LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects

This follow-up study (n=10) found long-term (12-month) positive outcomes from a single high-dose of LSD (200 μg) in combination with psychotherapy. The positive effects included reduced anxiety and a higher quality of life.

Abstract

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view.

Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.”

Authors: Peter Gasser, Katharina Kirchner & Torsten Passie

Notes

This is a follow-up to Gasser et al. (2014).

This paper is included in the meta-analytical review by Galvão-Coelho and colleagues (2021) that found psychedelics to improve mood (for those with mood disorders) both in the short and long term (up to 60 days).

Summary

Introduction

When LSD was discovered in 1943, a rich period of scientific and therapeutic investigations into mind-altering substances started. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction.

Psychological treatment of people suffering from a life-threatening disease is still mostly inadequate. The present study investigated the use of LSD in conjunction with intensive psychotherapy for patients suffering from existential anxiety.

Psychological effects of LSD

LSD increases sensory perception, induces a dream-like alteration of consciousness, and enhances mental imagery. Affectivity is intensified, thoughts are accelerated, and ego identification and ego boundaries are weakened.

LSD is a ‘non-specific amplifier of the unconscious’ that promotes access to thoughts, associations, feelings and inner processes normally excluded from consciousness.

Neurobiological effects of LSD-like hallucinogens

Indolealkylamine hallucinogens have high affinity to 5-HT receptors and significant modulation by 5-HT2C and 5-HT1A receptors. They also have effects on dopamine and adrenergic receptors.

Hallucinogens activate 5-HT2A receptors in the prefrontal cortex, which in turn activates glutamatergic transmission in the PFC and has downstream effects on serotonergic and dopaminergic activity in the dorsal raphe and ventral tegmental area.

The initial phase II double-blind, active placebo-controlled, randomized clinical trial was conducted in accordance with Good Clinical Practices. The Long-Term Follow-Up investigation was designed when the initial study was already running.

Procedure

Two LSD experiences were embedded in the therapeutic process at a 4 – 6-week interval. The participants stayed overnight in the physician’s office after the session.

Participants

Twelve participants qualified to participate in the initial study, 8 were given 200 g of LSD in 2 guided sessions, 4 were given 20 g of LSD in 2 guided sessions, and 10 were given 200 g of LSD in 2 guided sessions at the 2 month follow-up therapy session.

Seven out of 10 participants had life-threatening cancer, and the rest suffered from autoimmune, neurological and rheumatological diseases.

Psychometric measures for LTFU

The Spielberger State and Trait Anxiety Inventory (STAI) Form X served as the primary outcome measurement of anxiety, and other measures were taken during the treatment phase.

Qualitative measures

Qualitative semi-structured interviews were conducted with participants to explore subjective experiences, changes in daily life, quality of life, anxiety, attitudes and values as related to the LSD-assisted psychotherapy.

The Qualitative Content Analysis (QCA) summary type was used to evaluate the interviews. The interviews were formatted to allow comparisons between different participants’ experiences, impressions and statements.

Quantitative measures, STAI

Nine participants who received two doses of LSD (200 g) were evaluated. LTFU results showed that STAI state and STAI trait scores did not rise after end of the study.

Qualitative measures: semi-structured interviews

Nine participants reported positive benefits from LSD-assisted psychotherapy, including sustained reductions in anxiety, less fear of death, and an improved quality of life. All reported feeling more relaxed and patient with themselves and others.

None of the participants reported lasting negative effects from the LSD sessions, and there were no psychotiform reactions or suicides.

The following quotes are chosen to illustrate the core elements of the subjective experiences and some of the sustained changes reported.

Facilitated access to emotions and catharsis

LSD enhances affectivity, and this effect can be especially relevant when confronting an existential threat, such as a life-threatening disease. This may be interpreted as a psychological tightening up induced by grave anxiety and fear.

The LSD session set things free in my mind, which under normal conditions may not have appeared, because they might have been suppressed. I was surprised to find real stirring of emotions, which usually would not have felt with all my self-control and restraint.

I was very sad, I cried, never desperate, but a lot of sad things came up. Later on, I felt lightness, but I went relatively deep inside.

It is possible that the intensified emotional experiences can disturb an individual, but most patients valued the intensified emotional experiences as positive, and none reported any serious psychological problems resulting from their LSD treatments.

De-schematizing and viewing experiences in another perspective

LSD can alter the frame of reference, and therefore the perspective, of an individual. This can be compared to a set of photographic lenses, which can focus or enable the observation of things from a much more distant perspective.

LSD sessions allow you to relax, connect to your inner world, and put your illness into perspective. You start to think less about yourself, and you start building relations with plants and the entire living world around you.

Some patients experienced impressive changes in their emotional state during the LSD experiences. Some experienced these changes during the experience itself, while others manipulated the emotional state in the second LSD session after getting accustomed to the state during their first LSD experience.

The first trip was a panic trip, the second trip was a little tensed, but soon it became bright, everything was light, and I felt like floating, clear, being carried and together with the music.

During the session, I thought about whether I am on the right path. LSD gave me the feeling that I was, and that everything I do is actually good.

The patients initially experienced aspects of their situation related to negative emotions, but later on they experienced a much more positive basic emotional tone, which gave them a new baseline for how to feel in their life situation.

perspectives, attitudes, values

After the trips, I think certain changes happened, like a shift in values, taking time to listen to music, and realizing other values are more important than material values. This helped me to draw boundaries with my biological daughter.

LSD gave me total confidence that everything I do is actually good, and I was able to take a lot of things with me into my daily life.

After taking LSD for six hours, I was able to let go of my mother’s family’s Nazi past history and realize that it is not my fault. I became relaxed, more patient and I believe LSD helped me realize that it is okay.

Increases in quality of life

The long-term increase in quality of life was another frequently mentioned benefit of LSD-assisted psychotherapy.

Quality of life changed enormously for the patient due to becoming calmer, taking things easier and approaching death with equanimity. She was also able to express herself much more freely and was not afraid anymore of saying things in community with others.

Participant #6 experienced intense joy, which he called desirable, pleasant and important. Participant #8 noticed that falling asleep was possible again without revolving thoughts.

Comparing LSD in psychotherapy with usual psychotherapy

Most clients mentioned facilitated access to emotions, important insights, faster progress, accessing feelings of safety and facilitation of ‘letting go’ as the main features of LSD-assisted psychotherapy in comparison with usual psychotherapy.

Possible negative aspects of the treatment

All patients reported that there were no negative effects that lasted beyond the duration of the sessions. Some subjects felt a little threatened in the beginning, but this feeling did not last.

It felt like a glass of water being stirred with mud, and then sinking to the ground. The next day it felt like being stirred again.

Observations on headaches

Two of the study participants reported reduced migraine cycles after LSD treatment. One participant reported no migraine in the 12 months up to the LTFU.

Discussion

The present study has shown that psychological improvement achieved during 3 months of LSD-assisted psychotherapy is stable over a 12-month period. The improvement was accompanied by positive psychological changes in the subjects.

The present study is in some major components equivalent to psychedelic therapy, but allowed for more cognitive, psychodynamic and interpersonal aspects. The typical psychological reaction to a life-threatening disease is an anxiety/depression-driven tendency for interpersonal isolation and the attempt to harden oneself against the threat.

psychological level

LSD-assisted psychotherapy involves a combination of mechanisms operating in conventional psychotherapy, such as facilitating emotional and intellectual insights.

The cognitive experience is characterized by astonishingly lucid thoughts and altered associations, the psychodynamic experience by an emergence of material into consciousness that was previously excluded, and the psychedelic peak experience by meaningful new insights.

LSD may have therapeutic effects in some individuals, especially those who have psychedelic peak experiences.

The most moving subjective experiences reported in the present study were intense emotional experiences, characterized at first by a tense and anxiety-laden confrontation with emotions and aspects of their actual life situation.

I got from dark to light, from tensed to total relaxation, and I felt sublime. Love, expansion, holding, I knew that sometimes this happens, that participants talk about spiritual experiences.

Patients reported experiencing a tension-free state of well-being, a relative freedom from concerns of the past as well as from guilt, depression and anxiety, and an accentuated orientation in the here and now.

Several authors have shown that LSD-like substances can facilitate peak experiences or mystical experiences, but these experiences do not match the criteria for mystical experiences on the Pahnke – Richards Mystical Experience Scale. Maslow’s definition of peak experiences is “moments of pure, positive happiness” when all doubts, all fears, all inhibitions, tensions, all weaknesses are left behind. These experiences may be similar to mystical experiences, but without some essential features.

The central characteristic of enlightenment is the loss of all worry, the sense that all is ultimately well with one, and the sense of perceiving truths not known before.

During altered basic emotional experiences, intellectual functions were to a greater degree intact, and ego boundaries were certainly loosened, but not completely absent. Patients may gain a new perspective on themselves and a reduction of ruminations and ego-centredness.

James describes how a mind is a system of ideas, which can be changed by a sudden emotional shock. This can explain the changes seen in our patient population.

The psychophysical mechanisms of psychedelic peak experiences are essentially unknown, but may be related to an alteration of the homoeostasis of the individual’s psychological system, resulting in a breaking up of fixated psychological habits, defence mechanisms and entrenched thought patterns.

Possible neurobiological mechanisms of action

Neuroimaging studies suggest that psilocybin alters the integrity of the default-mode network (DMN), which is responsible for mood regulation and high-level constructs such as the self and the ability for self-reference. This may lead to changes in perspective and re-evaluations of situations and persons.

Long-term results suggest that LSD-like hallucinogens may improve patients’ psychological traits, behaviour and basic emotional tone by ‘breaking up’ a more fixated and less dynamic neurobiological matrix of functioning, accompanied by emotional bias, altered responsiveness and reduced flexibility in the emotional and cognitive sphere.

Patients with depressive and anxiety disorders show reduced PFC activity and hyperactivity within the amygdala in response to negative stimuli. Hallucinogenic indolealkylamines may strengthen PFC activity and thereby reverse the emotional-cognitive bias.

The administration of the hallucinogenic 5-HT2A agonist DOI increases the brain neurotrophic factor BDNF in different regions of rat brain, which may contribute to the sustained psychological effects of some hallucinogens.

Rates of improvement

In studies in the past, patients with end-stage-cancer treated with LSD-assisted psychotherapy showed dramatic improvement, one-third moderate improvement, and one-third was essentially unchanged. In the present study, moderate improvement was observed in all patients, but no dramatic improvement was seen.

Possible harmful aspects of the LSD experience

It is possible that intensified emotions/thoughts/experiences may disturb an individual’s ability to cope with a difficult situation, but if the dose and setting are appropriate, only those emotions/thoughts/experiences enter the consciousness which can be coped with within the patient’s psychological capacity.

Limitations of the study

The cross-over design of the study was ethically problematic, so a placebo control group was not used in the follow-up.

Conclusion

LSD-assisted psychotherapy demonstrated safety and positive stable treatment outcomes in patients with life-threatening diseases.

Study details

Compounds studied
LSD

Topics studied
Anxiety

Study characteristics
Follow-up Interviews Qualitative

Participants
10 Humans

Authors

Authors associated with this publication with profiles on Blossom

Peter Gasser
Peter Gasser has done work on LSD and life-threatening diseases in Switzerland since 2008. He is a psychiatrist, psychotherapist, and study lead, working in private practice.

Torsten Passie
Torsten Passie has done work on the psychedelic experience (altered states of consciousness) and the pharmacology of hallucinogenic drugs. He is currently a visiting professor at Harvard Medical School.

Institutes

Institutes associated with this publication

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

Compound Details

The psychedelics given at which dose and how many times

LSD 20 - 200
μg

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases
This double-blind, cross-over study (n=12) showed that LSD (200 μg, 2 sessions) in combination with psychotherapy was safe to use and trended towards a positive effect on end-of-life anxiety.

Linked Clinical Trial

Lysergic Acid Diethylamide (LSD)-Assisted Psychotherapy in People With Illness-related Anxiety
This study will find out whether psychotherapy combined with lysergic acid diethylamide (LSD) is safe and is helpful in people who are anxious because they have a potentially fatal disease. The study will measure anxiety and quality of life before and after people have two sessions with either full or active placebo dose of LSD. They expect LSD-assisted psychotherapy to reduce anxiety and improve quality of life.

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