Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer, Charles S. Grob et al., 2010

Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

Charles S. Grob,  Alicia L. Danforth,  Gurpreet S. Chopra,  Marycie Hagerty, Charles R. McKay, Adam L. Halberstadt,  George R. Greer

Archive of  General Psychiatry, 2010, 68, (1), 71–78

doi: 10.1001/archgenpsychiatry.2010.116


Context : Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer.

Objective : To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety.

Design : A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin.

Setting : A clinical research unit within a large public sector academic medical center.

Participants : Twelve adults with advanced-stage cancer and anxiety.

Main Outcome Measures : In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment.

Results : Safe physiological and psychological responses were documented during treatment sessions.
There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance.

Conclusions : This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field.

Trial Registration : clinicaltrials.gov Identifier: NCT00302744


IN RECENT YEARS, THERE HAS BEEN a growing awareness that the psychological, spiritual, and existential crises often encountered by patients with cancer and their families need to be addressed more vigorously. 1-4 From the late 1950s to the early 1970s, research was carried out exploring the use of hallucinogens to treat the existential anxiety, despair, and isolation often associated with advanced-stage cancer.5-15 Those studies described critically ill individuals undergoing psychospiritual epiphanies, often with powerful and sustained improvement in mood and anxiety as well as diminished need for narcotic pain medication. Despite these promising results, there has been no follow-up research.

Today, the medical value of hallucinogens is again being examined in formal psychiatric settings. One substance under investigation is psilocybin, 4-phosphoryloxy- N,N-dimethyltryptamine, which occurs in nature in various species of mushrooms. Psilocybin is rapidly metabolized to psilocin, which is a potent agonist at serotonin 5-HT1A/2A/2C receptors, with 5-HT2A receptor activation directly correlated with human hallucinogenic activity. 16 Psilocybin was studied during the 1960s to establish its psycho-pharmacological profile; it was found to be active orally at around 10 mg, with stronger effects at higher doses, and to have a 4- to 6-hour duration of experience. Psychological effects were similar to those of lysergic acid diethylamide (LSD), with psilocybin considered to be more strongly visual, less emotionally intense, more euphoric, and with fewer panic reactions and less chance of paranoia than LSD.17,18

Recent clinical examinations of psilocybin have indicated that it is not hazardous to physical health.19 Positron emission tomographic studies demonstrated that psilocybin produces a global increase in cerebral metabolic rate of glucose, most markedly in the frontomedial and frontolateral cortex, anterior cingulate, and temporomedial cortex. These changes were correlated with measures of psychological state and consistent with potential neurobiological substrates of major mental illnesses.20

In one recent study, 36 healthy volunteers received a high dose (30 mg/70 kg) of psilocybin with no sustained deleterious physiological or psychological effects. The investigators corroborated previous findings that psilocybin could reliably catalyze mystical experiences leading to significant and lasting improvements in quality of life.21 In another study, the effects of psilocybin were examined in patients with severe, refractory obsessive- compulsive disorder. Researchers concluded that psilocybin is safe and well tolerated in subjects with obsessive- compulsive disorder and may be associated with “robust acute reductions” in core obsessive-compulsive disorder symptoms, although there was no clear doseresponse

During the first wave of hallucinogen research from the 1950s through the early 1970s, investigators who administered hallucinogens to patients with end-stage cancers reported results that included improved mood and reduced anxiety, even in those with profound psychological demoralization.23-26 The present study is the first in more than 35 years to explore the potential utility of a psilocybin treatment model for patients with reactive anxiety associated with advanced-stage cancer.27