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. Psilocybin was studied during the 1960s to establish its psychopharmacological 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.
Recent clinical examinations of psilocybin have indicated that it is not hazardous to physical health. 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. 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 dose-response relationship.
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. 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.
Grob CS, Danforth AL, Chopra GS, et al. Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer. Arch Gen Psychiatry: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.
Recent clinical examinations of psilocybin have indicated that it is not hazardous to physical health. 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. 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 dose-response relationship.
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. 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.
Grob CS, Danforth AL, Chopra GS, et al. Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer. Arch Gen Psychiatry: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.

