Psychedelics burst into modern life with the discovery of LSD. The chemical lysergic acid diethyl amide, known as LSD, was discovered in 1938 by the Swiss chemist Albert Hoffman, working for Sandoz Pharmaceuticals, while studying ergotamine, a chemical from grain fungus. Five years later in 1943 Hoffman accidently ingested it and had an experience, which he described as an “uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors”
Other major psychedelics psilocybin (found in mushrooms) and mescaline (from peyote cactus) had a long history of use with distinctive psilocybin mushrooms seen in ancient rock paintings implicating use in religious rituals from prehistoric North Africa, and from Mexico and Guatemala from thousands of years ago. Mescaline was used, possibly for thousands of years, in Native American religious ceremonies.
From 1950 to 1970, while still legal and widely unknown by authorities, many well-known people became interested in psychedelics because of the reports of unusual and positive mental effects from LSD. Aldous Huxley famously wrote the book the Doors of Perception about his experience with mescaline. He chose that title from the poet William Blake, who in the Marriage of Heaven and Hell wrote, “If the doors of perception were cleansed everything would appear to man as it is, infinite.” In addition, William James wrote about his experience with mescaline.
As LSD became popular, a subculture related to psychedelic experiences flourished including musicians and artists such as the Grateful Dead. Underground chemists started synthesizing and widely distributing it. This chemical experimentation also brought about the discovery of many other compounds that have psychedelic properties.
In the 60′s and 70s legitimate psychiatric researchers studied the effects of LSD and psilocybin and found unusual therapeutic properties. Dr. Walter Pahnke and Dr. Stanislav Grof studied them with a variety of patients. Dr. Walter Clarke with Dr. Timothy Leary studied them with recidivist criminals.
A scandal at Harvard stimulated the fame of the psychology professor Timothy Leary, who became very enamored with the effects and coined the phrase “tune and drop out”. As psychedelic use became more widespread, a very strong reaction against their use developed and lead to a very unusual response. All of the known psychedelic compounds were considered to be drugs so dangerous that they were not only outlawed but all research was stopped. LSD and other psychedelics became a “schedule I” drug, which means that they have a “high potential for abuse” and without “any accepted medical use.” All legal sources of LSD for research were closed. This ban on legitimate scientific research was unfortunate but maintained until recently when new research is now being done. The underground illegal use has continued, but with compounds whose origin and real chemical nature are unknown.
Research in the 1960’s and 1970’s
Before all scientific research into the effects of psychedelics was eliminated for thirty years, many very interesting studies were performed.
In the early research there were two basic approaches to psychedelic studies, high dose and low dose. High dose therapy, called “psychedelic therapy” involved dramatic mental changes for part of one day, then an evaluation period. Low dose therapy, called “psycholytic therapy” involved subtle mental changes, where evaluation could proceed during the effect of the drug. With high dosage research settings were provided for subjects to stay for an entire day or more in a protected environment with much of the questioning done just after the experience. In the low dose therapy, patients were able to be in therapeutic relationships with ongoing discussions.
One of the early high dosage researchers was Walter Pahnke, M.D.,Ph.D, a psychiatrist and a minister, who performed his research at the Maryland Psychiatric Research Center. In 1962 he administered psilocybin versus placebo in a double blind study to twenty theological students on Good Friday in a religious setting. Nine of the psilocybin group reported significant religious experiences, while one of the ten in the control group did. Dr. Pahnke also did research with terminal cancer patients and alcoholics which showed significant results for acceptance of death and longer abstinence.
Dr. Stanislav Grof, used low dosage psycholytic therapy. Dr. Grof began with an analytical background based on Otto Ranks concept of birth trauma, and was later one of the pioneers in transpersonal psychotherapy. He also demonstrated significant findings in use of psycholytic therapy with psychedelics.
Dr. Humphrey Osmond found that LSD significantly helped 50% of a group of alcoholics stay abstinent for over a year. Sidney Cohen studied effects of LSD therapy in facilitating psychotherapy, helping alcoholics and increasing creativity. His research into creativity included work with Aldous Huxley.
The C.I.A was interested in LSD for brain washing and chemical warfare and experimented with it for up to twenty years, then lost interest.
In 1972, I was one of the authors of a study published in the American Journal of Psychiatry, which used psychometric testing and interviews to determine the effects of moderate use of psychedelics after six months of discontinuation. The study showed that those who had discontinued had no psychological impairment and had a tendency to become more “spiritual” or “religious” in a variety of different ways including traditional and non-traditional religions.
Thirty Years of Underground Use and No Legitimate Research
In the past ten years, the restrictions on legitimate research have lessened and there have been increasing studies of the brain effects of psychedelics. With modern brain imaging, very interesting results have appeared.
What do we now know about the effects of psychedelics on the brain?
Current Clinical Research
Studies with normal subjects and psychiatric patients are just now being done. Perhaps the most thorough completed study is from John’s Hopkins Medical School published in the Journal of Psychopharmacology, and Science.
This well designed study, using psilocybin with 36 volunteers, showed that a year after the one strong dose most (64%) rate the experience as one of the most spiritually significant experiences of their life. More than half (58%) rated it among the 5 most meaningful experiences of their life. The group consisted of middle-aged people who had never taken psychedelic drugs, and all had some previous participation in religious activities. They were directed to go inward during the experience. Reports were made immediately after the experience, at two months, and a year later. They describe a sense of greater truth, unity, and improvement of their life satisfaction.
Because of the earlier research showing that terminal cancer patients can have decreased anxiety related to dying studies are now ongoing in this area. Early current findings in research with cancer patients show some improvement in capacity to cope with a terminal illness. If dying patients can have a transcendent spiritual experience with a view outside of concerns for the body, profession, family, and any other issues, then coping with death is easier.
Other studies involve posttraumatic stress, anxiety and depression. One recent study in the British Journal of Psychiatry shows that psilocybin increases memory center brain activities. In addition the drug improved personal memory, which is possibly helpful in psychotherapy.
Current Brain Research
Three major chemical groups seem to have somewhat similar neuronal receptor effects. The tryptamines such as psilocybin, the phenethylamines such as mescaline, and ergolines such as LSD all affect serotonin receptors — 5HT2 mainly, but also 1, 4, 5, 6, 7. Ergolines also affect dopamine D2 receptors and alpha-adrenergic receptors. All also affect complex signaling of glutamate in pyramidal neurons. These neuroreceptor actions are brief however, and the subjective mental effects are much longer. This implies that, like antidepressants, there is an immediate effect, then a much longer cascading effect of which we understand very little. In one recent study selective serotonin 2A antagonists blocked the effects of LSD.
While the subjective experiences with psychedelics show a flooding of sensory data, and imagery, the most recent brain studies show something unusual. An older study showed increased blood flow in some regions, but in this study the drug was administered orally and it’s not clear what time frame of effects they were measuring.
A new study, in which psilocybin was injected into the veins with immediate action, shows something quite different: despite the flood of sensory imagery, the changing sense of time, space, color and scenes, the brain activity in the default mode network, DMN, related to self-identity, was dramatically reduced. This study showed that blood flow was reduced in the thalamus (the center of sensory input), as well as centers involved with introspection, the medial prefrontal cortex (mPFC), and the posterior cingulate cortex PCC. The stronger the subjective experience, the more was the reduction.
This finding is very counter intuitive. Previous to this study, everyone assumed the increased subjective experience would correlate with increased brain activity.
The ACC and mPFC are both part of the default mode network DMN and are generally considered to be related to introspective thought, calm mind wandering and our sense of identity. These regions ordinarily inhibit limbic emotional structures with a sense of control over impulse and emotion. By decreasing or disconnecting these hubs, deeper sensory cortex and emotional limbic experiences may emerge. This great decrease in connectivity of mPFC and PCC could be enabling a state of unconstrained cognition.
Counter Intuitive Brain Effect
Most of the evidence points to psychedelics frequently triggering religious or spiritual experiences. These experiences can become a reference for a shift in lifestyle toward religion and spirituality. It is the transcendent vantage point that has been helpful with dying patients, alcoholics and recidivist criminals.
A conclusion of these brain studies is that the most active hubs of brain activity show the most decrease in activity with psychedelics. As was seen in the posts about savants and out of body experiences, the decrease in activity somehow triggers the transcendent experiences. It is generally thought that an increase in thought, or internal experience, would correlate with increased neuronal activity, and more blood flow. But, increase in activity is not necessarily involved in increased subjective experience. For example, seizures increase activity but do not cause increased cognition.
The default mode network, DMN, has been discussed in several earlier posts. The post on meditation showed that with practice the DMN is changed to include other regions including more focus. Here, we see that psychedelics inhibit the DMN and directly affect this ordinary sense of identity. By decreasing normal brain activity, underlying experiences emerge.
In previous posts, the sense of “I” has been discussed in relation to extraordinary mental states. Brain injuries and transcranial magnetic stimulation, TMS, inhibit normal neuronal circuits and release underlying unusual talents in accidental savants. Inhibition of brain circuits by injuries, TMS and experimental virtual reality show that body consciousness is altered and out of body experiences are released. Psychedelics, it appears, also inhibit the normal sense of identity and allow experiences that are not usually available.
Much of the ordinary mind operates by constraining and filtering energy and experiences of the world. Long before modern brain science, Freudian theory postulated that the super ego and the ego inhibit underlying deeper experiences.
Psychedelics, by inhibiting circuits related to identity, seem to increase memory and related emotions. This flood of new perceptions might also increase creativity. Decreasing activity in hubs allows a less filtered conscious experience and lifts the filters that ordinarily determine perception. (See post on the Limits of Perception, Expectation Determining Perceptions)
The studies on psychedelics appear to show that by inhibiting the normal sense of identity, there is a possible shift to spiritual and religious experience, a transcendent experience that would require the lessening of the identity’s restraints.
In previous posts it has been noted that ordinary self-identity, or the sense of “I”, has a great attachment to the body consciousness, as well as the personal narrative involving family, profession, possessions, and strongly held beliefs and feelings. In the case of accidental savants, out of body experience, and now psychedelics, transcendent experiences occur when the sense of “I” can be separated from these, even for a brief time.
The next post will further discuss what is scientifically known about extraordinary spiritual experiences.