Nocebo Left Behind

The first principle is that you must not fool yourself, and you are the easiest person to fool. ― Richard Feynman

Most everyone is familiar with the placebo effect (e.g., taking a sugar pill will make your symptoms diminish if you believe the drug is real). During a placebo experiment, the expectation of the patient is the mechanism that affects the outcome of treatment rather than the nature of the drug. The power of suggestion alone can have a strong influence on our experience despite the content of the proposed intervention. Conversely, but less familiar, is the nocebo effect (e.g., taking a sugar pill will make you feel worse if you believe the drug is real and has consequential side-effects). The word nocebo in Latin essentially means “I will be harmful.” For example, if a discussion between a doctor and patient includes the topic of experiencing negative side-effects when ingesting a substance, the likelihood that those symptoms will be manifested increases. There are valid public safety reasons for clinical trials, peer-reviewed data, and understanding the chemistry involved whenever medication is administered (e.g., pharmacodynamics, pharmacokinetics) to minimize undesirable side-effects. Likewise, comprehensive studies are also conducted for the perceived efficacy of less invasive, non-pharmaceutical treatment modalities. However, outcomes based on objective treatment measurements can be subjectively or suggestively influenced. How much does personal opinion impact the safety of treatment and how much does the power of suggestion dictate the experience of treatment?

As a psychotherapist who does not specialize in biochemistry, pharmacology, or internal medicine, I realize that presenting many treatment dilemmas is beyond my domain of expertise (hence armchair deductions). Nonetheless, what remains interesting to me is the psychology of motivated reasoning, anecdotes as evidence, suggestive priming, subjectivity, correlation/causation errors, and logical fallacies. In fact, one of my pet peeves in the museum of logical fallacies is know as the fallacy of illicit transference. The fallacy of illicit transference contains two subsets of fallacious reasoning. The first being the fallacy of composition, which involves believing that what is true of the parts is also true of the whole (e.g., negative experiences for a few people will equal negative experiences for all). In the opposite direction, but on the same continuum, the fallacy of division refers to the belief that what is true of the whole is also true of the parts (e.g., the treatment facility is corrupt and that clinician lied to me … therefore, all treatment facilities are corrupt and all clinicians lie). I cannot tell you how frequently these fallacies are generated and how appealing they can be when the mind seeks resolution in lieu of cognitive dissonance. Throw in a bit of anecdotal allure and you’ve got a two-for-one in the department of erroneous reasoning (e.g., my aunt received treatment last year for her arthritis and then complained of experiencing severe migraines for several months … so I’ll never trust a doctor again). Understandably, people want to feel empowered as consumers and value their health just as much as their time, but jumping to conclusions based on limited information is evidence of yet another fallacy: hasty generalization. Correlation may not equal causation any more than snoring would infer lucid dreaming. Asking critical questions and being an advocate for your health is admirable, but asserting unfounded claims while irresponsibly influencing others is not. Of course, as we will see, most controversies are not born in a vacuum.

Sturgeon’s law, named for the science fiction author Theodore Sturgeon, is an amusing proposition that boldly states “ninety percent of everything is crap.” Despite the dubious mathematical accuracy of this summation, a very useful critique could be applied to the ways in which people seek information online (i.e., Google University Syndrome). With enough motivated reasoning, a person can uncover selective sources and tendentious articles via data mining that reinforce a previous conviction without involving the requisite fact checking. To make matters worse, most individuals do not know what qualifies as empirically valid information and can easily be seduced by “mavericks” who emphasize their academic or occupational qualifications as experts only to mislead anyone who does not have a sufficient background in their field of interest (often motivated by selling bogus products, exposing “the system,” selling books, and promulgating “natural” remedies). In other words, conspiracies are easy to manufacture, but long-term studies based on collective evidence and peer-reviewed data are challenging. With the world at our keyboard, the likelihood of being persuaded by specious claims can render us exponentially gullible. In addition, the local consensus of laypersons should never be persuasive in the way that a global consensus of highly-trained professionals should be regarding any scientific-based inquiry. For example, the opinion of most citizens in a small town regarding alternative forms of cancer treatment does nothing to invalidate the facts about legitimate treatment compiled by the World Oncology Network. Research takes time and “miracle cures” are probably less than miraculous once you take time to do the research. Similarly, a handful of op-ed articles written about vaccines for The Huffington Post are not going to obliterate peer-reviewed findings in Oxford’s International Immunology medical journal or dismantle CDC data collection systems for vaccination statistics.

Certainly, we shouldn’t be dismissive of physiological subjectivity and it’s often necessary to compare evidential information with personal experience while being mindful of our bodies. After all, no one can tell you what it feels like to be in pain or when to trust your intuition when it’s symptomatically obvious that you should (there have been plenty of false negatives during diagnostic examinations). Nonetheless, there remains no dispassionate control group of the mind once we have committed ourselves uncritically to a controversial narrative. How can we remain vigilant about factual data in the face of suggestive influences or learn to wait until all the evidence is available before assuming epistemic victory? Not every association is significant enough to warrant causation, and correlations should only be a guide for ruling out other possible (often more likely) variables. Wanting to believe something is not the best compass for truth and personal experience does not equal universality.

Publicly constructed fear mongering that encourages unenlightened self-interest is a pernicious form of cultural propaganda and it can have dire ethical consequences. Remember, there is a difference between informed speculation and unhinged credulity. We must also be willing to relinquish false propositions or behavioral trends when faced with a comprehensive analysis that indicates a different conclusiondespite our emotional investment in particular outcomes or our uncomfortableness with a current paradigm. Most importantly, we must be willing to listen carefully to those who have dedicated their entire lives to research and education regarding scientific-based subject matter and make sure that their findings have been supported on an international level. Specialty alone is not enough to validate knowledge, but overwhelming agreement from many specialists will benefit the reliability of any methodology when that process is also made verifiable, falsifiable, and repeatable.

When a psychic tells you to beware of bad karma, our pattern-seeking mind is going to be on high alert. If anything goes wrong, the psychic has been substantiated and we feel our money was well spent. Of course, this psychic knows there ain’t no business like the nocebo business.

Kaleidoscopic Interventions

If the doors of perception were cleansed everything would appear to man as it is, infinite. – William Blake (popularized by Aldous Huxley)

As a co-occurring therapist, I have spent more time discussing the liabilities of illegal drug use and how to avoid its psychosocial consequences than I have spent considering the potential utility value of specific substances for therapeutic purposes. Admittedly, it would seem counter intuitive and taboo for a mental health specialist to suggest that using a legally prohibited drug could be explored as a supplemental method for treating drug addiction in treatment-resistant patients let alone for mitigating symptoms of anxiety, depression, or recurring headaches.

In 1938 a Swiss scientist named Albert Hofmann synthesized an ergot derivative (grain fungus) to produce a molecular compound know as LSD (Lyseric acid diethylamide) for the purpose of creating a respiratory stimulant. After an unexpected lab accident, Mr. Hofmann experienced the direct effects of this mind-altering agent on human cognition and realized an endless sea of psychic possibilities. By the 1940s, LSD was intended to be a used for psychiatric prospects as a Schedule III drug (accepted for medical use with potential for abuse). However, after subsequent experimentation with LSD by the CIA and as a cautionary reaction against widespread public recreational use during the 60s, LSD became classified as a Schedule I drug (illegal, with no accepted medical use). Vilification and prohibition by the Federal Government further reinforced ideas about the inherent dangers of psychedelic substances and prematurely ended psychiatric experimental research on LSD. Nonetheless, many cultural icons of the 60s (Timothy Leary, Allen Ginsberg) continued to espouse the usefulness of the drug for tapping into unexplored reservoirs of consciousness. Fast forward to the twenty-first century, when a resurgence of interest in psychedelic research and its potential for therapeutic applications has reignited both fascination and controversy among the psychiatric community and general public.

What do we actually know about psychedelic drugs and why are they considered dangerous by many? In fact, there are several other hallucinogenic substances that have also been the source of recent debate in today’s sociopolitical atmosphere (MDMA, marijuana, psilocybin). In 1970, psilocybin (the molecular compound in “magic” mushroom spores) became classified as a Schedule I drug under the Controlled Substances Act with severe penalties for consumption or possession. Likewise, the federal laws for medical marijuana use have never been eager for rapprochement despite minor exceptions in select states. Certainly this reputation cannot be justified by scientific research since we know that drugs with the most potential for dependence coupled with the greatest risks to long-term health are already legal for consumption (i.e., alcohol, tobacco). Furthermore, there has been no evidence to demonstrate that hallucinogenic drugs can actually lead to physiological dependence. Without turning this essay into a platform for drug legalization polemics, it may be best to understand why exactly so many psychiatric specialists have taken an interest in psychedelics as potential treatment for those who have failed to respond to normative modalities. But, before we do that, we must first make sure we are being transparent about what these specialists are suggesting. To be clear, unregulated drug use for therapeutic purposes is not advisable and no responsible mental health clinician that I know of has proposed otherwise. Any potential treatment benefits from psychedelics are meant to be ascertained after the drugs are administered in a controlled environment with a carefully calibrated dose under close supervision. An inspection of how psychedelic properties are theorized to work at the level of the brain may provide a more comprehensive understanding of why they may be useful in particular circumstances.

Psychedelic-assisted psychotherapy has been implemented primarily in treatment-resistant patients suffering from PTSD, social anxiety, substance dependence, and cluster headaches. Although many details are opaque, the proposed mechanism of action for psychedelics such as LSD and psilocybin purportedly involves a combination of reduced blood flow to the cerebral cortex while innervating serotonin receptors throughout the brain. The agonist properties of specific hallucinogens create a simulacrum of serotonin and are referred to as serotonergic. The intended effect of therapeutically administered psychedelics would be to elicit the “optimum arousal zone” of the brain by allowing regulatory cognitive filters in the cerebral cortex to diminish thereby eliciting the sensory and emotional areas of the brain below the thalamus. A described synergistic effect of vivid realization may take place where the patient is able to purge psychic detritus such as anger or excessive fear.

Neuroscience has shown that the brain evolved for purposes of processing limited information without becoming overwhelmed by competing neuronal data streams. As a result, the brain’s navigation system provides an automatic elimination process so that unnecessary neuronal activity can be pruned to ensure optimum mental focus for purposes of daily functioning and basic survival. Serotonergic psychedelics increase neurotransmitter activity to stimulate areas of the brain that have been deactivated or over-activated because of trauma, anxiety, depression, chronic pain, or substance abuse. However, the psychological effects of psychedelics can vary greatly depending on the individual, the therapeutic setting, and the dosage. Likewise, screening patients who are willing to try psychedelic intervention is equally important. Of course, a caveat remains regarding the possible over-stimulation of the limbic system in some patients who cannot tolerate any diversion from a neurotypical range of experience. For these individuals, a strong dose of psychedelics in the wrong setting may result in a “bad trip” that could lead to adverse emotional reactions, increased anxiety, or terrifying experiential results. Emphasis on the importance of dosage purity, the amount ingested, and careful monitoring in a clinical setting could make all the difference between patients experiencing euphoric cognitive breakthroughs or descents into unhinged paranoia. One must also keep in mind that these substances would only be used intermittently as a catalyst for activating dormant neuronal pathways and are not intended to be a comprehensive solution for eradicating mental illness.

Several non-profit organizations, including the Multidisciplinary Association for Psychedelic Studies (MAPS), have been promoting new research into psychedelic treatment possibilities for a variety of psychiatric disorders. In addition, a recent book by author Tom Shroder entitled Acid Test: LSD, Ecstasy, and the Power to Heal has been keeping this topic in the forefront of modern psychology while documenting many success stories from advocating practitioners and their patients.

If your eyebrows have lifted beyond peak elevation after reading this, keep in mind that modern psychiatry is not promoting the lifestyle of Jim Morrison as a means for achieving optimum well-being. One day chemists may be able to isolate the hallucinogenic properties of psychedelic compounds to make these substances eligible for pharmaceutical use. Until then, what a long, strange trip it will continue to be.

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(This article is scheduled to appear in the NPI Newsletter, Winter 2014).