The Utility of Anxiety in Psychedelic-Assisted Therapy
The Utility of Anxiety in Psychedelic-Assisted Therapy
A Prospective Mediating Factor in the Treatment of Psychiatric Disorders
Abstract
The recent renaissance of interest around psychedelic substances has inspired a multitude of assessments on the therapeutic potential of these compounds. Several studies have found efficacy in multiple psychedelic substances for the treatment of anxiety and depression among many other disorders. The current understanding of the mechanism/s of action behind the therapeutic effect of these substances remains mostly speculative but theorized to be partly mediated by the mystical-type experience induced under these altered states. Nevertheless, a thorough phenomenological account of the psychedelic experience in the clinical literature is unsatisfactory relative to the significance of the proposed therapeutic potential. Transient anxiety during a successful psychedelic-assisted therapeutic experience, while evident in the clinical literature, has yet to be examined as a potential mediating factor. The phenomenon of transient anxiety in the psychedelic experience will be discussed further relative to its prospect of mediating therapeutic outcomes and its potential role in the mystical-type experience. Further speculation on the utility and practicality of modulating ad interim anxiety will also be discussed.
The Utility of Anxiety in Psychedelic-Assisted Therapy: A Prospective Mediating Factor
Revitalized by investigations initiated in the 1990’s by Dr. Richard Strassman, assessments of clinical significance and mechanisms of action on an array of classic psychedelic (e.g., LSD, psilocybin, mescaline, etc.) and psychedelic-like substances are currently underway. The considerable attention towards psychedelics, trailing the Controlled Substance Act of 1970, has suggested efficacy in the clinical application of psychedelic and psychedelic-assisted therapy of psychiatric disorders, as clinical utilization of psychedelics is gradually conforming to the Western medical perspective. Many contemporary investigations into the clinical significance of psychedelic use have utilized psychedelic-assisted psychotherapy models in which subjects are receiving psychotherapy in conjunction with a psychedelic drug. This research has led to the effective treatment of depression, anxiety, and end-of-life distress (e.g., anxiety and depression surrounding death) among other disorders. The safety profile of these substances has been widely reviewed and deemed safe, without lasting adverse effects within controlled environments. This is not without precaution as marked psychological distress is sometimes observed, yet almost always resolved within a month.
Richard Strassman courtesy of Rick Strassman
To date, most of the clinical literature has reported on the development of efficacious treatments for a variety of disorders and a few theoretical mechanisms of action. While these investigations have led to a respectable amount of clinical evidence, the current delineation of this phenomenology rests mainly outside of the clinical literature (i.e., books, anecdotal reports, articles, etc.). The only phenomenological component thoroughly covered within the current literature is that of the mystical-type experience, which has been implicated as a potential mediating factor in the therapeutic effect elicited by psychedelic-assisted therapy.
The mystical-type experience has been described and characterized by a multitude of sources albeit the majority share a universal phenomenological typology. In 1963, Walter Pahnke complied many of these descriptions and produced a categorical phenomenology of the mystical experience that has been the foundation upon which the contemporary depiction of mystical experiences are based. Pahnke’s original typology gave way to the current measurement of mystical-type experiences now referred to as the Pahnke-Richards Mystical Experience Questionnaire (MEQ-30). The MEQ-30 is a 43-item questionnaire, comprised in the States of Consciousness Questionnaire (SoCQ), consisting of seven categories: Internal Unity, External Unity, Transcendence of Time and Space, Ineffability and Paradoxicality, Sense of Sacredness, Noetic Quality, and Deeply-Felt Positive Mood.
Although partially lacking in thorough phenomenological description, the mystical-type experience has been suitably described. Nonetheless, there is a gap of understanding in the mechanism of action or phenomenology between, at one point, taking a psychedelic substance, and another at which a mystical-type or psychedelic experience is induced and subsequently mediates therapeutic effect. Some phenomenology is occurring after administration of the substance and before a mystical-type or ‘peak’ experience, possibly involved as a mechanism of action prompting the mystical-type experience. This intermediate period has been popularly named the ‘come-up’, and is characterized by a variety of qualities– namely anxiety. The intermediate period has been described in detail throughout well-known anecdotal reports and stories, although only lightly mentioned in the scientific literature.
Walter Pahnke and family
Due to the lack of empirical investigation surrounding this intermediate period, there is inherent ambiguity in discussing this element of the psychedelic experience and its role in the therapeutic effect. Nonetheless, it is essential to examine every element of the psychedelic experience considering the multiplicity of variables involved in the process of the phenomenon. The highly-variable and considerably unexplainable (subjective) nature of the psychedelic experience makes it one of the most difficult phenomenology to fully assess and modulate. While neural mechanisms, pharmacology, and treatment efficacy can be studied with respectable cogency, the variable nature and relative lack of scientific research on these experiences gives sufficient reason to suspect an inadequate phenomenological account. Moreover, the lack of literature on the phenomenon of anxiety during the intermediate period in the psychedelic experience is disappointing given the importance of the aggregate experience. The role of anxiety during this period may prove to be a far-reaching utility, despite it commonly getting a bad name. An uncharted territory remains to be traversed, in light of which a more holistic understanding of these substances/experiences can be fulfilled scientifically and philosophically.
Hypothesis
A modest review of the literature revealed a crucial element of the psychedelic experience – the ad interim period, and a lack of qualitative data surrounding it. The role of this ad interim experience with accompanying anxiety during the psychedelic experience resembles that of the mystical-type experience. With several sources finding such an experience pivotal in mediating therapeutic effects, it seems likely that the anxiety component may play a pivotal role. This study hypothesizes that transient anxiety during the psychedelic experience plays a mediating role in the therapeutic effect. The hypothesis is based on the prevailing occurrence of anxiety during the psychedelic experience and the subsequent therapeutic effect observed in a multitude of studies. Further, it is hypothesized that transient anxiety during the intermediate period (after ingestion and before peak effects) may play a role in mediating the mystical-type experience. It is also assumed that, within reason, modulation of transient anxiety may correlate with the variability in therapeutic effect.
Benzodiazipines
Evaluation of the Hypothesis
This discussion addresses the phenomenon of transient anxiety during the psychedelic experience and its relation to the subsequent therapeutic effect. To date, there is only one clinical study examining the effect of anxiety modulation during the psychedelic experience. However, the expression of transient anxiety during the psychedelic experience has continued to occur in a great number of studies on these substances. The common phenomenon of transient anxiety originating during the psychedelic experience gives rise to questioning as to what effect it may have in psychedelic-assisted therapy.
Induced suppression of anxiety
The one study which partly discusses the role of anxiety during the psychedelic experience found the deliberate suppression (pharmacological intervention of benzodiazepines) of anxiety after its occurrence aided in the therapeutic effect, while the inhibition of anxiety all together (before its possible occurrence) correlated to more severe adverse effects. While not directly addressed, this early study unintentionally stumbled upon evidence supporting the notion that anxiety plays a role in the therapeutic effect. Furthermore, not only do these findings show that the purposeful occurrence of transient anxiety aids in therapeutic outcome, but also that without this anxiety, more severe adverse effects are expected.
Blood pressure and heart rate
Many psychedelic substances have been examined for short-term and long-term safety, having been deemed relatively innocuous and without lasting psychological or physiological adverse effects. Nonetheless, many clinical trials have found noteworthy physiological response induced during the acute effects of many psychedelics. Several studies have shown significant and dose-dependent increases in heart rate and systolic/diastolic blood pressure during treatment. These findings correlate to the noted occurrence of transient anxiety, as such physiological responses have been found to be indicative of an increase in anxiety.
Differentiating the mystical-type experience and transient anxiety
The occurrence of the mystical-type experience induced under psychedelic-states, first characterized by Walter Pahnke, has been implicated as a mediating factor in the therapeutic outcome. Although this phenomenon has considerable evidence supporting this notion, it is not yet conclusive and there have been therapeutic outcomes without the occurrence of the mystical-type experience. It should be clarified that the mystical-type experience and transient anxiety are two distinct phenomena. While it is not the scope of this paper to deliberate upon the mystical-type experience, it is important to note the difference between the two phenomena and to not compromise the validity of either variable. The mystical-type experience itself is not associated with anxious symptoms, instead quite the opposite as many questions on the Pahnke-Richards Mystical Experience Questionnaire depict experiences of ecstasy, infinite love, sense of awe, etc. It may be the case that transient anxiety plays a mediating role in the occurrence of the mystical-type experience, which subsequently mediates a therapeutic effect.
Pre-Clinical observations
A nonhuman study conducted using N,N-Dimethyltryptamine (DMT) to study rat behaviors (relevant to anxiety and depression) found DMT to elicit initial anxiogenic effects followed by later anxiolytic effects. While extrapolation from nonhuman trials is complicated, the results here correlate to the observed pattern in human trials i.e., initial occurrence of transient anxiety followed by therapeutic effect.
Consequences of the Hypothesis
The current evidence shows that transient anxiety induced by psychedelic substances, under suitable conditions (i.e., set, setting, integration, etc.), may play a role in mediating the therapeutic effect. Further, it may be that transient anxiety plays a mediating role in the mystical-type experience, and subsequently mediates therapeutic effect. If the proposed hypotheses are true, then it can be assumed that all of the clinical data collected on the use of psychedelic-assisted therapy has overlooked the fundamental variable of anxiety– modulation of which may correlate to more efficacious treatments for a variety of disorders. The phenomenology of transient anxiety has been identified and discussed here, albeit in rudimentary form. While data is limited, the route of future investigation is beginning to be paved. Forthcoming investigations, either pre-clinical or clinical, must evaluate the influence of transient anxiety during the psychedelic experience if comprehensive treatments are expected.
Future Directions
As discussed above, there is a significant lack of investigation into the role of transient anxiety during the psychedelic experience. In order to bridge this gap in our understanding, future clinical studies should directly assess the presence of anxiety during these experiences. While it is imperative to assess this phenomenon in human trials, it is not necessary to begin with human assessments. Pre-clinical or nonhuman methods of assessment are readily available to assess for the presence of anxiety during the psychedelic experience. That being said, there are already several methods in which clinicians measure anxiety in these associated human studies (e.g., the Beck Anxiety Inventory (BAI), State-Trait Anxiety Index (STAI), Hamilton Anxiety Rating Scale (HAM-A), etc.). However, these studies have only employed these inventories before and after the psychedelic experience, not during or throughout the experience. Up to this time, these studies have relied on self-reports and experimenter observation to indicate the occurrence of anxiety during these experiences; a more reliable measure should be made. Moreover, if the presence of transient anxiety is found to be as prevalent as discussed here, clinicians should measure the chronology of anxiety during these experiences. In doing so, a clearer depiction of transient anxiety will be made. There is insufficient data to being further speculation on treatment approach, as initial exploratory analysis is required to suggest any additional guidance.
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