Drug-Assisted Psychotherapy PDF

C H A P T E R T W E L V E Drug-Assisted Psychotherapy By Ingmar Gorman Learning Objectives In this chapter, we will focus primarily on clini- To u...

C H A P T E R T W E L V E Drug-Assisted Psychotherapy By Ingmar Gorman Learning Objectives In this chapter, we will focus primarily on clini- To understand the psychological effects of 3, cal research with the classical hallucinogen psilocy- 4-methylenedioxy-N-methylamphetamine (MDMA) bin (the compound found in magic mushrooms) and psilocybin. and the empathogen 3, 4-methylenedioxy-N- To understand how the psychological effects of methylamphetamine (MDMA). Other pharmaco- MDMA and psilocybin may be used logical agents such as lysergic acid diethylamide psychotherapeutically. (LSD) and ibogaine will also be mentioned. Yet, a Be able to describe “set and setting” and to be able to whole host of substances including the class of dis- articulate the importance of these factors. sociatives, cannabis, peyote, ayahuasca, and others Be able to discuss the psychotherapeutic approach are worthy of further research but beyond the used in conjunction with MDMA-assisted psychother- scope of the current chapter. apy for Post-Traumatic Stress Disorder (PTSD). Be able to describe the risks associated with the use of MDMA or psilocybin. WHAT DO PSILOCYBIN AND MDMA DO? INTRODUCTION The entactogen MDMA and the hallucinogen psi- Drug-assisted psychotherapy is defined by the use of locybin belong to different classes of substances, and a pharmacological substance’s acute psychological although distinct in their effects, they share a pro- and physiological effects to catalyze and enhance pensity to bring about an acute “altered” or “non- psychotherapy. This chapter will cover various sub- ordinary” psychological state. We can understand stances used in drug-assisted psychotherapy, the psy- this alteration to refer to changes in our thoughts chopathologies being currently investigated in clinical (cognitions), emotions (mood), and incoming sen- trials, future avenues of research, and the benefits it sory information (perception). An example of a may hold for people who are confronted with psychi- day-to-day alteration in one’s state is when a calm atric illness. Although these studies are often associ- person becomes angry. Anger is associated with ated with decades past, there is a current resurgence physiological changes such as increased perspiration, of research in the United States supported by mod- changes in facial expression, and other body lan- ern psychotherapeutic and psychopharmacological guage. When angry, a person is likely to appraise understandings. risks more optimistically and, in interpersonal con- texts, blame others for his or her circumstances (Cox & Harrison, 2008). This chapter is dedicated to Alexander “Sasha” Shulgin ( June 17, 1925–June 2, “Non-ordinary” states are distinct in that they 2014), without whom current psychedelic research would not have been the same. are alterations in psychological states which are 308 Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 309 uncommon or rare (Barušs & American Psycholog- With the discovery of lysergic acid diethylamide’s ical Association, 2003). Examples of such states (LSD’s) psychoactivity in 1943, other terms entered include sensations of oneness with the external the lexicon. These included: “psycholytic” translated world, profound feelings of well-being, or sacred- as “soul dissolving” or “mind dissolving” introduced ness. However, delineating the effects of these by Sandison in the 1960s, “psychedelic” translated as substances by their frequency of occurrence is not “soul manifesting” or “mind manifesting” introduced entirely sufficient. by Osmond in 1957 (Murray, 2003), and “psychody- Another way to conceptualize similarities in the sleptic” emphasizing impairment of psychological states induced by MDMA and psilocybin is to focus function, and similar to “psychotomimetic” translated on their ability to increase the intensity of one’s as “mimicking psychosis.” “Oneirophrenica” or cognitions, emotions, and perceptions. In this “oneirogen” emphasized dreamlike states as coined by way, Grof, Hofmann, and Weil (2008) have Turner (1964), and “entheogen” (god-manifesting) described hallucinogens as nonspecific amplifiers, emphasized the use of these substances strictly in a reli- which interact with the psychological factors and gious or spiritual context as coined by Ruck, Bigwood, social context of the individual taking the sub- Staples, Ott, and Wasson (1979). stance. In other words, psilocybin can intensify Of these terms, “hallucinogen” is most dominant how a person feels at a given moment, making in the scientific field today, which emphasizes the the person sensitive to changes in his or her physical hallucinatory effects of these drugs. This is consid- and social environment. For example, someone ered to be a misnomer by many in the hallucinogen under the influence of psilocybin in an enclosed research world, as outright hallucinations are very poorly lit room may begin to experience anxiety rare. However, the utility of using the term “hallu- or claustrophobia, but after the window shades are cinogen,” aside from tradition, is that it can be used opened to a view of a sunlit forest, the person may in reference to “classical hallucinogens.” Classical feel a profound alleviation of anxiety and a flooding hallucinogens can be further subdivided into tryp- feeling of well-being. tamines (e.g., psilocybin), ergolines (e.g., lysergic Describing these substances as catalysts of nonor- acid diethylamide), and phenethylamines (e.g., dinary states or as nonspecific amplifiers helps convey mescaline). In this chapter, hallucinogen and psy- a sense of how varied the specific effects of these chedelic will be used interchangeably, and will substances can be. To speak of changes in thought, serve as a reference to the classical hallucinogens emotion, and perception is nearly equivalent to strictly. speaking about changes in human experience gener- ally. Although these definitions are limited, these THE SUBJECTIVE EFFECTS terms help convey the difficulty in pinpointing the exact psychological effect of these substances. OF PSILOCYBIN In their book, Stafford and Golightly (1967) describe HALLUCINOGEN TERMINOLOGY the onset of hallucinogens as being associated with anxiety and suspense. These sensations are described OVER TIME as “weird” and “difficult to describe” by participants; The challenge of describing the effects of these sub- however, these feelings often pass an hour after stances is clearly reflected in the varied terminology administration. Typical effects of psilocybin and that has emerged to label them over the course of other classical hallucinogens, include somatic symp- time. The terms chosen often reflect the theoretical toms (e.g., dizziness, nausea, drowsiness), perceptual orientation of those originating the label. One of symptoms (e.g., altered colors, sharpened sense of the earliest of such labels was “phantastica,” coined hearing), and psychological symptoms (changes in in 1924 by the first person to discover the active mood, distorted sense of time, dreamlike feelings, alkaloid in the peyote cactus (Lewin, 1998). depersonalization) (Jacobs, 1984). Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 310 PART THREE Newer Issues To better understand what happens with psilocybin mood, euphoria, a feeling of closeness with others, after onset, we can briefly examine some recent and increased sociability (Stevens, 2009). MDMA is research from the field. A study examining the not a hallucinogen, but rather classified as an mystical-like experiences of healthy humans who empathogen or entactogen, emphasizing the emo- had been administered psilocybin found significant dif- tional and social effects of the substance. However, ferences between psilocybin and placebo on a number individuals may experience psychological phenom- of measures (Griffiths, Richards, McCann, & Jesse, ena similar to those that occur under the influence 2006). Using a self-report instrument that captures ele- of hallucinogens. ments of alteration in consciousness, such as positive In a controlled study, Liechti, Gamma, and shifts in consciousness or anxiety of losing control Vollenweider (2001) found significant differences (Dittrich, 1998), participants reported feelings of between MDMA and placebo on positive mood, oceanic boundlessness, dread of ego dissolution, and visual hallucinations or pseudohallucinations, synes- visionary restructualization. On another similar mea- thesia, changed meaning of percepts, facilitated rec- sure in the same study, participants reported feelings ollection or imagination, and altered perception of of internal unity, external unity, sacredness, noetic space and time. These effects were not always posi- quality, transcendence of time and space, deeply felt tive and included mania-like experience, anxious positive mood, and ineffability. derealization, thought disorder, and fears of loss of Vollenweider and Kometer (2010) present quan- thought or body control. On another measure used titative data of the subjective effects of psilocybin in the study (Liechti et al., 2001), self-confidence, using the five-dimensional altered states of con- heightened mood, apprehension–anxiety, thought- sciousness rating scale (Dittrich, Lamparter, & fulness–contemplativeness, extroversion, dazed state, Maurer, 2006). The intensity of the subjective sensitivity, and emotional excitation were elevated. responses was found to be dose-dependent and Within the context of therapy, MDMA has been included elementary visual alterations, audio–visual reported to decrease fearfulness, while allowing for synesthesia, vivid imagery, changes in meaning of a clear-headed and alert state of consciousness percepts, experience of unity, and blissful states. (Greer & Tolbert, 1986; Mithoefer, Wagner, Effects also included sensations of disembodiment Mithoefer, Jerome, & Doblin, 2011). However, and impaired control and cognition. the complete picture of the subjective experience It is important to highlight that not everyone of MDMA is complex. Although the effects of will experience the same exact effects, and varia- MDMA are largely predictable and consistent across tions in these effects may be partly explained by users, there is variability in the amount of anxiety additional factors such as “set” and “setting,” (particularly the fear of loss of control) individuals which will be explained later in this chapter. After may experience. Liechti et al. (2001) found these acute effects subside, usually after 4–6 hours, it increases in anxiety or no substantial decrease in is hypothesized that there are persistent effects such anxiety, whereas others (Cami et al., 2000) have as a decrease in existential fear, feelings of well- found sedation-like subjective effects in some being, improved mood, and an increase in healthier participants. behaviors (anecdotally referred to as “afterglow”). These persistent effects are thought to be associated with therapeutic utility; however, they are cur- CLINICAL RESEARCH WITH rently not well understood or empirically verified. PSILOCYBIN AND MDMA A Note About Psychoactive Biota Use THE SUBJECTIVE EFFECTS OF MDMA Among Indigenous People The subjective effects of MDMA are commonly This chapter focuses entirely on psychiatric research reported to include a sense of well-being, elevated from the 20th century onward. Such a discussion Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 311 excludes a wealth of knowledge accumulated by substance to be an exceptional psychotherapeutic indigenous cultures over many centuries. It would adjunct. Although no randomized clinical data were be an injustice to not acknowledge the historical gathered from this period of underground therapy, it and cultural antecedents to current research. Many has been estimated that thousands of sessions took of the pharmacological agents under investigation place throughout the decade. Some estimates indicate today were first used within indigenous contexts that up to 500,000 doses were administered in a psy- for religious and healing purposes. These include: chotherapeutic setting within North America during psilocybin, ayahuasca, peyote, iboga, and others. It its period of legality (Stolaroff & Multidisciplinary is, however, beyond the scope of the current chap- Association for Psychedelic Studies, 2004). It was said ter to include findings from anthropology, ethno- that the drug was exceptional in its utility to facilitate botony, ethnopharmacology, sociology, literature, couples counseling. and other important fields pertaining to indigenous and ancient plant use. If the reader is interested in additional resources on these topics, an excellent THE NATURE OF EARLY DRUG- start would be “Plants of the Gods” by Schultes, ASSISTED PSYCHOTHERAPY Hoffman, and Rätsch (2001) or “Psychedelics Encyclopedia” by Stafford (1992). RESEARCH When discussing the potential clinical benefits of A Short History of MDMA drug-assisted psychotherapy, it is essential to prop- Unlike psilocybin, there are no plants that contain erly contextualize current research of these sub- MDMA and it is thus produced by laboratory stances. The current clinical studies using synthesis. The plant sassafras does contain safrole, psilocybin and MDMA are in early stages of inves- which is an oily liquid used as a precursor in the tigation. This means that small sample sizes are used production of MDMA. Due to the complexity of to evaluate efficacy. Efficacy can be understood as a its production, MDMA does not have an extensive treatment providing positive results in a controlled history of human use. It has been misreported that research trial. Efficacy does not equate to effective- MDMA was first synthesized in 1914 as an ness, which refers to finding positive therapeutic appetite suppressant. However, an investigation by results in routine care outside the controlled exper- Freudenmann, Öxler, and Bernschneider-Reif imental setting. It is therefore very important to (2006) found no support for this claim when inves- highlight that none of the treatments discussed in tigating Merck’s historical archive in Darmstadt, this chapter have been evaluated for effectiveness. Germany. Freudenmann et al. (2006) located a pat- There is however early evidence supporting the ent for MDMA dating back to 1912 with additional efficacy of these treatments. documentation highlighting a search for a new type Small sample studies, such as some of those of blood clotting agent. And although MDMA was included in this chapter, are vulnerable to a Type resynthesized in 1927 and 1959, there was no I error and expectancy effects. A Type I error is the evidence for human testing until 1960. incorrect rejection of a true null hypothesis. In It wasn’t until the mid-1970s that MDMA was other words, it is the incorrect conclusion that a rediscovered by the biochemist Alexander Shulgin treatment should provide symptom relief, when it (who died as this edition of the book was going to may not. An expectancy effect occurs when a par- press), who observed that the substance can evoke ticipant or researcher expects a given result (symp- “an easily controlled altered state of consciousness tom improvement) and this affects the outcome of with emotional and sensual overtones, and with lit- the study (participant reports fewer symptoms). The tle hallucinatory effect” (Shulgin & Nichols, 1978, issue with classical hallucinogen research from the p. 77). Shulgin proceeded to introduce psychiatrists 1960s and 1970s is that many early studies suffered and psychologists to the drug, who found the from such flawed research designs. Although current Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 312 PART THREE Newer Issues research still encounters these issues, more modern measure consistent effects (e.g., Griffiths et al., 2006; research methodologies are allowing for increased Hasler, Grimberg, Benz, Huber, & Vollenweider, confidence in the measured effects. 2004), it is difficult to predict with absolute accuracy how an individual will respond to psilocybin. It is thought that through proper screening, prep- SET AND SETTING aration, dosage, and the maintenance of a supportive We discussed how psilocybin and MDMA may be setting, some of the variables that contribute to a thought of as nonspecific amplifiers; substances that negative response (“bad trips”) can be controlled. strengthen or intensify a person’s thoughts, feelings, However, it has also been hypothesized that an over- and perceptions, throughout the duration of the emphasis on controlling a person’s experience can substance’s effect. We have also briefly mentioned contribute to negative responses as well. Drug- how these effects interact with a person’s psycho- assisted psychotherapy has adapted to this dialectic logical, social, and physical context. Because these by including an element of nondirectedness, to factors can influence a person’s experience on the allow the participant greater agency in their experi- substance, guidelines for facilitating sessions with ence when under the acute effects of the drugs. More these drugs have evolved over the past 50 years, will be mentioned on this topic in the “Psychothera- formally beginning with “set and setting” (Leary, peutic Methods of Action” section of this chapter. Litwin, & Metzner, 1963). Due to the significance of “set, setting, and cast,” “Set” can be understood as the current state of Johnson, Richards, and Griffiths (2008) published a mind of the person taking the substance. This can seminal article titled “Human Hallucinogen Research: include their personal psychological, social, and Guidelines for Safety,” which outlines a set of safe- spiritual history and the context of the intoxication guards against factors that may contribute to an over- (intention or expectation of the drug’s effect). whelmingly distressing experience. Johnson et al. “Setting” pertains to the environment or external (2008) re-emphasized the importance of a trusting rela- factors, which include sounds, the appearance of tionship between the participant or patient and the the room, time of day, and so on. This is particu- therapists, preparing the participant for what the psy- larly significant when contrasting the therapist’s chedelic experience may entail, and a safe setting. In office and a concert hall, where recreational use addition to these factors, we must not forget about the may occur. In addition to “set and setting,” we dose administered. Research has shown that psilocybin may think of “cast” as the presence of other persons has an optimal dose range for inducing mystical-like who accompany the individual under the acute experiences, which when exceeded, increases the like- effect of the drug. It is hypothesized that clinicians’ lihood of an anxious response (Griffiths et al., 2006). and researchers’ interaction with the individual before, during, and after the administration of the PSILOCYBIN-ASSISTED psychedelic is of particular importance. Clinicians will be familiar with this as the therapeutic alliance PSYCHOTHERAPY IN BRIEF (Lambert, 2004), a topic which will be expanded Psilocybin occurs in various species of mushrooms on further in the chapter. and after ingestion is metabolized into psilocin, a Empirical studies have attempted to examine the serotonin receptor agonist (Presti & Nichols, psychological factors (set) that may influence or pre- 2006). In clinical research, psilocybin is given in dict the quality of a person’s experience with psilocy- doses ranging from 10 to 30 mg/kg, with effects bin. A person’s recent emotional excitability or their including the aforementioned changes in perception, openness to experience has been shown to predict the cognition, and affect. The duration of these effects positive or negative valence of a response to psilocy- often lasts between four and six hours. Psilocybin has bin (Studerus, Gamma, Kometer, & Vollenweider, a very low physiological toxicity profile, with no 2012). And although clinical research has been able to organ damage or negative neuropsychological effects Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 313 (Gable, 1993; Halpern & Pope, 1999; Hasler et al., characterized by efforts to avoid thoughts or remin- 2004; Nichols, 2004; Strassman, 1984). However, as ders of the traumatic event; negative cognitions and with other hallucinogens, there may be complica- mood, such as negative beliefs about the self and feel- tions for individuals with a family history of ings of detachment from others; and alterations in psychosis. arousal, characterized by difficulties falling asleep, The clinical application of psilocybin has focused on outbursts of anger, difficulty in concentrating, and its utility in the treatment of anxiety related to cancer. A hypervigilance. person diagnosed with cancer will often face physical, PTSD has often been shown to be a chronic ill- emotional, and existential challenges. Being confronted ness, with patients receiving treatment experiencing with the possibility of an untimely death can induce symptoms for an average duration of 36 months, hopelessness, anxiety, depression, and these feelings patients not receiving treatment experiencing symp- can persist even after successful cancer treatment. Per- toms for 64 months, and more than one-third of sons living with a cancer diagnosis often live with dread patients never fully recovering from PTSD (Kessler, over the feeling of imminent death and may experience Chiu, Demler, & Walters, 2005). restlessness, fatigue, problems concentrating, and an The reported lifetime prevalence of PTSD is inability to live their life to the fullest. It is thought approximately 8% in the United States (American that a mystical-like experience with psilocybin may Psychiatric Association, 2013a). Incidence among help patients better understand their condition so that U.S. soldiers involved in the current Iraq War is they may experience less anxiety. estimated to be as high as 18%, with estimates of The three institutions associated with this research 75,000 to 225,000 soldiers suffering from PTSD. are Habor-UCLA, New York University, and Johns In 2004, the U.S. Veterans Administration spent Hopkins University. The study at Habor-UCLA has $4.3 billion on PTSD disability for veterans who been completed and published (Grob et al., 2011), were mostly from the Vietnam War (MAPS, 2009). whereas the two remaining studies are ongoing. In a within-subject, double-blind, placebo-controlled The First Randomized Controlled Pilot Study study, researchers administered psilocybin to 12 sub- The first randomized controlled pilot study with jects with advanced-stage cancer diagnosed with acute MDMA to treat chronic, treatment-resistant PTSD stress disorder, generalized anxiety disorder, anxiety was completed by Mithoefer et al. (2011). Participants disorder due to cancer, or adjustment disorder with in the study were enrolled only if they received a score anxiety. The study found significant decreases in of 50 on the Clinician-Administered PTSD Scale, a depressive symptoms at six-month follow-up and clinician-administered measure of PTSD (Weathers, significant decreases in trait anxiety scores at one Keane, & Davidson, 2001) and had at least one month to six months post treatment. However, state unsuccessful treatment with an SSRI and at least one anxiety scores demonstrated a nonsignificant increase unsuccessful treatment with psychotherapy. The parti- at six months post treatment, with the authors specu- cipants included in the study suffered from chronic lating the deteriorating medical condition of the PTSD with an average duration estimated at over participants as being a factor. 19 years. Fifteen of the 20 participants had been previ- ously prescribed an average of 4 different psychiatric drugs, and 15 had completed more than one course of MDMA-ASSISTED PSYCHOTHERAPY psychotherapy (Mithoefer et al., 2011). FOR POST-TRAUMATIC STRESS Individuals excluded from the study included those who did not suffer from a crime or combat- DISORDER related traumatic event and women who were Post-Traumatic Stress Disorder (PTSD) is marked by pregnant, nursing, or who were not taking birth intrusive symptoms such as nightmares, or distress control. Individuals with a history of psychotic, on exposure to trauma-related cues; avoidance, bipolar, dissociative identity, an eating disorder Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 314 PART THREE Newer Issues with purging, or borderline personality disorder whereas 2 of the 8 participants showed such a were also excluded from the study. A list of contra- response in the placebo group. In addition, seven indicative medical complications was excluded, of the eight participants in the placebo control along with anyone who met the criteria for sub- group who had chosen to partake in the crossover stance abuse or dependency, or anyone who had arm of the MDMA-assisted therapy, and all seven prior use with “ecstasy” more than five times or demonstrated a clinical response. Mithoefer et al. anytime within the preceding six months of the (2011, p. 10) also note that “all three subjects who study (Mithoefer et al., 2011). reported being unable to work due to PTSD were The CAPS served as the primary outcome able to return to work.” No serious side effects took measure, with efficacy measured via subsequent place and the neurophysiological and cognitive mea- assessments after MDMA-assisted psychotherapy. sures did not measure any impairment in functioning In addition to the CAPS, the Impact of Events as resulting from the MDMA-assisted therapy. Scale-Revised (IES-R), a measure of psychological response to stress, and the Symptom Checklist Long-Term Follow-Up Study 90-Revised (SCL-90-R), a measure of psychiatric A long-term follow-up (LTFU) evaluating the out- symptom categories, were administered. Also, the comes of the aforementioned was completed to Repeatable Battery for the Assessment of Neuro- assess the durability of these improvements psychological Status (RBANS), the Paced Auditory (Mithoefer et al., 2013). The follow-up assessment Serial Addition Task (PASAT), and the Rey-Osterreith was administered on an average of 45.4 months Complex Figure (RCFT) were used to assess potential after the study’s final MDMA session. Of the 16 neurocognitive changes (Mithoefer et al., 2011). participants who completed the CAPS, no statisti- In the blinded segment of the study, participants cally significant differences were found between the underwent two experimental sessions with MDMA CAPS score at follow-up and the CAPS score or placebo. First, physiological and psychological obtained at the final end point for each individual measures were taken, which were then followed prior to LTFU. However, two of these participants by two 90-minute sessions with therapists. The par- relapsed with a CAPS score above 50, indicating ticipants then underwent their first MDMA session moderate-to-severe PTSD symptoms. The 19 par- followed by a 90-minute therapy session the next ticipants who completed a questionnaire designed morning. Psychological measures were administered to assess perceived harms and benefits of the study four days after the experimental session, followed by indicated experiencing some benefit and did not three 90-minute therapy sessions for integration report any harm. An open-label proof-of-principle approximately once a week. Following the last inte- study has been completed to test the use of an addi- gration session, one more experimental session with tional MDMA-assisted psychotherapy session to MDMA took place and the preceding stages were treat the participants who relapsed in the previous repeated. At the end of this process, psychological clinical trial. The participants have been treated and measures were once again assessed (Mithoefer follow-up interviews are currently taking place. et al., 2011). After the primary evaluation, the blind was broken for each participant. Participants assigned to the placebo control condition could HEALTHY VOLUNTEER RESEARCH enroll in an open-label crossover arm. All, save one This textbook focuses on the use of psychopharma- of the eight participants in this condition, went on to cology in the treatment of psychiatric disorders; yet, enroll in the crossover arm with the active drug. this chapter would not be complete without the In the study, a clinical response was defined as a inclusion of studies with healthy volunteers. Psy- minimum of a 30% reduction in baseline CAPS total chopathology is thought of as a condition in severity score. Ten of the 12 participants demon- which illness must be extracted or removed from strated such a reduction after MDMA treatment, a person. Attention is rarely paid to the possibility of Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 315 using psychopharmacology to prevent psychopa- Another extensive area of research in healthy thology or as a means to enhance the well-being humans pertains to understanding the basic neuro- of individuals not diagnosed with a psychiatric psychological, cognitive, and behavioral effects of disorder. MDMA and hallucinogens. A very large contribu- Griffiths et al. (2006) published results of a double- tion in this regard has been made by Franz blind study that reliably produced mystical-like Vollenweider (Vollenweider & Kometer, 2010). experiences in a sample of 36 healthy volunteers. At Other important figures contributing to this research two-month follow-up, participants reported having include: Baggott (Baggott, Coyle, Erowid, Erowid, sustained positive changes in attitudes and behaviors, & Robertson, 2011), Bedi (Bedi, Hyman, & de which was corroborated by two preselected commu- Wit, 2010), Carhart-Harris (Carhart-Harris et al., nity observers familiar with the participants. The par- 2012), Dumont (Dumont et al., 2009), Gouzoulis- ticipants attributed these changes to the mystical-like Mayfrank (Gouzoulis-Mayfrank & Daumann, experience, which was reported to have substantial 2006), and Kuypers and Ramaekers (Kuypers & personal and spiritual significance. A 14-month Ramaekers, 2007). follow-up study was conducted in which 58% of the volunteers rated the psilocybin experience as one of the top five most personally meaningful, and THE USE OF MDMA AND 57% reported it to be one of the top five most spiri- HALLUCINOGENS IN CLINICAL tually significant experiences of their lives (Griffiths, Richards, Johnson, McCann, & Jesse, 2008). TRAINING Griffiths et al. (2011) found the positive changes in It is suggested by some researchers that it is impor- attitude and behavior to persist at 14-month follow- tant for therapists who will be working with parti- up. Commonly reported positive changes included cipants under the influence of psychedelics to have better relationships with friends and family, increased familiarity with nonordinary psychological states. physical and psychological self-care, and increased The manual for MDMA-Assisted Psychotherapy spiritual practice. The benefit reported by volunteers for the Treatment of Posttraumatic Stress Disorder was related to the sequence of psilocybin doses they (MAPS, 2013a) includes the therapist’s comfort received. Participants who received ascending doses with “intense emotional experience and its expres- of psilocybin had more sustained positive changes in sion,” “first-hand validation of and trust in the attitudes and behaviors than participants in the des- intelligence of the therapeutic process as it arises cending dosage condition. from an individual’s psyche,” as it helps “familiarize In another recently published study (MacLean, therapists with the terrain … of non-ordinary Johnson, & Griffiths, 2011), researchers found evi- states,” “help therapists to identify features of the dence of personality change as a consequence of experience that might be most helpful,” allows psilocybin administration in healthy adults. Measur- the therapist “to be comfortable supporting people ing changes in the five broad domains of personality during times when the process is difficult and unset- (also known as the Big Five), Maclean and collea- tling,” and “provides the therapist with intraper- gues found a significant increase in the domain of sonal working knowledge of the integration Openness. This personality change remained signif- process” (MAPS, 2013a). Such experience also icantly altered in participants one year after the alludes to the practice of psychotherapists to psychedelic experience in those participants who undergo therapy of their own to understand the had a mystical experience. The construct of Open- psychotherapeutic process in themselves and ness consists of six facets: fantasy, aesthetics, feelings, others. ideas, values, and actions. It can generally be In a 40-year follow-up study, of the 20 psy- thought of as open-mindedness to new ideas and chotherapists interviewed, who conducted drug- experiences. assisted psychotherapy during the 1950s and 1960s Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 316 PART THREE Newer Issues with LSD, all showed high levels of agreement MECHANISMS OF ACTION when asked whether their experiences with auto- Potential Mechanisms of Action in intoxication, conducted during their training, were Psilocybin-Assisted Psychotherapy a valuable didactic experience for their work as psy- chotherapists (Winkler & Csémy, 2014). Similar Classical hallucinogens are also known as serotoner- findings have been established in the case of gic hallucinogens as they act as 5-HT2A receptor MDMA, where one study found that of the 20 agonists. This activation is necessary but not suffi- psychiatrists interviewed with personal histories of cient in the explanation of hallucinogens’ effects MDMA, 85% had reported an increased ability to (Nichols, 2004). Yet, their action is far more com- interact with others, 80% reported decreased defen- plex, causing alterations in glutamatergic, dopami- siveness, 65% reported decreased fear, 60% nergic, and serotonergic transmission. Studies decreased sense of separation from others, 50% conducted by researchers in Zurich found that increased awareness of emotions, and 50% reported most of the subjective effects of psilocybin were decreased aggression (Liester, Grob, Bravo, & attenuated by drug that inactivates 5-HT2A recep- Walsh, 1992). It is important to emphasize that tors (Carter et al., 2005). The evidence for contri- this does not suggest that therapists “need to bution of dopaminergic receptors is weaker but the have” prior experience with these substances, but research in this area is incomplete. Recent neuro- that research suggests that it may have benefits. scientific advances have allowed for the neurobio- To aid therapists in their understanding of the logical correlates of psychedelic states to be better MDMA-induced state, a study has been approved understood. in which therapists will receive MDMA as part of Desynchronization of oscillatory rhythms in the their training in MDMA-assisted psychotherapy posterior cingulate cortex (PCC) has been found to (MAPS, 2009). The purpose is to “provide an in- be one of the mechanisms associated with the sub- depth understanding of how to maximize the jective psychedelic experience with psilocybin therapeutic effects of MDMA-assisted psychother- (Muthukumaraswamy et al., 2013). The cerebral apy,” and “allow participants to better draw dis- cortex is composed of interconnected neurons that tinctions between common, self-limiting side make up networks that allow the brain to function. effects of MDMA-assisted psychotherapy and When these neurons fire in a particular pattern, brain those effects that require intervention” (MAPS, waves may be observed using an electroencephalo- 2009, p. 7). gram (EEG). Desynchronization is when this syn- In a recent interview, Dr. Herb Kleber (White, chronization decreases. The function of the PCC is 2013) discussed how in the late 1960s, he was inter- complex and unclear, but it is associated with the ested in comparing therapists who had personal procession of emotion, memory, and is a central experiences with LSD to those who did not. node in the default mode network (DMN). The There were anecdotal reports that therapists DMN is a network of brain regions that are active with the LSD experience had better outcomes in when a person is not focused on the outside world group therapy than those who did not. Dr. Kleber and the brain is restfully awake. began the study but had to close the study prema- A recent study using fMRI found evidence for turely due to Sandoz recalling the LSD after its the association between subjective effects of psilo- widespread recreational use. In the interview, cybin and decreased connectivity and activity in the Dr. Kleber states, “… in general, most of the people key connection hubs (thalamus, anterior and poste- did not seem to change very much. I was not terri- rior cingulate cortex, medial prefrontal cortex), bly impressed with the outcome of the study.” which enabled a state of unconstrained cognition However, this research was never completed and (Carhart-Harris et al., 2012). These hubs are central therefore, no empirical evidence exists to support to communication and integration across the brain, an interpretation. and thus play an important role in a diverse set of Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 317 cognitive functions. In the past, it was thought that trauma-related thoughts, memories, and feelings. psychedelics increase brain activity, leading to their The drug may deepen emotions, empathy, and con- subjective psychological effects. This research shows tribute to a “clearer perspective of the trauma as a past evidence of the contrary. event with a heightened awareness of the support and Aldous Huxley and Huxley (1977) theorized safety that exist in the present” (Gorman 2013a, p. 3). that the brain functions as a reducing valve, acting Another mechanism of action implicated in to filter out unnecessary information and external MDMA-assisted therapy may be linked to changes stimuli, so we are not overwhelmed. The work of in neurobiological abnormalities, particularly in the Dr. Carhart-Harris and colleagues indicates that amygdala and ventral/medial prefrontal cortex, psychedelics initiate a decrease in brain activity in which has been hypothesized to result from areas responsible for constraining our sensory PTSD. MDMA has been associated with increased experience and our subjective experience of self- blood in the ventromedial front and occipital cor- consciousness. As a result of this decrease, these tex, and decreases in the left amygdala (Gamma senses are less constrained. et al., 2000). There is much more to learn about the neurobi- ological underpinnings of the psychedelic state. For The Psychotherapy in MDMA-Assisted a more detailed description of the effects of psyche- Psychotherapy delics, please see Vollenweider and Kometer (2010) The psychotherapy provided in clinical trials of and Nichols (2004). MDMA-assisted psychotherapy for PTSD is a mul- tifaceted integration of various treatment modalities. Potential Mechanisms of Action in The following section outlines several components MDMA for PTSD of the psychotherapy and how it may interact with The psychopharmacological profile of MDMA is the acute effects of MDMA. Although not compre- complex. It is associated with the release of seroto- hensive, these psychotherapy processes and techni- nin, norepinephrine, and dopamine, and can act ques are considered to be key aspects of the directly on adrenaline and serotonin receptors, and treatment (Mithoefer, 2013). elevate vasopressin (Cami et al., 2000). The most One of the earliest goals at the beginning of common effects of MDMA include stimulant MDMA-assisted psychotherapy is the establishment effects (cardiovascular, autonomic, and perceptual). of the therapeutic alliance (Mithoefer, 2013). This MDMA is relatively short acting (lasting four to alliance or relationship between the therapist and six hours) and has been reported to facilitate intro- client has been one of the most consistent psycho- spection, interest and capability for intimacy, tem- therapy factors to be associated with therapeutic porary freedom from anxiety, and emotional outcome (Lambert, 2004). In the case of persons openness (Greer & Tolbert, 1986). The symptoms living with PTSD, the alliance can be of particular of increased and uncontrolled fear response and importance due to the impact interpersonal trauma avoidance in PTSD can both be hurdles in the ther- and shame may have on developing trust. Thera- apeutic process. Psychotherapies for PTSD such as peutic alliance is developed in MDMA-assisted psy- cognitive-behavioral therapy involve the recall of chotherapy through introductory sessions with the traumatic memories, their updating, and integration therapists prior to MDMA administration. It may (Ehlers & Clark, 2000). be further supported by the effects of MDMA. The reduction of a fear response induced by This hormone oxytocin is thought to be affili- MDMA may facilitate the revisiting of traumatic ated with the establishment of trust and the facilita- experiences during psychotherapy without associated tion of bonding in humans, and has been emotional numbing (Mithoefer et al., 2011). hypothesized to be a component of MDMA’s Another proposed model is that MDMA increases psychophysiological effect. This is supported by the window of tolerability for engaging with indirect evidence showing levels of oxytocin to be Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 318 PART THREE Newer Issues elevated in the blood of healthy volunteers who In clinical studies for PTSD, participants are had been administered MDMA and to be positively administered MDMA on only 2 or 3 occasions correlated with the prosocial effects of the drug out of approximately 12 psychotherapy sessions. (Dumont et al., 2009; Hysek et al., 2013). In this During these sessions, it is possible that the partici- way, oxytocin may facilitate the establishment of pants may experience increased anxiety and strong the therapeutic alliance (Johansen & Krebs, 2009). affective states. To support participants during these However, conclusive evidence is yet to be experiences, mindful diaphragmatic breathing collected. techniques are taught prior to drug administration, The highly affective nature of PTSD symptoms which are similar to the relaxation exercises used in and the content of trauma itself can present a chal- other psychotherapies such as Cognitive Behavioral lenge to establishing an alliance, and if left unad- Therapy (CBT) and Prolonged Exposure (PE). dressed, can impede the therapeutic process. Cloitre, MDMA-assisted psychotherapy shares other Stovall-McClough, Miranda, and Chemtob (2004) similarities to PE, Cognitive Processing Therapy found negative affect management to mediate the (CPT), and Eye Movement Desensitization and relationship between the therapeutic alliance and Reprocessing (EMDR). This includes an emphasis treatment outcome. In other words, the relationship on the importance of directive preparation sessions, between the patient and therapist is more likely to which includes the establishment of the aforemen- lead to better results if the patient is able to manage tioned therapeutic alliance, psychoeducation about the negative feelings he or she experiences. In the PTSD, socialization to the treatment model, and case of MDMA-assisted psychotherapy, the pharma- preparing the participant for the process and cological intervention can be thought of as a way of consequences of exposure to traumatic material. enhancing negative affect management. It allows the What makes MDMA-assisted psychotherapy person to engage with traumatic content without a distinct from the aforementioned treatments is an heightened fear response or dissociation, and within emphasis on the therapist’s largely nondirective a highly supportive environment. stance after the preparation sessions. A nondirective The potential for MDMA to manage negative approach allows the participant to direct the affect is supported by preliminary neurobiological pace and direction of the therapy session. This is evidence. Extensive studies into the neurobiology done so that the participant can bring up traumatic of PTSD have found symptoms such as intrusive content when optimally prepared to do so. To memories and hyperarousal to be associated with maintain an exposure component in MDMA- decreased hippocampal and medial prefrontal cor- assisted psychotherapy, in cases where the partici- tex signaling and increased amygdala activity pant avoids discussing the trauma entirely, the (Ravindran & Stein, 2009). In contrast, healthy participant and therapist prior to the drug adminis- volunteers who were acutely administered tration, have informally agreed that the therapist MDMA showed decreased activity in the left can bring up the traumatic content at a later point amygdala, which is associated with fearful associa- during treatment if needed. However, therapists in tions and memories (Gamma et al., 2000). A recent the current clinical studies have noted that partici- study by Carhart-Harris et al. (2014) found that the pants discuss the trauma spontaneously, without the decrease in amygdala activity was associated with need for prompting by the therapist, in almost all self-reported intensity of MDMA effects. The (nearly 100) MDMA sessions. potential for MDMA to dampen an overactive A nondirective approach allows for several addi- amygdala remains a tentative hypothesis, which is tional advantages. Participants may elect to discuss currently being evaluated empirically in an fMRI traumatic content not initially conceptualized in the substudy examining persons living with PTSD case formulation. These experiences may be associ- before and after MDMA-assisted psychotherapy ated with intense shame or guilt, which the partici- treatment (MAPS, 2014). pant may not have been willing to share during Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.  CHAPTER TWELVE Drug-Assisted Psychotherapy 319 intake. Providing the participant greater agency therapists offer guidance and support when needed or allows for unexpected, yet potentially important requested. therapeutic content to surface. The active role of the therapist becomes more Habituation to anxiety, fear, or other affective prevalent during integration sessions. Participants dis- responses associated with the traumatic content is cuss the content of the MDMA sessions, their not the goal or process emphasized in MDMA- reactions to it, and discuss the insights gained. The assisted psychotherapy. Rather, in MDMA-assisted therapist must make clear to the participant that the psychotherapy, emphasis is placed on emotional process catalyzed by the MDMA session will connection, increased clarity into traumatic memo- continue for several weeks and participants are ries and a sense of mastery over the process and encouraged to discuss any distress that may arise. recall of traumatic events. Habituation can be “Integration involves the ability to access and apply understood as a form of learning, a consequence to daily life the lessons, insights, changes in percep- of repeated exposure, in which a person shows a tion, awareness of bodily sensations, and anything decreased response to a stimulus. In the case of else that has been revealed during the MDMA ses- PTSD, this may be a repeated exposure to a trau- sions (MAPS, 2013a).” There are at least three inte- matic event, with the aim of reducing a fear grative meetings planned after each MDMA-assisted response and avoidance of stimuli associated with psychotherapy session in which to address the ses- the event. sions. Participants are also encouraged to use forms of Part of the trauma processing relates to cognitive self-expression, such as journaling or drawing, to restructuring in which negative thoughts, beliefs, confront or integrate material from the sessions. and distortions are challenged in a nondirective They also have option to view recordings of their way to help the participant understand the meaning sessions, though they are not required to do so. of their trauma. When a traumatic experience is reflected upon without psychophysiological dysre- gulation, aided by the MDMA, the traumatic IS IT THE DRUG, THE memories can be safely recontextualized with the support of the therapist. PSYCHOTHERAPY, OR BOTH? Perhaps the most central aspect of MDMA- Now that we have covered both MDMA- and assisted psychotherapy, particularly in the sessions psilocybin-assisted psychotherapy, we can begin to in which the participant is under the effects of the address a central question in this form of treatment. MDMA, is the emphasis on the participant’s inward When drug-assisted psychotherapy successfully treats focus. This is done with the participant closing his a patient, is it an effect of the substance, the psycho- or her eyes and listening to appropriate music. As a therapy, or the combination of the two. The impor- consequence, the participant leads much of the tance of the therapist cannot be underestimated, as therapy, with the therapists facilitating the partici- he or she can assist in the optimization of the afore- pant’s process. It is not assumed the therapist is the mentioned set and setting, assist in preparation before expert, but rather that the patient, with the help of the substance is administered, and help with the inte- the MDMA, will engage in the therapeutic process at gration of the experience afterward. least partially independently. In relation to cognitive In his article, Bogenschutz (2013) succinctly restructuring, the participant may come to understand describes the unique methodological issues encoun- his or her trauma with a greater sense of agency and tered in clinical trials using psychedelics, and it is self-efficacy. In a traumatic event, the victim encoun- likely that these extend to MDMA as well. Psyche- ters powerlessness and helplessness over the situation. delics have both acute psychoactive effects and Allowing the person to regain some sense of power hypothesized persistent effects that last longer than and control in MDMA-assisted psychotherapy is a the acute drug response. Bogenschutz (2013) high- reversal of this circumstance. In this situation, the lights that the therapeutic brain changes induced Copyright 201 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. 320 PART THREE Newer Issues may be dependent on the subjective experience of treatment with psilocybin, symptoms of OCD the patient. Unlike other psychopharmacological decreased by 23 to 100%, with improvement lasting medications, the set and setting of the patient will beyond 24 hours post administration. In these studies, impact the experience on the medication, which is no formal psychotherapy was provided, although some hypothesized to impact the treatment outcome. participants reported the psychedelic experience to be Thus, a combination of psychotherapy and medica- psychologically and spiritually enriching. The reduc- tion effect is being measured. This can be problematic tion in symptoms after the acute effects of psilocybin because clinical trials focus on isolating variables, so brings us back to the question of mechanism of action. that specific mechanisms of either drug or psychother- To this date, there has been no follow-up to this apy can be defined. We will address these questions research. It is thus unknown whether the therapeutic by using two clinical illustrations. effect of the psilocybin treatment was only pharmaco- logically mediated or a combination of pharmacologi- CLINICAL EFFECT WITHOUT cally and psychotherap