Risks, abuse potential
The abuse potential of psychedelics is an ongoing concern for the public, researchers, and regulators, but the consensus among nearly all of these experts is that when administered by medical professionals in controlled settings, these drugs are associated with extremely low risk.
It is recreational use that presents an abuse concern, said Dr. Ferreri, but with the low doses used in psychiatry, the risk is “very limited or even nonexistent.”
Dr. Nutt said the abuse potential of psychedelics is so low that they can be used to treat addiction.
“Functionally, psychedelics are antiaddictive,” Dr. Nutt said. “The fact is, if you take them repeatedly, you develop tolerance, and the effect disappears. You can’t overcome it. But everyone believes they’re addictive because they’re scheduled drugs.”
Dr. Velásquez is something of an outlier. He believes the abuse potential with psychedelics is poorly understood and that some patients may develop tolerance, which is a potential gateway to dependence.
“Such is the case with LSD,” he said, “where this substance also favors tolerance to other psychedelic drugs such as psilocybin.”
Dosing also seems to play a key role in mitigating potential abuse, said Luca Pani, MD, professor of pharmacology and psychiatry at the University of Modena, Italy. Dr. Pani explained that with low doses and microdoses of psychedelics, the potential for abuse is eliminated.
Dr. Nutt, Dr. Pani, and Dr. Ferreri also noted the importance of medical supervision. For instance, said Dr. Ferreri, when administering ketamine, his team closely monitors both mental and physical parameters – heart rate and blood pressure, in particular – because the drug can have hypertensive effects.
Dr. Schenberg noted that ibogaine, a naturally occurring psychedelic frequently used by traditional communities in Africa in rituals and for healing purposes, could cause potentially fatal arrhythmias, so it’s critical that the treatment is administered in a hospital setting that has a cardiac unit.
Dr. Pani said there is a need for more research, especially regarding the molecular mechanisms behind the behavioral effects of low-dose psychedelic therapy and the potential risks of multiple treatments with the drugs.
“Although extensive toxicology has been conducted on a single active dose of psilocybin, which has been proven to be safe, further research is required to understand better the possible health risks, especially in relation to cardiac and lung tissue,” he said.
Psychologically challenging
The experts note that given the relative lack of experience with psychedelic therapy, preparing patients for potential adverse effects is paramount. This is particularly relevant in the research setting and highlights the need for adequate patient screening and aftercare.
Dr. Gründer and Dr. Dolengevich-Segal emphasized the importance of having qualified personnel available in the event that patients experience adverse psychological events during treatment.
For Dr. Gründer, the potential for psilocybin to cause patients to lose control, experience psychotic symptoms, or become paranoid warrants considerable preparation by treating physicians.
Patients occasionally experience fear and anxiety during treatment, though it’s usually short-lived, said Dr. Griffiths. Nevertheless, these experiences may open the door to greater insight. “A number of people report that these psychologically challenging states are a valuable part of the overall experience,” he said.
The situation is similar in Spain, where Dr. Dolengevich-Segal noted that typical treatment regimens have a strong focus on the patient’s experience as a therapeutic tool. As in the United Kingdom and the United States, her team guides patients to what they call a “peak experience,” which allows them to gain a better understanding of the trauma underlying their mental health problems.
Dr. Nutt said that in the United Kingdom, they haven’t seen adverse reactions in patients receiving psychedelic therapy, although sedatives such as benzodiazepines could be used to manage them. He added that at his center, two therapists are present at every treatment session, and all personnel are “trained medics or psychologists.”