Psychedelic medicine: a re-emerging therapeutic paradigm

This commentary (2015) analyses emerging research on psychedelic drugs for therapeutic purposes that involve humans and considering both the potential benefits and the possible harmful effects of using psychedelics in combination with psychotherapy or counselling for mental disorders illness.

Abstract

“In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes.

The public is often well-versed in the potential harms of psychedelic drugs, but much of this knowledge is from cases involving patients who used illicit substances in unsupervised nonmedical contexts. We discuss the emerging research for therapeutic purposes involving human subjects, considering both the possible benefits and the potential harms of using psychedelic agents as adjuncts to psychotherapy or counselling for mental illness.“

Authors: Kenneth W. Tupper, Evan Wood, Richard Yensen & Matthew W. Johnson

Summary

Renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder. These studies acknowledge the importance of set, setting and the therapeutic clinician-patient relationship.

Public knowledge of the potential harms of psychedelic drugs is based on cases involving patients who used illicit substances in unsupervised nonmedical contexts.

Types of psychedelic drugs

There are two classes of psychedelic drugs: classic psychedelics and “entactogens”. The classic psychedelics act as agonists at the 5-HT2A receptor, while the entactogens act as serotonin-releasing agents.

This review will focus on clinically relevant studies with patient populations in which psychedelic drugs are used as adjuncts to psychotherapy.

Contexts and indications

Psychedelic-assisted treatments are currently being researched for anxiety, addiction and PTSD. Further study is warranted before any unambiguous clinical utility may be confirmed.

Anxiety

A randomized controlled trial in Switzerland showed that LSD-assisted psychotherapy could reduce the anxiety associated with terminal illness. The study showed no acute or chronic drug-related severe adverse events, and no adverse effects lasting more than one day after an LSD-assisted session.

Psilocybin has shown promise as a treatment for anxiety in patients with terminal illness, and MDMA-assisted therapy is being studied as a treatment for social anxiety in adults with autism.

Addiction

Researchers in the 1950s and 1960s studied the use of psychedelic-assisted therapy for the treatment of addictions, and found that it had a significant beneficial effect. In renewed clinical research, psilocybin-assisted therapy reduced alcohol dependence in participants by more than half.

Research shows that psilocybin-assisted psychotherapy can help people who are addicted to tobacco to quit smoking. The research team is currently designing a follow-up study to compare psilocybin-assisted psychotherapy with nicotine-replacement therapy.

Ayahuasca is a plant-based preparation with the psychoactive constituents DMT and harmala alkaloids. Observational research shows that people who regularly drink ayahuasca have better mental health and lower rates of substance use than people who do not drink ayahuasca.

Posttraumatic stress disorder

In a pilot randomized controlled trial, 20 participants with chronic treatment-resistant PTSD received two MDMA-assisted psychotherapy sessions. All participants showed a significant and sustained reduction in PTSD symptoms, and 74% of participants still showed meaningful, sustained reductions in their CAPS scores three and a half years later.

A small randomized controlled trial in Switzerland comparing full-dose MDMA-assisted psychotherapy with low-dose active placebo showed that self-assessment of PTSD symptoms was significantly reduced.

Historical lessons

Experience from previous research has provided important lessons for current methodological designs, ethical strictures and clinical protocols, and for renewed research on psychedelics involving human participants.

Although methodological and political challenges remain to some degree, recent clinical studies have shown that psychedelics can conform to the rigorous scientific, ethical and safety standards expected of contemporary medical research.

Potential risks and their mitigation

Most psychedelic drugs have no medical purpose and a high potential for abuse. They may precipitate psychotic breaks in people with psychotic disorders.

A risk associated with psychedelic drugs is Hallucinogen Persisting Perception Disorder (HPPD), but the incidence of adverse effects is believed to be relatively low and is generally associated with illicit use of psychedelics in uncontrolled settings without supervision.

Under clinical supervision, psychedelics may cause anxiety, fear, heart rate and blood pressure increases, delayed-onset headache, and possibly other adverse effects. These effects are manageable, and no long-term harms have been reported.

Contemporary psychedelic studies take place in health care facilities, in quiet treatment rooms with pleasant and comfortable decor, and include a two-person cotherapist team. The patient is encouraged to spend much of the time engaging in self-reflection while listening to carefully selected music.

Questions for future research

Numerous scientific and empirical questions remain in the field of psychedelic medicine. Further research is needed to understand how psychedelic drugs work neuropharmacologically and to determine optimal therapeutic protocols for these forms of treatment.

Beyond basic research on neuropharmacological mechanisms and clinical outcomes, psychedelic therapies may prove to be economically viable in comparison with currently available treatments.

Conclusion

Scientific interest in psychedelic medicine is generating new knowledge about a class of pharmacologic substances that humans have long used for ceremonial, therapeutic and cultural purposes. Medical school curricula may need to be updated to include the latest knowledge about psychedelic drugs.

Policy-makers should be aware of and open to new approaches to treatments emerging in the field of psychedelic medicine, as these may offer new ways to treat mental illness and addiction in patients who do not benefit from currently available treatments.