Can psilocybin and psychotherapy help relieve distress in long-term AIDS survivors?

• Clinical trials with hallucinogens in people with serious illness have been done or are underway
• Scientists in San Francisco undertook a pilot study with psilocybin in older HIV-positive men
• Although psilocybin appears promising, it is not ready for widespread use in HIV-positive people

The epidemic of HIV caused high rates of illness and death in communities of gay and bisexual men in the 1980s and early to mid-1990s. The subsequent development and distribution of effective HIV treatment (ART) has greatly reduced the risk of AIDS-related infection. Furthermore, the effects of treatment are so transformative that researchers increasingly expect that many ART users will have near-normal lifespans. However, clinicians and mental health specialists have found that there is a legacy of grief, loss, trauma, depression and demoralization among survivors of that era.

There are many potential combinations of interventions that can be applied to help relieve mental health issues, including group and individual psychotherapy, guided meditation and mindfulness, a combination of psychotherapy and antidepressants and/or anti-anxiety drugs. Mental health is complex—what works for one person may not work for another. Scientists are continually conducting clinical trials to refine existing approaches or find new ways of treating mental health conditions.

Psychedelics

Historical records indicate that some cultures used hallucinogens—derived from certain mushrooms—in spiritual practices. In the late 1950s, scientists isolated the chemical psilocybin from these mushrooms. In the 1960s, psilocybin was sold by the pharmaceutical industry to help treat mental health conditions when used together with psychotherapy. However, shortly thereafter, the sale and use of hallucinogens was restricted in many high-income countries, so clinical research on these compounds gradually diminished.

In the 21^st century there has been a renewed interest in hallucinogens as part of psychotherapy. Results from small clinical trials suggest that psilocybin together with psychotherapy has the potential to relieve distress—including anxiety and depression—in some people with terminal cancer. Spurred by these initial and promising findings, research teams are testing the combination of psilocybin and psychotherapy in other populations.

Psilocybin and psychotherapy in long-term survivors of AIDS

A team of neuroscientists in San Francisco recruited 18 long-term survivors of AIDS for a pilot study of psilocybin. All of the men were diagnosed with what the scientists called “moderate-to-severe demoralization.” They received a single dose of psilocybin followed by eight to 10 sessions of group therapy. Participants were monitored for at least three months.

Over time, scientists found what they called a “clinically meaningful” decrease in demoralization in the men. Although there were no life-threatening complications from psilocybin exposure, seven men experienced what the scientists called “self-limited, severe expected adverse reactions” to psilocybin. The study team hopes to conduct further research with a combination of psilocybin and individual psychotherapy in adults with diagnoses of severe medical illness in the future.

Study details

The scientists screened 91 volunteers with HIV but found that only 18 were eligible for the study. The average profile of participants was as follows:

• age – between 50 and 66 years
• all had been diagnosed between 1981 and 1996
• half of the participants had mental health diagnoses, including anxiety, depression and borderline personality disorder

Procedures

Prior to their first session of group therapy, participants met with two study therapists at the research clinic to do the following:

• build trust and rapport
• be educated about group therapy and psilocybin

At a subsequent visit to the research clinic, participants took a capsule of psilocybin (0.30 to 0.36 mg/kilogram of body weight). This visit was called the “medication visit.”

Safety was extensively evaluated, as psilocybin can affect blood pressure and heart rate. During the medication visit, participants had their blood pressure and heart rate monitored for several hours before and after they took the study drug. They were also extensively assessed for the drug’s impact on their mental health.

A day after the medication visit, participants met with the study therapists to discuss their experiences as a result of taking the drug and attempted to connect the experience with their everyday lives. Subsequently, participants attended group therapy sessions twice weekly.

Results – Safety

As psilocybin has not been formally studied in large clinical trials for decades, it is important to collect safety information. According to the scientists:

“No serious adverse events were attributed to psilocybin. During the medication visit, no participant required physical restraint or [new medications] for psychiatric or medical concerns, and all psilocybin-related adverse events were self-limited and expected, although there were two unexpected post-medication visit psilocybin reactions.” These are detailed later in this report.

Adverse events that occurred during the medication visit were temporary, as follows:

• eight people had anxiety reactions; some were moderate or severe
• four men developed paranoia
• one person developed a thought disorder whereby he felt disconnected from reality and engaged in conversation with himself

Four people developed significantly higher-than-normal blood pressure. The scientists felt that this was related to symptoms of anxiety. Eight others developed moderate elevations in blood pressure.

According to the scientists, these side effects were expected. However, two other people developed unexpected side effects, as follows:

• One person experienced a “moderate post-traumatic stress flashback” and developed nausea, ringing in the ears, panic and sleep problems.
• Another participant, who had been diagnosed with borderline personality disorder and had a history of what the scientists called “heavy polysubstance use,” initially lost much of his chronic anxiety. However, the scientists stated that “10 days later he reported severe anxiety, which he described as a deeply felt sense of being rejected by the other [group therapy] members. He then had a lapse in his methamphetamine use (after having been [free] from all substances for one month prior to entering the study) and withdrew from [group therapy] but completed most subsequent [study] assessments.”

None of the participants developed thoughts of suicide or attempted suicide during the study.

Changes to pre-existing issues

The scientists found a “robust” reduction in feelings of demoralization that persisted in many participants for up to three months after they took psilocybin.

The scientists also stated that participants’ degree of PTSD (post-traumatic stress disorder) and complex grief “seemed to improve over time.”

Bear in mind

According to the scientists, “this pilot study demonstrated the feasibility and relative safety and potential efficacy of psilocybin-assisted group therapy.”

The scientists suspect that the relatively high rate of adverse reactions was related to “the clinical complexity” of the people in the study.

The cardiovascular side effects of psilocybin have been documented in other studies that used a dose similar to that in the present study. Also, in the present study, when participants developed anxiety after taking psilocybin, scientists were able to calm the majority of them by simply speaking soothingly to them. This reduced the blood pressure of participants.

One participant who had a history of significant trauma developed severely elevated blood pressure for hours after taking psilocybin. The scientists normally would have offered him an anti-anxiety pill but could not do so because he also developed paranoia. Instead, clinicians dimmed the lights in the room and played soothing music; this caused his blood pressure to fall within the normal range.

The results of this study indicate that future clinical trials of psilocybin need to be done with carefully selected volunteers, with close clinical monitoring and in a setting of individual rather than group psychotherapy. Psilocybin is clearly not for everyone struggling with mental health issues, as the drug can elicit different reactions in different people. Perhaps future consideration should be given to testing reduced doses of the drug.

HIV infection and psilocybin

HIV infection causes chronic inflammation that is only partially reduced with ART. One consequence of this inflammation is an increased risk for cardiovascular disease. Fortunately, the temporary spikes in blood pressure did not lead to heart attacks or stroke in the present study. But this possibility, however unlikely, could cause scientists to limit their use of the drug in further experiments with older HIV-positive people.

More work that is exploratory needs to be done in the future if psilocybin is to be tested again in people with HIV. For instance, does psilocybin have the potential to interact with commonly used HIV drugs (and vice versa)? That is, do HIV medicines raise the level of psilocybin and the compounds into which it is broken down in the blood? Drugs that can raise the concentration of psilocybin in the blood have the potential to increase this compound’s side effects. Or, does psilocybin have any effect on HIV medicines and how they are broken down in the blood?

A large fraction of participants had mental health issues arising from the psychological effects of experiencing the early years of the HIV pandemic. This study underscores that mental health issues are a concern for long-term survivors of HIV/AIDS.

—Sean R. Hosein

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