The paper reviews renewed interest in psychedelic-assisted therapies for drug dependence, summarising emerging studies of psilocybin, ketamine, ibogaine and ayahuasca. Despite clinical and legal limitations, it argues that the potential to improve patient outcomes warrants further research.
SummaryAfter a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.
After a century of modern psychiatry, enduring remission from dependence on alcohol, opiates, stimulants and nicotine remains difficult to achieve. Although some pharmacological treatments exist, failure rates are substantial and consensus on the most efficacious approaches is lacking. Research into psychedelic drug-assisted therapy was substantial in the 1950s and 1960s but largely halted for sociopolitical reasons; interest has re-emerged and contemporary studies are now exploring psilocybin, ketamine, ibogaine and ayahuasca specifically for substance dependence. Harkins and colleagues set out to examine whether psychedelic compounds might contribute to drug-dependence therapy. The paper surveys historical and cross-cultural uses of psychedelics, outlines possible psychological and biological mechanisms, summarises contemporary clinical and observational findings, and discusses theoretical objections, practical limitations and regulatory barriers to clinical implementation. The aim is to make the case for renewed, rigorous research into psychedelic-assisted interventions for substance misuse.
Papers cited by this study that are also in Blossom
Doblin, R. · Journal of Psychoactive Drugs (1998)
Hendricks, P. S., Clark, B., Johnson, M. W. et al. · Journal of Psychopharmacology (2014)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
Bogenschutz, M. P., Pommy, J. A. · Drug Testing and Analysis (2012)
The paper reviews substance-specific burdens and existing treatments to contextualise the potential role of psychedelics. For alcohol, the authors note that about one adult in 20 in the UK is alcohol dependent and one quarter of adults drink hazardously. A 2002 meta-analysis of 361 controlled trials identified 46 interventions, with brief interventions and motivational enhancement ranking highest and pharmacotherapies such as the GABAergic agent acamprosate and the opioid antagonist naltrexone ranking third and fourth; however, no single coherent best treatment has emerged. The societal cost of alcohol misuse in England is estimated at around £20 billion a year. Regarding opioids, the authors report over 123,000 people injecting heroin in the UK and a 12-fold increase in mortality among users compared with the general population. Methadone and buprenorphine improve retention and reduce misuse, mortality and criminality but carry medical risks and limitations, including dangers when combined with sedatives. For stimulants such as cocaine, no widely accepted substitution pharmacotherapy exists; psychosocial approaches (contingency management, cognitive–behavioural therapy, motivational interviewing) remain the mainstay. Tobacco causes more deaths than any other legal or illegal drug, with around 1.2 million deaths annually in Europe; varenicline, bupropion and nicotine replacement improve quit rates but most patients still relapse. The authors mention an ongoing open-label pilot in M.W.J.'s laboratory suggesting promising results for psilocybin combined with cognitive–behavioural therapy for smoking cessation, and an open-label psilocybin pilot for alcohol dependence registered at the University of New Mexico. Historically, clinicians such as Humphry Osmond and Abram Hoffer used LSD in the 1950s and 1960s for alcohol dependence, reporting high abstinence rates and suggesting that mystical or spiritual experiences—rather than drug-induced psychosis—were associated with successful outcomes. Cross-cultural reports are cited in which indigenous use of iboga (ibogaine), ayahuasca (DMT) and peyote (mescaline) has been associated with reductions in alcohol dependence. The authors discuss proposed therapeutic mechanisms. Psychedelic experiences have been linked to sustained changes in personality, attitudes and behaviour in observational studies, and to pronounced personal meaning and spiritual significance in volunteer trials with psilocybin. An ‘‘afterglow’’ period lasting several weeks was described in early research and proposed to confer emotional strength and reduced craving, supporting abstinence. A recent paper by Bogenschutz and Pommy is noted as further exploring psychological and biological mechanisms. Contemporary empirical work is summarised. A team in Russia during the 1990s conducted placebo-controlled ketamine studies in more than 1,000 patients with alcoholism, reporting total abstinence for more than a year in 66% of the ketamine group versus 24% in controls; nonetheless, the authors report that the Russian Federation now forbids further ketamine research. Observational studies of ibogaine-assisted therapy have been conducted in Mexico and New Zealand, and a Canadian study has investigated ayahuasca for dependence. The authors emphasise that most contemporary research remains early-stage, often open-label or observational, and that methods and efficacy need more rigorous evaluation.
The authors interpret the collected evidence as indicative of potential utility for psychedelic-assisted psychotherapy in substance dependence, while emphasising that the evidence base is nascent and constrained by methodological and legal limitations. They reiterate historical and cross-cultural signals of efficacy and highlight contemporary positive, though preliminary, findings (for example, the Russian ketamine trials and pilot psilocybin work), but caution that these do not yet establish standard clinical practice. Several practical and ethical limitations are acknowledged. Psychedelic-assisted sessions can be long and resource-intensive, raising cost and scalability concerns. Safety exclusions will prevent some patients from receiving these treatments. Legal restrictions are a major barrier: many candidate compounds are classified at Schedule I or Class A levels, which prohibits medical use outside tightly regulated research. The authors argue that a change in regulatory status and plans for approved manufacture would be necessary for clinical translation. They also address the objection that treating dependence with other psychoactive or potentially misused drugs is problematic, noting that maintenance pharmacotherapies already use controlled drugs and that several psychedelics (psilocybin, LSD) do not appear to support compulsive drug-seeking. Harkins and colleagues conclude that, given the high burden of substance dependence and the limitations of current treatments, there is an ethical imperative to investigate whether psychedelic drug-assisted psychotherapy can improve outcomes. They call for rigorous randomised trials, further mechanistic research and careful attention to safety, cost and regulatory pathways before these approaches could be recommended in routine clinical care.
People who are drug-dependent are often stigmatised, maligned by society and blamed. However, the experience of the authors -a child psychiatrist who now works in adult substance misuse (B.S.) and a behavioural psychologist who studies the environmental determinants of drug use (M.W.J.) -is that many of these patients are helpless, needy victims of adverse psychosocial circumstances. Their trajectory into drug dependence has been a journey from childhood trauma. Now they face not only their unresolved trauma but also the plight of drug dependence that ties them to a lifestyle of psychosocial and financial dysfunction. Because of the complexity of their aetiology and the psychological and physiological dependence that results, these disorders are very difficult to treat.
One adult in 20 in the UK is a dependent drinker and one quarter of all adults drink in a hazardous fashion.Alcohol dependency and misuse is a major factor in offending behaviour. It is strongly related to crime, including domestic abuse, antisocial behaviour, public disorder, sexual assault and motoring offences.A metaanalysis of 361 controlled studies of treatments for alcohol dependence in 2002 identified 46 possible interventions.The brief intervention approach ranked highest and motivational enhancement ranked second. Pharmacotherapy with the gamma-aminobutyric acid (GABA) agonist acamprosate and the opiate antagonist naltrexone ranked third and fourth respectively. The lowest ranked approaches were designed to educate, confront, shock or foster insight regarding the nature of alcoholism. There remains a lack of coherence and agreement about the most efficacious alcohol dependence treatment. Meanwhile, taking into account alcohol-related health disorders and disease, crime and antisocial behaviour, accidents, loss of productivity in the workplace and domestic problems, the Department of Health estimates alcohol misuse is now costing around £20 billion a year in England alone.
Misuse of heroin and related opioids is a major public health concern, with over 123 000 people injecting heroin in the UK. Those who use heroin have a 12-fold increase in mortality relative to the general populationand often present with severe physical, mental, social and criminal legal complications. Methadone and buprenorphine are the most commonly prescribed medications for opioid dependence. They have consistently been found to increase treatment retention and decrease opioid misuse, mortality, HIV risk and crime. However, these substitution treatments have limitations. Methadone is associated with medical risk and is contraindicated for some patients, and both medications are dangerous in combination with sedative drugs.
Cocaine is the second most popularly used illegal drug in the UK. In its powder form it may be snorted or injected, and in its freebase form crack cocaine can be smoked and injected. There is no accepted substitution treatment for cocaine or other stimulants as there are for opiates. Treatments rather involve psychological strategies including contingency management, cognitive-behavioural therapy and motivational interviewing. Drug therapies are largely symptomatic (i.e. addressing comorbid depression, anxiety and insomnia) or treat coexisting opiate dependence.
Although people who smoke are less marginalised than those using other drugs, tobacco is associated with more deaths than any other legal or illegal drug. The numbers are staggering -1 Can psychedelic compounds play a part in drug dependence therapy? Ben Sessa and Matthew W. Johnson Summary After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.
None. The British Journal of Psychiatry (2015) 206, 1-3. doi: 10.1192/bjp.bp.114.148031
Ben Sessa (pictured) is a consultant psychiatrist in substance misuse working for 'AddAction' in Weston-Super-Mare, North Somerset, and a senior research fellow at Cardiff University Medical School, UK. Matthew W. Johnson is Associate Professor at Johns Hopkins School of Medicine, Baltimore, USA tobacco kills over 1.2 million people annually in Europe alone.Although the most effective medications (varenicline, bupropion, nicotine replacement) improve success rates, the large majority of patients relapse even with these medications.There is a desperate need for improvement. An ongoing open-label pilot study in the laboratory of one author (M.W.J.) is showing promising results using psilocybin combined with cognitive-behavioural therapy for smoking cessation. If efficacy and safety are supported by a randomised trial, this approach may hold potential to have a substantial public health impact given the shocking mortality caused by smoking.
In the 1950s and 1960s psychiatrists Humphry Osmond and Abram Hoffer at the Weyburn Mental Hospital, Saskatchewan, Canada, used lysergic acid diethylamide (LSD) to provide a clinician-induced organic psychosis to encourage sobriety. They found that it was mystical spiritual experiences -not psychotic experiences -with the drugs that were associated with treatment success. With LSD they reported abstinence rates far surpassing other treatments before or since. Osmond, who famously coined the term 'psychedelic', also administered LSD to Bill Wilson, the founder of Alcoholics Anonymous, who recognised LSD therapy as beneficial for alcohol dependence. A large number of studies to treat alcohol dependence with LSD psychotherapy were conducted by other researchers in the 1960s until psychedelic research collapsed for sociopolitical reasons in the wake of largescale recreational drug use.
There are examples of the naturalistic use of psychedelic plants to tackle addictions by indigenous populations: these include the West African use of the iboga root (containing ibogaine), the South American use of ayahuasca (containing dimethyltryptamine) and the North American use of the peyote cactus (containing mescaline); all of which have been reported to reduce rates of alcohol dependence.
Personality change is relevant to drug dependence, given that maladaptive personality traits often accompany drug use disorders. Two observational studies from the early 1960s suggested positive personality and other therapeutic changes in criminal offenders.With colleagues, M.W.J. has recently revisited prisoner personality change interventions with positive results.This idea of mystical-spiritual experience resulting in personality change was also explored recently in studies in which volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance. Subsequently sustained positive changes in attitudes and behaviour were consistent with changes rated by community observers.Another possible mechanism for the anti-addictive properties of hallucinogens may involve an 'afterglow' period of several weeks described in early clinical research. It was suggested that this period gave patients emotional strength to continue abstinence and experience decreased cravings.A recent paper by Bogenschutz & Pommy further explored potential psychological and biological therapeutic mechanisms of psychedelics in the treatment of substance misuse disorders.
A team in Russia in the 1990s, driven by the theory behind Osmond's 1950s studies, investigated the potential role for psychedelic drug-assisted psychotherapy with ketamine for both alcohol and opiate addictions. The results of subsequent placebo-controlled studies on more than 1000 patients with alcoholism showed that ketamine produced total abstinence for more than a year in 66% of those in the ketamine group, compared with just 24% of the control group.Despite positive published results the Russian Federation forbids further research with ketamine. In addition to the previously mentioned study of psilocybin and nicotine addiction, an open-label pilot study investigating psilocybin-assisted psychotherapy in alcohol dependence is under way at the University of New Mexico (clinicaltrials.gov registration number NCT01534494). There are also observational studies in Mexico and New Zealand of ibogaine-assisted therapy and a study conducted in Canada looking at the role of ayahuasca in the treatment of drug dependence (seefor details of all these studies).
There may be objections to treating drug dependence with other potentially misused drugs. However, current treatments for drug dependence already involve maintenance pharmacotherapy with controlled drugs. In seeking enduring remission, psychedelic drug-assisted psychotherapy is not simply maintenance therapy. Moreover, although psychedelic drugs can be misused, many of them (psilocybin, LSD) do not support compulsive drug-seeking.
After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry.Research teams at major academic institutions worldwide are investigating psychedelic drug-assisted therapy and several independent research groups have emerged to work collaboratively on the cohesive organisation of research. This research is still in its early stages and the most effective methods have yet to be evaluated. There are several limitations. For example, psychotherapy sessions that last for many hours would be expensive and are unlikely to be a first-line intervention. Moreover, some individuals would be excluded from psychedelic therapy for safety reasons. Another challenge is that many of these drugs are restricted at the Schedule I or Class A level, forbidding all medical use outside of highly regulated medical research. A medical future for these compounds would require a change in regulatory status (e.g. to the level at which compounds with accepted medical use such as morphine and amphetamine are regulated) and a plan for the manufacture of approved compounds. Patients with drug dependence deserve the opportunity for the best available treatments from their psychiatric services. If there is a chance that psychedelic drug-assisted psychotherapy could improve outcomes for this population of patients, we owe it to them to research this area.
Create a free account to open full-text PDFs.
Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)
Papers in Blossom that reference this study
Forstmann, M., Sagioglou, C. · European Psychologist (2022)
Maia, L. O., Massarentti, C. M., Tófoli, L.F. · Psychopharmacology (2022)
Perkins, D., Opaleye, E. S., Simonová, H. et al. · Drug and Alcohol Review (2021)
Sessa, B., Sakal, C., O'Brien S. et al. · BMJ Case Reports (2019)
Garcia-Romeu, A., Davis, A. K., Fire Erowid et al. · Journal of Psychopharmacology (2019)
Noorani, T., Garcia-Romeu, A., Swift, T. C. et al. · Journal of Psychopharmacology (2018)
Johnson, M. W., Griffiths, R. R., Hendricks, P. S. et al. · Neuropharmacology (2018)
Barsuglia, J. P., Polanco, M., Palmer, R. et al. · Progress in Brain Research (2018)
Argento, E., Strathdee, S. A., Tupper, K. et al. · BMJ Open (2017)
Elsey, J. W. B. · Drug Science Policy and Law (2017)
Forstmann, M., Sagioglou, C. · Journal of Psychopharmacology (2017)
Talin, P., Sanabria, E. · International Journal of Drug Policy (2017)
Johnson, M. W., Garcia-Romeu, A., Johnson, P. S. et al. · Journal of Psychopharmacology (2017)
Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M. et al. · Journal of Psychedelic Studies (2016)
Kuypers, K. P. C., Riba, &. J., De La Fuente Revenga, &. M. et al. · Psychopharmacology (2016)
Soler, J., Elices, M., Franquesa, A. et al. · Psychopharmacology (2015)