In an Observations opinion article published on July 17, 2018, Rick Strassman critiqued our recent peer-reviewed assessment of medical psilocybin abuse liability, which was published in Neuropharmacology. Strassman's description of our review was vague (i.e., “the Hopkins group’s recent publication of a paper suggesting rescheduling psychedelics into Schedule IV”), and no citation sufficient for locating our review was provided.
In our publication, we reviewed the empirical evidence relevant to the abuse liability of medical psilocybin, following the eight-factor structure of the U.S. Controlled Substances Act (CSA) that is used to determine whether a drug should be scheduled and if so, into what schedule the drug should be placed.
We strongly agree with the author that psilocybin and related psychedelics are associated with risks. Studies by our group and others provide the evidentiary basis for the elements to ensure safe use (ETASU) that were discussed in our recent review. In 2008 our group published detailed recommended safety guidelines for clinical research with psychedelics (Johnson et al., 2008). For hundreds of research volunteers receiving psilocybin in our research, and for a growing number of volunteers at other research sites, these guidelines have minimized risks, including the potential that a participant might flee the laboratory while under the influence of a psychedelic, as has occurred in Strassman’s research.
We are also in agreement with the author that the risks of psilocybin should not be underestimated, whether in clinical research or in potential non-research approved clinical use. Indeed, our recent review concluded that psilocybin, if approved as a medicine, should remain scheduled. Moreover, our conclusion was that, if psilocybin were approved as a medicine, the empirical evidence per the eight-factor framework suggests that the most appropriate schedule for psilocybin would be Schedule IV.
While others might argue for another conclusion based on the empirical data, our conclusion neither dismissed the risks associated with psilocybin administration nor promoted wide clinical dissemination or incautious clinical use.
In reference to benzodiazepines, the Strassman critique stated that “[e]quating their risks and benefits with those of the psychedelics is clinically untenable and borders on the unethical.” This statement is offensive and misses the point. Benzodiazepines were only mentioned once in our review among several examples of Schedule IV compounds. Our objective was not to compare or equate psilocybin with other substances in Schedule IV but rather to follow the approach of the CSA, which considers eight factors that include clinical and nonclinical pharmacology and public health impact.
Nevertheless, while some risks are likely greater for psilocybin than for benzodiazepines (e.g., exacerbating psychotic disorders in those vulnerable to them), benzodiazepines carry greater risk with regard to habitual use and fatal overdose, especially when combined with other substances such as opioids.
Readers of Strassman’s critique might assume that we had recommended an immediate schedule change for “psychedelics.” In the abstract, and repeatedly in our review, we framed the empirically based appropriateness of Schedule IV as applying to psilocybin and only if phase III research eventually led to FDA clinical approval—a step that would require a schedule change. We stated clearly that this additional research is required before clinical approval of psilocybin and rescheduling.
Far from recommending widespread or incautious clinical use, our review proposed the use of legally binding risk mitigation strategies, such as the widely used FDA framework of Risk Evaluation and Mitigation Strategies (REMS). These mitigation strategies would restrict distribution, necessitate specialized training of clinicians, forbid at-home use, and require specialized clinical settings with appropriate safeguards. Quoted from our review:
"These drug formulation and intervention parameters would be addressed in an agreed upon risk management plan and would also likely be addressed in a legally binding Risk Evaluation and Mitigation Strategies (REMS) plan (U.S. Food and Drug Administration, 2015). The REMS would be based on the studies and approaches used to ensure safe and effective use and could include: a) limitations on the dose and the number of doses that could be administered to a given patient, b) administration of the drug in clinic settings with psychological support of specially trained staff, c) a variety of restrictions on distribution, access and storage, and d) a post-marketing surveillance plan to provide the FDA with timely and comprehensive communication of unintended consequences (Blanchette et al., 2015; Brandenburg et al., 2017; Dart, 2009; Dasgupta and Schnoll, 2009; U.S. Food and Drug Administration, 2015; Wu and Juhaeri, 2016)."
This approach is markedly different from the one that Strassman implies: "Moreover, veterinarians, nurse practitioners, physicians’ assistants, dentists, orthopedists and, in some states, psychologists, can prescribe Schedule II–V drugs. Making psychedelics readily available through these practitioners is not in the public interest."
Safety has been our top priority in research with psilocybin, and we have played a strong role in encouraging safety and responsibility in research and in potential future clinical use should the data eventually support FDA clinical approval. We therefore appreciate this opportunity to correct the record for the readers of Scientific American.