or Just Another Fad?
*Those of us of a certain age probably remember this PSA about the evils of taking drugs. Prior to the 1970’s there had been a fair amount of research done on psychoactive drugs and their possible use in treating a wide variety of human ailments. Chemicals such as those found in magic mushrooms, peyote, and ayahuasca have been used in religious ceremonies in some areas of the world for thousands of years. But with the indiscriminate use of these drugs and newer versions of hallucinogens such as lysergic acid diethylamide (LSD), came a backlash against psychedelics that led to their being classified by the FDA as schedule 1 drugs, which are drugs that have a high potential for abuse and the potential to create severe psychological and/or physical dependence. Psychedelic drugs, whether for therapeutic or recreational use, are illegal. They were considered the third rail of research in psychopharmacology (touch it and die) from the mid-1960’s to the early 1990’s.
To be sure the “war on drugs” is ongoing. However, interest in whether and how psychedelics may be useful in the treatment of some mental health disorders is getting a second look. An early study conducted by Roland Griffith at Johns Hopkins Center for Psychedelic & Consciousness Research enlisted healthy subjects that had never used any kind of psychedelic substances. They were in a safe living room-like setting, blind-folded, with headphones playing music, and remained there for eight hours or more with a person to help the subject in case they had a “bad trip”, which, I am told, can be terrifying.
The control group was given an amphetamine (Adderall) while the test group received psilocybin. There is no way to use an inactive placebo drug in a clinical trial of hallucinogens but, since these people had never taken a psychedelic drug, they would be less likely to figure out what they had ingested. Most published studies today use an open label process where the subject knows exactly what they are taking. Given the highly personalized nature of psychedelic-induced patient experiences, clinicians recorded the patients’ subjective descriptions rather than objective measures such as blood pressure or temperature.
In these clinical trials, great care is taken to conduct them as safely as possible. The setting is one where if the person has a “bad trip”, there are protocols in place to bring them out of it. The person does not leave the session in an altered state. Typically, people with first- or second-degree relatives with a history of psychotic disease such as schizophrenia are excluded from participating in these trials. This is because of anecdotal stories of people who experienced a psychotic break that affected them long after taking the psychedelic drug. It should be noted, however, that the onset of mental disorders such as schizophrenia is typically in the late teens or twenties. These people may be ascribing their life-long mental disorders with a drug that they believe pushed them over the edge when they might have become schizophrenic even without the drug. There is no way in retrospect to know whether the drug caused the break from reality. Still if there is reason to believe the person might become mentally unstable, it isn’t worth the risk.
This is very different from recreational use of these drugs at a concert or a party where everyone is high and there are no safeguards in place.
Drugs used in psychedelic-assisted
psychotherapy and other applications:
The drugs used most often in clinical trials are psilocybin (magic mushrooms), LSD, and MDMA (ecstasy). Aside from the hallucinations these drugs induce, participants commonly describe a kind of connectedness with everything, where the “self” dissolves, and the person enters an altered reality that feels as real to them as their usual non-medicated state of being. Proponents claim that these effects can be transformational even in people with no clinical mental health disorder and may last months or years.
The Amazonian brew ayahuasca has recently been touted by Green Bay Packers’ quarterback Aaron Rodgers after two trips to Peru and consuming this tea. This substance is not banned by the NFL and, given his performance in week one of the regular season, it doesn’t appear to be a performance-enhancing drug. (He did much better in week two). Ayahuasca is typically consumed in shamanic, religious, and hybrid ceremonies. The amount of the tea a person consumes is determined by the shaman based on their intuitive sense of how much is needed. It has also been reported that the First People of the Amazon basin use it socially to visit loved ones that are far away or, perhaps, crossed over.
Mental health disorders:
There have been several studies conducted on a wide variety of mental health challenges including depression, end-of-life anxiety, post-traumatic stress disorder (PTSD), eating disorders, and ironically given their classification as a schedule 1 drug, substance use disorder (SUD).
An interesting study of psilocybin in conjunction with cognitive behavioral therapy for smoking cessation was published in the American Journal of Drug and Alcohol Abuse in 2017. In this trial, 15 people were given two or three sessions of psilocybin and cognitive behavioral therapy (CBT) for smoking cessation. All 15 of these subjects completed a follow-up study 12 months after their first psilocybin treatment and 12 of them had laboratory-confirmed abstinence from tobacco (67%). This is compared to the most successful smoking cessation medication that shows less than 30% abstinence at 12 months. Another interesting finding in the psilocybin trial at the 12-month follow-up was that 13 of the participants (86.7%) rated their psilocybin experience as among the five most meaningful and spiritually significant experiences of their lives! I don’t know what that equates to, but I think it would be up there with the birth of a child or the death of a parent.
Preclinical trial—often the first tests done of a new treatment, researchers do lab tests and animal studies that give them an idea to see if it might work and to get an idea what a safe dosage might be.
Phase 0—usually involves 15 or fewer participants using low doses of the medication as a proof of concept.
Phase I—usually involves 20-80 participants at higher doses and may include different modes of administration such as orally or in an IV. This phase is used to determine what a safe dose may be and what an ideal dose may be. About 70% go on to Phase II.
Phase II—involves several hundred participants who are given the dose determined to be appropriate in the Phase I trial. Hoping to come up with the best way to conduct a larger trial.
Phase III—may include up to about 3000 participants. Usually, a head-to-head trial using a different treatment as a control. Necessary to obtain FDA approval.
Phase IV—thousands of participants from the public. Looking for rare and long-term side effects.
Take the smoking cessation study for example. An example of a phase III trial might include a psilocybin-assisted treatment compared to nicotine replacement (patches or gum). The participants would randomly be assigned to one group or the other. Both groups would receive the same CBT sessions and they would be followed up at twelve months with laboratory testing to verify which of the participants were still abstinent. Phase III trials are very expensive, and they typically take 2-3 years to accomplish.
At this point, studies using psilocybin on major depression and treatment resistant depression are the furthest along in the FDA approval process, with phase IIb clinical trials. If the psilocybin treatment is shown to be safe and effective, that would be very valuable. Depression is an enormous disease burden in and of itself and is found to be common in other diseases such as substance abuse.
Here is a list of clinical trials currently underway on psilocybin at the Center for Psychedelic & Consciousness Research at Johns Hopkins.
Outside of the academic environment, microdosing psychedelics using dosages too small to create hallucinations is popular. These encounters usually involve a person who stays with the person receiving the drug that can act as a kind of designated driver. That person has not taken the drug and is there to guide the patient along. The first problem with this approach is that it is not legal no matter how knowledgeable the undrugged person is. It is also problematic since there is no way to know exactly what the “tripper” is taking. J Raymond DePaulo Jr, MD, at Johns Hopkins has noted that one of his patients thought he was microdosing psilocybin. When a chemical analysis was done, the agent consisted of THC (found in marijuana), a stimulant, morphine, and fluoxetine (Prozac). There wasn’t a trace of psilocybin. “Mislabeling is the rule, not the exception,” according to DePaulo.
“Mislabeling is the rule, not the exception”
Comparisons to contemplative practices:
There is a fair amount of overlap between the experiences described by proponents of psychedelics and people who have engaged in contemplative practices such as meditation for a long time. Both describe useful insights, altered self-perception, increased connectedness, an expanded emotional spectrum, and ineffable benefits that continues beyond the activity of the drug or the meditation session. These experiences are transformative according to their supporters. One explanation is that the “default mode network”, which is the habitual pathway in our brains, is shut off which allows different parts of our brain to connect with our awareness. Why this would be advantageous, if true, especially to people suffering from depression, is obvious. People who are depressed often ruminate on thoughts of how worthless and unlovable they are. If psychedelics can shut off the negative self-talk and replace it with better messages, the benefit would be life changing, especially for those who have not had success with our current options for medical management. That said, the advantage of accomplishing this goal through a person’s own contemplative practices which are free, carry no risk of destabilizing one’s mind, and legal is equally obvious. There are a range of approaches to treating mental illness that work for many people but there is no one size fits all answer.
The jury is still out as to whether substances such
as psilocybin has a place in treating mental illness
or expanding human happiness.
Mary Minor, ND