LSD redux: Psychedelics may help brain functioning


By the late 1960s, hallucinogenic drugs like LSD and psilocybin were part of the “hippie” counterculture. “Turn on, tune in, drop out” was a catchphrase, and even then-serious researchers like Harvard psychologist Timothy Leary were singing the praises of tripping.

But psychedelics weren’t always playthings—they had been the subject of reputable research in the 1950s and 1960s. And today, more researchers are tuning in on examining how LSD and other drugs work in the brain, and their possible value in understanding consciousness, adding value to psychotherapy, and possibly directly treating mental disorders.

In 1970, the Nixon administration declared LSD, psilocybin, mescaline and other hallucinogens a class 1 substance, meaning that it was illegal to make or use, and had no meaningful purpose of any kind. While former Nixon aide John Ehrlichman was quoted as saying the administration’s “war on drugs” was a political move to defang opposition from the anti-war left (i.e., the hippie movement) and African-American voters, the move was very effective at halting all research on hallucinogens for decades.

Today’s researchers—armed with better knowledge of how the brain works, and more sophisticated research techniques in both clinical trials and animal-based mechanisms—are moving beyond the 1950s studies, which were largely qualitative and focused on user experiences. Now, researchers are looking at what hallucinogens can tell us about:

  • How consciousness works, and where (and if) there is an unconscious part of the brain
  • The basis of diseases involving hallucinations, including schizophrenia
  • How well psychotherapy can work against diseases
  • Whether drugs can be designed to for a number of mental disorders, or even just reduce stress and anxiety from terminal illness

Seeing unconsciousness

Robin Carhart-Harris, David Nutt and their colleagues at Imperial College London have been looking at the changes in brain function caused by hallucinogens. Using fMRI neuroimaging data and psilocybin, Carhart-Harris and Nutt showed that the drug parallels a “primary state” of consciousness, which is marked by disorder mind that most likely occurs during sleep, and may have “preceded the development of modern, adult, human, normal waking consciousness,” they wrote in Frontiers in Human Neuroscience. This primary, semi-hallucinatory state is suppressed during normal wakefulness.

The authors pointed to areas of the brain called the default-mode network, which usually carefully controls awareness and signals from the cerebral cortex (and also receives more blood flow and burns more energy than any other part of the brain). Drugs like psilocybin, they found, uncouple the cortex-default mode link, allowing dream like states to be felt.

Model—and treatment—for schizophrenia


Marked by frequent hallucinations among other symptoms, schizophrenia is one of the most common, most intractable and most debilitating mental disorders, affecting 51 million people worldwide. Many patients don’t respond to currently available treatments, while for many, severe side effects remain a problem.

Current therapies focus on dopamine neurotransmitter function, but Carhart-Harris and colleagues explored other neurological pathways that are often exploited by hallucinogens as potential models for how schizophrenia may work. All psychedelic drugs work on the serotonin receptor, but other receptors and neurotransmitter networks in the brain might take part in the hallucinogenic response, as well. His group, as well as other researchers, also found that LSD works along with NMDA receptors in animal brains, and could present a useful animal model for studying schizophrenia.

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Breathing new life into psychotherapy

The practice of psychotherapy, or “talk therapy” (though which also includes cognitive-behavioral therapy, targeted techniques and other methods), has taken a few hits in the last few years, as psychiatry focused on providing biological basis (and medications) for behaviors. However, researchers like Carhart-Harris have suggested that by creating a state of “primary consciousness” using psychedelics, psychologists and other researchers could look directly at what happens in the brain during the so-called unconscious state. Previously (and currently), psychotherapy could only use sleep patterns and psychotic states to draw conclusions on the existence and functions of the unconscious brain.


A new therapeutic magic mushroom

The earliest studies on psychedelics pointed to potential therapies emanating from LSD, psilocybin and the like. But these studies were largely experiential and not properly controlled. However, new animal models have started to provide some mechanism information, and better clinical work has once again pointed to therapeutic value:

  • In 2014, the results of the first FDA-approved study on LSD in 40 years, conducted on Swiss subjects, showed that LSD dosages, when combined with psychotherapy, helped reduce anxiety in terminal patients. Low dosages made anxiety worse, patients reported, while higher dosages combined with “talk” therapy showed a better ability to handle anxiety.
  • A clinical study in Denmark is one of the latest to examine the effects of psilocybin in the brain, to see if it has any impact on depression and other mental disorders. Ironically, the study will take place even though the mushrooms themselves are illegal in Denmark.
  • Another study in 2011 by Californian and New Mexican researchers found that psilocybin improved the mood of patients with terminal cancer. The study indicated that the mushroom extract, even in small doses used in this study, could help with managing anxiety and depression among terminal patients. Current treatments are not very effective at treating mental issues with this group of patients.
  • A non-profit group based in Santa Cruz, California, called MAPS (Multidisciplinary Association for Psychedelic Studies) helps with education and conducts its own research on psychedelics, including psychotherapy assisted by LSD, treatments for post-traumatic stress disorder (PTSD) using MDMA (which is found in the drug ecstasy), and effects of ayahuasca (a psychoactive tea brewed from a South American vine) on drug addiction.

These trials, and others like them, are starting to show the value of using LSD, psilocybin and other hallucinogenic chemicals, but not in the free-for-all ways in the 1960s. Here, careful control, supervised clinical settings, and validated dosages are showing the way for patients (at least) to tune in and drop in safely.

Andrew Porterfield is a writer, editor and communications consultant for academic institutions, companies and non-profits in the life sciences. He is based in Camarillo, California. Follow @AMPorterfield on Twitter.

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