Safety is of the utmost importance when discussing any sort of drug. Not only do scientists have to prove drugs are therapeutically effective, but they must also ensure drugs are safe for human consumption. Various procedures are in place in order to determine the safety and efficacy of drugs. Regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are tasked with ensuring these procedures are strictly adhered to during the drug development process. The development process generally begins with the submission of an Investigational New Drug (IND) application which contains the results of preclinical tests of the drug in animal models. The IND is then reviewed by the FDA or EMA and an independent panel consisting of both scientists and non-scientists. Clinical trials involving humans can only begin if the review finds that the proposed clinical trial protocols are satisfactory. Researchers must explicitly state the drug under investigation, what dose it will be administered in and the type of people it will be administered to, amongst other things. Once approved for testing, clinical trials can begin. In Phase-I of the clinical trial process, healthy volunteers are given the drug in order to determine levels of toxicity, how the drug is metabolized and if there are any side effects. Phase-II is more focused on the effectiveness of the drug although safety is continually evaluated. Phase-III studies then begin which further assess safety and effectiveness in a much larger and more diverse sample. Upon completion of Phase-III, those sponsoring the trials must submit a New Drug Application (NDA) to the regulatory authorities before bringing the drug to market. The NDA contains all the data for both animal and human studies to further assess safety and effectiveness (FDA, 2017). The entire process of drug development is a lengthy and expensive process, with many drug candidates failing at some stage of the process. At present, a whole range of psychedelics drugs are at various stages of the clinical trial process, proving that these drugs are both safe and effective.

Psychedelics have a relationship with society like no other pharmacological agent. Research into this class of psychoactive drugs in the middle of the 20th century is notoriously marred with methodological flaws and practices which are considered unsafe by today’s standards. For years the media have largely portrayed psychedelics as extremely dangerous drugs (Nichols, 2016). Today, researchers must contend with the fallout from this era of research in order to prove that these drugs are both effective and safe. To do so, psychedelics are being put through the gold-standard testing procedures of drug development, randomized-controlled trials (RCTs). In RCTs, the study population is carefully selected and then randomly assigned to either a treatment group or a control group. The treatment group receives the drug being studied and the control group receives a placebo, all while randomization reduces the likelihood of biased results (Hariton & Locascio, 2018). However, treatment models using psychedelics do not fully align with this gold-standard and problems do exist. Firstly, RCTs do not account for how extra pharmacological variables influence the drug experience yet these extra pharmacological variables have been deemed essential to facilitating the psychedelic experience (Carhart-Harris et al., 2018). Furthermore, the effects of psychedelics are potent which makes blinding in these trials difficult (Muthukumaraswamy et al., 2021). Regulatory bodies also tend to require large sample sizes to prove a drug’s efficacy and safety but at present, sample sizes in trials using psychedelics tend to be quite low. Reasons for this could relate to psychedelics being expensive and difficult to procure, as well as psychedelic-assisted psychotherapy being a labour-intensive process given the time required for preparation, integration and the experience itself. Nevertheless, researchers are working within the regulatory requirements with great success.

On the basis of a wide range of research, psychedelics are considered physiologically safe and do not lead to dependence or addiction (Nichols, 2016). This evidence stands in contrast with psychedelics current position as Schedule I substances, which have no accepted medical value and also possess high abuse potential. Interestingly, Matthew Johnson and his colleagues at Johns Hopkins used the very same factors of the Control Substance Act which classify psychedelics as Schedule I substances to assess the abuse potential of psilocybin. Johnson and his colleagues found that although potential harms exist for unprepared, unsupervised users, and in those with or predisposed to psychotic disorders, modern research addresses these concerns with dose control, patient screening, preparation and follow-up, and session supervision in a medical facility (Johnson et al., 2018). Moreover, these researches suggest that psilocybin would be more appropriately classed as Schedule IV substances given its therapeutic potential and safety.

What makes psychedelics all the more interesting is the ability of extra pharmacological factors to influence the experience, be it positively or negatively. As a result, therapy rooms in which psychedelics are administered are manipulated to ensure patients have a safe and positive experience. Again, Johnson and his colleagues at John Hopkins are accredited with writing the go-to guidelines for conducting psychedelic research in humans (Johnson et al., 2008). In their seminal paper, Johnson and his team emphasize that the physical environment be free of extraneous medical or research equipment, in combination with careful volunteer screening, volunteer preparation and interpersonal support from two or more trained monitors, may help to minimize the probability of acute psychological distress during psychedelic studies and ensure the safety of patients (Johnson et al., 2008).

Overall, adverse physiological reactions to classic psychedelics are rare (Nichols, 2016). Nonetheless, psychedelics can create severe psychological distress and should be approached with caution. As psychedelic research is progressing, researchers and regulators are working together to realize the potential of psychedelic drugs in a manner that is safe for all those involved.

References

• FDA. (2017). The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective. Food and Drug Administration. Retrieved from https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-ensuring-drugs-are-safe-and-effective

• Hariton, E., & Locascio, J. (2018). Randomised controlled trials—the gold standard for effectiveness research. BJOG. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235704/#

• Johnson, M., Griffiths, R., Hendricks, P., & Henningfield, J. (2018). The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology, 143-166. Retrieved from https://blossomanalysis.com/papers/the-abuse-potential-of-medical-psilocybin-according-to-the-8-factors-of-the-controlled-substances-act/

• Johnson, M., Richards, W., & Griffiths, R. (2008). Human Hallucinogen Research: Guidelines for Safety. Journal of Psychopharmacology, 603-620. Retrieved from https://blossomanalysis.com/papers/human-hallucinogen-research-guidelines-for-safety/

• Muthukumaraswamy, S., Forsyth, A., & Lumley. (2021). Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Review of Clinical Pharmacology, 1133-1152. Retrieved from https://blossomanalysis.com/papers/blinding-and-expectancy-confounds-in-psychedelic-randomised-controlled-trials/

• Nichols, D. (2016). Psychedelics. Pharmacological Reviews, 264-355. Retrieved from https://blossomanalysis.com/papers/psychedelics/