Hallucinogen May Reduce Cancer Anxiety

No "Bad Trips"; More Studies on the Way

Nick Mulcahy

September 08, 2010

September 8, 2010 — Psilocybin, a hallucinogen that occurs naturally in "magic mushrooms," appears to be a safe and possibly effective treatment for anxiety in patients with advanced-stage cancer, say California researchers.

A 12-patient pilot study conducted at the Harbor-UCLA Medical Center in Torrance, California, showed that a single experience with the drug was associated with a significant reduction in anxiety at 1 and 3 months after treatment and improvement of mood that reached significance at 6 months.

The study is the first research on psilocybin for cancer-related anxiety in more than 35 years.

A variety of hallucinogens were the subject of studies from the 1950s to the early 1970s in cancer patients suffering from anxiety and despair, say the authors of the pilot study, led by Charles S. Grob, MD, professor of psychiatry at the UCLA David Geffen School of Medicine.

Despite "promising results," these previous studies were never followed up with more research, write Dr. Grob and colleagues in a paper published online September 6 in the Archives of General Psychiatry.

The compound was stigmatized from what occurred in the 1960s.

"The compound was stigmatized from what occurred in the 1960s," explained Roland Griffiths, MD, professor of behavioral biology at Johns Hopkins School of Medicine in Baltimore, Maryland.

Dr. Griffiths was not involved in the study and was asked for comment by Medscape Medical News.

He is leading another larger trial of psilocybin at Johns Hopkins for the treatment of anxiety in cancer patients who are at a variety of stages — not just advanced disease. There is a similar study being conducted at New York University. Both of these studies are now enrolling cancer patients.

"Anxiety in cancer patients can be enormously difficult to treat," said Dr. Griffiths. "These patients are facing core questions such as 'What is the meaning of life?' and 'Is there life after death?'. Xanax is not going to take care of that."

Safety and appropriate use are concerns, noted Dr. Griffiths, who has coauthored guidelines for responsibly conducting medical research trials with psilocybin and other hallucinogens in humans.

"These drugs are thought to be more dangerous than they actually are," he said, explaining that potential dangers can be diminished if they are administered to "carefully screened and prepared volunteers under monitored circumstances."

Nevertheless, oncologists might have a difficult time embracing the idea of using a hallucinogen for a common cancer symptom, suggested Dr. Griffiths.

It's not conventional pharmacotherapy.

"This protocol is really out of the box. It's not conventional pharmacotherapy," he said.

In terms of biochemistry, psilocybin is a 4-phosphoryloxy-N,N-dimethyltryptamine and 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," write the study authors.

Dr. Griffiths explained how psilocybin, when taken in supportive conditions, can create a "shift in anxiety that is completely unlike conventional therapies."

People receiving psilocybin, which has been taken for centuries for religious purposes, can have a "radical" shift in worldview, sense of self, and life, he said. In cancer patients, "the fear of death often melts away."

Such mystical revelation can also be experienced spontaneously through meditation, prayer, and religious practice, said Dr. Griffith.

"We know that psilocybin increases the probability of having such an experience," he said, citing research in the field among healthy individuals.

The psychological and spiritual revelations derived from psilocybin do not induce a lazy, passive state, Dr. Griffiths emphasized. "The experience often creates a desire to connect with friends, family, and caregivers."

"People generally have a deep sense of the interconnectedness of things," he pointed out, adding that this sensibility is at the "foundation of all moral and ethical codes of all major religions."

No Severe Anxiety Induced

The new study was a double-blind placebo-controlled study of a "moderate dose" (0.2 mg/kg) of psilocybin, in which subjects acted as their own control. The placebo was niacin, which was chosen because it often induces a mild physiological reaction, such as flushing, but no psychological alterations, explain the authors.

The 12 subjects had durations of cancer that ranged from 2 months to 18 years. All were in advanced stages of disease at the time of the study and suffering from anxiety.

Eight of the subjects had previous hallucinogen experience; in 4 cases, it was more than 30 years ago. The hallucinogens that were previously taken included lysergic acid diethylamide (LSD; 7 subjects), hallucinogenic mushrooms (5 subjects), peyote (2 subjects), and ayahuasca (2 subjects).

The subjects were informed about the range of potential emotional reactions to the drug, including "challenging psychological issues."

The study design called for participants to stay in a hospital clinical research room for a 6-hour session after ingesting either drug or placebo and then to return for another session weeks later. Thus, there were 2 sessions in total: 1 with the drug and 1 with placebo.

The room was decorated with flowers and fabric wall hangings to "provide a pleasing and comfortable environment," write the authors. A cardiac monitor was attached to the participants for 24 hours. Staff briefly checked in with study subjects every hour.

The overall scenario was relaxed, suggest the authors.

"The subject was encouraged to lie in bed wearing eye shades during the first few hours, as well as to put on headphones to listen to preselected music," they write.

The investigators found that the moderate dose of psilocybin produced no clinically significant adverse events, including cardiac events.

"All subjects tolerated the treatment sessions well, with no indication of severe anxiety or a 'bad trip'," write the authors.

Psychological testing was undertaken before and after the sessions, for up to 6 months. All 12 of the subjects completed at least 3 months of follow-up; however, 2 died and 2 became seriously ill during follow-up.

The State–Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 month (P = .001) and 3 months (P = .03) after treatment. Also, a "substantial but nonsignificant decrease" was evident for the state anxiety subscale 6 hours after psilocybin administration; this was not observed after placebo, write the authors.

The Beck Depression Inventory showed an improvement in mood that reached significance at 6 months. The authors note that the scores dropped — which indicates a positive response — early on, but only reached statistical significance at the end of the testing.

The Profile of Mood States test identified mood improvement after treatment with psilocybin "that approached but did not reach significance," said the authors.

Study Subjects Critical of Placebo

It was "almost always apparent" to study participants and staff which compound had been taken. A "consistent subject critique of the study was that the placebo sessions were perceived as far less worthwhile than those with psilocybin," report the Dr. Grob and his authors.

"Many of the subjects suggested that future protocols provide the opportunity for a second psilocybin session several weeks after the first," the authors add, explaining that the study subjects felt that a follow-up experience would "reinforce and extend the perceived therapeutic effects of the initial session."

Dr. Griffiths' ongoing study at Johns Hopkins provides just that. In a second session, participants will receive a higher dose of psilocybin.

According to the study authors, a higher dose might be more effective because previous researchers "reported more pronounced therapeutic effects with a higher-dose model."

Most of the volunteers self-referred.

Either way, conducting clinical trials of psilocybin is not easy, explained Dr. Griffiths, because of the difficulty in getting patients referred from oncologists.

"Recruitment has been slow," said Dr. Griffiths. "Most of the volunteers self-referred." He encouraged interested parties to visit the study Web site for more information.

The authors have disclosed no relevant financial relationships.

Arch Gen Psychiatry. 2010. Published online September 6, 2010. Abstract


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