Patients compare psychedelic treatments favorably with conventional treatments, emphasizing the importance of non-pharmacological factors such as trust, safety, interpersonal rapport, attention, the role of music, and the length of treatment sessions. |
Pharmacologically distinct psychedelics exhibit overlapping therapeutic processes for different mental disorders, including insights, altered self-perception, increased feelings of connectedness, transcendental experiences, and an expanded emotional spectrum. |
Patients frequently report on clinical effects beyond their own psychiatric diagnosis, which may be indicative of the cross-diagnostic action of psychedelic drugs, by setting in motion therapeutic processes that address core elements of a shared psychopathology across mental disorders. |
1 Introduction
2 Methods
2.1 Selection Criteria
Population | Patients with a mental disorder seeking treatment |
Phenomenon of Interest | Experiences elicited/induced by the deliberate administration of psychedelic substances, including classic psychedelics such as psilocybin, LSD, mescaline, and ayahuasca, as well as atypical psychedelics such as ibogaine, salvinorin A, MDMA and ketamine, but excluding cannabis |
Context | Therapeutic setting, context that facilitates therapeutic experiences |
2.2 Search Strategy and Study Selection
2.3 Data Analysis and Synthesis
3 Results
3.1 Study Selection
3.2 Study Characteristics
Ayahuasca | Ibogaine | Ketamine | LSD | MDMA | Psilocybin | |
---|---|---|---|---|---|---|
End-of-life anxiety | Gasser et al. (2015) [85] | Swift et al. (2017) [81] Belser et al. (2017) [82] | ||||
Depressive disorder | van Schalkwyk et al. (2017) [84] | Watts et al. (2017) [53] | ||||
Eating disorder | Renelli et al. (2018) [88] Lafrance et al. (2017) [87] | |||||
Post-traumatic stress disorder | Barone et al. (2019) [80] | |||||
Substance use disorder (specific drug used) | Loizaga-Velder and Verres (2014) (mixed) [90] Talin and Sanabria (2017) (not specified) [89] | Camlin et al. (2018) (opioids) [86] | Noorani et al. (2018)(tobacco) [83] Nielson et al. (2018)(alcohol) [77] |
3.3 Critical Appraisal of Study Quality
Study | Study aims | Substance, dose, and frequency | Population: n, sex, age range (years) | Diagnosis/symptoms | Treatment context | Data sources | Qualitative methodology |
---|---|---|---|---|---|---|---|
Loizaga-Velder and Verres (2014) [90] | To broaden knowledge of ayahuasca-assisted therapy for substance dependencies To describe possible psychotherapeutic mechanisms To identify variables that may influence treatment outcomes To identify possible risks To explore the possibilities of integrating this approach into Western countries | Ayahuasca Dose and frequency not reported | n = 14 Sex not reported Age range 24–52 | Substance dependence | Diverse treatment settings in South America providing ayahuasca-assisted therapy for addiction Participation in ayahuasca ritual without formal treatment | Field observations Participative observation Problem-centered interviews Textual resources (e.g. patient files and statements) | CA |
Gasser et al. (2015) [85] | To evaluate the long-term effects on anxiety To explore subjective experiences and lasting psychological changes To explore subjective experiences and elements of the therapeutic process To gain a more holistic understanding from a client-centered perspective | LSD 1 × 200 μg LSD | n = 10 (4 females) Age range 39–64 | Anxiety associated with a life-threatening disease | Phase II, double-blind, active placebo-controlled, randomized clinical trial, conducted in a private psychiatric practice in Switzerland | Semi-structured interviews, conducted 12 months after the last session, in the patient’s home or over the phone | QCA |
Lafrance et al. (2017) [87] | To explore possible psychological and physical effects To explore the perceived impact of the preparatory diet and experience of the ayahuasca purge | Ayahuasca 1–30 × ceremonies Dosage not reported | n = 16 (14 females) Age range 21–50 (mean 33.5) | ED Anorexia nervosa (10) Bulimia nervosa (6) | Ayahuasca ceremonies in various settings in North, Central and South America | Semi-structured telephone interviews: < 1 month (n = 6), 1–12 months (n = 6) and 1–3 years (n = 4) after last ayahuasca session | TA |
Schenberg et al. (2017) [78] | To test the hypothesis that ibogaine treatment combined with cognitive therapy is beneficial for patients with SUDs | Ibogaine HCl 12 mg/kg (females)/15 mg/kg (males) Frequency not reported | n = 22 (7 females) Age range 22–53 (mean 33) | SUDs | Psychotherapy in a private clinic, ibogaine administration in a hospital setting in Brazil | Semi-structured face-to-face interviews, time after session not reported | Deductive content analysis |
Schenberg et al. (2017) [79] | To explore (acute) subjective experiences induced by ibogaine | Ibogaine HCl 12 mg/kg (females)/15 mg/kg (males) Frequency not reported | n = 22 (7 females) Age range 22–53 (mean 33) | Drug dependence | Psychotherapy in a private clinic, ibogaine administration in a hospital setting in Brazil | Semi-structured face-to-face interviews, time after session not reported | IPA |
Belser et al. (2017) [82] | To research form and content of participant experiences during psilocybin sessions To describe subjective experiences of the intervention in context To understand embedded meanings of participants’ lived experiences | Psilocybin 2 × 0.3 mg/kg psilocybin | n = 13 (6 females) Age range 50 ± 15.77 | A projected life expectancy of at least 1 year, and a primary diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety | Phase II, double-blind, crossover, placebo-controlled pilot study to assess the efficacy and safety of psilocybin in conjunction with psychotherapy on psychosocial distress with cancer | Semi-structured interviews conducted 1 week (n = 5) or 12 months (n = 7) after the treatment | IPA |
Swift et al. (2017) [81] | To explore psilocybin therapy experiences related to cancer and death To capture a more complete understanding of the treatment | Psilocybin 2 × 0.3 mg/kg psilocybin | n = 13 (6 females) Age range 50 ± 15.77 | Projected life expectancy of at least 1 year, and a primary diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety | Phase II, double-blind, crossover, placebo-controlled pilot study to assess the efficacy and safety of psilocybin in conjunction with psychotherapy on psychosocial distress with cancer | Semi-structured interviews conducted 1 week (n = 5) or 12 months (n = 7) after the treatment | IPA |
Talin and Sanabria (2017) [89] | To examine people’s attempts to heal substance use they see as problematic To examine the biomedical concept of addiction in relation to ayahuasca healing practices | Ayahuasca Dose and frequency not reported | n = 7 Sex and age range not reported | Substance dependence (heroin, cocaine, crack, methadone, alcohol, tobacco and antidepressants) | Ayahuasca ceremonies—in Santo Daime churches in Italy. Urban ayahuasca ceremonies in Brazil | Participant observations Semi-structured, in-depth interviews | Ethnographic analysis |
Watts et al. (2017) [53] | To determine and communicate underlying psychological mechanisms in this treatment modality | Psilocybin 2 × 10 and 25 mg | n = 19 (6 females) Age range 30–64 | Treatment-resistant depression | Open-label feasibility trial of psilocybin with psychological support for treatment-resistant depression | Semi-structured interviews conducted at 6 months post psilocybin dose | TA |
Camlin et al. (2018) [86] | To understand the subjective ibogaine experience To understand how ibogaine impacts individuals attempting to stop problematic opioid use | Ibogaine Dose and frequency not reported | n = 10 (3 females) Age range 21–48 (28.8 years) | Opioid use disorder | An ibogaine treatment center in a medical facility in Mexico | Semi-structured interviews conducted 3 days (n = 9) and 3 months post treatment (n = 1) | Constant comparative method |
Nielson et al. (2018) [77] | To explore how patients talk about change-related phenomena during debriefing sessions | Psilocybin 2 × 0.3 and 0.4 mg/kg | n = 10 Sex not reported Age range 25–56 | Alcohol use disorder | Open-label pilot study of psilocybin-assisted treatment of alcohol use disorder | Transcripts from 17 debriefing sessions conducted 1 day post psilocybin session | QCA |
Noorani et al. (2018) [83] | To characterize perceived mechanisms of change To identify themes emerging from participant accounts To inquire about participants’ experiences of the study treatment To understand the ways the treatment may have helped them quit smoking | Psilocybin 2 × 20 and 30 mg/70 kg | n = 12 (5 females) Age range 31–67 (mean 54) | Nicotine dependence | Open-label pilot study of psilocybin-assisted treatment for smoking cessation, Baltimore (USA) | Face-to-face interviews conducted, on average, 30 months after the first psilocybin session | TA |
Renelli et al. (2018) [88] | To report on the perspectives of participants who experienced both ceremonial ayahuasca drinking and conventional ED treatments | Ayahuasca Dosage not reported 1–30 × ceremonies | n = 13 (12 females) Age range 21–49 (mean 30) | ED: Anorexia nervosa (8) Bulimia nervosa (5) | Various (1–30) ayahuasca ceremonies, rooted in Amazonian traditions | Semi-structured interviews via telephone, conducted 1 month or less (n = 5), 1–12 months (n = 5) or 12–36 months (n = 3) after the most recent ceremony | TA |
van Schalkwyk et al. (2018) [84] | To explore the dissociative experience from first-person patient narratives | Ketamine Frequency not reported 0.5 mg/kg over 40 min intravenously | n = 10 (7 females) Mean age 52.6 | Unipolar major depressive disorder (9) Bipolar disorder (1) | Randomized controlled trials of ketamine vs. placebo, open-label trial of ketamine, or ketamine as clinical treatment (n not reported) | Semi-structured interviews | Mixed methods Inductive TA |
Barone et al. (2019) [80] | To examine MDMA-assisted psychotherapy in a long-term follow-up context To complement, clarify, and expand upon quantitative findings | MDMA 3 × 100–125 mg | n = 19 (6 females) Age range 24–56 | Treatment-resistant PTSD | Phase II RCT investigating the safety and efficacy of MDMA-assisted psychotherapy for military veterans and first responders with treatment-resistant PTSD | Semi-structured interviews, conducted 12 months after the end of the trial | TA and IPA |
3.4 Nature of Patient Experiences
3.4.1 Phenomenology of the Psychedelic Experience
“It sent me back to when I was very first born and felt like I was inside the womb … I fought the devil … he was telling me to give up and die, but I didn’t want to and I somehow beat him. And that I thought was my addiction at the time … I was able to float up in the atmosphere and I felt my grandma, I just felt her presence everywhere and I realized that she was all around the whole time.” [86] [ibogaine, SUD].
“There was a little NASA space guy that came flying in and he was zapping my brain … it felt like they were scrubbing my brain, they were just doing surgery… it felt like brain receptors being cleaned.” [86] [ibogaine, SUD].
“I saw myself as a rotting, decaying skeleton and then I saw myself as this beautiful full-bodied, just beautiful woman with this long hair, and I, like, I wanted to be that woman. I wanted to be that full, loving woman that has so much to offer my family and world. It was, and then I felt my ribs and I could feel them, they were so hollow and I was just, I was like, I can’t wait to get back and just start gaining some weight.” [87] [ayahuasca, eating disorder].
“It was a feeling beyond an intellectual feeling—it was a feeling to the bottom of my core … that’s one reason that it’s hard to talk about … it’s beyond words.” [81] [psilocybin, end-of-life anxiety].
3.4.2 Perspectives on the Intervention
3.4.2.1 Context and Structure of the Intervention
“It’s not just the psilocybin sessions [but] it’s that human connection, and the support that comes with that human connection, that ultimately leads to success at the end of the day.” [83] [psilocybin, smoking cessation].
“I mean besides the ayahuasca itself, besides the medicinal quality of you know, chemically what ayahuasca can do, I would say that (the most important therapeutic elements were) the trust, therapeutic trust in the medicine men and as well, the follow-up. The psychotherapy follow-up was crucial. And before and after (ceremony) I would say. I don’t know if I would ever recommend an ayahuasca ceremony without that therapeutic, the first one at least, without that therapeutic follow-up.” [87] [ayahuasca, eating disorder].
“Music was really how everything was conveyed to me, it all came through the music … like everything that I experienced did not really happen in the English language, it kind of happened through the music, like the music was the conduit for this experience to happen.” [82] [psilocybin, end-of-life anxiety].
3.4.2.2 Comparisons with Other Treatments
“Standard approaches—I guess to summarize—are very top-down … like suppressing symptoms so that you can become functional, whereas the work with the medicine [ayahuasca] … is more of a bottom up approach that is very much really rewiring things, it’s getting to the root cause and bringing in what was missing and resolving it on a deep, deep level that doesn’t I don’t think really get fully explored or touched upon in standard approaches.” [88] [ayahuasca, eating disorder].
“In usual psychotherapy it is mainly about talking, about words. In LSD-assisted psychotherapy it is mainly about inner processes, inner change, inner experience, it gets enriched by it.” [85] [LSD, end-of-life anxiety].
“I think that the MDMA gave me the ability to feel as though I was capable and safe of tackling the issues. Whereas before I feared those thoughts and I tried to avoid them at all times, and avoid things that reminded me of those thoughts, I think it allowed me to feel safe in my space. Of being able to fight it. I felt like I had the ability and tools, whereas before I was unarmed, unarmored, and had no support. And this type of environment, with [the therapists], the catalyst drug, and everything else, it felt as though I had backup. Now it was safe and I had my tools and weapons to be able to tackle the obstacles that I never had before.” [80] [MDMA, PTSD].
3.4.3 Therapeutic Processes
3.4.3.1 Insights
“I remember having a ceremony where I really saw that at the time binging and purging and restricting were actually adaptive coping mechanisms; at the time, they were the only coping mechanisms that I actually knew to use to deal with the difficulty that I was experiencing, that I had no words for and that no one was asking about.” [87] [ayahuasca, eating disorder].
3.4.3.2 Altered Self-Perception
“I learned a lot. I learned a lot about myself. I’d gotten to the point of questioning myself, my own morals, and for someone who hasn’t done this stuff, they’re not going to understand. You can see yourself like you can read a book and see everything that you stand for and kind of analyze your own self, your own thought, your own reasoning.” [80] [MDMA, PTSD].
“Ayahuasca helped me deeply connect with myself so that self-love has been the prevalent priority over self-criticism that […] self-love became more important and more prevalent. And that to me is the antidote for an eating disorder.” [87] [ayahuasca, eating disorder].
3.4.3.3 Connectedness
“(The psilocybin) just opens you up and it connects you … it’s not just people, it’s animals, it’s trees—everything is interwoven, and that’s a big relief … I think it does help you accept death because you don’t feel alone, you don’t feel like you’re going to, I don’t know, go off into nothingness. That’s the number one thing—you’re just not alone.” [81] [psilocybin, end-of-life anxiety].
“(During the dose) I was everybody, unity, one life with 6 billion faces, I was the one asking for love and giving love, I was swimming in the sea, and the sea was me.” [53] [psilocybin, depression].
3.4.3.4 Transcendental Experiences
“It was like being inside of nature, and I could’ve just stayed there forever—it was wonderful. All kinds of other things were coming, too, like feelings of being connected to everything, I mean, everything in nature. Everything—even like pebbles, drops of water in the sea … it was like magic. It was wonderful, and it wasn’t like talking about it, which makes it an idea, it was, like, experiential. It was like being inside a drop of water, being inside of … a butterfly’s wing. And being inside of a cheetah’s eyes.” [82] [psilocybin, end-of-life anxiety].
3.4.3.5 Expanded Emotional Spectrum
“Emotionally it was a roller coaster ride … The first time it was very brutal, painful, at least emotionally very painful. I could not even say in which direction—it just hurt, like heartache, like being disappointed, like everything you once had experienced as a negative feeling. … It was pure pain. Pain of memories, well, or memory of pain. … it was quite hard. During the second time it was sublime. Really. Love, expansion, holding, I knew that this sometimes happens, that participants talk about spiritual experiences. I thought they just meant this dissolution of oneself – everything is okay, everything is great. That was a very important experience for me. Very, very important.” [85] [LSD, end-of-life anxiety].
“That place was um, serene and peaceful, and um, just such a burden was lifted from me. And it was refreshing to feel something that was such a change from what I normally feel.” [84] [ketamine, depression].
“Excursions into grief, loneliness and rage, abandonment. Once I went into the anger it went ‘pouf’ and evaporated. I got the lesson that you need to go into the scary basement, once you get into it, there is no scary basement to go into (anymore).” [53] [psilocybin, depression].
“I kind of accepted my body for what it is, and I think up until that point I resisted that … I saw this body for what it’s worth. I picked it, it’s mine. It’s more matter-of-fact—this is what it is. I think that acceptance has been liberating.” [81] [psilocybin, end-of-life anxiety].
3.4.4 Outcomes of the Intervention
3.4.4.1 Symptom Relief
“When I first started [the study] I was taking 10 different things. And now no blood pressure medicine, no anxiety pills, no pain pills.” [80] [MDMA, PTSD].
“This is about a smoking study, I keep forgetting that. Because there’s so much more that happened… (Smoking) just seems so petty compared to some of the stuff that was happening.” [83] [psilocybin, smoking cessation].
3.4.4.2 Perspectives of Self
“[Ibogaine] gave me more self-love … I’m not so hard on myself.” [86] [ibogaine, SUD].
3.4.4.3 Sense of Connectedness
“[I feel] love, compassion, and it’s not just for family, it’s for everyone…[my parents and I] have a much better relationship now, no doubt… the study helped me really get there.” [80] [MDMA, PTSD].
“I think right after the trips … certain changes happened … Same things were not equally important anymore. A shift in values. … To take time to listen to music, to listen to music consciously. Maybe that material values were not that important anymore. That other values have priority. Health and family, such things… When you have a job and the job has priority and the family comes last. You don’t even notice it anymore. To realize there, stop, what is actually important? That the family is fine, that the kids are doing well …” [85] [LSD, end-of-life anxiety].
3.4.4.4 Emotions
“Though my problems obviously have not stopped to happen and appear, I changed in the face of them. So, I get to the end of my day very grateful, very happy.” [78] [ibogaine, SUD].
3.4.4.5 Quality of Life
“A veil dropped from my eyes, things were suddenly clear, glowing, bright. I looked at plants and felt their beauty. I can still look at my orchids and experience that: that is the one thing that has really lasted.” [53] [psilocybin, depression].
“I had lost desire to do anything, I lacked will to go to the gym, to the park, the cinema, I only wanted to stay home. After ibogaine the first thing I wanted to do was going to the park, to the movies” [78] [ibogaine, SUD].