50 shades of research for psychedelics (Chapters 3-5)


Expert Pharmacologist
Jul 6, 2021
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Chapter 3. It is still unknown for what reason psychedelics cause such a powerful trip.

In a recent study, British researchers used brain imaging techniques to assess how the brain looks under the influence of LSD compared to a placebo. They found big differences between LSD and placebo: brain images under the influence of LSD show much greater connectivity between different parts of the mind.

This may help explain visual hallucinations because it means that different parts of the brain are communicating during an LSD trip, not just the visual cortex deep in the brain.

This, according to the researchers, may show not only why psychedelic drugs cause hallucinogenic experiences, but also why they can help people. In many mental disorders, the brain can be seen as entrenched in pathology, causing basic behaviors to become automated and rigid. Consistent with their «entropic» effect on cortical activity, psychedelics can disrupt such disorders by destroying the activity patterns on which they are based.

«The idea of psychedelics is to try to shake up the brain a little bit. To try to give the suffering person a new perspective and try to change their behavior»
— explained Rucker, who was not involved in the brain imaging study.

This is one of the few studies to analyze how the mechanical and physical effects of psychedelics on the brain can help patients. Other studies are unclear about the exact mechanisms, but they suggest that classic psychedelics affect serotonin and, in the case of LSD, dopamine receptors in ways that may help lift people's moods.

According to Garcia-Romeu of Johns Hopkins University, it's likely that these physical factors work together with spiritual experiences to help people. They're all happening at the same time.

«It's not like right now when I'm talking to you, there is no activity in the temporal lobe of your brain that is both chemical and electrical at the same time. It's all happening at the same time. But what we are experiencing is obviously primary. You are hearing my voice, so your subjective experience is centered on what is happening in your field of consciousness, not on the electrical and neurochemical signals in your brain»
— says Garcia-Romeu

«My personal opinion is that the reason these types of conditions are so difficult to treat from a standard medical standpoint is because there is more to them than just a disease» — Garcia-Romeu said, pointing to addiction as an example.

«Often we have to do real therapy. We can't just give them a pill to get rid of their problems. We need to really get into things like *****hood trauma, current life situations and relationships and whether those relationships are healthy or toxic and how people feel about themselves» — he added.


Kumar works closely with cancer patients as a psychologist at the South Florida Cancer Center. He believes that psychedelic treatment can be a great boon to his work with late-stage cancer patients who struggle with crippling end-of-life anxiety that often cannot be cured.

Patients with advanced cancer often lack healthy coping tools that often require a lifetime of practice to achieve — healthy stress management, a set of spiritual beliefs that can be comforting, or an understanding or sense of purpose and meaning in their lives. As a late-stage cancer patient, you are suddenly faced with a situation in which you have little time, your physical health is at risk, your cognition is in jeopardy, and there just isn't much time to put a lot of things in place. Psychedelics are a very quick way to induce very meaningful changes in people.

Chapter 4. Per aspera ad astra.
However, as promising as the studies are now, they are still quite preliminary. The big problem with the studies done so far is that they tend to have quite small sample sizes, usually less than 60 participants. There are other methodological problems: first, some studies don't test the efficacy of the drug compared to placebo and don't have a strong control group.

For example, the Johns Hopkins University smoking study found that 80% of participants abstained from smoking for six months after psilocybin treatment — an astounding result. But it had only 15 participants, 14 of whom were white. And there was no control group or placebo, so it's unclear whether psilocybin or some other variable — such as the psychotherapy that accompanied psilocybin — produced the results.


These tiny sample sizes currently represent a huge hole in research. As Michael Slezak writes, small studies can be very misleading: they can exaggerate the benefits of a treatment or perhaps suggest benefits that aren't actually there. So once studies of psychedelic substances scale up to larger samples, the positive results for these drugs may become much less impressive or even disappear altogether. We just don't know yet.

«I don't know if it reaches 80 percent. That's an awful lot. But I expect they can demonstrate good efficacy and safety»
Grob, a researcher at the University of California, Los Angeles, said of the smoking study.

In addition, the researchers would like to address many other questions:
  • How will different doses of different psychedelic drugs perform under different conditions?
  • How long do the benefits last weeks, months, years, decades?
  • Are there other mental disorders, such as eating disorders, for which psychedelic treatment may be beneficial?
  • Are some benefits reduced or eliminated for people who are not spiritual or religious?
Perhaps the biggest of these questions is how long the effects of psychedelic psychotherapy last. For example, one review of studies of psychotherapy with LSD and alcoholism found no statistically significant effects after 12 months. A recent study of the effects of psilocybin on depression concluded that the benefits of taking psilocybin had significantly diminished after three months, although some improvement did remain.

A recent series of studies of the effects of psilocybin treatment on cancer-related anxiety and depression at the end of life have produced more promising results, showing significant increases in measures of anxiety, depression and well-being after at least six months. And because the sample sizes were larger — one study had 51 participants, the other had 29 — they're a little more reliable, although the sample sizes are still quite small.


Perhaps the most promising study examining duration is one conducted by Rick Doblin in 1991 following a study conducted in 1962. In the 1962 study, called the Good Friday Experiment, half of the participants were given a placebo and the other half were given psilocybin while watching. a Good Friday sermon.

Decades later, Doblin followed up with these participants and found that all of those who received psilocybin reported that the experiment
«made an extremely valuable contribution to their spiritual lives» while none of those who received placebos did.

But the follow-up evaluation was based on self-reports from the original participants, which was a small sample of 20 people, only 16 of whom participated in the follow-up. Again, stricter standards and a larger sample size are needed to know if the results will hold true.

Another challenging aspect of the study is to provide double-blindness, a research method that ensures that neither the researchers nor the participants know what medications they are being prescribed. The idea is that knowledge could affect the results if participants act differently or researchers treat participants differently depending on the drug they receive. Obviously, this is difficult when the effects of psychedelic drugs are so obvious.

Rucker, of King's College London, said providing double-blindness is a big challenge. But he expects researchers to find ways around the problem — such as using placebos, which are psychoactive but not known to provide certain benefits — and replicate the results sufficiently with different methodologies to compensate for the lack of pure double-blindness.


Although hallucinogens are reasonably safe for patients who have been pre-screened and are taking them in a controlled clinical setting, they are not without risk.

A review of studies of classic psychedelics found, for example, stories of people trying to fly and falling from tall buildings. And, the researchers said, there's always the risk of people trying to roam the streets in cars, trying to drive and getting into other dangerous situations when they're too high to know anything.

There is also a risk that people, especially those predisposed to psychotic states, will have traumatic experiences that will permanently damage them psychologically. This is of particular concern with classic psychedelic drugs, which activate receptors associated with schizophrenia, psychosis and other psychotic states.

«Some people probably shouldn't take these drugs at all. We do a very careful job of excluding those people from our research. And that's why, even though we've given drugs — fairly high doses of psilocybin — to people here in the lab, we've never had any serious events. where people continue to have psychotic illness post facto» — said Garcia-Romeu of Johns Hopkins University.

Aside from these two big risks, psychedelic drugs are actually not particularly dangerous. They are not addictive, and LSD and psilocybin in particular do not carry a significant risk of overdose.


A review of a 1999 study found that they do not cause personality changes or other chronic psychological problems. A 2005 study found that long-term religious use of peyote does not appear to have negative cognitive or psychological effects on Native Americans.

One study of psilocybin and a review of psychedelic studies found no serious physical effects other than dizziness, headaches, and fatigue for several days after using the drug.

However, the risks involved are why
researchers emphasize that these drugs should only be used in controlled clinical settings. So far, studies have found psychedelic drugs to be beneficial only in settings where trained experts monitor the process to see if things go wrong. And researchers expect that if the drugs eventually move beyond research institutions and into the real world, limiting their use to controlled clinical environments will be critical to their success.

«First of all, it's important to maintain strict safety parameters. Without that, the work really can't proceed» — said Grob of the University of California, Los Angeles.

Chapter Five. Final.
Currently, psychedelic research is focused on really sick people. But there is no obvious reason to believe that the benefits are limited exclusively to this group. After all, almost everyone faces some form of anxiety related to death. Psychedelics can help alleviate that anxiety.

The obvious uses for psychedelics are people who are currently dying with an incurable diagnosis. But birth is an incurable diagnosis. And people's lives might be better off if they lived outside the valley of the shadow of death.

Some studies of psychedelics have supported this idea. For example, one study conducted in 2011 by Johns Hopkins University researchers found that people who reported mystical experiences induced by psilocybin showed greater openness in personality tests. Other Johns Hopkins studies conducted in 2008 and 2011 found that participants in psilocybin sessions reported higher life satisfaction and positive effects on mood, especially among those who described the most intense mystical experiences.


Again, the researchers emphasize that these studies are preliminary and do not support uncontrolled personal use. But they suggest that many people could potentially benefit from psychedelic therapy, even if they don't have a severe diagnosed disorder or condition.

The initial research on psychedelics is so promising that many researchers and experts are taking it very seriously and are actively pursuing additional research. Unfortunately, much of the work is hampered by regulatory barriers.

Classic psychedelics are classified as Schedule 1 substances, which means they are considered by the federal government to have no medical use and a high potential for *****. There are unique constraints associated with this schedule, so psychedelic research, in addition to receiving Food and Drug Administration approval like other clinical trials, must meet standards set by the Drug Enforcement Administration. All of this can add months or years to a study, with higher financial costs.

Another major obstacle is funding. In the 1950s and 1960s, the federal government spent a significant amount of money to fund research on psychedelics. So, LSD was something that you could become a psychiatrist in the 1950s, submit a grant to the government and get a lot of money to do research to see what the effects of this drug were or how it could be used the*****utically and clinically.

Today, the story is different. After the widespread ***** of psychedelics in the 1960s, a huge cultural and political backlash against these drugs led to the withdrawal of most federal funding. Now federally funded research on psychedelics focuses on the dangers of these substances rather than their potential benefits. After all, the feds don't even recognize that these drugs have any medical value.

Usually, pharmaceutical companies can make up the funding gap. But the pharmaceutical industry has no incentive to do the same with psychedelics: these drugs cannot be patented because they are existing, well-known substances.

Thus, a pharmaceutical company would not be able to claim all the financial rewards if it funded a large and expensive study that found great benefits from psilocybin therapy.

Incidentally, situations like this are one of the reasons why some politicians want to completely reform drug research.

This leaves private organizations to fund much of the research on psychedelics through private donations. MAPS, the Beckley Foundation and the Heffter Research Institute are the main groups doing this kind of work. Some of the next waves of research that are already underway or in development include psilocybin treatment for alcoholism and cocaine addiction, as well as additional work on the efficacy of psilocybin for treating tobacco addiction and end-of-life anxiety.


But research is expensive and time-consuming, requiring a lot of time and preparation, as psychedelic therapy and psychotherapy sessions can last tens of hours over months or years. So these small private groups have only been able to fund small studies, hence the small sample sizes and less rigorous methodology.

As a result, we have many anecdotes, such as Kevin's story, and a few small studies that show the promise of psychedelic drugs for treating some serious illnesses. However, the gaps in our knowledge can easily be filled. There is more than enough promise here to merit further research and further funding for that research.
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