Abstract
Currently, individuals with personal or familial histories of psychopathological experiences of psychosis, psychotic spectrum disorders, bipolar disorder, and similar conditions are excluded from most psychedelic clinical trials, studies, and treatment programs. This study sought to determine why such an exclusion exists, what the implications of the exclusion criteria are, and if there was agreement in expert opinion. In-depth interviews with 12 experts in the fields of psychiatry, clinical psychology, medicine, and the effects of psychedelics were conducted in an expert consultation format. Interviews were transcribed, and themes were produced using an interpretative phenomenological analysis (IPA) approach. We found that while the exclusion criteria may be justified for psychedelic protocols that provide minimal psychological support for participants, experts agreed that psychedelic-, ketamine-, and MDMA-assisted psychotherapy are not necessarily contraindicated for all individuals within this group. Rather, results suggest that psychedelic-assisted psychotherapy as well as therapy with MDMA and ketamine, which include high levels of support, may be of benefit to some individuals experiencing said conditions and symptoms. Potentially relevant factors for predicting treatment outcomes include specific symptom endorsement, illness duration, symptom severity, quality of therapeutic alliance, role of trauma in symptom etiology and perpetuation, and the level of other supports in the client’s life. An analysis of expert opinions revealed that psychedelic-assisted psychotherapy can potentially benefit people with psychopathological psychosis and psychotic conditions under the right conditions. However, more research needs to be carried out to determine the risks and develop a protocol specific to this population.
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Due to privacy concerns and agreements surrounding confidentiality, raw datasets, transcripts, or video recordings obtained from anonymous experts cannot be shared. As per agreement with the interviewees, any data not included in the paper must remain private and is subject to deletion from any hardware or cloud-based storages upon the completion of the study.
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Acknowledgements
This study would not have been possible without the assistance of Ron Unger, LICSW, Reverend Dr. Jessica Rochester, D.Div.; Charlotte Jackson, M.A., RCC; Dr. Robert Krause, RN; Maria Mangini, Ph.D.; Tim Michaels, Ph.D.; Zoe Jahn B.A.; and Dana Strauss B.Sc. Their expertise and experience provided great insight and directed our attention towards several unexplored perspectives regarding psychedelic-assisted psychotherapy and experiences of psychosis. We are likewise grateful for all comments and feedback suggested by multiple anonymous reviewers.
Funding
This research was undertaken, in part, thanks to funding from the Canada Research Chairs Program, Canadian Institutes of Health Research (CIHR) grant number 950-232127 (PI M. Williams), and the Usona Institute Graduate Fellowship (J. La Torre).
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JL and MW contributed to the conception and design of the study. JL, MM, SF, and KG wrote sections of the manuscript. JL and MM helped to transcribe and code data. All authors contributed to manuscript revision, read, and approved the submitted version.
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This study was approved by the Research Ethics Board of the University of Ottawa. The study was approved by the institutional review board (file number H-02-21-6651). All methods were performed in accordance with the relevant guidelines and regulations, including the Helsinki Declaration.
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This article is being published as part of the dissertation of Joseph La Torre for his Ph.D. in psychology at the University of Ottawa.
Appendix
Appendix
References for Studies on Individuals with Psychotic Symptoms from the First Wave of Psychedelic Research
During the first wave of psychedelic research, hundreds of clinical research studies were conducted with psychedelic compounds. Many of these studies incorporated inappropriately high dosing, used poor settings, and lacked methodological rigor. Studies also experimented on vulnerable and marginalized groups such as those with substance use disorders, BIPOC, incarcerated and institutionalized persons, and those with severe and persistent mental illness. The studies produced highly varied findings and must be scrutinized, which is why we have chosen not to cite them directly in the manuscript text. Some of these studies have been included in this appendix to help illustrate how people with what clinical researchers identified as schizophrenia and psychotic symptoms at time responded to inconsistent psychedelic administration with the intention of demonstrating the highly nuanced responses and outcomes, with many being positive and therapeutic.
Reference | Substance | Population type | Observed symptomatology | Results |
|---|---|---|---|---|
Guttmann, E. (1936). Artificial Psychoses Produced by Mescaline. Journal of Mental Science, 82(338), 203–221 | Mescaline 0.1–0.4 g | 60 “normal persons” (Medical students Undergraduate students 3 psychopathic patients Etc.) | Physiological Rapid pulse Mydriasis Nausea Salivation Sweating or dryness Anaphrodisiac | Short-term introspective thinking Short-term fatigue |
Psychological Euphoria Hallucinations Anxiety Impaired reasoning and perception | ||||
Hoch, P.H., Cattell, J.P., & Pennes, H.H., (1952). Effects of mescaline and lysergic acid (dLSD-25). American Journal of Psychiatry, 08, 579-584. https://doi.org/10.1176/ajp.108.8.579 | Mescaline 0.4–0.6 grams | 59 schizophrenic patients (mescaline) | Physiological Mescaline Hostility Sexual tendencies | Short-term aggravated mental symptomatology in people with schizophrenia |
24 males 39 females | ||||
LSD 10–120 μg | 21 schizophrenic patients (LSD) | LSD Headache Trembling Nausea Relaxation | Some patients with obsessive-phobic tendencies had symptom disappearance under the influence of mescaline | |
Psychological Mescaline & LSD Anxiety increase Depression Paranoia Hallucinations Somatic disturbances Euphoria LSD Emotional disturbances Relaxation Depressed with retardation Anxiety | ||||
Liddell, D. W., & Weil-Malherbe, H. (1953). The effects of Methedrine and of Lysergic Acid Diethylamide on mental processes and on the blood adrenaline level. Journal of Neurology, Neurosurgery, and Psychiatry, 16(1), 7 | LSD 40–60 μg | 10 LSD Patient cases | Physiological Adrenaline increase Blood sugar increase Increased Tension Abreaction | No long term negative symptoms recorded Short-term insomnia (methedrine) |
Methedrine 40–60 mg | 11 methedrine patient cases Age: 22–61 y | |||
Various mental disorders with ≈ equal sex ratio | Psychological Mood swings (LSD) Hallucinations (methedrine) Euphoria Movement and speech delay; unworthiness (Depressed patients) Catalepsy and catatonia (schizophrenic patients) | |||
Pennes, H.H. (1954) Clinical reactions of schizophrenics to sodium amytal, pervitin hydrochloride, mescaline sulfate, and d-lysergic acid diethylamide (LSD25) Journal of Nervous and Mental Disease, 119, 95–112 | Sodium amytal 0.25–0.50 g | 55 schizophrenic patients received amytal, pervitin, and mescaline | Physiological Amytal Central depression Sedation Hypnosis Pervitin Central stimulation Mescaline & dLSD Transient psychotic phenomena Commonly intensified symptoms | “Normalization” in some patients — decreased symptomatology during drug experience, especially with amytal and pervitin, a small minority with dLSD-25 |
Pervitin hydrochloride 20–40 mg | 28 males 27 females | A small minority of subjects experienced nearly complete normalization under the influence of amytal | ||
Mescaline sulfate 0.4–0.6 g | 25 of the 55 schizophrenic patients also received LSD-25 | Diphasic response in some patients — mixture of aggravated symptoms and suppression of symptoms | ||
dLSD-25 0.010–0.120 mg | ||||
Psychological Emotional lability Instability Depression Self-deprecation Shame Hostility Suspicion Tension Anxiety Auditory hallucinations Paranoia Euphoria Relaxation Sedation | Intensification of pre-existing symptoms in some patients, especially with mescaline and dLSD-25 | |||
Sandison, R.A., Spencer, A.M., & Whitelaw, J.D., (1954). The therapeutic value of lysergic acid diethylamide in mental illness. Journal of Mental Science 100, 491e507. https://doi.org/10.1192/bjp.100.419.491 | dLSD-25 0.025–0.400 mg, administered regularly over the course of weeks or months | 36 psychoneurotic patients observed over a period of 1 year | Physiological Disturbed or violent behavior Flushed face Fixed eyes Disturbance of menstrual function in some women Nausea Dizziness Warmth or coldness | Many patients re-lived repressed childhood memories while under the influence of LSD 25; experimenters used this as a treatment modality to help subjects process past traumas |
14 patients “recovered” from their psychoneurotic condition, 3 improved, 2 not improved, 1 too early to assess results | ||||
Psychological Increased emotional activity (giggling, laughing, crying) Distress Hallucinations Anxiety attack Depersonalization Detachment of the conscious self Obsessional reactions | Clinicians concluded that LSD is an effective adjunct to psychotherapy for treating anxiety and mental tension, but only under controlled conditions with skilled staff and therapists | |||
Denber, H.C.B., & Merlis, S., (1955). Studies on mescaline I. Action in schizophrenic patients. Psychiatry Quarterly. 29, 421e429. https://doi.org/10.1007/BF01567467 | Mescaline Sulfate (0.5g) | 25 schizophrenic patients 18 female 7 male | Physiological Alpha wave frequency increase Sweating Nausea Vomiting | Mescaline-induced psychotic symptoms in remission patients |
Age: 18–51 y | Emotional reactions of patients preceded ideational reactions | |||
Transitory increases in alpha wave activity were correlated to the appearance of physiological changes | ||||
Psychological Hallucinations Catatonic withdrawal Depression Acute anxiety Tension/panic | One hour following an increase in alpha wave activity, the majority of the patients experienced a decrease in mescaline-induced symptoms | |||
Cholden, L.S., Kurland, A., & Savage, C., (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous Mental Disease, 122, 211 | LSD (100–500 μg) Daily (2 weeks) | 20 schizophrenic patients | Physiological Crying/screaming Frantic laughing Appetite loss | Resolved symptoms of catatonic patients while under the influence of LSD |
Age: <40 y | 2–3 days into daily LSD administration, tolerance to the drug developed. Four to 6 days were estimated to reset LSD tolerance. Increasing dosage to 500μg did not allow patients to overcome tolerance | |||
Mescaline (100–500μg) used for reaction comparison | Psychological Hallucinations Euphoria Mood swings Increased eroticism Hypochondria Depression | Cross-tolerance between LSD and mescaline tolerance was not observed | ||
Similar symptoms were observed between LSD and Mescaline cases | ||||
Merlis, S., (1957). The effects of mescaline sulfate in chronic schizophrenia. J. Nerv. Ment. Dis. 125, 432 | Mescaline sulfate 0.50–0.75 g | 24 female schizophrenic patients | Physiological Accelerated pulse rate Facial flushing Blood pressure changes Pupillary dilation | One patient experienced significant improvement from her condition after the mescaline experience |
Age: 29–58 y | Seven patients had partial temporary improvement in their condition | |||
Psychological Anxiety Apprehension Hallucinations Delusions Sexual thoughts | Sixteen patients showed no change | |||
Monroe, R. R., Heath, R. G., Mickle, W. A., & Llewellyn, R.C. (1957). Correlation of rhinencephalic electrograms with behavior: A Study of Humans Under the Influence of LSD and Mescaline. Electroencephalograph y and Clinical Neurophysiology, 9(4), 623–642. https://doi.org/10.1016/0013-4694(57)90084-6 | dLSD-25 50–200 μg | 6 patients with chronically implanted intracranial electrodes | Physiological Inappropriate laughing Restlessness Overactive Blurring of vision Pain in the shoulder and chest Nausea | Experimenters used cortical leads to observe that there was a decrease in cortical alpha activity and an increase in fast activity in the beta range, thought to underlie symptoms of anxiety, overactivity |
1-LSD-25 1000 μg (no clinical effect) | 5 patients were diagnosed with varying levels of schizophrenia | Paroxysmal activity was observed in the hippocampal, amygdaloid, and septal regions and was attributed to psychotic behavior while under the influence of mescaline or dLSD-25 | ||
Mescaline 400–500 mg | 1 patient suffered from paralysis agitans | |||
Psychological Anxiety Hostility Negativism Fear Emotional responsiveness Depression Hallucinations Alert Responsive Confused Agitation | ||||
Pauk, Z. D., & Shagass, C. (1961). Some test findings associated with susceptibility to psychosis induced by lysergic acid diethylamide. Comprehensive Psychiatry, 2(4),188–195. https://doi.org/10.1016/S0010-440X(61)80010-2 | LSD 15–500 μg | 14 psychiatric patients | Physiological Pupillary dilation Increased patellar reflex response Increased systolic BP Poor motor dexterity | 7/14 patients experienced LSD-induced psychosis at high doses (500μg) |
Min. of 3 injections per patient; Injection interval 2–40 days. | Age: 19–37y | No correlation found between age/sex and chance of induced psychosis | ||
Physiological differences between psychotic and nonpsychotic reactors were not significant | ||||
Psychological Delusions Violent behavior Catatonia Disorientation Cognitive disorganization | ||||
Chessick, R. D., Haertzen, C. A., & Wilker, A. (1964). Tolerance to LSD-25 in Schizophrenic Subjects: Attenuation of Effects on Pupillary Diameter and Kneejerk Threshold After Chronic Intoxication. Archives of General Psychiatry, 10(6), 653–658. https://doi.org/10.1001/archpsyc.1964.01720240107012 | LSD-25 1.0μg, 1.5μg, 3.9μg/kg | 10 chronic schizophrenic patients | Physiological Pupillary dilation | Psychotic and Nonpsychotic patients recorded to develop tolerance towards LSD-25 |
Age: 30–55y | Decreased knee jerk threshold | |||
LSD injected at varying intervals over the course of 99 days | Increased LSD-25 dose at 3.9 μg/kg amplified the physiological responses relative to 1.0μg, 1.5μg dosage | |||
Psychological Delusions Hallucinations Catatonia | Physiological symptoms decreased 6 days post treatment | |||
No correlation found between age/sex and physiological changes | ||||
Vanggaard, T. (1964). Indications and counter-indications for LSD treatment: Observations at Powick Hospital, England. Acta Psychiatrica Scandinavica, 40(4), 427–437. https://doi.org/10.1111/j.1600-0447.1964.tb07495.x | LSD 0–400μg | 22 LSD users | Physiological Sweating Tachycardia Rigid/cold feeling Facial flushing | Improved consciousness and confidence in fields of relationships, career, and self-acceptance after long term LSD treatment |
Age and sex varied | ||||
3-year-long study | ||||
Injections at varying intervals | Patients with mental disorders (schizophrenia, psychopathy, psychosis) showed greater degree of negative symptoms | |||
Psychological Anxiety Depression Delusions Hallucinations Euphoric déjà vu Hypochondria | High ego of patients was correlated to positive LSD treatment outcomes, while low ego along psychopathological states correlated with negative/ineffective outcomes | |||
Tietz, W. (1967). Complications following ingestion of LSD in a lower class population. California medicine, 107(5), 396 | LSD-25; inconsistent dosage due to self-administration of LSD | 49 patients observed over a 3-month period | Physiological Panic reactions | 57% of patients developed an extended psychosis state following their bad experience with LSD, despite them not having a psychotic history |
27 male 12 female | ||||
Reported dosage ranged from 100–2000 μg | Majority under 25 years of age | Psychological Reappearance of drug symptoms without re-ingestion of the drug Overt psychosis Acute anxiety reaction Hallucinations | ||
Most patients reported taking other various drugs in conjunction with LSD | Patients admitted to the psychiatric unit of Los Angeles County Hospital due to complications from LSD ingestion | |||
Langs, R.J., Barr, H.L., 1968. Lysergic acid diethylamide (LSD-25) and schizophrenic reactions. J. Nerv. Ment. Dis. 147, 163 | LSD-25 Dosage unspecified | 52 LSD users and 29 matched schizophrenic patients | Physiological Passivity | LSD patients relative to schizophrenic patients had: - Less frequent delusions -Higher depressive characters |
Initial 2 weeks: controlled, no drugs | Age: 14–39 y (Mean: 20.5) White Male majority | Psychological Hallucinations -Mainly auditory Delusions Depression Guilt feelings Suicidal thoughts Mental impairment | LSD and Schizophrenic patients shared more symptomatic similarities than differences | |
Week 2: first dose | ||||
Week 5-6: Second Dose | ||||
Tomsovic, M., Edwards, R.V., 1970. Lysergide treatment of schizophrenic and nonschizophrenic alcoholics: a controlled evaluation. Q. J. Stud. Alcohol 31, 932-949 | LSD 500μg | 75 alcoholics (23 schizophrenics) | Physiological Prolonged panic Confusion | Nonschizophrenic alcoholics showed a greater frequency of positive experiences, and greater chance of alcohol abstinence |
Injections at varying intervals | Mean age: 44 y | LSD was not significant enough at treating alcoholism | ||
1-year-long study | Psychological Delusions Psychosis Paranoia Suicidal thoughts Detachment of the conscious self Spiritual connections | LSD symptom recrudescence was more common in drinking patients versus abstrainers | ||
Data collected at 3, 6, and 12 months post hospital discharge |
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La Torre, J.T., Mahammadli, M., Faber, S.C. et al. Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychopathological Psychotic Experiences and Psychotic Disorders. Int J Ment Health Addiction (2023). https://doi.org/10.1007/s11469-023-01149-0
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DOI: https://doi.org/10.1007/s11469-023-01149-0