Psychedelic Clinical Trials
Psychedelics are a class of psychoactive drugs that can alter perception, thoughts, and feelings. Psychedelics can produce changes in consciousness and can lead to intense sensory experiences and altered states of mind.
The current therapeutic strategies for psychiatric disorders are associated with 20% to 60% treatment resistance, defined as non-response or inadequate response in patients who have been correctly diagnosed and adequately treated. Treatment resistance is associated with a risk for functional impairments in the patients and high healthcare and social costs.
Currently, prescribed antidepressant medications have a delayed response onset, a phenomenon associated with significant morbidity and healthcare costs. Therefore, the development of novel and improved therapeutics for the treatment of psychiatric disorders is urgently needed. Some drug candidates showing the greatest promise for developing novel therapeutics for psychiatric disorders include psychedelics.
Clinical Development of Psychedelic Pharmaceuticals
A number of psychedelic clinical trials have indicated that psychedelic-supported psychotherapy has the potential to alleviate symptoms of psychiatric disorders in a significant and sustained manner without serious adverse events. However, the most appropriate means to administer psychedelic pharmaceuticals to potentiate their therapeutic effects and minimize their adverse effects is still being investigated.
The clinical drug development of different psychedelic pharmaceuticals is at various stages. Notably, the U.S. Food and Drug Administration (FDA) has approved the combination of an esketamine nasal spray with an oral antidepressant for the therapy of treatment-resistant depression.
Other psychedelic drug candidates are still in the development and evaluation stage. Thus, psilocybin and MDMA have received “breakthrough therapy” designations for post-traumatic stress disorder (PTSD) and treatment-resistant depression, respectively. Findings regarding other psychedelic compounds stem primarily from observational psychedelic clinical trials, even though promising results have been demonstrated.
Dose Selection for Candidate Psychedelic Pharmaceuticals
Psychedelic compounds can be administered in high doses and microdosing psychedelics. High doses of psychedelics may cause hallucinations, sensory perceptual alterations, and changes in consciousness. Therefore, high-dose psychedelics are given during one or a few sessions, in a clinical setting, under continuous monitoring, and in combination with psychological support.
High-dose
High-dose psychedelics are administered in a private therapeutic setting with a qualified, explicitly trained mental health professional (a facilitator) who facilitates a preparatory, a treatment, and an integration session.
Microdosing
Microdosing psychedelics refers to administering sub-perceptual psychedelic pharmaceutical doses under the threshold, inducing observable perceptual alterations. The microdosing approach eliminates the experience of psychedelic effects, which may be intimidating or too intense for certain individuals.
Check out our blog written by our experts on
High and Microdosing Psychedelics in Clinical Research Trials
Phase 1 Clinical Trial Design of Psychedelic Clinical Trials
Read our FAQ regarding this question to find your answer. It is to be noted that participants can be dosed in small groups in a typical Phase 1 facility and without the involvement of a specialized facilitator. The safety monitoring of microdosed participants can be performed by the principal investigator (PI) and safety staff explicitly trained to identify and manage potential psychedelic-associated side effects.
Single ascending dose study design may be used to identify the optimal dose of psychedelic pharmaceutical compounds for use in future studies. Pharmacodynamic assessments evaluating the subjective effects of microdosed psychedelics can also be included. After selecting the optimal dose and formulation, outpatient studies may be conducted using this microdosing psychedelics approach, enabling drug administration in an outpatient setting that does not interfere with patients’ daily activities.
In the case of high-dose psychedelics, the presence of a facilitator and continuous safety monitoring are required. The safety and study assessments and blood sampling should be performed in a manner that is minimally disruptive for the study participants. High-dose psychedelic drugs may be employed in early-stage clinical trials in healthy volunteers and trials involving patients. Including psychological support or supportive psychotherapy for the patients and risk mitigation of adverse responses in healthy volunteers are essential.
Challenges Associated With Psychedelic Clinical Trials
BioPharma Services, Inc. offers comprehensive bioanalytical services in the context of early-phase clinical trials. As a full-service contract research organization (CRO), we readily integrate the acquired bioanalytical data in the design and conduct of early-phase clinical trials.
Difficulties masking (blinding) study participants
Due to the pronounced subjective effects of high-dose psychedelics, it is difficult to mask study participants regarding their treatment condition.
Recruitment of representative samples
The recruitment of study participants that are representative of the general population may be challenging because there may be a self-selection of individuals expecting beneficial effects among those choosing to participate in psychedelic clinical trials.
Abuse potential of psychedelic drug candidates
There are concerns regarding the human abuse potential of psychedelic pharmaceutrical drug candidates. Most psychedelic drugs have been classified as Schedule I drug regarding their abuse potential, whereas ketamine has been classified as a Schedule III substance.
Potential effects of participant expectations
The extensive media coverage of psychedelic compounds and their effects may influence participants’ expectations regarding the potential therapeutic benefit.
Susceptibility to large placebo and nocebo effects
The masking difficulties and participants’ expectations increase the risk of pronounced placebo and nocebo effects.
Impact of the scarcity of long-term follow-up data
Many psychedelic clinical trials use cross-over designs that impede the follow-up of long-term effects.
Considering the challenges associated with psychedelic clinical trials, various strategies have been proposed to improve their scientific rigor. They include explanation of the drug effects in neutral terms, incomplete disclosure of the treatment arms, use of active comparators, participation of psychedelic- and active placebo-naive individuals, controlling for the preliminary expectations, and evaluation of the test-masking efficacy.
Early-Phase Clinical Trials for Psychiatric Conditions
BioPharma Services, Inc. is a full-service contract research organization (CRO) with comprehensive experience in early-stage clinical trials. Our team — including more than 250 multidisciplinary experts and at least 8 Ph.D. graduates — has completed over 2,000 early-phase clinical trials that include psychedelic clinical trials.
BioPharma Services principal investigators have over 50 years of cumulative experience in:
- Phase 1 clinical trial pharmacology
- Clinical studies in various therapeutic areas
- Human abuse potential (HAP) research
- Product development
- Biostatistics in public health
- Clinical trial data management
- Regulatory and scientific affairs
Our PIs include BioPharma’s chief scientific officer (CSO), Dr. John Oldenhof, Dr. Isabella Szeto, and Dr. Janice Faulknor.
Established Bioanalytical Methods for Psychedelic Compounds and Metabolites
The bioanalytical studies at BioPharma Services are overseen by Dr. Nicki Hughes, who has over 20 years of experience in bioanalytical research, and are conducted by our competent and experienced bioanalytical lab team, including 25 staff members. Our in-house bioanalytical laboratory is equipped with a state-of-the-art platform for liquid chromatography with tandem mass spectrometry.
Dr. Hughes and her bioanalytical team have developed a range of sensitive, selective, accurate, and precise bioanalytical methods suitable for exploring the therapeutic benefits of psychedelic drugs for the treatment of psychiatric disorders. Some of these bioanalytical methods enable the pharmacokinetic assessment of psilocybin, psilocin, ketamine, norketamine, and hydroxynorketamine in human clinical trials.
These techniques are based on optimized extraction procedures and enable bioanalytic detection with liquid chromatography with tandem mass spectrometry. No impact of other main metabolites and no matrix effects were observed. The calibration ranges for the different analytes were 0.5–500 ng/mL for psilocybin, 0.1–100 ng/mL for psilocin, 0.4–100 ng/mL for ketamine, 4–1000 ng/mL for norketamine, and 0.25–50 ng/mL for hydroxynorketamine.
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Psychedelics FAQ
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What Are Psychedelics?
Psychedelics (sometimes also designated as hallucinogens) have been defined as compounds that cause hallucinations and apparent expansion of consciousness and may facilitate brain plasticity. Psychedelics can be subdivided into four classes according to their pharmacological and chemical characteristics, including3:
- Classic psychedelics
- Empathogens or entactogens
- Dissociative anesthetic agents
- Atypical hallucinogens
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What Are Some Different Types of Psychedelics?
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and ayahuasca, are serotonin 2A (5-HT2A) receptor agonists. Empathogens or entactogens, such as 3,4-methylenedioxymethamphetamine (MDMA), are mixed serotonin and dopamine reuptake inhibitors and releasers. Dissociative anesthetic agents, including ketamine, are N-methyl-D-aspartate (NMDA) antagonists. Finally, atypical hallucinogens affect multiple neurotransmitter systems.
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How are Psychedelic Clinical Trials Designed?
Regulatory agencies, such as Health Canada and the FDA, generally require the conduct of Phase 1 clinical trials, even for drug candidates previously administered to humans, such as psilocybin, to evaluate the specific drug formulation. The requirements for designing psychedelic clinical trials depend on the drug candidate and the selected dose. Early-phase psychedelic clinical trials involving microdosing are generally performed in healthy volunteers in clinical facilities, where the dose and formulation of the microdosed psychedelic are selected.
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What is the Importance of Psychedelic Clinical Trials?
With increasing evidence of efficacy, companies are beginning to study additional psychedelics and alternative formulations that could improve the usability of psychedelics on a larger scale. Mounting evidence is supporting the efficacy of psychedelics for the treatment of conditions such as depression, end-of-life distress, and alcohol addiction.
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Who Can Facilitate Psychedelic Clinical Trials?
BioPharma Services has two state-of-the-art Phase 1 facilities with controlled substance licenses in Toronto, Canada, and St. Louis, Missouri, that offer extensive safety monitoring by well-trained and motivated staff. Our multidisciplinary team has extensive experience in clinical studies involving drug candidates for psychiatric conditions, including antidepressants, anesthetics and stimulants. Our Psychedelic Clinical research is driven by Dr. John Oldenhof and Sofia Raitsin, BioPharma Services Senior Clinical Pharmacology Scientist.