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Psychedelics and Personality Marc Aixalà,† Rafael G. dos Santos,†,‡,§ Jaime E. C. Hallak,‡,§ and José Carlos Bouso*,† †
ICEERS Foundation (International Center for Ethnobotanical Education, Research and Services), 08015 Barcelona, Spain Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, 3900 Ribeirão Preto, Brazil § National Institute of Science and Technology − Translational Medicine, 05508-901 São Paulo, Brazil ‡
ABSTRACT: In the past decade, an increasing number of clinical trials are reporting evidence that psychedelics or serotonergic hallucinogens (such as lysergic acid diethylamide, psilocybin, and ayahuasca/dimethyltryptamine) could be effective in the treatment of mood, anxiety, and substance use disorders. The mechanisms responsible for these effects are not fully understood but seem to involve changes in bran dynamics in areas rich in serotonergic 5-HT2A receptors and in personality. In the present text, we present a brief and critical overview of the current research in this field, pointing out both promises and limitations of these studies. KEYWORDS: Psychedelics, hallucinogens, personality, mood, anxiety, substance abuse
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sychedelicsderived from the Greek words psyche (“mind”) and delein (“to manifest”), thus “mind manifesting”)or serotonergic hallucinogens are a group of psychoactive drugs that profoundly alter perceptions, cognitive processes, and consciousness by their agonism action on cortical 5-HT2A serotonergic receptors.1 These drugssuch as mescaline, psilocybin, and dimethyltryptamine (DMT)have been used since immemorial times by several ethnic groups worldwide for ritual and therapeutic purposes, but they became widely known in Western cultures with the discovery of lysergic acid diethylamide (LSD) by Dr. Albert Hofmann in 1943. In the following decades, psychedelics became important tools for psychiatry and psychotherapy, as well as new recreational, introspective, and spiritual search drugs used by the counterculture and the New Age subcultures. Unfortunately, the recreational use of these drugs, the counterculture associated with this use, and other cultural factors resulted in the restriction of human research of these compounds for the next 25 years.2 Although several experimental and clinical studies were performed with these compounds in that time, most studies had important methodological limitations, such as lack of placebo or control groups.2 However, after more than 20 years of silence, recent studies with better methodologies are being performed again with these drugs both in healthy volunteers and in clinical populations, as well as in basic pharmacology, psychotherapy, epidemiology, and public health, and the psychological, biological, and social bases of personality.1−3 Traditionally used psychiatric medications, mostly antidepressants, antipsychotics, and anxiolytic drugs, have limited efficacy for a significant proportion of patients, and they are also associated with significant adverse reactions. Moreover, they are taken daily for long periods, often years, and many patients are treatment-resistant, in many cases taking several © XXXX American Chemical Society
medications at the same time. Thus, better treatments, with increased efficacy and less side effects, should be investigated. Indeed, this scenario provoked a new wave of research into new pharmacological agents that can prove helpful in easing the suffering of psychiatric patients without intoxicating them, and that can promote healing to treatment-resistant disorders. In the last 25 years, we have been witnesses of an increasing number of clinical trials researching the therapeutic potential of psychedelic substances have been performed.2 For instance, a recent systematic review of clinical trials with LSD and psilocybin (from so-called “magic mushrooms”) for the treatment of anxiety and depression in patients with lifethreatening diseases showed that, from 1960 to 2017, 11 studies with a total number of 445 participants were published, with promising results.4 Four of the 11 studies were randomized controlled trials (RCTs) recently performed, most showing that psychedelic drugs significantly reduced symptoms of depression and anxiety, increased quality of life, and reduced fear of death. Moreover, these studies often used only a single dose of the compounds and reported with few side effects. Therefore, these drugs are promising candidates to be future treatments for this clinical population. Moreover, recent studies (mostly openlabel) also reported that psilocybin was effective in reducing drug-related problems associated with tobacco and alcohol dependence, and significantly reduced symptoms of obsessive− compulsive disorder.2 There is also evidence that ayahuasca (a plant decoction from the Amazon that contains beta-carbolines and dimethylSpecial Issue: DARK Classics in Chemical Neuroscience Received: May 15, 2018 Accepted: May 24, 2018
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DOI: 10.1021/acschemneuro.8b00237 ACS Chem. Neurosci. XXXX, XXX, XXX−XXX
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ACS Chemical Neuroscience
modifications could be the basis of any future therapeutic change.1,3 However, the results of studies involving psychedelics and personality are mixed and inconsistent, and, as exposed above, protocols vary a lot in terms of the duration of the treatment, the kind and amount of psychotherapeutic sessions, and the type of drug and its dose.1−4 At the same time, interventions that imply the use of a psychedelic substances can be much more emotionally impactful than talking therapy procedures; therefore, more dramatic changes in personality traits could be found after a single exposure. As some studies show, even if these changes are not permanent, they could open a time-span in which therapeutic change could be more likely to happen and therefore the therapeutic outcomes that would combine personality traits change and symptomatic-state variations due to therapeutic procedures could strengthen one another and make a shorter, more effective and more complete therapy.3 If a small number of psychedelic-assisted therapy sessions can treat symptomatology for specific conditions such as treatmentresistant MDD, substance abuse disorders, and anxiety disorders, and at the same time induce enduring changes in personality, will this new therapeutic approach be the treatment of choice for mental disorders? And if it is the case, will psychedelics be the drugs of choice in the future of mental health? It is too soon to say, and more basic and clinical research is urgently needed, but both researchers and the public are looking at (and using) psychedelics in a new way.
tryptamine) and psilocybin can be effective for treatmentresistant depression, a form of Major Depressive Disorder (MDD) that does not respond to usual pharmacotherapy and psychotherapy.2 Indeed, a recent placebo-controlled study showed that a single dose of ayahuasca was associated with significant decreases in depressive and anxiety symptoms in patients with treatment-resistant MDD.5 MDD has a high prevalence worldwide and is associated with other psychiatric disorders and to substantial problems in social functioning. Moreover, treatments are often chronic and induce significant adverse reactions, and a significant proportion of patients do not respond to available treatments. Thus, serotonergic psychedelics are promising candidates for the treatment of MDD, especially in treatment-resistant patients. An important characteristic of treatments using psychedelics is that these drugs are often used only a few times, and often associated with a psychotherapeutic approach. For instance, most studies published in the last 25 years used single doses of these drugs, associated with psychotherapy.2,4,5 Psychedelic drugs are not intended to be a chronic type of medication, but an adjuvant to the therapeutic process. If the limited data available so far shows that psychedelic drugs are effective treatments for these incapacitating disorders, research must be promoted, as these compounds introduce a new therapeutic paradigm in which psychotherapy and pharmacotherapy join efforts in a nonchronic treatment, limited in time and with promising ratios of cost-effectiveness. However, it is important to acknowledge that the role of psychotherapy in these new treatments remains to be established, since the form of therapy varies significantly among studies, and some studies do not use any kind of psychotherapy at all and still report significant results.2,4,5 Clinical trials have yet to explain the mechanisms that operate in the improvement of the patients receiving psychedelics, but there is evidence that changes in brain function1 and personality3 could be possible for the reported improvements. In the case of personality, this is especially intriguing. Personality has been traditionally considered a stable construct; therefore, changes in its dimensions were not usually expected or aimed for during psychotherapeutic or pharmacological treatments. Personality traits have been found to change across the life span, although it is less clear if change is gradual or sudden. Studies have shown certain traits to change in short periods of time, after clinical and nonclinical interventions, as well as related to the occurrence of an emotionally intense event, such as the development of a mental illness like MDD or Post-Traumatic Stress Disorder (PTSD).3 Personality plays an important role in the perception of personal reality, including symptoms and diseases, and certain dimensions (for example, neuroticism, extraversion, and conscientiousness) correlate with higher tendencies to experience anxiety or depression, and appear to have an influence on the beginning and development of these disorders. Correspondingly, clinical interventions aimed to treat negative symptoms of anxiety and depression have been found to produce changes in personality traits, implying that positive corrective experiences can also have a positive influence in personality. An increasing number of studies is showing that administration of psychedelics in controlled settings, often with single or few doses, is associated with positive and emotionally significant experiences. Therefore, if psychedelics can have a positive impact on some dimensions of personality traits, this opens a new field of therapeutic possibilities, where personality and associated brain
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AUTHOR INFORMATION
Corresponding Author
*Mailing address: ICEERS Foundation, C/Sepúlveda 65, Despacho 2, 08015, Barcelona, Spain. E-mail: jcbouso@iceers. org. Author Contributions
All authors contributed in a significant way to the manuscript and have read and approved the final manuscript. Funding
R.G.S. is Fellow of the Brazilian National Post-Doctorate Program (PNPD/CAPES). J.E.C.H. receives a CNPq (Brazil) Productivity Fellowship Award. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Notes
J.C.B. is the Scientific Director of ICEERS. M.A. is the Support and Integration Services Director of ICEERS. R.G.S. is a member of the ICEERS Advisory Board. ICEERS is a nonprofit organization that promotes the scientific research of plant hallucinogens such as ayahuasca and ibogaine. The authors declare no competing financial interest.
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REFERENCES
(1) dos Santos, R. G., Osório, F. L., Crippa, J. A. S., and Hallak, J. E. C. (2016) Classical hallucinogens and neuroimaging: A systematic review of human studies. Neurosci. Biobehav. Rev. 71, 715−728. (2) dos Santos, R. G., Osório, F. L., Crippa, J. A., Riba, J., Zuardi, A. W., and Hallak, J. E. (2016) Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Ther. Adv. Psychopharmacol. 6, 193−213. (3) Bouso, J. C., Dos Santos, R. G., Alcázar-Córcoles, M.Á ., and Hallak, J. E. C. (2018) Serotonergic psychedelics and personality: A B
DOI: 10.1021/acschemneuro.8b00237 ACS Chem. Neurosci. XXXX, XXX, XXX−XXX
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ACS Chemical Neuroscience systematic review of contemporary research. Neurosci. Biobehav. Rev. 87, 118−132. (4) Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., and Majić, T. (2018) Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 81, 1−10. (5) Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M., Pessoa, J., Sergio A. Mota-Rolim, S. A., Osório, F., Sanches, R., dos Santos, R. G., Tófoli, L. F., de Oliveira, G., Yonamine, M., Riba, J., Santos, F. R. R., Silva-Junior, A. A., Alchieri, J., GalvãoCoelho, N. L., Lobão-Soares, B., Hallak, J. E. C., Arcoverde, E., Maiade-Oliveira, J. P., and Araújo, D. B. (2018) Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol. Med., DOI: 10.1017/ S0033291718001356.
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DOI: 10.1021/acschemneuro.8b00237 ACS Chem. Neurosci. XXXX, XXX, XXX−XXX
