Psilocybin

To examine the effect of two psilocybin doses on symptoms of anxiety and depression among patients with advanced cancer

Participants were assigned to two groups: one received low-dose psyilocybin in the first session and high-dose psyilocybin in a second session. The other group received psilocybin doses in reverse order. The first session was done about one month after study entry, and the second session was five weeks later. Study measures were obtained at baseline, during, and at the end of each session, and approximately six months later. Session monitors met with patients prior to sessions to establish rapport and prepare the patient for the sessions. Drug session were done in a living room-like environment with two monitors present.

• N: 56 (46 at 6 months)   
• MEAN AGE: 56.3 years (SD = 1.4)
• MALES: 51%  
• FEMALES: 49%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: All had life-threatening cancer diagnoses and DSM-IV diagnoses of anxiety or mood symptoms  Various tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: 69% married, 47% used cannabinoids, 51% had prior medication for anxiety or depression.  Almost all had at least a college education

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Johns Hopkins, Maryland

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care

Crossover, double blind, randomized study

• Cardiovascular monitoring during sessions
• Session monitor ratings of participant behaviors and mood throughout session
• Hallucinogen Rating Scale
• 5 Dimension Altered States of Consciousness
• Mysticism Scale
• States of Consciousness Questionnaire
• Mystical Experience Questionnaire
• GRID-HAM-D-17 (for depression)
• HAM_A (for anxiety)
• Beck Depression Inventory
• Hospital Anxiety and Depression Scale 
• POMS 
• Spiritual Religious Outcomes Scale
• STAI State trait anxiety

There were no serious adverse effects of the intervention. There were transient moderate increases in blood pressure after psilocybin. Transient psychological distress was seen in some patients with high-dose psilocybin. All measures of depression, anxiety, and total mood disturbance showed significant improvement with high dose (p < 0.001). Death acceptance and optimism also were increased with high-dose intervention (p < 0.01). These changes were maintained at 6 months.

High-dose psilocybin under supportive conditions was shown to decrease symptoms of depression and anxiety, and improve mood, optimism, acceptance of death and spirituality. These effects were generally maintained for months after drug use.

• Small sample (< 100)
• Risk of bias (no control group)
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Subjects took a large battery of tests repeatedly raising the question of possible testing affect and subject fatigue. The intervention was provided in a controlled supportive environment

Administration of psilocybin under controlled supportive conditions was shown to have multiple benefits for patients with terminal cancers. Further confirmatory research is warranted, and research comparing outcomes with psilocybin to other appropriate interventions would be helpful.

To explore the safety and efficacy of psilocybin in patients with advanced cancer and anxiety

Each participant received two treatment sessions, one with placebo and one with psilocybin, provided in random order. A niacin placebo was used, and psilocybin was given orally at a 0.2 mg/kg dosage. Sessions took six hours, provided in a clinical research unit with direct constant staff observation. Vital signs were measured 30 minutes before drug ingestion and at hourly intervals. All had continuous Holter monitoring. Study instruments were administered the day before each session, the day after the session, two weeks after sessions, and at monthly intervals for the next six months. At the end of each session, participants discussed their experiences. Participants were followed via monthly phone calls.

• The study reported on a sample of 12 patients.
• Patient age range was 36–58 years (average not reported).
• The sample was 92% female and 8% male.
• All patients had advanced stage cancer, including breast, colon, ovarian, peritoneal, salivary gland, and multiple myeloma. Duration of diagnosis ranged from 2 months to 18 years. All patients had a DSM-IV diagnosis of acute stress disorder, generalized anxiety disorder, or adjustment disorder with anxiety.
• Patients were excluded if they had central nervous system disease, cardiovascular illness, other severe comorbid uncontrolled conditions, or lifetime history of psychiatric disorders.
• Of the sample, 75% had prior experience using hallucinogenic agents, including LSD, mushrooms, peyote, and ayahuasca.

• Single site
• Outpatient setting
• California

• Patients were undergoing end-of-life care.
• The study has clinical applicability for end-of-life and palliative care.

A within-subjects, double-blind, placebo-controlled study design was used.

• Beck Depression Inventory (BDI)
• Profile of Mood States (POMS)
• State-Trait Anxiety Inventory (STAI)
• Brief Psychiatric Rating Scale
• Five Dimension Altered States of Consciousness Profile

All patients completed three months of follow-up, and eight patients completed six months of follow-up. Psilocybin induced a mild but statistically significant elevation of heart rate and diastolic blood pressure compared to the placebo. Heart rate peaked at two hours, with a peak rate of 81.5 on average. Blood pressure also peaked at two hours at a mean of 138.9 systolic, compared to a baseline average of 117. Holter monitor recording showed no significant differences from placebo session results. BDI scores dropped by almost 30% from the first session to one month after the second session (p = 0.05). This difference was sustained for six months (p = 0.03). Improvement in POMs were observed in 11 patients after psilocybin administration. STAI results showed improvement in state anxiety at one month (p = 0.001) and three months (p = 0.03).

As administered here, psilocybin administration was associated with sustained improvement in depression and anxiety, with no serious cardiovascular adverse effects.

• The study sample was small, with less than 30 patients.
• Patients did know the difference in experience between psilocybin and placebo, so patient blinding was not realistically accomplished.
• Given the results with potential of long-term effect, the control condition was not really valid, except for immediate vital signs responses.

Studies done in the 1960s and 1970s showed that hallucinogens had therapeutic benefits for patients with terminal cancer, and this pilot feasibility study shows similar results. As provided here, administration of psilocybin was accomplished in a clinical research unit with constant staff monitoring, which may not be widely practical in terms of cost and manpower. Further research in the use of hallucinogens in patients with anxiety and depression are needed to determine the most appropriate dosages, and whether they can be used in a less controlled setting for therapeutic benefit. The majority of patients had prior experience with hallucinogens; it is not clear if similar results would be seen if patients had no such prior experience.