and after preparation sessions, and 11 participants received the same preparation and treatment after an eight-week delay.
Treatment consisted of two psilocybin doses given by two clinical monitors who provided guidance and reassurance. The doses were given two weeks apart between August 2017 and April 2019 at the Johns Hopkins Bayview Medical Center Behavioral Biology Research Building. Each treatment session lasted approximately five hours, with the participant lying on a couch wearing eyeshades and headphones that played music, in the presence of the monitors.
All participants were given the GRID-Hamilton Depression Rating Scale – a standard depression assessment tool – upon enrollment, and at one and four weeks following completion of their treatment. On the scale, a score of 24 or more indicates severe depression, 17–23 moderate depression, 8–16 mild depression and 7 or less no depression. At enrollment, participants had an average depression scale rating of 23, but one week and four weeks after treatment, they had an average depression scale score of 8. After treatment, most participants showed a substantial decrease in their symptoms, and almost half were in remission from depression at the follow-up. Participants in the delayed group didn’t show decreases in their symptoms before receiving the psilocybin treatment.
For the entire group of 24 participants, 67% showed a more than 50% reduction in depression symptoms at the one-week follow-up and 71% at the four-week follow-up.
Overall, four weeks post-treatment, 54% of participants were considered in remission – meaning they no longer qualified as being depressed.
“I believe this study to be a critically important proof of concept for the medical approval of psilocybin for treatment of depression, a condition I have personally struggled with for decades,” says entrepreneur and philanthropist Tim Ferriss, who supported the funding campaign for this study. “How do we explain the incredible magnitude and durability of effects? Treatment research with moderate to high doses of psychedelics may uncover entirely new paradigms for understanding and improving mood and mind. This is a taste of things to come from Johns Hopkins.”
Griffiths, whose research with psilocybin, begun in the early 2000s, was initially viewed by some with skepticism and concern, says he is gratified by Johns Hopkins’ support and heartened by the dozens of startups and research labs that have followed suit with their own research. He says numerous companies are now actively working to develop marketable forms of psilocybin and related psychedelic substances.

 

Psilocybin vs. Placebo (SSRI)

Scientists at UC San Francisco and Imperial College London found that a general process through which psychedelics may act therapeutically on the brain – possibly alleviating depression and other psychiatric conditions – can be furthered by fixed patterns of thinking.
By analyzing the fMRI brain scans from nearly 60 people who had participated in two psilocybin microdosing trials, they found that the participants were less emotionally avoidant, and their cognitive functioning had seemed to improve.
All the participants received the same type of psychotherapy in addition to the drugs.
In the first trial, all the participants had treatment-resistant depression and knew they were being given psilocybin.
In the second trial, the participants were depressed but not as severely, and they were not told whether they had been given psilocybin or a placebo – escitalopram, which is an SSRI antidepressant.
The scans, conducted before and after treatment, demonstrated that the psilocybin microdosing treatment reduced connections within brain areas which are connected in depression, including the default mode, salience, and executive networks. They additionally increased connections to other regions of the brain which were not formerly well integrated.

“For the first time we find that psilocybin works differently from conventional antidepressants – making the brain more flexible and fluid”

The improvement in depression symptoms lasted until the study ended three weeks after the second psilocybin dose.
Interestingly, there were no changes seen in the brains of those who received escitalopram, suggesting that psilocybin acts differently on the brain than SSRIs (antidepressants).
A hypothesis for these positive changes can be that the psilocybin briefly disrupts connections in the brain, giving them a chance to reform in new ways in the ensuing days and weeks.
Psilocybin and other serotonergic psychedelics like ayahuasca affect 5-HT2A receptors, which are plentiful in brain networks which become overactive in depression.
Robin Carhart-Harris, PhD, the senior author of the study, said: “In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a carry-over of the acute drug action.”
Carhart-Harris, Professor of Neurology, Psychiatry, and Behavioural Sciences added: “We don’t yet know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this. We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.”
David Nutt, DM, head of the Imperial Centre for Psychedelic Research, said: “For the first time we find that psilocybin works differently from conventional antidepressants – making the brain more flexible and fluid, and less entrenched in the negative thinking patterns associated with depression.
“This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments.”

 

Anxiety:

Social phobia is marked by a persistent fear of embarrassment or humiliation in social situations.
Anticipatory anxiety and avoidance occur when an individual is under scrutiny during public speaking or other public activities. This highly prevalent and chronic disorder significantly impairs psychosocial functioning, with pharmacological and psychosocial treatments showing limited results.
However, psychedelic-assisted therapy used in combination with psilocybin may offer an additional treatment option for patients who fail to respond to conventional treatments.

 

Psilocybin study on social anxiety in adolescents
A study done in 2021 reported on a 16-year-old male patient treated in a psychiatric clinic with the symptoms of social distancing, increased intensity of anxiety, and poor school performance. He experienced learning disabilities, lack of motivation for schoolwork with poor academic results, and isolation from his peers and teachers.
The transfer to a new school failed to bring about any improvement.
The adolescent started attending a psychotherapeutic group but found it difficult to communicate with other members and express his feelings, so he often avoided sessions due to anxiety.
He occasionally consumed marijuana, which failed to reduce anxiety and improve his functioning. After being offered psilocybin by a friend, he consumed two grams of Psilocybe mushrooms, corresponding 20 to 30 mg of the substance, on three separate occasions over an 18-month period.
The patient described the effect as a feeling of sublimity and enlightenment. After this experience, he more frequently participated in group activities, communicated better with other group members, expressed emotions without inhibition, and felt less anxious.
The patient’s feelings of “connection with people around him” and “sublimity” can be explained by the activation of certain neural systems of the brain, particularly the so-called seeking systems, which play a role in fighting depression and anhedonia. In other words, people are motivated to accept pleasure and avoid discomfort.
These neuroanatomical changes form the basis for opioid addiction. Once this system is activated, the experience of “solving the problem of anhedonia” remains in the memory engrams and is quickly and easily accessible.
Psilocybin increases the concentration of extracellular serotonin and dopamine in the nucleus accumbens and the median prefrontal cortex. This system, particularly nucleus accumbens, is an important part of the “seeking system.”
In addition, the medial bundle of the forebrain, which is connected to the nucleus accumbens and is located in the immediate vicinity of the median prefrontal cortex, could be simultaneously activated.
Accordingly, even if these neural areas are stimulated only once or twice, in the patient’s memory an impression is created that “everything will be fine.”
The guilt that the patient experiences helps him to refrain from taking this substance again. However, he is aware that by consuming psilocybin his problem was “magically solved.” The feeling that “everything can be fine” continues to exist only at the level of an idea due to the stimulation of the mentioned neural circuits and nucleus. The same system is also stimulated by frequent psychotherapeutic treatment.
During psychotherapeutic treatment, a sense of satisfaction arises from repeated conflict resolution or pleasure due to identifying with the psychotherapist.
In addition, separation and reuniting subconsciously suggest that although the patient is alone, he or she will be reconnected with his favorite object. In this way, a so-called safe attachment is established, which creates new collaterals and dendritic shoots in the mentioned neural pathways.
Ideally, completed psychotherapy enhances “collateral and dendritic” neural pathways that increase patient’s confidence in other people, enabling him or her to function in everyday life.
Conventional therapy often shows limited effectiveness in resolving the symptoms of anxiety and depression. The present case highlights the potential benefit of psilocybin when used concomitantly with psychotherapy led by an experienced therapist in adolescents with neurotic personality structures and generalized anxiety disorder and social phobia.
To date, only a few double-blind studies have investigated the use of psilocybin in psychiatric treatment, with a sample size of fewer than 200.
Further research is warranted to determine the value of psychedelic substances in psychiatry.
Based on the studies to date, the European Medicine Agency and Food and Drug Administration have approved a multicenter multinational trial of psilocybin that began in early 2019, with the first results expected in the near future.

PTSD:

Overview
After a person experiences a traumatic or life-threatening event such as a natural disaster, a car accident, or military combat, they may develop PTSD. While it is typical to have anxiety about the traumatic event weeks or months after it happens, people with PTSD find it difficult to perform daily functions for an extended period of time. Sometimes certain treatments can cure PTSD, while other times it could go away on its own.

 

PTSD Treatment Types
There are typically two types of treatment for PTSD.
One is psychotherapy, which is the use of psychological methods usually based on regular and personal interaction to help a person change in the ways that he or she would like. The main type of psychotherapy used to help patients with PTSD is cognitive processing therapy. The goal of this type of therapy is to teach a patient with PTSD how to evaluate and change the upsetting thoughts that they are having in the wake of their trauma. Therapists believe that when a person changes their thought patterns, he or she can change the way he or she feels. If a patient has experienced a traumatic event, psychotherapy can change the way he or she thinks about or sees the world. Patients often blame themselves for what happened, and therapists help patients try to look at their experiences from a new perspective.
Most of the time, patients are taken to an office where they are met by a mental health professional. In other situations, patients attend group therapy sessions in which all the patients present have PTSD.
The second way to treat PTSD is with antidepressant medication. Antidepressants affect the hippocampus, an area of the brain involved in memory formation, to counteract the effects of stress.
There are two types of antidepressants: selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
The four main antidepressants effective for treating PTSD are sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac)—all SSRIs—and venlafaxine (Effexor), an SNRI.
Additionally, three antipsychotic drugs are sometimes used to help treat PTSD: olanzapine, quetiapine, and risperidone.
Treating PTSD with psilocybin
While therapy, antidepressants, and antipsychotics can help some patients, these methods often fall short.
Studies have suggested that antidepressants do not work well for people who have had multiple traumas over the course of years or chronic PTSD.
A new study found that the antipsychotic risperidone worked no better than a placebo in alleviating typical PTSD symptoms in patients who had the disorder long-term or who continued to experience symptoms after being treated with antidepressants.
Because these drugs can also cause intolerable side effects, many patients are left to experience PTSD with no sign of relief. Many of these patients turn to substance abuse, develop anger management issues, or commit suicide. A study analyzing data from the National Comorbidity Survey showed that out of six anxiety diagnoses, PTSD was significantly associated with suicide attempts.
There is some evidence in animal studies to show that psilocybin may act by stimulating nerve cell regrowth in parts of the brain responsible for emotion and memory.
A 2013 study from the University of South Florida  that psilocybin stimulates neurogenesis—the growth and repair of brain cells in the hippocampus, which is the brain’s center for emotion and memory. In the study, mice that were given psilocybin overcame fear conditioning far better than mice that were given a placebo. The study supported the hypothesis that psilocybin can help break the traumatic cycle that occurs in patients with PTSD.
Stephen Ross, MD., a psychiatrist at NYU Langone, conducted a study on terminally ill cancer patients, and found that one-time treatment with psilocybin very quickly brought relief from distress that had lasted more than 6 months in 80 percent of study subjects.
In Dr. Ross’s study, half of the participants were randomly assigned to receive psilocybin. The rest received a control drug of niacin, which is known to produce a “rush” similar to that associated with a hallucinogenic drug experience. Halfway through the seven-week study period, all of the participants switched treatments. Neither the researchers nor the patients knew which patients had first received psilocybin or which received the control. All of the patients, mostly women, had advanced gastrointestinal, blood, or breast cancers and had been diagnosed as having serious psychological distress related to their disease.
Patients noted that after being treated with psilocybin, they felt their quality of life improve. They noted that they wanted to engage more with external activities, had more energy, experienced improved relationships with their family members, and performed better at work. The researchers concluded that if psilocybin could reduce psychological distress in terminally ill cancer patients, it could apply to less extreme medical conditions related to psychological distress as well.b
Dr. Ross says that the findings “…have the potential to transform the care of cancer patients with psychological and existential distress, but beyond that, it potentially provides a completely new model in psychiatry of a medication that works rapidly as both an antidepressant and anxiolytic and has sustained benefit for months.” Dr. Ross has hope that the drug will become legal in the next five years. “If larger clinical trials prove successful, then we could ultimately have available a safe, effective, and inexpensive medication—dispensed under strict control—to alleviate the distress that increases suicide rates among cancer patients.”

 

ADHD:

Overview
Besides mood disorders, another therapeutic area where psychedelics might be applied is the treatment of attention deficit and hyperactivity disorder (ADHD).
Attention deficit hyperactivity disorder (ADHD) is defined as a neurodevelopmental disorder that features “a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development”, which may greatly impact one’s quality of life.
The symptoms typically include problems with cognition and executive functions, such as focusing and maintaining attention, finding motivation for doing work, and issues with learning and memory, but the disorder also features mood disturbances and impulsivity.
Hyperactivity-impulsivity can also manifest itself as: frequent fidgeting, running or climbing, feeling restless and having difficulty staying seated, excessive talking, and frequent interruption of others.
ADHD current medication
Current first-line treatment for ADHD are stimulant medications, which are safe and effective in the short-term when taken in the prescribed doses.
These stimulants have poor efficacy in the long-term, however, as they can lead to unpleasant side effects and withdrawal-like symptoms. It is also estimated that in about 30% of ADHD patients, stimulants are either not effective enough, or the adverse effects cannot be tolerated.

 

Microdosing for ADHD
While research on ADHD is still scant, it is slowly picking up and preliminary anecdotal evidence shows promising results.
A microdosing approach to administering psychedelics might be more suitable for this purpose, as this does not involve any type of subjective experience. It nevertheless offers cognitive and emotional benefits which make it more appropriate for every-day tasks. This is similar to how one would take chronic stimulant medication for ADHD.
In fact, Albert Hoffmann himself, the Swiss chemist who synthesized LSD, was pro using small doses of the psychedelic as an alternative to Ritalin. James Fadiman, a pioneer of microdosing research, has also been reported to suggest the use of microdoses as an “extremely healthy” alternative to Adderall.
Psychedelics are one of the safest classes of “drugs” known, as they have negligible effects on the body, cannot cause death due to purely physical complications or an overdose, nor do they result in any long-lasting physiological changes. Psychedelics also have very low potential for addiction, as they are not physically rewarding.
The intensity of the ‘trip’ experience nevertheless carries inherent risks. Higher doses might increase the occurrence of psychological adverse effects. This can be the experience of a ‘bad trip’ accompanied by confusing thoughts and unpleasant emotions.
Although the incidence of unwanted psychological events is greatly reduced when there is a proper set and setting in place, a potentially safer route of using psychedelics is microdosing. Microdosing does not intoxicate the user and allows for going about everyday tasks as one normally would.

How do psychedelics affect the brain?

Changes in neurotransmitter levels
Classical psychedelics, including LSD, DMT, and psilocybin, exert their effects mainly through the release of serotonin, but they also affect the levels of other neurotransmitters, like dopamine and glutamate.

 

Serotonin
Activating serotonin receptors in the frontal regions of the brain can enhance certain brain functions that are involved in executive functioning, attention, and memory.
As ADHD features as dysfunctions in some of these frontal cerebral regions, psychedelics might be especially beneficial for this attention disorder.

 

Dopamine
On top of that, increasing dopamine might be involved in the enhancement of learning and memory mechanisms, and increasing motivation for goal-directed behavior. Difficulties with learning, motivation, and executing goals, is a crucial impairment in ADHD that may seriously impair quality of life.
Increasing dopamine levels can act to diminish some of these symptoms.
In addition, brain imaging studies show that repeated exposure to psychedelics leads to a longer-lasting increase in dopamine receptors. Since ADHD patients have a deficit in their dopaminergic system, psychedelics seem like a good fit to improve dopamine levels.

 

Glutamate
Glutamate is the major excitatory neurotransmitter in the brain, so an increase in its activity might contribute to the greater connectivity between different brain areas, as well as to greater neuroplasticity and improved learning and memory.
This might also constitute a potential match with ADHD, since the disorder includes impairments in the connections and thus, communications, between some brain areas.

 

Changes in brain function
The use of psychedelics can also lead to functional changes in some areas of the brain, mainly frontal regions and parts of the limbic system. As those brain areas are generally involved in emotion regulation, memory, learning and executive functions, altering their function is crucial for ADHD.

 

Amygdala
Psilocybin has been shown to reduce activity of the amygdala – a part of the limbic system, mainly involved in the experience of fear and negative emotions. Reducing activity in this region might be beneficial for mood disorders like depression, but can also benefit those that have disorders like ADHD, since ADHD also features hyperactivity in the amygdala.

 

Cortico-striatal-thalamo-cortical (CSTC) circuit
Psychedelics also act on the so-called cortico-striatal-thalamo-cortical (CSTC) circuit, which is a feedback loop of interconnected brain regions in both frontal and deeper parts of the brain, which regulate executive functions, like learning and memory.
This circuit is also impaired in ADHD, leading to some of the executive dysfunctions seen in the disorder. By altering its activity, psychedelics might contribute to normalizing the functioning of this feedback loop and thus, relieve some of the symptoms in ADHD.

 

Changes in brain structure
With long-term and repeated use of psychedelics, the structure of certain brain areas might change with time. This might point to a potentially longer-lasting therapeutic effect compared to current stimulant medication, but this would have to be more explicitly tested in future studies.

 

Levels of BDNF
Some research has found that psychedelic use increases the levels of brain-derived neurotrophic factor (BDNF). This trophic factor plays a role in the growth and development of neurons, and promotes the expression of certain genes associated with neural plasticity. Brain plasticity, also known as neuroplasticity, is a term that refers to the brain’s ability to change and adapt as a result of experience. This might be particularly useful for learning, and thus also be beneficial for ADHD patients.

 

Brain Plasticity
The same study demonstrated that psychedelics are able to promote structural brain plasticity by increasing the number of places in neurons where they can communicate with other neurons (called dendritic spines).
This effect is also achieved when administering amphetamines like Adderall.
Psychedelics, however, were also able to increase the density of these dendritic spines, while amphetamine could not. This might point to a potentially similar working mechanism in both psychedelics and stimulants and suggest that psychedelics might be at least as effective as stimulant medication for ADHD treatment.

 

Scientific research: the effects of microdosing on ADHD

Rigorous scientific research that includes controlled experimental trials for the effects of microdosing on ADHD patients is lacking. Some anecdotal evidence, however, points to the usefulness of psychedelics in treating the attention deficit disorder.
Many of these effects are self-reported by microdosers in observational studies, and are not yet confirmed by placebo-controlled experimental trials, so they should not be taken as a fact. Nevertheless, these studies do point to a possible beneficial effect of psychedelics on ADHD patients.

 

Studies in Healthy Volunteers

It is quite well-known that microdosing psychedelics can be helpful with productivity, attention, creativity, and learning, and has been used by silicon-valley professionals to boost their performance at work.
Research into microdosing in healthy volunteers also finds that psychedelics are associated with improvements in cognition, attention and focus. Participants observed a decrease in mind wandering and distractibility, and saw improvements in processing and expressing their emotions, thus improving mental health.

 

Psychedelics superior to stimulant meds?

A research study done by the Marine Corps for the search of new performance enhancing drugs concluded that psychedelic microdoses might be superior to ADHD medications for cognition enhancement, and do not produce as many negative effects.
These results are yet to be confirmed in other studies, however.

 

Studies in ADHD patients
Unfortunately, as also mentioned above, only anecdotal research with ADHD patients is currently available. Nevertheless, many people diagnosed with ADHD share their positive experiences with microdosing online, and this data also reveals the potential use of psychedelics in treating this disorder.

 

Less side effects
Observational studies of microdosing volunteers illustrate that there is a specific interest in microdosing from ADHD patients. These studies reveal that a large percentage of microdosers are diagnosed with the disorder and want to reduce the side effects they experience from their stimulant medication by combining or replacing it with psychedelic microdoses.
In another observational self-report study, the researchers found a sub-group of participants who microdosed specifically to relieve their ADHD symptoms, and those participants reported improvements after microdosing, with less side effects compared to stimulants.

 

No crash after dose wears out
A recently published paper conducting an online questionnaire among users of psychedelic-themed websites found that those diagnosed with ADHD consistently rated psychedelic microdoses as more effective than conventional stimulant medications.
The authors of the paper states that this might be due to the lack of unwanted effect connected to microdosing – these do not produce a ‘crash’ after their effect has worn off and do not require daily dosing, like stimulants do, which might act to further decrease any instances of side effects.

Grief:

How Grief Manifests Psychologically and Physiologically
Grief manifests in different ways and varying levels of severity depending on the person, the situation, and the intensity of the trauma.
There are, however, some psychological and physiological effects that are common in most people who are grieving the loss of someone they love.
The psychological effects of grief and loss are fairly well-known. They include emotional ups and downs ranging from sadness to anger to numbness, feelings of detachment from others, and a loss of personal meaning or faith. Some people experiencing grief may feel survivor’s guilt, or they may feel abandoned by the person they lost. Grief can also cause a person to undergo repeated stress, worry, and anxiety.
Although we often think about those psychological effects of grief and are probably all familiar with them to some extent, we may be less familiar with the role grief also plays a physiological in our bodies. Our minds and bodies are closely connected, and as we process our feelings, we often also experience unpleasant physical sensations. For instance, people may experience chronic pain or physical illness as they process the death of a loved one.
They may experience symptoms such as: chronic headaches, fatigue, digestive upset, insomnia and lack of appetite, just to name a few.
Psychologists have found that grieving patients often suffer from higher levels of stress and may develop mental health conditions such as anxiety, depression, or PTSD.

 

Additional resources:

https://maps.org/2014/10/02/using-psychedelic-drugs-to-treat-mental-disorders/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753862/
file:///C:/Users/Kathy/Downloads/I.Totomanova_Bachelor.Thesis.pdf
https://clinicaltrials.gov/ct2/show/NCT04501653