Can Psychedelics Help Treatment Resistant Depression & Suicide?

Recently published studies on using psychedelics for treatment resistant depression in peer-reviewed journals and high-profile articles in the New Yorker, New York Times  and Wall Street Journal, have rekindled professional and public interest in the therapeutic use of psychedelic drugs. It is easy to understand the enthusiasm. The magazine and newspaper articles include accounts of patients with profound depression, demoralization associated with terminal illness, and anxiety related to post-traumatic stress disorder (PTSD), who experienced remarkable improvements, including some who had previously considered suicide.

Psychedelic properties of specific plants (mushrooms and cactuses) have been used for centuries by indigenous cultures to induce expanded states of consciousness and spiritual experiences. 

The recently published research strengthens findings of earlier studies, showing significant efficacy and few adverse effects when these medications are administered as adjuncts to psychotherapy to carefully screened patients, under medical supervision.

Three drugs, psilocybin, ketamine, and MDMA, have attracted most of the recent attention. Psilocybin, a naturally occurring drug found in psilocybe mushrooms, has strong and durable benefits for some patients with treatment-resistant depression, and for those with demoralization, anxiety, and depression associated with terminal illness. Ketamine, a Federal Drug Administration (FDA)-approved anesthetic with analgesic and psychedelic properties, has been used off-label in patients with treatment-resistant depression. In case studies and small clinical series, ketamine has shown notably positive effects. MDMA, a drug synthesized in 1912 as a potential anticoagulant, was later found to have strong psychoactive properties. In the 1970s and early 1980s, psychiatrists who administered MDMA in the context of psychotherapy observed sometimes dramatic improvements in patients suffering from severe, treatment-resistant PTSD.

Screening, Supervision, Set and Setting

Prescribed to carefully screened patients, in recommended doses, in the context of professional counseling and supervision, psilocybin and MDMA have proven to be notably safe. They have no tissue toxicity, do not interfere with liver function, have scant drug–drug interactions, and carry no long-term physical effects.

These drugs are not intoxicants in the usual sense. They do not dull the senses or induce sleepiness. On the contrary, sensory perception is intensified and attention is aroused. Although abuse syndromes have been reported, few people become habituated to these drugs.

Clinicians and researchers familiar with this class of pharmaceuticals emphasize the importance of screening, supervision, and “set and setting.”

Set and setting

Anthropologists studying traditional use of psychedelics by shamans and indigenous people recognized the influence of expectations and motivation on subjective experience. Since the earliest psychological research into pharmaco-assisted therapy with psychedelics, clinicians have emphasized the importance of “set and setting.”

The dissolution of assumptions and diminution of barriers caused by these drugs extend to psychological and interpersonal realms of experience. An enhanced sense of connection to others not only underpins some of the therapeutic effects, but also results in vulnerability to emotional contagion. When taken without adequate preparation and when surroundings are anxiety-provoking—either physically uncomfortable or emotionally intimidating—the psychedelic experience predictably results in fear, a prolonged sense of dread, or full panic. Conversely, in controlled settings with elements of soft light, art, and appropriate music, or nature, and gentle, compassionate people, such adverse reactions are rare.

With adequate counseling and preparation, and when psychedelic experiences unfold in calm, aesthetically pleasing environments, they prove beneficial in a high proportion of cases. In these situations, the healing motivations of both therapists and patients may contribute to therapeutic outcomes.

Therapeutic Effects

Clinical case studies and research trials describe common patterns of subjective experiences that are associated with therapeutic benefits for people with severe anxiety and depression. As the initial phase of psychedelic experience wanes and people regain familiar barriers between visual, auditory, tactile, olfactory senses, people typically report heightened cognitive clarity and expanded emotional receptivity. Previously unrecognized or unquestioned assumptions related to one's place in the world and relationships to nature, one's physical and social environments become available to being considered anew.

While psychedelic experiences vary significantly from one individual to another, research subjects and people interviewed for journalistic articles commonly express attributes, which include heightened clarity and confidence about their personal values and priorities, and a renewed or enhanced recognition of intrinsic meaning and value of life. People often voice a sense of exhilaration, insight, and strengthened connection to others, as well as a richer sense of relationship with nature or God. People who take psychedelics with an intention of spiritual introspection often report that the drugs opened windows into deeper realms of existential experience. In safe and supportive environments, these effects typically induce a state of wonder, conceptual frame shift, expanded capacity for love, and an intensified sense of connection. Patients living with medical conditions that had robbed them of hope or reason to live may experience a transformative shift in perspective and experience of inherent meaning, value, and worth.

Not all psychedelics drugs are alike and subcategories have been described. Drugs, such as psilocybin and LSD, classified as entheogens, are associated with introspection and new insights, shifts of perspective, and reframing of experience and relationship to others and the world. MDMA is characterized as an empathogen, referring to prominent emotional effects of interpersonal warmth, empathy, and openness. These properties may underlie the benefits of MDMA in the context of therapy for those suffering from severe PTSD.

For most of these drugs, a single six to eight-hour session or short series of sessions suffices for therapeutic benefit. Alleviation of anxiety and depression may persist for weeks to months and, for some, proves permanent. Exceptions to this treatment pattern include protocols of daily low-dose ketamine for depression and recent nonmedical reports of daily or every third day micro-dosing of LSD.

Treatment-resistant depression and anxiety associated with PTSD causes untold suffering and contributes to thousands of deaths each year. A few population health studies suggest that rising suicide rates may in part be due to suicide becoming less shameful and more socially acceptable, lowering barriers for people who feel hopeless. A person with severe depression, who has a coexisting serious, life-threatening physical condition, may feel that his or her quality of life is not worth living and may forgo arduous, but potentially life-saving treatments. Additionally, nearly one sixth of Americans live in states where physician-hastened death is legal and those with terminal illness may choose this option in absence of alternative sources of relief.

This article can be read in its entirety in the Journal of Palliative Medicine.