The paper reviews the natural abundance and millennia‑long human use of psychedelics (LSD, mescaline, psilocybin, MDMA, DMT) and argues they warrant renewed consideration for therapeutic applications in psychiatry.
Psychedelic or hallucinogenic drugs such as lysergic acid diethylamide (LSD), 3, 4, 5-trimethoxy-β-phenethylamine (mescaline), psilocybin, 3, 4-methylenedioxymethamph-etamine (MDMA), N, N-dimethyltrypta-mine (DMT) and their relations occur in abundance throughout the natural world, and have been used by humankind for thousands of years.
Psychedelic or hallucinogenic compounds such as LSD, mescaline, psilocybin, MDMA and DMT occur widely in nature and have a long history of human use for spiritual and ritual purposes. Abramson frames these substances as having an under-appreciated chapter in psychiatric practice: between the 1940s and 1960s there was intense clinical and scientific interest in their potential therapeutic and investigative uses, but that work largely disappeared amid legal restrictions and social controversy. This paper offers a concise historical overview of that era and of more recent developments, and asks whether interest in psychedelic compounds is re-emerging for psychiatry. It aims to sketch what was known from earlier clinical work, to describe ongoing research lines, and to highlight barriers and opportunities for reconsidering these drugs in modern psychiatric practice and research.
Abramson summarises the historical trajectory of psychedelic research and the clinical reports arising from mid-20th-century work. The Swiss chemist Albert Hofmann's accidental discovery of LSD in the 1930s initiated experimental use of psychedelics in psychiatry by the late 1940s. Two broad psychotherapeutic approaches were described in that period: psycholytic therapy, involving repeated low doses of LSD within ongoing psychodynamic therapy to loosen defences and allow exploration of repressed material, and psychedelic (or 'mind-manifesting') therapy, consisting of preparatory sessions, a single high-dose experience and subsequent non-drug integration sessions. By 1965 over 2 000 papers had been published reporting positive results among more than 40 000 patients treated with psychedelic drugs, with reported few side-effects and a high level of safety according to the literature cited. Clinical applications reported in the historical literature included treatment trials for anxiety disorders, obsessive–compulsive disorder, depression, bereavement reactions, sexual dysfunction and addiction. In addiction treatment, Abramson reports that repeated controlled experiments from that era showed consistent recovery and 6-month abstinence rates of 50-90% after brief psychedelic therapy. Another reported area of benefit was relief of pain and anxiety in terminal cancer patients. The paper also documents methodological and contextual problems with that earlier body of work: much of the published material consisted of anecdotal case reports lacking adequate control groups and follow-up by contemporary standards, and by the 1970s research had largely ceased following legal prohibition and public concern about recreational misuse. Abramson notes that illicit use and the 1960s drug culture damaged the public and governmental perception of these substances, leading to restrictive research climates that persistently limited clinical investigation. More recent research activity is summarised next. MDMA has seen underground therapeutic use since the 1970s and is described as an 'empathogen' with potential to lower defences and aid psychotherapy. A temporary lifting of restrictions in Switzerland between 1988 and 1993 permitted a brief recommencement of psycholytic psychotherapy using LSD and MDMA for personality, affective and adjustment disorders. Ongoing projects in Spain, Israel and the USA are reported to be exploring MDMA-assisted psychotherapy for post-traumatic stress disorder and for anxiety and depression associated with cancer. Between 1990 and 1995, extensive human studies of DMT were conducted in the USA. A double-blind placebo-controlled ketamine trial in Russia for heroin addiction is cited as demonstrating improved abstinence rates maintained at 2-year follow-up (Krupitsky 2002). Abramson also notes emerging studies of psilocybin for obsessive–compulsive disorder and for reducing anxiety and pain in cancer patients. The Multidisciplinary Association for Psychedelic Studies (MAPS) and the Heffter Research Institute are identified as organisations summarising and promoting current research efforts.
Papers in Blossom that reference this study
Erritzoe, D., Timmermann, C., Godfrey, K. et al. · Nature Mental Health (2024)
Tagliazucchi, E. · Frontiers in Pharmacology (2022)
Romeo, B., Hermand, M., Pétillion, A. et al. · Journal of Psychiatric Research (2021)
Butler, M., Seynaeve, M., Nicholson, T. R. et al. · Therapeutic Advances in Psychopharmacology (2020)
Abramson interprets the historical and contemporary material as indicating both promise and substantial caveats. He emphasises that while early reports suggested broad therapeutic potential and relative safety in controlled settings, most of that literature would not meet modern methodological standards because of limited controls and follow-up. The legal prohibition and the drugs' association with recreational misuse and 1960s counterculture are presented as major non-scientific factors that halted systematic research and left contemporary psychiatrists with little training or knowledge about these compounds. In positioning current research, the paper suggests that psychedelics and related agents could be valuable tools for probing neurobiological links between mental and bodily states and that traditional psychedelic-assisted psychotherapy—used as a brief adjunct to psychological treatment—shares features with modern cognitive–behavioural approaches. Abramson acknowledges ongoing public and governmental scepticism, and he highlights the role of advocacy and research organisations in re-establishing clinical trials. Key limitations are reiterated: stigma, restrictive regulatory environments and the uneven quality of past studies. Finally, the author calls for renewed, dispassionate scientific enquiry. Rather than allowing social or political pressures to determine the research agenda, Abramson urges that psychedelic compounds be examined with rigorous scientific methods to establish whether they can have a useful and evidence-based role in contemporary psychiatry.
Abramson concludes by noting the surprising degree of ignorance about the therapeutic potential of psychedelic substances within psychiatry itself. He draws an analogy to past scientific revolutions that challenged prevailing worldviews, arguing that studies of alternative states of consciousness and their neurobiological substrates are likely to provoke resistance from clinicians who equate such work with 'mysticism'. The paper closes with an explicit appeal for criticism grounded in scientific reasoning, free from social or political bias, to properly investigate whether these substances can play a useful role in psychiatry today.
Despite their history, psychedelics have Despite their history, psychedelics have dropped out of psychiatric dialogue for dropped out of psychiatric dialogue for today's trainee psychiatrists (Strassman, today's trainee psychiatrists. In my own training, references to 2001). In my own training, references to compounds like LSD, psilocybin and compounds like LSD, psilocybin and MDMA were usually followed by state-MDMA were usually followed by statements such as 'have no medical use'. But I ments such as 'have no medical use'. But I was taught about the acute emergencies was taught about the acute emergencies and social problems associated with their and social problems associated with their misuse. misuse. Yet in the years between the first synth-Yet in the years between the first synthesis of LSD in the 1930s and the disappear-esis of LSD in the 1930s and the disappearance of psychedelic research by the late ance of psychedelic research by the late 1960s, there was a furious growth of scien-1960s, there was a furious growth of scientific interest in these substances. Many tific interest in these substances. Many pioneers gave their careers to this field, pioneers gave their careers to this field, hoping that psychedelic drugs could be to hoping that psychedelic drugs could be to psychiatry what the microscope is to psychiatry what the microscope is to biology or the telescope is to astronomy: biology or the telescope is to astronomy: an essential tool to explore the parts of the an essential tool to explore the parts of the internal world that are usually inaccessible internal world that are usually inaccessible..
The Swiss chemist, Albert Hoffman first The Swiss chemist, Albert Hoffman first synthesized LSD-25 while studying deriva-synthesized LSD-25 while studying derivatives of the fungus ergot for use as potential tives of the fungus ergot for use as potential medicines. When he accidentally absorbed medicines. When he accidentally absorbed some LSD during a laboratory session there some LSD during a laboratory session there followed an intense experience of perceptual followed an intense experience of perceptual and emotional effects. and emotional effects. By the late 1940s psychiatrists were By the late 1940s psychiatrists were beginning to experiment with LSD as a beginning to experiment with LSD as a tool, and in 1951 it was the subject of a pre-tool, and in 1951 it was the subject of a presentation at the annual conference of the sentation at the annual conference of the American Psychological Association. Initial American Psychological Association. Initial work explored the possibility that psyche-work explored the possibility that psychedelics might be used as 'psychotomimetics', delics might be used as 'psychotomimetics', to mimic the mental states of patients with to mimic the mental states of patients with schizophrenia, and many schizophrenia, and many health professionals were encouraged to health professionals were encouraged to partake in self-discovery or shared psyche-partake in self-discovery or shared psychedelic experiences with their patients. Other delic experiences with their patients. Other research looked into using psychedelic research looked into using psychedelic drugs as adjuncts to psychotherapy. The drugs as adjuncts to psychotherapy. The therapy took the form of two broad therapy took the form of two broad types: first, psycholytic ('mind loosening') types: first, psycholytic ('mind loosening') psychotherapy involved taking low doses of psychotherapy involved taking low doses of LSD as part of ongoing psychoanalytical LSD as part of ongoing psychoanalytical therapy. The drug had a loosening effect therapy. The drug had a loosening effect and facilitated the exploration of repressed and facilitated the exploration of repressed material. The second type, psychedelic material. The second type, psychedelic ('mind manifesting') psychotherapy in-('mind manifesting') psychotherapy involved preparation sessions without LSD, volved preparation sessions without LSD, then one single large-dose session that then one single large-dose session that encouraged an intense reaction, followed encouraged an intense reaction, followed by further non-drug sessions to explore by further non-drug sessions to explore the meaning of the material that emerged the meaning of the material that emerged.. By 1965 over 2000 papers had been By 1965 over 2000 papers had been published describing positive results for published describing positive results for over 40 000 patients who took psychedelic over 40 000 patients who took psychedelic drugs with few side-effects and a high drugs with few side-effects and a high level of safety (Masters & Houston, level of safety. The techniques were applied to the 1970). The techniques were applied to the treatment of anxiety disorders, obsessive-treatment of anxiety disorders, obsessivecompulsive disorders, depression, bereave-compulsive disorders, depression, bereavement reactions and sexual dysfunction, ment reactions and sexual dysfunction, among others. In the treatment of addiction, 2001). In the treatment of addiction, repeated controlled experiments demon-repeated controlled experiments demonstrated a consistent recovery and 6-month strated a consistent recovery and 6-month abstinence from drinking in abstinence from drinking in 50-90% of 50-90% of participants after brief psychedelic therapy participants after brief psychedelic therapy. Another. Another area where therapy was used successfully area where therapy was used successfully was in relieving pain and anxiety in was in relieving pain and anxiety in terminal cancer. terminal cancer.
Despite the volume of publications from Despite the volume of publications from this period, most of the published material this period, most of the published material refers to anecdotal case reports that are of refers to anecdotal case reports that are of little value by contemporary research little value by contemporary research standards because they lack sufficient standards because they lack sufficient follow-up and control participants (Grob, follow-up and control participants. Even though results appeared 1994). Even though results appeared promising, by the 1970s, under pressure promising, by the 1970s, under pressure from the US justice department, virtually from the US justice department, virtually all research had ended. LSD had leaked all research had ended. LSD had leaked from from the scientific community to a wider the scientific community to a wider audience. audience. By 1966 LSD misuse had become By 1966 LSD misuse had become a problem and its possession was made a problem and its possession was made illegal. This prompted the scientific illegal. This prompted the scientific community to distance themselves from community to distance themselves from interest in such substances. Governments interest in such substances. Governments clamped down on research licences, and clamped down on research licences, and increasing reports of adverse reactions to increasing reports of adverse reactions to psychedelics taken recreationally as op-psychedelics taken recreationally as opposed to those used in controlled, scientific posed to those used in controlled, scientific circumstances (which remained safe) circumstances (which remained safe) appeared in the literature (Strassman, appeared in the literature. As a result, 2001). As a result, research use ceased while research use ceased while illicit use remained, illicit use remained, fuelled by a growing fuelled by a growing criminal distribution and financial system. criminal distribution and financial system. Until very recently, research on psy-Until very recently, research on psychedelic drugs has been severely restricted, chedelic drugs has been severely restricted, which explains the current lack of knowledge which explains the current lack of knowledge among psychiatrists. among psychiatrists.
Since the 1970s, MDMA psychotherapy Since the 1970s, MDMA psychotherapy has seen an emerging underground use by has seen an emerging underground use by analysts. MDMA, strictly speaking an analysts. MDMA, strictly speaking an 'empathogen' rather than a psychedelic 'empathogen' rather than a psychedelic drug, is less intense and shorter-acting than drug, is less intense and shorter-acting than LSD. It appears to offer a similar thera-LSD. It appears to offer a similar therapeutic potential for lowering a patient's peutic potential for lowering a patient's defences and aiding the psychotherapeutic defences and aiding the psychotherapeutic process. process. A lifting of the government ban on psy-A lifting of the government ban on psychedelic research in Switzerland between chedelic research in Switzerland between 1988 and 1993 allowed a brief recom-1988 and 1993 allowed a brief recommencement of psycholytic psychotherapy mencement of psycholytic psychotherapy using LSD and MDMA for patients with using LSD and MDMA for patients with BEN SESSA BEN SESSA personality disorders, affective disorders personality disorders, affective disorders and adjustment disorders. There are and adjustment disorders. There are currently projects under development in currently projects under development in Spain, Israel and the USA looking at Spain, Israel and the USA looking at MDMA-assisted psychotherapy in the MDMA-assisted psychotherapy in the treatment of post-traumatic treatment of post-traumatic stress disorder stress disorder and as a treatment for anxiety and depres-and as a treatment for anxiety and depression associated with cancer. Between 1990 sion associated with cancer. Between 1990 and 1995 extensive studies of DMT, a and 1995 extensive studies of DMT, a strong but short-acting strong but short-acting agent, were con-agent, were conducted with human participants in the USA ducted with human participants in the USA. Other research. Other research includes includes a double-blind placebo controlled study in a double-blind placebo controlled study in Russia using ketamine in the treatment of Russia using ketamine in the treatment of heroin addiction, which has demonstrated heroin addiction, which has demonstrated improved rates of abstinence, maintained improved rates of abstinence, maintained at 2-year follow-up (Krupitsky at 2-year follow-up. Also in progress are studies looking 2002). Also in progress are studies looking at psilocybin in the treatment of obsessive-at psilocybin in the treatment of obsessivecompulsive disorder and for reducing compulsive disorder and for reducing anxiety and pain in cancer patients. All anxiety and pain in cancer patients. All of this research is well summarised on of this research is well summarised on the Multi the Multidisciplinary Association for disciplinary Association for Psychedelic Studies (MAPS) website Psychedelic Studies (MAPS) website (www.maps.org). (www.maps.org).
Although drug misuse remains a growing Although drug misuse remains a growing phenomenon in our global society the phenomenon in our global society the public and governments are suspicious of public and governments are suspicious of psychedelic research. The image of psyche-psychedelic research. The image of psychedelics, severely damaged by the 1960s drug delics, severely damaged by the 1960s drug culture, is further spoiled by drug use in culture, is further spoiled by drug use in today's 'rave' scene. Finding unbiased today's 'rave' scene. Finding unbiased information about psychedelic research is information about psychedelic research is often difficult. often difficult. However, many of the early pioneers However, many of the early pioneers of psychedelic research continue to of psychedelic research continue to promote it for the field of mental health. promote it for the field of mental health. Dr Humphrey Osmond, the British psy-Dr Humphrey Osmond, the British psychiatrist who, in communication with the chiatrist who, in communication with the author Aldous Huxley, coined the term author Aldous Huxley, coined the term 'psychedelic' in the 1950s, strongly sup-'psychedelic' in the 1950s, strongly supported psychedelic research until his death ported psychedelic research until his death last year aged 86 years, when he received last year aged 86 years, when he received a fitting tribute in the a fitting tribute in the BMJ BMJ (Hopkins. Albert. Albert Hoffman, who celebrated his 99th celebrated his 99th birthday this year, birthday this year, maintains contact with organisations maintains contact with organisations promoting scientific research into medical promoting scientific research into medical uses for psychedelic drugs, such as MAPS uses for psychedelic drugs, such as MAPS and the Heffter Research Institute and the Heffter Research Institute (www.heffter.org). (www.heffter.org). Researchers believe these drugs are Researchers believe these drugs are important tools for further academic study. important tools for further academic study. Their recognised psychological effects fit Their recognised psychological effects fit well into an approach looking for the well into an approach looking for the neurobiological links between mental and neurobiological links between mental and physical states. Also from a clinical point physical states. Also from a clinical point of view, the practice of traditional psyche-of view, the practice of traditional psychedelic psychotherapy -using the drugs as delic psychotherapy -using the drugs as an adjunct to brief, time-limited psycho-an adjunct to brief, time-limited psychotherapy -has much in common with the therapy -has much in common with the current practice of cognitive-behavioural current practice of cognitive-behavioural therapy. therapy.
Perhaps it is surprising that there remains Perhaps it is surprising that there remains such considerable ignorance about the such considerable ignorance about the potential of these substances from within potential of these substances from within psychiatry itself. As with Galileo's telescope psychiatry itself. As with Galileo's telescope and Darwin's suggestion of our ascendancy and Darwin's suggestion of our ascendancy from apes, radical scientific challenges tend from apes, radical scientific challenges tend to take the form of an attack on the to take the form of an attack on the anthropocentric model of the world. In anthropocentric model of the world. In the light of this, research that explores the light of this, research that explores alternative states of consciousness and then alternative states of consciousness and then offers a viable neurobiological substrate for offers a viable neurobiological substrate for the very human experience of religious the very human experience of religious encounter is bound to meet with objection encounter is bound to meet with objection from a generation of psychiatrists who have from a generation of psychiatrists who have been conditioned to consider such work as been conditioned to consider such work as 'mysticism'. Perhaps a more dispassionate 'mysticism'. Perhaps a more dispassionate criticism based upon scientific reasoning criticism based upon scientific reasoning and not influenced by social or political and not influenced by social or political pressures is called for if we are truly to pressures is called for if we are truly to investigate whether these substances can investigate whether these substances can have a useful role in psychiatry today. have a useful role in psychiatry today.
Create a free account to open full-text PDFs.
Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)
Geiger, H. A., Wurst, M. G., Daniels, R. N. · ACS Chemical Neuroscience (2018)
Elices, M., Soler, J., Domínguez-Clavé, E. et al. · Frontiers in Pharmacology (2018)
Johnstad, P. G. · Nordic Studies on Alcohol and Drugs (2018)
Elsey, J. W. B. · Drug Science Policy and Law (2017)
Sampedro, F., de la Fuente Revenga, M., Valle, M. et al. · International Journal of Neuropsychopharmacology (2017)
Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
Haden, M., Emerson, B., Tupper, K. W. · Journal of Psychoactive Drugs (2016)
Das, S., Barnwal, P., Ramasamy, A. et al. · Therapeutic Advances in Psychopharmacology (2016)
McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)
Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
Alonso, J. N., Romero, S., Mañanas, M. A. et al. · International Journal of Neuropsychopharmacology (2015)
Nutt, D. J., Carhart-Harris, R. L. · Current Drug Abuse Reviews (2015)
Winkler, P., Csémy, L. · Journal of Psychoactive Drugs (2014)
Hendricks, P. S., Clark, B., Johnson, M. W. et al. · Journal of Psychopharmacology (2014)
Tylš, F., Páleníček, T., Horacek, J. · European Neuropsychopharmacology (2013)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Substance Use (2010)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)